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A growing body of evidence suggests that decision-making and action execution are governed by partly overlapping operating principles. Especially, previous work proposed that a shared decision urgency/movement vigor signal, possibly computed in the basal ganglia, coordinates both deliberation and movement durations in a way that maximizes the reward rate. Recent data support one aspect of this hypothesis, indicating that the urgency level at which a decision is made influences the vigor of the movement produced to express this choice. Here we investigated whether conversely, the motor context in which a movement is executed determines decision speed and accuracy. Twenty human subjects performed a probabilistic decision task in which perceptual choices were expressed by reaching movements toward targets whose size and distance from a starting position varied in distinct blocks of trials. We found strong evidence for an influence of the motor context on most of the subjects’ decision policy but contrary to the predictions of the “shared regulation” hypothesis, we observed that slow movements executed in the most demanding motor blocks in terms of accuracy were often preceded by faster and less accurate decisions compared to blocks of trials in which big targets allowed expression of choices with fast and inaccurate movements. These results suggest that decision-making and motor control are not regulated by one unique “invigoration” signal determining both decision urgency and action vigor, but more likely by independent, yet interacting, decision urgency and movement vigor signals.NEW & NOTEWORTHYRecent hypotheses propose that choices and movements share optimization principles derived from economy, possibly implemented by one unique context-dependent regulation signal determining both processes speed. In the present behavioral study conducted on human subjects, we demonstrate that action properties indeed influence perceptual decision-making, but that decision duration and action vigor are actually independently set depending on the difficulty of the movement executed to report a choice.

Speed-accuracy tradeoff adjustments in decision-making have been mainly studied separately from those in motor control. In the wild however, animals coordinate their decision and action, freely investing time in choosing versus moving given specific contexts. Recent behavioral studies support this view, indicating that humans trade decision time for movement time to maximize their global rate of reward during experimental sessions. Besides, it is established that choice outcomes impact subsequent decisions. Crucially though, whether and how a decision also influences the subsequent motor behavior, and whether and how a motor error influences the next decision is unknown. Here we address these questions by analyzing trial-to-trial changes of choice and motor behaviors in healthy human participants instructed to perform successive perceptual decisions expressed with reaching movements whose duration was either bounded or unconstrained in separate tasks. Results indicate that after a bad decision, subjects who were not constrained in their action duration decided more slowly and more accurately. Interestingly, they also shortened their subsequent movement duration by moving faster. Conversely, we found that movement errors not only influenced the speed and the accuracy of the following movement, but those of the decision as well. If the movement had to be slowed down, the decision that precedes that movement was accelerated, and vice versa. Together, these results indicate that from one trial to the next, humans are primarily concerned about determining a behavioral duration as a whole instead of optimizing each of the decision and action speed-accuracy trade-offs independently of each other.

The role of norepinephrine (NE) in visuo-spatial attention remains poorly understood. Our goal was to identify the attentional processes influenced by atomoxetine (ATX) injections, a NE-reuptake inhibitor that boosts the level of NE in the brain, and to characterize these influences. We tested the effects of ATX injections, on seven monkeys performing a saccadic cued task in which cues and distractors were used to manipulate spatial attention. We found that when the cue accurately predicted the location of the upcoming cue in 80% of the trials, ATX consistently improved attentional orienting, as measured from reaction times (RTs). These effects were best accounted for by a faster accumulation rate in the valid trials, rather than by a change in the decision threshold. By contrast, the effect of ATX on alerting and distractor interference was more inconsistent. Finally, we also found that, under ATX, RTs to non-cued targets were longer when these were presented separately from cued targets. This suggests that the impact of NE on visuo-spatial attention depends on the context, such that the adaptive changes elicited by the highly informative value of the cues in the most frequent trials were accompanied by a cost in the less frequent trials.

Inherited factor VII (FVII) deficiency is considered to be a haemorrhagic disease. Nonetheless, some patients paradoxically present with venous thrombosis. We assessed whether there was a link between phenotype and genotype in seven patients with inherited FVII deficiency and thrombosis (eleven venous thrombotic events). For each patient (FVII:C < 50%), clinical data were collected, aetiological assessment of risk factors for thrombosis was investigated, and direct sequencing of the nine exons and promoter of the FVII gene (F7) was performed. We present the second series ever published on FVII patients with thrombosis. In nine of the eleven thrombotic events, there was at least one classical triggering risk factor; clinical (n = 4), familial antecedent (n = 2), or biological, defined by phospholipid-binding antibodies or elevated FVIII:C levels (n = 7). In contrast to a previous series, only two events occurred after surgery, performed both with and without replacement therapy. The thrombotic event remained unexplained in one young patient, highlighting the lack of 'protection' against venous thrombosis by low FVII:C levels. Genetic mutations were found to be heterogeneous. Among the seven F7 sequence alterations identified in the present study, only two (p.Ala354Val and p.Arg364Gln) have previously been reported in FVII-deficient patients presenting with venous thrombosis. Our genetic analyses of the F7 mutations in these patients show the complexity of FVII deficiency associated with thrombosis. These data justify a holistic, clinical and biological approach for patients with these specific symptoms. This series also strongly suggest that mild FVII deficiency should not prevent physicians from using antithrombotic prophylaxis in FVII-deficient patients.

Purpose Decreased reflectance within the retinal nerve fiber layer (RNFL), observable using optical coherence tomography (OCT), appears to be related to functional loss in glaucoma. In order to investigate this in a quantitative manner, reliable measurements of reflectance intensity are needed. However, reflectance may not only be affected by pathophysiological changes in tissue properties but also confounded by other effects of ocular media and image quality. This study assesses the repeatability of intensity measurements, before and after normalization aimed to reduce test-retest variability. Methods Data were taken from participants with glaucoma in a test-retest study. Each had peripapillary circle scans acquired from both eyes 5 times within 10 weeks. For each scan, the following were extracted: average RNFL thickness; RNFL intensity, defined as the mean reflectance intensity of pixels within the delineated RNFL; sub-RNFL intensity, defined as the mean intensity of pixels between the outer boundary of the RNFL and Bruch's Membrane; and intensity ratio, defined as RNFL intensity divided by sub-RNFL intensity. For each parameter, deviations from the per-eye mean were calculated. The intra-eye standard deviations (SD) were expressed as percentage of the width of the range of observed measurements. Results The intra-eye SD of RNFL intensity was 12.5% of the range. Normalization reduced the intra-eye SD of intensity ratio to 4.9% of the range, representing a significant reduction in absolute deviations with p

Four wild Ribes species (R. alpinum L., R. uva-crispa L., R. rubrum L. and R. petraeum Wulf.) were surveyed for their polyphenolic patterns. These patterns were very uniform within R. alpinum and R. uva-crispa, each displaying a single chemotype. In contrast, great variations were detected within the other species. R. petraeum showed two chemotypes and several intermediate profiles. In R. rubrum, variations were qualitative and quantitative. One chemotype was clearly identified in a few samples. Variations between the other samples were important, but we could not characterise precise chemotypes. Species comparisons showed that R. alpinum differed from other species. In conclusion, an important infrageneric polyphenolic variability was detected in the genus Ribes. This kind of analysis should be performed on other Ribes species.

Numerical simulations of superfluid helium are necessary to design the next generation of superconducting accelerator magnets at CERN. Previous studies have presented the thermodynamic equations implemented in the Fluent CFD software to model the thermal behavior of superfluid helium. Momentum and energy equations have been modified in the solver to model a simplified two-fluid model. In this model, the thermo-mechanical effect term and the Gorter-Mellink mutual friction term are the dominant terms in the momentum equation for the superfluid component. This assumption is valid for most of superfluid applications. Transient thermal and dynamic behavior of superfluid helium has been studied in this paper. The equivalent thermal conductivity in the energy equation is represented by the Gorter-Mellink term and both the theoretical and the Sato formulation of this term have been compared to unsteady helium superfluid experiments. The main difference between these two formulations is the coefficient to the power of the temperature gradient between the hot and the cold part in the equivalent thermal conductivity. The results of these unsteady simulations have been compared with two experiments. The first one is a Van Sciver experiment on a 10 m long, and 9 mm diameter tube at saturation conditions and the other, realized in our laboratory, is a 150×50×10 mm rectangular channel filled with pressurized superfluid helium. Both studies have been performed with a heating source that starts delivering power at the beginning of the experiment and many temperature sensors measure the transient thermal behavior of the superfluid helium along the length of the channel.

Factor VII (FVII) deficiency is a rare haemorrhagic condition, normally inherited as an autosomal recessive trait, in which clinical presentation is highly variable and correlates poorly with laboratory phenotype. The FVII (F7) gene was sequenced in 48 unrelated individuals with FVII deficiency, yielding a total of 23 novel lesions including 15 missense mutations, 2 micro-deletions, 5 splice junction mutations and a single base-pair substitution in the 5' untranslated region. Family studies were performed in order to distinguish the contributions of individual mutant F7 alleles to the clinical and laboratory phenotypes. Specific missense mutations were evaluated by molecular modelling in the context of the FVIIa-tissue factor crystal structure. Single base-pair substitutions in splice sites and the 5' untranslated region were studied by in vitro splicing assay and luciferase reporter gene assay, respectively. All probands were also typed for four previously reported F7 polymorphisms. In the majority of cases of FVII deficiency studied here, consideration of both mutational and polymorphism data permitted the derivation of plausible explanations for the FVII activity and antigen levels measured in the laboratory. Inter-familial variation in FVII activity and the antigen levels of heterozygous relatives of probands was found to be significantly higher than intra-familial variation, consistent with the view that the nature of the F7 gene lesion(s) segregating in a given family is a prime determinant of laboratory phenotype. Although no relationship could be discerned between laboratory phenotype and polymorphism genotype, the frequencies of the A2 and M2 polymorphic alleles were significantly higher in the FVII-deficient individuals tested than in controls. This suggests that the presence of these alleles may have served to increase the likelihood of pathological F7 gene lesions coming to clinical attention.

Factor XIII deficiency is an uncommon inherited disorder which is characterized by umbilical cord bleeding and an unusually high incidence of intracranial hemorrhage. We report here a case of Factor XIII deficiency in a child that presented a caput. succedaneum as the first manifestation of the disease and then an umbilical cord bleeding. The importance of performing a quantitative FXIII assay in the presence of strong clinical suspicion is strengthened because of the normality of the standard screening tests and the important therapeutic consequences.

The literature suggests that variations in anticoagulant effect occur when acenocoumarol is administrated in a daily dose. We assessed the anticoagulant effects of acenocoumarol with INR, factors VII and X and protein C in 12 randomly selected hospitalised patients with deep-vein thrombosis, six of them receiving a daily dose of acenocoumarol, the other six receiving twice-daily doses. When the drug effect had been at a steady-state for at least 72 h. five blood samples were drawn per patient over a period of 24 h. No nycthemeral significant variations were noted for INR, factor X and protein C in the two groups (P > 0.10). Nyethemeral significant variation in factor VII when acenocoumarol was administered once daily was noted (P = 0.02), but the clinical relevance of factor VII variation at steady-state is uncertain. In spite of the short pharmacokinetic half-life of acenocoumarol, a stable nycthemeral pharmacodynamic activity was observed after once daily administration; twice-daily administration of acenocoumarol does not appear to be justified.

We present two distinct truncated variants of ankyrin associated with mild to moderate hereditary spherocytosis. Ankyrin Saint-Etienne 1 was manifested by an additional band located between bands 2.1 and 2.2. It was associated with a nonsense mutation in exon 39: TGG-->TGA; W1721X. Ankyrin Saint-Etienne 2 appeared as two faint bands underlining bands 2.1 and 2.2. It was associated with a nonsense mutation in exon 41: CGA-->TGA; R1833X. Overall ankyrin was diminished in splenectomized patients. Messenger RNAs Saint-Etienne 1 and 2 amounted to 20 and 37% of the total ankyrin mRNA, respectively. Ankyrin molecules truncated in their C-terminal region retain some ability to bind to the membrane whereas the bulk of nonsense mutations, located in more upstream regions, result in the mere disappearance of one haploid set of ankyrin. In the present cases, it was not possible to apportion the roles of ankyrin reduction and truncation in the pathogenesis of hereditary spherocytosis.

Thermal bias annealing experiments have been carried out on aluminum/silicon nitride/hydrogenated amorphous silicon top gate structures, and analyzed by quasistatic capacitance measurements. The quasistatic capacitance versus bias curves always show a well defined minimum which reflects the minimum in the density of states at the intercept between the conduction band tail and the deep defect distribution. Thermal bias annealing treatments lead to shifts of the capacitance versus bias curves of the same sign as the bias-anneal voltage, along with an increase of the capacitance minimum. These modifications can be qualitatively described by changes in the defect densities in the framework of the defect pool model. However, numerical calculations show that additional defects must be introduced to fully and quantitatively account for all experimental data.

Quasistatic capacitance measurements are used to study the effect of thermal bias annealing where small gate bias stresses ranging from − 5V to + 6V are applied at 200°C for 15 min on top nitride amorphous silicon-silicon nitride MIS structures. After negative gate bias stresses, the C ( V G ) curves (capacitance versus gate bias) are found to be slightly shifted towards negative voltages and their shape is altered. The minimum of the C ( V G ) curves increases with the stress amplitude indicating the creation of defects in the probed energy range. After positive gate bias stresses, C ( V G ) curves are shifted towards positive voltages without showing any significant shape changes. This indicates either that negative charges have been injected into the insulator, or that negatively charged defects have been created in the a-Si:H layer (or at the a-Si:H/nitride interface) outside the probed energy range (0.15–0.65 eV below the conduction band edge). The results can be qualitatively described by changes in the defect distribution in agreement with what is expected in the framework of the defect pool model.

A chemical analysis of the polyphenolic patterns of diploid and tetraploid populations of Lotus corniculatus s.l. (Fabaceae) growing in the southern French Alps showed that diploids from Mont Ventoux and from Montagne de Lure belong to the same chemotype. On the other hand, tetraploids showed two different chemotypes. This paper suggests the following hypothesis about the evolution of Lotus corniculatus in this area since the last glaciation: diploids could be derived from a relic diploid population scattered by glaciation and restricted within very narrow areas, whereas the tetraploids originating from the diiploids were more competitive and radiated into larger areas cleared from ice. Key words: Lotus corniculatus, birdsfoot trefoil, Fabaceae, polyploidy, polyphenolic metabolism, evolution.

CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider (LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking - through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start-up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb-1 or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z′ and supersymmetric particles, Bs production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb-1 to 30 fb-1. The Standard Model processes include QCD, B-physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z0 boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2-6 describe examples of full analyses, with photons, electrons, muons, jets, missing E T, B-mesons and τ's, and for quarkonia in heavy ion collisions. Chapters 7-15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model. © 2007 IOP Publishing Ltd.

Factor XIII deficiency is an uncommon inherited disorder which is characterized by umbilical cord bleeding and an unusually high incidence of intracranial hemorrhage. We report here a case of Factor XIII deficiency in a child that presented a caput. succedaneum as the first manifestation of the disease and then an umbilical cord bleeding. The importance of performing a quantitative FXIII assay in the presence of strong clinical suspicion is strengthened because of the normality of the standard screening tests and the important therapeutic consequences.

Patients with mild/moderate hemophilia A (MHA) may develop inhibitors to factor VIII (FVIII). In this condition, FVIII clotting activity (FVIII:C) baseline levels may remain stable for some patients, but may be reduced to less than 0.01 U/mL for others. Several risk factors for the development of inhibitors in MHA have been proposed. Genetic factors, such as mutations in the FVIII gene, may play a central role; however, other influences, such as intensive treatment with FVIII products, may also be important. Optimal treatment regimens have yet to be determined, not only for the eradication of inhibitors, but also for the management or surgical prophylaxis of hemorrhages associated with this condition. Several treatment options for the control of bleeding in patients with MHA and inhibitors (MHAI) are currently available, and the choice of therapeutic strategy should be given careful consideration; some treatments may produce an anamnestic response, thus delaying the return to FVIII:C baseline levels and adversely affecting the duration of the severe bleeding phenotype. To increase our knowledge of MHAI, a retrospective collection of data is currently being performed among hemophilia centers in France and Belgium. Based on five examples of patients with MHAI collated from preliminary study data, we illustrate the impact on inhibitor outcome of the therapeutic choices used to treat bleeding episodes in these patients.

Iterative deconvolution algorithms exhibit increased ringing artifacts at higher number of iterations. Quantitative image analysis techniques such as optical flow algorithms are sensitive to these artifacts. We propose to use an image quality metric to identify the terminal step of iterative restoration algorithms. Frequency based metrics have difficulties in distinguishing the ringing artifacts from the image features. Spatial analysis techniques require extensive processing making them unsuitable for real-time image quality measurement as needed in iterative image restoration. We propose a novel ringing metric using binary morphological operators and demonstrate the method on the images of random cotton fibers acquired using white light confocal microscope.

In the course of a preliminary chemosystematic study of Asphodelus species, six flavonoids were first isolated and identified from A. ramosus subsp. ramosus var. ramosus. Only flavone structures were found. Two of them are rare C-glycoside structures and were observed only in the samples from one of the two geographic areas. So, flavonoids might be used as markers in the study of the Asphodelus genus organization. Key words: Asphodelus ramosus, Liliaceae, flavonoids, C-glycosylflavones, chemosystematics.

We present a noise filtering technique using Karhunen-Loeve expansion by the method of snapshots (KLS) using a small ensemble of 3 images. The KLS provides a set of basis functions which comprise the optimal linear basis for the description of an ensemble of empirical observations. The KLS basis is computed using the eigenvectors of the covariance matrix R of the ensemble of images. The significance of each of the basis functions is determined by the magnitude of the corresponding eigenvalues of R , the largest being the most significant. Since all the three images in the ensemble represent the same scene and are registered, the KLS basis construct using the eigenvectors of R with the least eigenvalues typically represent the non-significant and uncommon features in the ensemble. We show that most of the noise in the scene can be removed by reconstructing the image using the KLS basis function constructed using the eigenvector of R with the largest eigenvalue. R is 3x3 symmetric positive definite matrix and hence has a full set of orthogonal eigenvectors. The KLS filtering scheme described here is faster and does not require prior knowledge about the image noise. We show the performance of the proposed method on the images of random cotton fibers acquired using white-light confocal microscope (WLCM) and compare the performance with a median filter. Also, we show that a simple inverse-filter deconvolution algorithm provides an impressive image restoration by pre-filtering the images using the proposed KLS filtering technique.

Summary. This retrospective, open-label, non-comparative study evaluated continuous infusion of recombinant factor VIII (ReFacto®), B-domain deleted recombinant FVIII (BDDrFVIII), in patients with haemophilia A undergoing surgery and requiring >5 consecutive days of treatment. Sixteen patients from eight centres underwent a total of 20 procedures. Haemostatic outcome was assessed as ‘excellent’ or ‘good’ in 75% of procedures, and target FVIII:C levels were maintained throughout the continuous infusion period. The reported volume of blood loss during surgery was also within the normal range for non-haemophilic patients for the type of surgery performed. Red blood cell transfusions were required to balance excessive blood loss during BDDrFVIII continuous infusion in eight (40%) procedures (seven patients), five with bleeding or requiring volume replacement and three to treat anaemia secondary to blood loss. Non-serious adverse events considered by investigators as possibly or probably related to BDDrFVIII continuous infusion were infrequent (n = 5) considering the duration of treatment (n =239 cumulative days of continuous infusion), and all of these were mild-to-moderate in severity. No thromboembolic complications were reported except for one case of thrombophlebitis occurring at the infusion site. Only two patients (four events) experienced serious adverse bleeding; BDDrFVIII was otherwise well-tolerated. These data show that continuous infusion of BDDrFVIII provides reliable haemostasis and is an effective and well-tolerated regimen for patients with haemophilia A undergoing surgery.

Summary. Tissue factor pathway inhibitor (TFPI) is of major importance in regulating the coagulation triggering effects of tissue factor. An association between TFPI deficiency and thrombosis has still not been clearly demonstrated. We evaluated the anticoagulant activity of exogenous TFPI added either to the plasma of patients with venous thrombosis (n = 118) or to the plasma of healthy controls similar in terms of mean age and sex ratio (n = 107). A poor anticoagulant response to TFPI, defined as TFPI resistance, was observed in 4.7% of controls and in 11.0% of patients. TFPI resistance was associated with an almost threefold increase in the risk of thrombosis and could therefore represent a novel hemostatic risk factor for venous thrombosis.

Crude water extract and a flavonoid fraction of Myrtus communis were found to possess molluscicidal activity against the aquatic snail Biomphalaria glabrata involved in the transmission of schistosomiasis.

Visualization of the complex structure composed of oriented axons leaving the retina in a loose connective tissue matrixhas been carried out in living tissue using white light confocal microscopy. Optical sections were acquired at normal andelevated intraocular pressures. A 3D model of the lamina was produced and techniques were developed to study theeffects of intraocular pressure on the structural integrity of the lamina cribrosa.Keywords: Real-time confocal microscopy, 3-D imaging, eye, lamina cribrosa, matrix, glaucoma, retina 1. INTRODUCTION Glaucoma, the leading cause of blindness in the United States and Europe, has generally been considered to be caused byan imbalance in the production and outflow of aqueous humor leading to high intraocular pressure. Blindness fromglaucoma is now known to be associated with structural changes in the region of the optic nerve head. Recent studieshave found that the mechanical effects of high intraocular pressure on the connective tissue matrix are transmitted to theoptic nerve axons, which pass through this region in their course to higher visual centers. It is theorized that thisdeformation has biochemical consequences, stimulating a series of events that lead to the death of retinal ganglioncells.

The NATO Research and Technology Organization (RTO), Advanced Vehicle Technology (AVT), Working Group (WG) 016 (formerly AGARD/PEP Working Group #27) undertook to evaluate methods in use within the NATO propulsion community to measure burning rate in solid propellent rocket systems, with the purpose of identifying similarities and differences between the participating nations. This WG was formed in 1996, consisting of representatives from 6 of the 15 member nations of NATO, with inputs accepted from 4 other member nations and a couple non-member nations. This work was recently completed and a final report prepared. The NATO RTO/AVT WG 016 sought to contribute to improvements in the burning rate tools to address issues that have plagued the solid propulsion industry for over 40 years. This paper summarizes the objectives, approach, findings, and recommendations of this working group based on activity from October 1997 to March 2001. This paper represents the first release of the results of this study within the US. Recommendations are reviewed on direct and non-intrusive burning rate measurement methods, data analysis methods, and performance scaling to support improved prediction of internal ballistics of a fullscale solid propellant motor.

Visualization of the complex structure composed of oriented axons leaving the retina in a loose connective tissue matrix has been carried out in living tissue using white light confocal microscopy. Optical sections were acquired at normal and elevated intraocular pressures. A 3D model of the lamina was produced and techniques were developed to study the effects of intraocular pressure on the structural integrity of the lamina cribrosa.

Objective—To investigate the role of activated protein C resistance (APCR, factor V Leiden) in coronary artery thrombosis. Methods—The prevalence of APCR and of congenital deficiencies of antithrombin III, protein C, protein S, plasminogen, and factor XII was investigated in adult patients under 45 years of age with acute myocardial infarction. The results were compared with those of a group of 53 age and sex matched control subjects. Results—Among 75 patients under the age of 45 years who were admitted from November 1994 to April 1996 for acute myocardial infarction, 22 (29.3%) had normal coronary arteriography (group I) and 53 (70.7%) had significant coronary artery disease (group II). Inherited thrombophilia was more often found in group I (4/22, 18.2%) than in group II (4/53, 7.5%) but the difference was not significant (F test: p = 0.22). The prevalence of APCR was 9.1% (2/22) in group I, 3.8% (2/53) in group 2 (p = 0.57), and 3.8% (2/53) in the normal control group (p = 0.57). Conclusions—The prevalence of congenital thrombophilias, including APCR, does not seem to be increased in young patients with myocardial infarction and normal coronary angiograms, compared with young patients with coronary atherosclerosis and with normal control subjects. However, the statistical power of the study is too low to detect a significant difference and these results are published to allow a meta-analysis of this problem in the future. Keywords: myocardial infarction; factor V Leiden; coagulation factors; inherited thrombophilia

We present two distinct truncated variants of ankyrin associated with mild to moderate hereditary spherocytosis. Ankyrin Saint-Etienne 1 was manifested by an additional band located between bands 2.1 and 2.2. It was associated with a nonsense mutation in exon 39: TGG--TGA; W1721X. Ankyrin Saint-Etienne 2 appeared as two faint bands underlining bands 2.1 and 2.2. It was associated with a nonsense mutation in exon 41: CGA--TGA; R1833X. Overall ankyrin was diminished in splenectomized patients. Messenger RNAs Saint-Etienne 1 and 2 amounted to 20 and 37% of the total ankyrin mRNA, respectively. Ankyrin molecules truncated in their C-terminal region retain some ability to bind to the membrane whereas the bulk of nonsense mutations, located in more upstream regions, result in the mere disappearance of one haploid set of ankyrin. In the present cases, it was not possible to apportion the roles of ankyrin reduction and truncation in the pathogenesis of hereditary spherocytosis.

Heparin-induced thrombocytopenia is a relatively common and potentially serious adverse complication of heparin treatment. After heparin withdrawal initiation of an alternative anticoagulant is often indicated. Org 10172 or Orgaran is a mixture of several non-heparin low molecular weight glycosaminoglycans with proven antithrombotic efficacy. Unlike low molecular weight heparins, Org 10172 has a low cross reaction rate (about 10%) with the heparin-dependent antibody.We present nine patients with heparin induced thrombocytopenia. Org 10172 was prescribed to treat or to prevent a thromboembolic event.Seven patients required further parenteral anticoagulant at diagnosis of heparin-induced thrombocytopenia. Org 10172 was given at prophylactic doses for three patients with a high thrombosis risk and at therapeutic doses for four patients who presented either a venous or an arterial thrombosis related to thrombocytopenia. Two patients presented heparin-induced thrombocytopenia four to six years earlier and needed a parenteral anticoagulation treatment in a post-operative period.For the nine patients, Org 10172 was a safe and effective antithrombotic treatment. However, strict monotoring of the platelet count is absolutely mandatory during Org 10172 therapy.

Missense mutations, three of them novel (Gly47-->Cys, Arg178-->Pro, Ala259-->Thr), were found in the protein C genes of four patients with inherited protein C deficiency associated with venous thrombosis. Comparison with the phenotypic effects of mutations in the analogous residues of factor IX and the use of a molecular model of protein C provided explanations as to how these lesions might alter either the structure, function or stability of the protein C molecules encoded.

The local and systemic fibrinolytic response to the placing of elastic compression in healthy volunteers was studied to determine whether this method of preventing venous thromboembolism has any profibrinolytic effect, as previously demonstrated with intermittent pneumatic compression. Variations in the major parameters of fibrinolysis (euglobulin lysis time, t-PA antigen, PAI-1 antigen, PAI-1 activity) were studied in an open randomized cross-over study in 21 healthy volunteers, in which three types of treatment were tested for periods of 24 h each (without elastic compression, elastic compression of an upper limb, elastic compression of the lower limbs). Four blood samples were taken from the upper limb during each period (at 08:00 h, 10:00 h, 18:00 h, 08:00 h on the following day). The placing of elastic compression did not cause any statistically significant change in the four parameters tested between the three types of treatment. In contrast, circadian rhythm was confirmed for all the fibrinolytic factors studied with a minimal fibrinolytic activity in the morning and a maximal activity in the evening. Elastic compression does not seem to have any profibrinolytic effect in healthy volunteers but other studies are needed in patients before a definitive conclusion can be reached.

Trisomy 12 is the most common cytogenetic abnormality in chronic lymphocytic leukaemia (CLL) and may be a prognostic indicator. In the present study, fluorescence in situ hybridization (FISH) is shown to be a method of choice for detection of trisomy 12 in interphase cells. Seventy-five cases of B-cell CLL were analysed with a chromosome 12 specific alpha satellite DNA probe and results compared with those from cytogenetic analysis. FISH showed the three hybridization spots characteristic of trisomy 12 in 32/75 patients (42.6%). Sixty-three patients were also studied by conventional cytogenetics: failure in 7 cases, normal karyotype in 28, trisomy 12 in 9 (14.3%) and in 19 cases abnormalities other than trisomy 12. In these same 63 patients, trisomy 12 was detected on 29 occasions by FISH (46%): in one case of failure by cytogenetic analysis, in 9 cases thought to have a normal karyotype, in 10 cases carrying abnormalities other than trisomy 12 and in all 9 cases showing trisomy 12 by conventional cytogenetic investigation. Correlation between trisomy 12 and the three stages of the Binet classification indicated an increasing proportion of trisomy 12 from stage A to stage C. It is concluded that fluorescence in situ hybridization is a powerful and sensitive technique for detection of trisomy 12 in CLL and although more cases will be required to confirm a correlation between the incidence of trisomy 12 and the stage of the disease, this link could be important from a prognostic point of view.

This study evaluated the effect of injection time on pharmacodynamic of a single subcutaneous bolus of nadroparine (7500 anti-Xa IC U) evaluated by anti-Xa activity (Hepaclot and Heptest) and by activated partial thromboplastin time (APTT by auto PTT reagent). 10 healthy male volunteers were studied at 4 different 24 hours periods with 4 different injection times (6 am, 12 am, 6 pm, 12 pm) and with a one week wash-out period between each period. No chronopharmacological variation of the anti-Xa activity evaluated by Hepaclot was found. However the anti-Xa activity evaluated by Heptest was higher at the sixth hour after 12 am injection (p = 0.0022). No difference on APTT values was observed whatever the injection time. So the injection time of nadroparine has a weak influence on anti-Xa activity and no effect on APTT; Before to conclude on the lack of chronopharmacological effect of nadroparine, it seems necessary to evaluate such a possibility with higher dosage, with sick and older subjects.

A 3-year old child was admitted for a third relapse of nephrotic syndrome associated with intracranial hypertension related to dural sinus thrombosis (tomodensitometry). The treatment consisted in the association of low dose heparin and fresh frozen plasma. After a 3 year-follow-up, there was no neurologic sequelae, and the nephrotic syndrome was on complete remission. The radiologic features and the management of sinus thrombosis are discussed.

We report a 56-year-old male patient with refractory anemia with excess of blasts in transformation (RAEB-T) who had an ins(8;3)(q24;q21q26) as the sole chromosome abnormality in bone marrow (BM) cells. The findings of disturbed thrombocytopoiesis with numerous micromegakaryocytes suggest that it could be a variant of the classic ins(3;3)(q26;q21q26) described in hematologic malignancies with abnormal thrombopoiesis.

Alexander disease, or hypoproconvertinemia is a rare autosomic recessive coagulation disorder. The features include familial and/or personal history of bleeding, with an abnormal prothrombin period and a normal activated partial thromboplastin period. Coagulation and genetic studies allow subclassification with prognosis incidence for this disease. The authors report on a case of one family with Alexander disease.