bluuebunny/crossref_metadata_2025 huggingface dataset:
Operative treatment of anterior heterotopic bone formation of the elbow in a patient with severe haemophilia A
Authors: MORTAZAVI S. M. J. , ASADOLLAHI S. , MOTAMEDI M.
Published: June 2006

Summary.  There is no statistical data on the incidence of heterotopic ossification among patients with haemophilia, and a few reports documenting this entity in haemophilia are available. Although post‐traumatic heterotopic ossification about the elbow is a well‐recognized complication, we are not aware of any previously reported case in haemophiliacs. An 8‐year‐old boy with severe haemophilia A presented with fixed elbow in 80° of flexion. Radiographs disclosed a mature anterior heterotopic ossification in the form of complete ulnohumeral bony bridge. Surgical excision of the heterotopic bone was performed. A full elbow range of motion was obtained after long‐term physiotherapy. We conclude that this surgery is safe and successful in haemophilic patients, if performed at the right time under optimal situation.
Tyr2105Cys mutation in exon 22 of FVIII gene is a risk factor for the development of inhibitors in patients with mild/moderate haemophilia A
Authors: FRANCHINI M. , GIRELLI D. , OLIVIERI O. , CASTAMAN G. , LIPPI G. , POLI G. , SALVAGNO G. L. , TAGARIELLO G. , GIUFFRIDA A. , DE GIRONCOLI M. , MORFINI M. , BERNTORP E. , GANDINI G.
Published: June 2006

Summary.  We report the case of a patient with mild haemophilia A, due to a Tyr2105Cys mutation in exon 22 of the C1 domain, who developed a high‐titre factor VIII inhibitor (maximum titre 1600 BU) with recurrent severe haemorrhages and fatal intracranial bleeding. Based on published data, it appears that although this mutation occurs rarely in patients with mild or moderate haemophilia A, it is frequently associated with the development of high‐titre inhibitors.
Identification of fetal gender in maternal blood is a helpful tool in the prenatal diagnosis of haemophilia
Authors: SANTACROCE R. , VECCHIONE G. , TOMAIYOLO M. , SESSA F. , SARNO M. , COLAIZZO D. , GRANDONE E. , MARGAGLIONE M.
Published: June 2006

Summary.  Fetal DNA identification in maternal circulation has provided a new approach for non‐invasive prenatal diagnosis. However, fetal DNA can persist in maternal blood long after the delivery, severely hampering this possibility. We addressed the issue of fetal DNA persistence in maternal blood. Thus, we investigated cell‐free fetal DNA as a reliable approach in prenatal diagnosis of haemophilia. Forty non‐pregnant women, who had had at least a male fetus, 29 control pregnant women, and 14 pregnant women, carriers of hemophilia A or B. The assessment of Y‐chromosomal sequences was performed by analysing SRY and amelogenin genes using PCR‐based techniques. A protocol consisting of double centrifugation at full speed followed by plasma filtration hampered the detection of Y chromosome‐specific sequence in non‐pregnant women. In 29 control pregnant women, blinded determination of fetal sex confirmed the specificity and sensitivity of the method applied. In 14 pregnant carriers of hemophilia, the investigation revealed a male fetus in nine pregnancies. Excluding the three cases in which a spontaneous miscarriage occurred, the sensitivity and specificity of fetal sex prediction by SRY and amelogenin gene analyses were both 100% as compared with the invasive approach and the fetal sex outcome at birth (six males and five females). Because of its high accuracy in prediction, fetal gender determination with cell‐free fetal DNA in maternal plasma may be a useful tool in prenatal diagnosis of haemophilia allowing for the avoidance of invasive procedures for female fetuses.
Fibrinogen Denver: a dysfibrinogenemia associated with an abnormal Reptilase time and significant bleeding
Authors: WALTER S. , STABLER S. , LEFKOWITZ J. B.
Published: June 2006

Summary.  This paper reports a new dysfibrinogenemia with an unusual pattern of laboratory assays. The patient, a 51‐year‐old female with a lifelong moderate bleeding history, was initially diagnosed with von Willebrand disease based on routine coagulation assays and the clinical bleeding presentation. During recent testing as part of a preoperative screen and without any current history of treatment, levels of von Willebrand factor (VWF) antigen, VWF activity, and factor VIII activity were all significantly elevated, which was unexpected given her previous diagnosis. Additional testing was performed looking for other heritable causes for her considerable bleeding tendency. Interestingly, the patient had a significantly prolonged Reptilase time, minimally short thrombin time, and an abnormal fibrinogen‐crossed immunoelectrophoresis pattern. Clearly, this patient had a fibrinogen abnormality that had been missed when only routine coagulation screening assays were performed. A brief review of the fibrinogen literature revealed no other dysfibrinogenemias reported with a similar pattern of test results, and thus this defect was designated fibrinogen Denver.
Sequencing of the factor 8(F8) coding regions in 10 Turkish hemophilia A patients reveals three novel pathological mutations, and one rediagnosis of von Willebrand's disease type 2N
Authors: BERBER E. , FIDANCI I. D. , UN C. , EL‐MAARRI O. , AKTUGLU G. , GURGEY A. , CELKAN T. , MERAL A. , OLDENBURG J. , GRAW J. , AKAR N. , CAGLAYAN H.
Published: June 2006

Summary.  The most common cause for severe cases of hemophilia A is the homologous recombination involving intron 22 and related sequences outside the F8 gene. F8 coding regions of the gene including the exon/intron junctions were sequenced in 10 Turkish hemophilia A patients all of whom have been typed negative for intron 22 inversion and who did not have a detectable change by DGGE analysis. Pathological changes including two novel deletions (c. 205del CT and c. 3699del ACAT), one novel missense mutation (9546A) and two recurrent missense mutations were observed in five patients. The c. 2110C > T is another novel pathological change affecting exonic splicing enhancer site in two patients. One of the remaining three patients had a recurrent vWD type 2N mutation in the F8 binding site of the vWF (C788R). The S1269S polymorphism (c. 3864A > C) detected phenotype. Conclusively, sequencing of the promoter and the coding regions of 10 hemophilia A patients contributes four novel pathological mutations to the F8 mutations list and reveals a rediagnosis of hemophilia A but is still not sufficient to confirm hemophilia A phenotype in two patients.
A variable number of tandem repeats polymorphism influences the transcriptional activity of the neonatal Fc receptor α‐chain promoter
Authors: Sachs Ulrich J. H. , Socher Ines , Braeunlich Christian G. , Kroll Hartmut , Bein Gregor , Santoso Sentot
Published: June 2006

The neonatal Fc receptor, FcRn, plays a central role in immunoglobulin G (IgG) transport across placental barriers. Genetic variations of FcRn‐dependent transport across the placenta may influence antibody‐mediated pathologies of the fetus and the newborn. Sequencing analysis of 20 unrelated individuals demonstrated no missense mutation within the five exons of the FcRn gene. However, a variable number of tandem repeats (VNTR) region within the FcRn promoter was observed, consisting of five different alleles (VNTR1–VNTR5). Alleles with two (VNTR2) and three (VNTR3) repeats were found to be most common in Caucasians (7·5 and 92·0%, respectively). Real‐time polymerase chain reaction revealed that monocytes from VNTR3 homozygous individuals express 1·66‐fold more FcRn transcript than do monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·002). In reporter plasmid assays, the VNTR3 allele supported the transcription of a reporter gene twice as effectively as did the VNTR2 allele (P = 0·003). Finally, under acidic conditions, monocytes from VNTR3 homozygous individuals showed an increased binding to polyvalent human IgG when compared with monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·021). These data indicate that a VNTR promoter polymorphism influences the expression of the FcRn receptor, leading to different IgG‐binding capacities.
CD43‐independent augmentation of mouse T‐cell function by glycoprotein cleaving enzymes
Authors: Berger Scott B. , Sadighi Akha Amir A. , Miller Richard A. , Garcia Gonzalo G.
Published: June 2006

Previous work has shown that the function of mouse CD4+ T cells can be augmented by an enzyme, O‐sialoglycoprotein endopeptidase (OSGE), which cleaves surface CD43, suggesting the idea that the high levels of glycosylated CD43 found on T cells from aged mice may contribute to immune senescence. New results now show that OSGE improves T‐cell function even in mice lacking CD43, showing that other glycoproteins must contribute to the OSGE effect on function. Evaluation of other enzymes found two whose ability to stimulate CD4 activation was higher in aged than in young T cells. One of these, PNGase F, is a glycosidase specific for N‐linked glycans, and the other, ST‐Siase(2,3) from Salmonella typhimurium, is specific for α2,3‐linked terminal sialic acid residues. Parallel lectin‐binding experiments showed that removal of α2,3‐linked sialic acid residues vulnerable to PNGase F and ST‐Siase(2,3) was also greater in old than in young T cells. The preferential ability of PNGase F and ST‐Siase(2,3) to improve the function of T cells from aged mice may involve cleavage of glycoproteins containing α2,3‐linked sialic acid residues on N‐linked or O‐linked glycans or both.
Determination of antibacterial effects and total phenolic contents of grape (Vitis vinifera L.) seed extracts
Authors: Baydar Nilgun Gokturk , Sagdic Osman , Ozkan Gulcan , Cetin Sema
Published: June 2006

In the study, antibacterial activities of the seed extracts of three different grapes were examined against fifteen bacteria, and total phenolic contents of the extracts were additionally determined. The contents of total phenolic compounds of the grape seed extracts were 589.09 (Hasandede), 506.60 (Emir) and 549.54 (Kalecik Karasi) mg gallic acid equivalent (GAE) per gram with acetone:water:acetic acid (90:9.5:0.5). These extracts at 1%, 2.5%, 5% and 10% concentrations were tested for their antibacterial effects by using the agar diffusion method against some pathogenic and spoilage bacteria including Aeromonas hydrophila, Bacillus cereus, Enterobacter aerogenes, Enterococcus faecalis, Escherichia coli, E. coli O157:H7, Klebsiella pneumoniae, Mycobacterium smegmatis, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Salmonella enteritidis, Salmonella typhimurium, Staphylococcus aureus and Yersinia enterocolitica. All tested bacteria were inhibited by the grape seed extracts using agar well diffusion method. The most sensitive of the bacteria was A. hydrophila while Hasandede grape seed extract was the most inhibitive extract on test bacteria. Hasandede seed extract at 10% concentration gave the largest inhibition zone diameter (30.67 mm) against A. hydrophila. According to serial dilution method, while all the grape seed extracts at 0.5% and 1% concentrations had generally bacteriostatic activities against E. coli O157:H7, the same extracts appeared to have bactericidal effects at concentrations above 2.5%. In addition, the extracts at all concentrations had bactericidal activities against S. aureus at the end of 48 h. and A. hydrophila at the end of 1 h.
Experimental and model analyses of the effects of competition on individual size variation in wood frog (Rana sylvatica) tadpoles
Authors: PEACOR SCOTT D. , PFISTER CATHERINE A.
Published: June 2006

Size variation is a ubiquitous feature of animal populations and is predicted to strongly influence species abundance and dynamics; however, the factors that determine size variation are not well understood.

In a mesocosm experiment, we found that the relationship between mean and variation in wood frog (Rana sylvatica) tadpole size is qualitatively different at different levels of competition created by manipulating resource supply rates or tadpole density. At low competition, relative size variation (as measured by the coefficient of variation) decreased as a function of mean size, while at high competition, relative size variation increased. Therefore, increased competition magnified differences in individual performance as measured by growth rate.

A model was developed to estimate the contribution of size‐dependent factors (i.e. based on size alone) and size‐independent factors (i.e. resulting from persistent inherent phenotypic differences other than size that affect growth) on the empirical patterns.

Model analysis of the low competition treatment indicated that size‐dependent factors alone can describe the relationship between mean size and size variation. To fit the data, the size scaling exponent that describes the dependence of growth rate on size was determined. The estimated value, 0·83, is in the range of that derived from physiological studies.

At high competition, the model analysis indicated that individual differences in foraging ability, either size‐based or due to inherent phenotypic differences (size‐independent factors), were much more pronounced than at low competition. The model was used to quantify the changes in size‐dependent or size‐independent factors that underlie the effect of competition on size‐variation. In contrast to results at low competition, parameters derived from physiological studies could not be used to describe the observed relationships.

Our experimental and model results elucidate the role of size‐dependent and size‐independent factors in the development of size variation, and highlight and quantify the context dependence of individual (intrapopulation) differences in competitive abilities.
Sensitivity analysis of Markov models for communities of competing sessile organisms
Authors: SPENCER MATTHEW
Published: June 2006

Communities of competing sessile organisms are often modelled using Markov chains. Sensitivity analysis of the stationary distribution of these models tells us how we expect the abundance of each organism to respond to changes in interactions between species. This is important for conservation and management.

Markov models for such communities have usually been formulated in discrete time. Each column of the discrete‐time transition matrix must sum to 1 (column stochasticity). Sensitivity analysis therefore involves defining a pattern of compensation that maintains column stochasticity as a single transition probability changes. There is little biological theory about the appropriate compensation pattern, but the usual choices involve changing only the elements of a single column of the transition matrix.

I argue that if the underlying dynamics occur in continuous time, each transition probability is the net outcome of direct and many indirect interactions.

Determining the consequences of changing a single direct interaction will often be of interest. I show how this can be achieved using a continuous‐time model. The resulting discrete‐time compensation pattern is quite different from those that have been considered elsewhere, with changes occurring in many columns.

I also show how to determine which direct interactions are being changed under any discrete‐time compensation pattern.
Predicting the ecological consequences of environmental change: a review of the methods*
Authors: SUTHERLAND WILLIAM J.
Published: June 2006

There is a clear need to increase our ability to predict the consequences of environmental change. The seven main approaches that are currently used are: extrapolation, experiments, phenomenological models, game‐theory population models, expert opinion, outcome‐driven modelling and scenarios. Each approach has different strengths and weaknesses. In practice, several approaches are often combined.

Adaptive management aimed at testing hypotheses is excellent in principle and widely advocated. In reality, however, it is almost never carried out because the changes in management usually have to be severe in order to bring about detectable changes in a reasonable time, and the political risks of such management are usually considered too high.

Game‐theory population models are used to determine population‐level phenomena based upon the decisions individuals make in response to resource depletion, interference, territoriality or rank. This allows predictions to be made regarding responses to novel conditions. The main drawback is that for some models considerable information is required.

Much of conservation practice is not based upon evidence. Evidence‐based conservation is the practice of accumulating, reviewing and disseminating evidence with the aim of formulating appropriate management strategies. Evidence‐based medicine revolutionized medical practice and similar opportunities exist to improve conservation practice.

Synthesis and applications. The conventional approach of making assumptions and deriving models to make predictions about the consequences of environmental change is often unsatisfactory for complex problems, with considerable uncertainty. Tackling such problems is likely to require greater exploration of techniques such as expert opinion, output‐driven modelling and scenarios.
Can management compensate for atmospheric nutrient deposition in heathland ecosystems?
Authors: HÄRDTLE WERNER , NIEMEYER MARION , NIEMEYER THOMAS , ASSMANN THORSTEN , FOTTNER SILKE
Published: June 2006

Atmospheric nutrient deposition has contributed to widespread changes in heathlands throughout Europe. As a consequence, management is now being considered as a potential tool with which to compensate for increased nutrient loads. Currently, only limited information is available on the extent to which management measures could compensate for atmospheric nutrient deposition. We hypothesized that low‐intensity management measures are not sufficient to counterbalance current nutrient inputs, particularly of nitrogen (N).

In order to improve heathland management schemes, we evaluated the effectiveness of different management measures in reducing the impact of ongoing atmospheric nutrient loads. We compared the effects of mowing, prescribed burning (low‐intensity management) and sod‐cutting (high‐intensity management) on heathland nutrient budgets [N, calcium (Ca), potassium (K), magnesium (Mg) and phosphorus (P)] in the Lueneburg Heath nature reserve (north‐west Germany). Nutrient balances were calculated by analysing the present‐day input, the output as a result of the removal of biomass/humus horizons, and changes in leaching rates.

Nutrient losses by increased leaching following management measures were negligible compared with nutrient losses caused by the removal of above‐ground biomass or humus horizons. The total quantities of nutrients removed by sod‐cutting were equivalent to between 37 and 176 years of atmospheric input (for N, 89 years).

In contrast, the quantities of N removed by mowing and prescribed burning were equivalent to only 5 years of atmospheric input. Thus, heathlands subjected to such treatments will accumulate N in the long term. In addition, output–input ratios for phosphorus (P) exceeded those for N in the mowing and sod‐cutting experiments. It is therefore likely that heathlands currently (co‐) limited by N will shift to being more P‐limited in the long term. This will promote species that are well adapted to P‐limited sites (e.g.Molinia caerulea).

Synthesis and applications. This study shows that low‐intensity management cannot compensate for atmospheric N loads in the long term. Consequently, high‐intensity management measures are an indispensable tool in preserving a long‐term balanced N budget in heathlands. In order to maintain a diverse structure, managers need to combine low‐ and high‐intensity management measures. Prescribed burning proved to be the best means of avoiding an increasing P shortage, because this measure causes very low P outputs.
Mitigation or disturbance? Effects of liming on macroinvertebrate assemblage structure and leaf‐litter decomposition in the humic streams of northern Sweden
Authors: MCKIE B. G. , PETRIN Z. , MALMQVIST B.
Published: June 2006

Stream liming can alleviate the effects of anthropogenic acidification but itself constitutes a substantial ecosystem‐level perturbation. Acidity in the humic streams of northern Sweden largely arises from natural causes but liming is extensively practised, with uncertain ecological outcomes.

We investigated macroinvertebrate assemblage structure and leaf‐litter decomposition in seven humic Swedish streams, each of which is limed at a single point using a dosing tower. Grey alder Alnus incana leaves were enclosed in replicate fine (mesh size 0·5 mm) and coarse (10 mm) mesh bags at three locations in each stream: upstream of the dosing tower, in the transitional ‘mixing zone’ immediately downstream of the tower, and at a site further downstream where the lime powder is completely dissolved, with marked changes to water chemistry. Benthic macroinvertebrate assemblages were characterized from each site via five replicate Surber samples.

Alkalinity, pH, conductivity and calcium (Ca) concentrations increased following liming, whereas dissolved organic carbon and aluminium concentrations decreased.

Decomposition in fine mesh bags, primarily mediated by microbes, was positively associated with pH and Ca and was significantly elevated by liming, probably attributable to stimulation of fungal pectin‐degrading enzymes that require Ca as a cofactor.

Decomposition attributable to detritivorous insects (shredders), assessed by subtracting decomposition observed in fine mesh bags from that observed in coarse bags, was reduced following liming, in concert with changes to shredder assemblages. Abundance of large caddisfly shredders declined in limed stream sections, whereas some smaller stoneflies increased in number. Shredder diversity declined following liming during spring. Species evenness fell overall, and richness was reduced in four of six streams.

Synthesis and applications. Water chemistry changes following stream liming in northern Sweden appear to overcompensate for the limited acid deposition observed in the region, with important ecosystem consequences. The potential deleterious impacts of liming need to be balanced against its desired outcomes in regions where acidity is largely attributable to natural causes.
Treatment of hepatitis C virus and human immunodeficiency virus coinfection: from large trials to real life
Authors: Cacoub P. , Rosenthal E. , Halfon P. , Sene D. , Perronne C. , Pol S.
Published: June 2006

Summary.  To analyse the barriers for anti‐hepatitis C virus (anti‐HCV) treatment in human immunodeficiency virus (HIV)–HCV coinfected patients, we surveyed 71 physicians specializing in infectious disease (39%), internal medicine (27%), HIV/AIDS information and care (17%), haematology (10%) and hepatology (6%). A standard data collection form was used to identify patients observed in 7 days in November 2004. Three hundred and eighty patients with the following characteristics were included: male gender 71%; mean age 41.5 years; HIV diagnosed 12 years ago; routes of transmission via injection drug use (78%); undetectable HIV viral load (235/373, 63%) or <10 000 copies/mL (86/373, 23%). HCV RNA was positive in 325 of 369 (88%) patients; HCV genotype was 1 or 4 in 65% and liver biopsy had been carried out in 56%. There were several explanations for the nontreatment of HCV in 205 of the 380 (54%) patients, with 2.4 reasons per patient: anti‐HCV treatment was deemed questionable (n = 109) because of minor hepatic lesions, alcohol consumption, or active drug use; no liver biopsy had been performed (n = 68); treatment was contraindicated (n = 62), mainly for psychiatric reasons; there was physician conviction of poor patient compliance (n = 62) and patient refusal (n = 33). Patients having received anti‐HCV treatment (n = 91) compared with those who had never received any (n = 205) were more commonly of European origin, had better control of their HIV infection, were followed by a hepatologist more often, had a liver biopsy more often and had more commonly a high HCV viral load (P < 0.001). In ‘real life’ in France in 2004, more than half of the HIV–HCV coinfected patients have never received anti‐HCV treatment. The main reasons are a treatment that may be deemed questionable (minimal hepatic lesions, alcohol, active drug use), a lack of available liver biopsy, a psychiatric contraindication and physician conviction of poor patient compliance.
Distribution of mosquito species in areas with high and low incidence of classic Kaposi’s sarcoma and seroprevalence for HHV‐8
Authors: ASCOLI V. , FACCHINELLI L. , VALERIO L. , ZUCCHETTO A. , DAL MASO L. , COLUZZI M.
Published: June 2006

Abstract The ‘promoter‐arthropod’ hypothesis, which postulates that exposure to the bites of certain species of haematophagous arthropods is an environmental risk cofactor linked to human herpes virus 8 (HHV‐8) and Kaposi’s sarcoma, was investigated in the Po River valley, northern Italy. The presence and density of adult female mosquitoes (Diptera: Culicidae) was determined by CDC light trap catches in two adjacent districts, at variance with respect to Kaposi’s sarcoma incidence and HHV‐8 seroprevalence. A total of 3910 specimens belonging to 11 species was collected in 34 rural sites (six municipalities) representative of the two districts. Five of these species are considered to be possible ‘promoters’ because of the irritation their bites cause humans: Aedes vexans (Meigen) and Ae. caspius (Pallas) (87% of sampled promoters), Culex modestus Ficalbi, Culiseta annulata (Schrank) and Coquillettidia richiardii (Ficalbi). Six are probable ‘non‐promoters’: Cx. pipiens s.l., Cx. martinii Medschid, Anopheles claviger (Meigen), An. maculipennis s.l., An. plumbeus Stephens and Uranotaenia unguiculata Edwards. The density of promoters by site was correlated with the incidence rates of Kaposi’s sarcoma at the district level (Pearson’s r= 0.33, P= 0.06) and at the municipal level (r= 0.50, P < 0.01). Similar correlations emerged for non‐promoters (r= 0.48, P < 0.01 and r = 0.42, P= 0.01, respectively). The density of promoters was higher than that of non‐promoters in sites with livestock (odds ratio, OR = 2.8, 95% CI 2.2–3.6) and in municipalities with Kaposi’s sarcoma cases (OR = 2.5, 95% CI 1.7–3.5). The study provides additional evidence of the association between the density of some mosquito species and Kaposi’s sarcoma.
Molecular characterization of the malaria vector Anopheles gambiae s.s. in Madagascar
Authors: LE GOFF G. , LÉONG POCK TSY J.‐M. , ROBERT V.
Published: June 2006

Abstract Anopheles gambiae s.s. Giles (Diptera: Culicidae), the primary African malaria vector, has been characterized at the subspecies level in Madagascar, where only the molecular form S and haplotype gIA occur. The haplotype gIC proposed by other authors was not observed amongst the 35 mosquito genomes sequenced. These S/gIA characteristics are also found on the Comoros archipelago and in continental Africa.
Population structure in a critically endangered arctic fox population: does genetics matter?
Authors: DALÉN L. , KVALØY K. , LINNELL J. D. C. , ELMHAGEN B. , STRAND O. , TANNERFELDT M. , HENTTONEN H. , FUGLEI E. , LANDA A. , ANGERBJÖRN A.
Published: June 2006

The arctic fox (Alopex lagopus) in Scandinavia is classified as critically endangered after having gone through a severe decline in population size in the beginning of the 20th century, from which it has failed to recover despite more than 65 years of protection. Arctic foxes have a high dispersal rate and often disperse over long distances, suggesting that there was probably little population differentiation within Scandinavia prior to the bottleneck. It is, however, possible that the recent decline in population size has led to a decrease in dispersal and an increase in population fragmentation. To examine this, we used 10 microsatellite loci to analyse genetic variation in 150 arctic foxes from Scandinavia and Russia. The results showed that the arctic fox in Scandinavia presently is subdivided into four populations, and that the Kola Peninsula and northwest Russia together form a large fifth population. Current dispersal between the populations seemed to be very low, but genetic variation within them was relatively high. This and the relativeFSTvalues among the populations are consistent with a model of recent fragmentation within Scandinavia. Since the amount of genetic variation is high within the populations, but the populations are small and isolated, demographic stochasticity seems to pose a higher threat to the populations’ persistence than inbreeding depression and low genetic variation.
Gregariousness and protandry promote reproductive insurance in the invasive gastropod Crepidula fornicata: evidence from assignment of larval paternity
Authors: DUPONT L. , RICHARD J. , PAULET Y‐M. , THOUZEAU G. , VIARD F.
Published: June 2006

According to the size‐advantage hypothesis, protandric sequential hermaphroditism is expected when the increase in reproductive success with age or size is small for males but large for females. Interestingly, some protandrous molluscs have developed gregarious strategies that might enhance male reproductive success but at the cost of intraspecific competition. The gastropod Crepidula fornicata, a European invading species, is ideal for investigating mating patterns in a sequential hermaphrodite in relation to grouping behaviour because individuals of different size (age) live in perennial stacks, fertilization is internal and embryos are brooded. Paternity analyses were undertaken in stacks sampled in three close and recently invaded sites in Brittany, France. Paternity assignment of 239 larvae, sampled from a set of 18 brooding females and carried out using five microsatellite loci, revealed that 92% of the crosses occurred between individuals located in the same stack. These stacks thus function as independent mating groups in which individuals may reproduce consecutively as male and female over a short time period, a pattern explained by sperm storage capacity. Gregariousness and sex reversal are promoting reproductive insurance in this species. In addition, females are usually fertilized by several males (78% of the broods were multiply sired) occupying any position within the stack, a result reinforcing the hypothesis of sperm competition. Our study pointed out that mating behaviours and patterns of gender allocation varied in concert across sites suggesting that multiple paternities might enhance sex reversal depending on sperm competition intensity.
Primary pulmonary choriocarcinoma combined with adenocarcinoma
Authors: Yamamoto Sohei , Tanaka Hiroyuki , Takeo Hiroaki , Yasuda Kazuyo , Mastukuma Susumu
Published: June 2006

An extremely rare autopsy case of primary pulmonary choriocarcinoma combined with adenocarcinomatous components in a 77‐year‐old Japanese man is described. The patient died of rapidly progressive respiratory dysfunction without ante‐mortem diagnosis. Autopsy revealed necro‐hemorrhagic areas of the primary lung tumor with a typical biphasic pattern of choriocarcinoma. Topographical analysis suggested that moderately to poorly differentiated adenocarcinoma components partially surrounded the choriocarcinomatous components. Moreover, dedifferentiated carcinomatous components were scattered next to both adenocarcinomatous and choriocarcinomatous areas, and a few cells of the dedifferentiated carcinomatous components had a similar immunoreaction to conventional adenocarcinomatous or choriocarcinomatous components, such as surfactant apoprotein A, placental alkaline phosphatase or β‐human chorionic gonadotropin. Additionally, epithelial membrane antigen‐positive cytotrophoblastic cells were rarely found in choriocarcinomatous areas. The present case suggests that primary lung choriocarcinoma can occur closely related to conventional pulmonary adenocarcinoma, although collision tumor was not completely ruled out.
The Pelican Cancer Foundation and The English National MDT‐TME Development Programme
Authors: Jessop J. , Beagley C. , Heald R. J.
Published: June 2006

The formation of The Pelican Cancer Foundation in 2000 was based around the pioneering work of Professor Bill Heald and colleagues, and the development of Total Mesorectal Excision (TME) for rectal cancer. A series of surgical workshops in Scandinavia in the mid 1990s and, later, six further workshops in the Trent region culminated in the commissioning of the fully multidisciplinary National MDT‐TME Development Programme by the National Cancer Director, Professor Mike Richards, in March 2003.
Emerging therapies for rectal cancer
Authors: Chua Y. J. , Cunningham D.
Published: June 2006

Preoperative treatment with either short‐course radiotherapy or chemo‐radiotherapy (CRT) is used routinely in some centres to reduce local recurrence rates in patients with operable rectal cancer prior to optimal surgery. However, there is a need for new treatment strategies to further improve the outcomes of these patients, particularly with regard to survival. Advances in the treatment of metastatic disease, such as the use of combination chemotherapy with oxaliplatin and irinotecan, and the targeted agents bevacizumab and cetuximab, have led to clinical research into alternative radio‐sensitizers during CRT and the novel use of neo‐adjuvant (preoperative) chemotherapy prior to preoperative CRT and surgery. Whilst these remain experimental, it is likely that these will serve as a platform for developing an expanded range of treatment options so that clinicians will be better able to tailor treatment to the needs of different patients.
Assessment and management of the complete clinical response of rectal cancer to chemoradiotherapy
Authors: Habr‐Gama A.
Published: June 2006

Preoperative chemoradiotherapy is considered by many as the preferred treatment strategy for distal rectal cancer. The observation of complete tumour regression has led to the proposition of nonoperative management of selected patients with complete clinical response (cCR) following treatment. We present results for the treatment of distal rectal cancer during 1991–2005. We have outlined the issues concerning adequate tumour assessment, the definition of complete response, and the advantages and disadvantages of conservative or surgical resection in patients with clinical and radiological evidence of cCR.
Laparoscopic surgery for colorectal cancer
Authors: Kienle P. , Weitz J. , Koch M. , Büchler M. W.
Published: June 2006

Traditionally open surgical resection has been recommended for colorectal tumours, but recently, laparoscopic surgery has gained popularity. This review summarizes the published data on laparoscopic colorectal cancer surgery with emphasis on recently published trials. For colon cancer laparoscopic resection appears to be associated with the same outcome as open surgery. However, whilst short‐term outcome was better in the laparoscopic group in most of the randomized trials, when comparing laparoscopic with fast‐track open surgery, no differences could be demonstrated in a randomized control trial. For rectal cancer the data are less clear. It seems that it may be feasible to resect at least small rectal cancers laparoscopically. Clearly the role of the laparoscopic technique needs to be better defined in rectal cancer. It has been well documented that short‐ and long‐term outcome of colorectal cancer surgery depends on the quality and experience of the team treating the patient. Therefore, the major future challenge in laparoscopic colorectal cancer surgery will be to provide and structure adequate training and introduce quality control measures.
Pathological assessment of rectal carcinoma after preoperative therapy
Authors: Wotherspoon A. C.
Published: June 2006

Increasingly neoadjuvant therapy is being used to improve outcomes in patients with rectal carcinoma in which the circumferential resection margins are considered to be at risk for involvement if primary surgery were to be undertaken. Assessment of the response to this approach relies on radiological examination, particularly magnetic resonance imaging (MRI) studies. Following definitive surgery, careful histological examination allows full assessment of the tumour response to these preoperative approaches. Histological examination requires careful fixation, examination of the entire area occupied by the tumour prior to down‐staging and careful lymph node harvesting. Adequate fixation helps in these endeavours and the lymph node harvest appears to be unaffected by neoadjuvant chemo‐ or radiotherapy. Correlation between preoperative assessment of response by MRI and the subsequent histological assessment is close, but the presence of isolated residual neoplastic glands in a post‐treatment fibrotic stroma is impossible to detect prior to resection. The clinical significance of these microscopic foci remains uncertain, particularly in view of the prolonged tumour doubling time associated with colorectal adenocarcinoma. The preoperative discussion with the patient requires a synthesis of their own scan results and the experience of detailed clinico‐pathological studies. While MRI frequently predicts the presence or absence of residual tumour the possibility of under‐staging remains and this is of crucial importance if a ‘watch and wait’ policy is to be adopted following apparent complete clinical and radiological remission. The significance of potential residual microscopic disease in patients with apparent radiological complete remission needs further investigation but may need to be interpreted in individual patients in the context of overall life‐expectancy.
MRI and SPECT studies of dural arteriovenous fistulas presenting as pure progressive dementia with leukoencephalopathy: a cause of treatable dementia
Authors: Waragai M. , Takeuchi H. , Fukushima T. , Haisa T. , Yonemitsu T.
Published: June 2006

We report two patients with dural arteriovenous fistulas (DAVFs) who presented with pure progressive dementia. Both patients showed only slowly progressive dementia, without headache, papilledema and other neurologic signs associated with diffuse white matter changes in MRI. MR cerebral angiography showed sigmoid sinus DAVFs that were mainly supplied by the occipital artery, together with retrograde filling of the superior sagittal and straight sinus and dilated cortical veins. SPECT studies showed extensive blood flow reduction in the occipital and parieto‐occipital areas and right temporal lobe in one patient. Selective embolization for treatment of the DAVF improved cognitive function associated with the abnormal white matter MRI signal. MRI and SPECT showed that severity of dementia correlated with diffuse white matter changes and regional cerebral blood flow. Our cases suggest that gradually impaired cerebral circulation due to venous hypertensive encephalopathy could be involved in slowly progressive dementia with leukoencephalopathy resulting from a DAVF. DAVFs may be particularly important for differential diagnosis in elderly patients with pure progressive dementia. Thus, early diagnosis of DAVFs and treatment by endovascular surgery is important as treatable or reversible dementia.
Primitive reflex evaluation in the clinical assessment of extrapyramidal syndromes
Authors: Borroni B. , Broli M. , Costanzi C. , Gipponi S. , Gilberti N. , Agosti C. , Padovani A.
Published: June 2006

The aim of the present study was to evaluate the role of primitive reflexes (PRs) as additional alert sign in routine clinical practice in patients with extrapyramidal syndrome. We considered glabellar, snout, palmomental and grasp reflexes in patients with mild stage of Lewy body dementia (LBD), corticobasal degeneration, progressive supranuclear palsy or Parkinson disease (PD). We also enrolled mild Alzheimer disease (AD) patients, and healthy subjects, as controls. LBD patients showed the highest prevalence of PRs compared with the other groups. The odds ratio of the risk of LBD in PRs ≥ 2 was 27.9 (95% CI 2.9–269.0) compared with control group, 14.6 (95% CI 2.7–79.6) compared with mild AD, and 19.7 (95% CI 3.7–104.3) compared with PD. These data suggest that the occurrence of combination of PRs might be an useful additional warning sign of possible diffuse Lewy body pathology more than other causes of extrapyramidal syndrome.
Neuropsychological profiles of manganese neurotoxicity
Authors: Klos K. J. , Chandler M. , Kumar N. , Ahlskog J. E. , Josephs K. A.
Published: June 2006

The etiology of manganese neurotoxicity is heterogenous and includes exposure to welding fumes, chronic liver failure, and chronic total parental nutrition (TPN). We recently reported that cognitive impairment occurs in welders and patients with chronic liver failure who had evidence of manganese neurotoxicity including abnormal magnetic resonance imaging (MRI) basal ganglia T1 hyperintensity. In this study, we compared the neuropsychological profiles of patients with manganese neurotoxicity and basal ganglia T1 hyperintensities from three different etiologies: welding, chronic liver failure, and chronic TPN. Across all three groups, the neuropsychological profiles suggest frontal and subcortical cognitive impairment, with more widespread abnormalities occurring in the non‐welding groups.
Bilateral facial palsy: Epstein–Barr virus, not Lyme disease
Authors: Diedler J. , Rieger S. , Koch A. , Parthé‐Peterhans S. , Schwaninger M.
Published: June 2006

Bilateral facial palsy is frequently linked with lyme disease. We report a patient with bilateral facial palsy due to Epstein‐Barr virus infection but with Borrelia burgdorferi IgM in serum caused by polyclonal B‐lymphocyte stimulation.
MRI evidence of bilateral hippocampal sclerosis in amnestic mild cognitive impairment
Authors: Sepe‐Monti M. , De Carolis A. , Bomboi G. , Castri P. , Giubilei F.
Published: June 2006

We present the case of a man affected by amnestic mild cognitive impairment (aMCI) who showed bilateral hippocampal sclerosis at magnetic resonance imaging (MRI). We argue the concept that aMCI is heterogeneous syndrome and suggested the utility of coronal T2‐weighted MRI images in the routine dementia workup.
A pilot study on systemic thrombolysis followed by low molecular weight heparin in ischemic stroke
Authors: Mikulík R. , Dufek M. , Goldemund D. , Reif M.
Published: June 2006

Low molecular weight heparin (LMWH) administered immediately after intravenous thrombolysis (IT) may reduce the risk of arterial re‐occlusion. Its benefit, however, may not outweigh the risk of intracranial hemorrhage (ICH). We sought preliminary data regarding safety of this combined therapy in an open‐label, non‐randomized study. The patients received either a standard anticoagulation (AC) starting 24 h after IT (the standard AC group) or AC with 2850 IU of nadroparin, given every 12 h immediately after IT (the early AC group). Sixty patients received IT treatment: 25 in the standard AC group [mean age 66, median National Institutes of Health Stroke Scale (NIHSS) 13, 64% men] and 35 in the early AC group (mean age 68, median NIHSS 13, 69% men). Symptomatic ICH occurred in one patient (4%) in the standard AC group and three patients (8.6%) in the early AC group [odds ratio (OR) 1.8; 95%CI 0.2–12.8]. At 3 months, nine patients in the standard AC group (36%) and 16 patients in the early AC group (45.7%) achieved a modified Rankin scale 0 or 1 (OR 1.2; 95%CI 0.5–3.2). Our study suggests that treatment with LMWH could be associated with higher odds of ICH, although it may not necessarily lead to a worse outcome. This justifies larger clinical trials.
The Long‐Term Price‐Earnings Ratio
Authors: Anderson Keith , Brooks Chris
Published: June 2006

Abstract:  The price‐earnings effect has been thoroughly documented and is the subject of numerous academic studies. However, in existing research it has almost exclusively been calculated on the basis of the previous year's earnings. We show that the power of the effect has until now been seriously underestimated due to taking too short‐term a view of earnings. Looking at all UK companies since 1975, using the traditional P/E ratio we find the difference in average annual returns between the value and glamour deciles to be 6%. This is similar to other authors' findings. We are able to almost double the value premium by calculating the P/E ratio using earnings averaged over the previous eight years.
Four‐bar linkage modelling in teleost pharyngeal jaws: computer simulations of bite kinetics
Authors: Grubich Justin R. , Westneat Mark W.
Published: June 2006

The pharyngeal arches of the red drum (Sciaenops ocellatus) possess large toothplates and a complex musculoskeletal design for biting and crushing hard prey. The morphology of the pharyngeal apparatus is described from dissections of six specimens, with a focus on the geometric conformation of contractile and rotational elements. Four major muscles operate the rotational 4th epibranchial (EB4) and 3rd pharyngobranchial (PB3) elements to create pharyngeal bite force, including the levator posterior (LP), levator externus 3/4 (LE), obliquus posterior (OP) and 3rd obliquus dorsalis (OD). A biomechanical model of upper pharyngeal jaw biting is developed using lever mechanics and four‐bar linkage theory from mechanical engineering. A pharyngeal four‐bar linkage is proposed that involves the posterior skull as the fixed link, the LP muscle as input link, the epibranchial bone as coupler link and the toothed pharyngobranchial as output link. We used a computer model to simulate contraction of the four major muscles, with the LP as the dominant muscle, the length of which determined the position of the linkage. When modelling lever mechanics, we found that the effective mechanical advantages of the pharyngeal elements were low, resulting in little resultant bite force. By contrast, the force advantage of the four‐bar linkage was relatively high, transmitting approximately 50% of the total muscle force to the bite between the toothplates. Pharyngeal linkage modelling enables quantitative functional morphometry of a key component of the fish feeding system, and the model is now available for ontogenetic and comparative analyses of fishes with pharyngeal linkage mechanisms.
Microcracks in compact bone: a three‐dimensional view
Authors: Mohsin S. , O’Brien F. J. , Lee T. C.
Published: June 2006

Microcracks have been implicated in the loss of bone quality for osteoporosis. In order to detect and monitor their growth, and to use these data to predict fractures, it is essential to obtain quantitative data regarding their shape in three dimensions. Beam‐shaped bone samples from sheep radii were prepared and stained with fluorochrome dyes and tested in cyclical fatigue under four‐point bending in a servo‐hydraulic fatigue‐testing machine. Samples were tested at a frequency of 30 Hz under load control at a stress range of 100 MPa. Holes were drilled into bone samples and used as reference points for reconstructions. A series of thin longitudinal sections were cut using a sledge macrotome. A two‐dimensional image of each section was examined using an epifluorescence microscope and images transferred to a PC via a CCD low‐light colour video camera. A three‐dimensional image of each microcrack was reconstructed using computer software, and its dimensions measured. Cracks were elliptical in shape, longer in the longitudinal direction and with a mean aspect ratio of 5.5 ± 1.05. The mean (± SD) length and width of labelled microcracks were 488 ± 151 and 88 ± 21 µm, respectively.