bluuebunny/crossref_metadata_2025 huggingface dataset:
Homocysteine levels in amniotic fluid
Authors: Colaizzo Donatella , Vecchione Gennaro , Sciannamè Natale , Notarangelo Angelo , Croce Anna , Margaglione Maurizio , Grandone Elvira
Published: March 2006

Hyperhomocysteinemia could playa similar role in the placenta to that played in adults at risk of thrombosis. Moreover, hyperhomocysteinemia in women is described to be associated with the birth of small for gestational age (SGA) newborns, although there are discrepancies on this issue. To date, there is no biochemical marker predictive of SGA in a given pregnancy. We verified the presence of a relationship between homocysteine in amniotic fluid at mid-pregnancy and birth-weight. Amniotic fluid was obtained from 459 healthy women undergoing midtrimester amniocentesis (17.1 ± 1.2 weeks) because of maternal age. Homocysteine levels were measured in 434 (10 twin) pregnancies. In addition, femur length (FL) and biparietal diameter (BPD) were measured. Outcome of pregnancy was recorded. 233 (53.7%) foetuses were males,201 (46.3%) females. The mean homocysteine concentration was 1.04 ± 0.72 µM, (95% C.I. 0.43–2.41). An univariate analysis showed the presence of an association with gestational age, FL, BPD. A multiple linear regression showed that homocysteine levels were significantly associated with FL (p<0.001) and BPD (p=0.011). After excluding twin pregnancies, 31 newborns (7.3%) were classified as SGA. Mean birth-weight was 2390 g in SGA, where as it was 3360 g in 393 adequate for gestational age (AGA) newborns (p<0.001).The adjusted mean level of homocysteine was significantly lower in AGA (1.01 µM; 95%CI: 0.94–1.08) than that recorded in pregnancies resulting in a SGA (1.29 µM; 95%CI: 1.05–1.51; p=0.03). In a large setting, these data provide reference values for homocysteine in amniotic fluids. Moreover, they suggest that homocysteine levels in amniotic fluids may be higher in pregnancies with a SGA newborn.
Less pronounced enhancement of thrombin-dependent inactivation of plasminogen activator inhibitor type 1 by low molecular weight heparin compared with unfractionated heparin
Authors: Nakamura Ryuta , Umemura Kazuo , Hashimmoto Hisakuni , Urano Tetsumei
Published: March 2006

Plasminogen activator inhibitor type 1 (PAI-1), the primary inhibitor of plasminogen activators, also forms high molecular weight complexes with either thrombin or factor Xa (FXa) in the presence of heparin, resulting in the loss of mutual activities of enzyme and inhibitor.We have proposed that the inactivation of PAI-1 by these activated coagulation factors is one of the mechanisms responsible for coagulation-associated enhancement of fibrinolysis. In the present study, we compared the effects of low molecular weight (LMW)- and unfractionated-heparin on the interaction between PAI-1 and either thrombin or FXa. Both types of heparin enhanced the inhibition of thrombin activity by PAI-1 with a bell-shaped pattern, though the magnitude of the enhancement was significantly weaker with LMW-heparin. In FXa inhibition by PAI-1, only unfractionated-heparin enhanced the inhibition. In the presence of vitronectin (Vn), the inhibition of thrombin and FXa by PAI-1 was further promoted by both types of heparin but toa significantly lesser extent with LMW-heparin.We then analyzed the possible enhancing effect of heparin on tissue plasminogen activator (tPA)-induced fibrinolysis. As a consequence of thrombin-dependent inactivation of PAI-1, tPA-induced fibrin clot lysis time in the presence of PAI-1 was shortened by unfractionated-heparin as well as by LMW-heparin with lesser extent, which was further enhanced by Vn. Less pronounced enhancement of complex formation between thrombin and PAI-1 by LMW-heparin appeared to be directly related to the weaker potential of LMW-heparin in enhancing fibrinolysis and accelerating hemorrhagic tendency via neutralization of PAI-1 activity.
Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors
Authors: Kavakli Khan , Makris Mike , Zulfikar Bulent , Erhardtsen Elizabeth , Abrams Zvi , Kenet Gili ,   for the NovoSeven ® trial (F7HAEM-1510) investigators
Published: March 2006

The aim was to evaluate the efficacy and safety of two recombinant factor VIIa (rFVIIa) dose regimens for treating haemarthroses in patients with congenital haemophilia A or B and inhibitors. This was a multi-centre, randomised, cross-over, double-blind trial. Patients were randomly allocated to treat a first joint bleeding episode with one 270 µg/kg rFVIIa dose followed by two doses of placebo at 3-hour intervals and a second joint bleed with three single doses of 90 µg/kg rFVIIa at 3-hour intervals, or vice versa. Efficacy was evaluated using a novel and robust treatment response-rating scale based on patient-assessment of pain and joint mobility. Outcome was rated at different timepoints, and an effective or ineffective treatment response was determined. Treatment “preference” was defined as effective treatment with one regimen and ineffective with the other. Patients with equally effective or ineffective treatments had no “preference”. Treatment was rated as effective for 65% of patients using the 270 µg/kg dose versus 70% for the 90 µg/kg ×3 regimen. An equal “preference” was noted for the two regimens (21% for each; p = 0.637); most patients (58%) had no “preference”. 37/42 bleeding episodes (88%) were successfully treated with rFVIIa; additional haemostatic medications were administered for five episodes. No safety issues were identified. Administration of rFVIIa as a single 270 µg/kg dose to treat haemarthroses in patients with haemophilia and inhibitors was at least as efficacious and safe as the 90 µg/kg ×3 regimen.
Comparison of three activated protein C resistance tests in the risk assessment of venous thrombosis in non-carriers of the factor V Leiden mutation
Authors: Guerrero Felipe , Arnaud Catherine , Nguyen Francoise , Boneu Bernard , Sié Pierre
Published: March 2006

Activated protein C resistance (APCR), measured using the original assay described by Dahlbäck, is a risk factor for venous thrombosis independent of the factor V Leiden (FVL) mutation. This assay is based on the activated partial thromboplastin time (APTT) after plasma exposure to activated protein C (APC).As this assay was sensitive to numerous interferences, new assays have been developed for FVL screening. The objectives of the study were to investigate the association of second generation assays for APCR with venous thrombosis in FVL non-carriers. One hundred ninety-seven subjects with a history of venous thrombosis and 211 controls were explored using 3 APCR assays, the original APTT-based assay (test A), an APTT-based assay with factorV depleted plasma pre-dilution (test B) and a direct factorX activation-based assay with the same pre-dilution (test C).We found that subjects with results in the lowest quartile of the APTT-based assays are at increased risk, compared to those in the highest quartile (test A Odds Ratio = 6.39; 95%CI 3.23–12.63; test B OR=2.72; 95%CI 1.50–4.94). There was no significant risk increase associated with test C results. After adjusting for FVIII levels, the ORs of tests A and B were similar (test A OR=3.22; 95%CI 1.47–7.08; test B OR=3.10; 95%CI 1.54–6.21). In conclusion, APTT-based assays, but not direct factor X activation-based assays, effectively detect the risk for venous thrombosis independent of FVL. Pre-dilution in factor V depleted plasma is an effective way to directly assess the risk independent of FVIII levels.
Dose- and time-dependent antiplatelet effects of aspirin
Authors: Perneby Christina , Wallén N. Håkan , Rooney Cathy , Fitzgerald Desmond , Hjemdahl Paul
Published: March 2006

Aspirin is widely used, but dosages in different clinical situations and the possible importance of “aspirin resistance” are debated. We performed an open cross-over study comparing no treatment (baseline) with three aspirin dosage regimens – 37.5 mg/ day for 10 days, 320 mg/day for 7 days, and, finally, a single 640 mg dose (cumulative dose 960 mg) – in 15 healthy male volunteers. Platelet aggregability was assessed in whole blood (WB) and platelet rich plasma (PRP).The urinary excretions of stable thromboxane (TxM) and prostacyclin (PGI-M) metabolites, and bleeding time were also measured. Platelet COX inhibition was nearly complete already at 37.5 mg aspirin daily, as evidenced by >98 % suppression of serum thromboxane B2 and almost abolished arachidonic acid (AA) induced aggregation in PRP 2–6 h after dosing. Bleeding time was similarly prolonged by all dosages of as- pirin. Once daily dosing was associated with considerable recovery of AA induced platelet aggregation inWB after 24 hours, even after 960 mg aspirin. Collagen induced aggregation in WB with normal extracellular calcium levels (hirudin anticoagulated) was inhibited <40% at all dosages. TxM excretion was incompletely suppressed, and increased <24 hours after the cumulative 960 mg dose. Aspirin treatment reduced PGI-M already at the lowest dosage (by ≈25%), but PGI-M excretion and platelet aggregability were not correlated. Antiplatelet effects of aspirin are limited in WB with normal calcium levels. Since recovery of COX-dependent platelet aggregation occurred within 24 hours, once daily dosing of aspirin might be insufficient in patients with increased platelet turnover.
Hyperprothrombinaemia-induced APC resistance: Differential influence on fibrin formation and fibrinolysis
Authors: Binetti Bianca , Rotunno Crescenza , Tripodi Armando , Asti Daniela , Semeraro Fabrizio , Semeraro Nicola , Colucci Mario
Published: March 2006

The prothrombin gene mutation G20210A is a common risk factor for thrombosis and has been reported to cause APC resistance. However, the inhibition of thrombin formation by APC not only limits fibrin formation but also stimulates fibrinolysis by reducing TAFI activation. We evaluated the influence of prothrombin G20210A mutation on the anticoagulant and fibrinolytic activities of APC (1 µg/ml). Thirtytwo heterozygous carriers and 32 non carriers were studied. APC anticoagulant activity was assessed by aPTT prolongation whereas APC fibrinolytic activity was determined by a microplate clot lysis assay. APC-induced aPTT prolongation was markedly less pronounced in carriers than in non carriers. On the contrary, fibrinolysis time was shortened by APC to a comparable extent in both groups. Accordingly, prothrombin levels were strongly correlated with APC-induced aPTT prolongation but not with APC-induced shortening of lysis time. The addition of purified prothrombin to normal plasma (final concentration 150%) caused APC resistance in the clotting assay over the whole range of tested APC concentrations (0.125–1.5 µg/ml). In the fibrinolytic assay, instead, prothrombin supplementation made the sample resistant to low but not to high concentrations of APC (>0.5 µg/ml). Thrombin and TAFIa determination in the presence of 1 µg/ml APC revealed that hyperprothrombinemia, although capable of enhancing thrombin generation, was unable to induce detectable TAFIa formation. It is suggested that APC resistance caused by hyperprothrombinaemia does not translate in impaired fibrinolysis, at least in the presence of high APC levels, because the increase in thrombin formation is insufficient to activate the amount of TAFI required to inhibit plasminogen conversion. These data might help to better understand the relationship between thrombin formation and fibrinolysis down-regulation.
Genetic analysis of CAV1 gene in hypertension and metabolic syndrome
Authors: Grilo Antonio , Fernandez Maria , Beltrán Manuel , Ramirez-Lorca Reposo , González María , Royo Jose , Gutierrez-Tous Reyes , Morón Francisco , Couto Carmen , Serrano-Rios Manuel , Saez Maria , Ruiz Agustin , Real Luis
Published: March 2006

Recently, we reported that the polymorphism 1132T>C (Gene-Bank: AF519768.1) of the NOS3 gene was associated with susceptibility to metabolic syndrome (MS) in hypertensive patients. This suggests that other genes such as CAV1, whose product (CAV1) regulates eNOS activity, could also be related to this phenotype.In this work we investigated the following:i) whether CAV1 is a quantitative trait locus of clustering of atherothrombotic traits associated with MS; ii) whether CVA1 is associated with hypertension or MS in hypertensive patients; and iii) whether genetic interaction between NOS3 and CAV1 is involved in the susceptibility or protection to hypertension associated with MS.To carry out the study, we genotyped 285 randomly selected individuals and 175 hypertensive patients, all of them ≤ 60 years old, with two polymorphisms of the CAV1 gene: the 22285 C>T and the 22375–22375 del AC (GeneBank AF125348), and the 1132T>C polymorphism of the NOS3 gene. To perform sample genotyping, we used pyrosequencing and FRET techniques.The 22285 C-22375–22375 del (Cd) haplotype of CAV1 gene was associated with low levels of blood pressure in the general population. Moreover, it was a genetic protection factor against MS in hypertensive patients. In addition, we found no evidence of gene-gene interaction between NOS3 and CAV1 genes with regard to that phenotype.
Biodistribution of covalent antithrombin-heparin complexes
Authors: Chindemi Paul , Klement Petr , Konecny Filip , Berry Leslie , Chan Anthony
Published: March 2006

We have developed a covalent antithrombin-heparin (ATH) complex with advantages compared to non-covalent antithrombin: heparin (AT:H) mixtures. In addition to increased activity, ATH has a longer intravenous half-life that is partly due to reduced plasma protein binding. Given ATH’s altered clearance, we investigated biodistribution of ATH in vivo. ATH made from either human plasma-derived AT (pATH) or recombinant human (produced in goats) AT (rhATH) was studied. 125I-ATH + unlabeled carrier was injected into rabbits at different doses. 131Ilabeled albumin was administered just before sacrifice as a marker for trapped blood in tissues. Immediately after sacrifice, animal components were removed, weighed, and subsamples were counted for gamma-radioactivity. Percent recoveries of ATH in various organs/compartments at different time points were calculated, and kinetic distribution plots generated. At saturating doses, early disappearance of rhATH from the circulation was much faster than pATH. Co-incident with clearance, 26 ± 3 % of dose for rhATH was liver-associated compared to only 3.7 ± 0.5 % for pATH by 20 min. Also, at early time periods, > 60% of all extravascular ATH was liver-associated. Analysis of the vena cava and aorta suggested that vessel wall binding might also account for initial plasma loss of rhATH. By 24 h, most of pATH and rhATH were present as urinary degradation products (51 ±3 % and 63 ±8 %, respectively). In summary, systemic elimination of ATH is greatly influenced by the form of AT in the complex, with liver uptake and degradation playing a major role.
Anti-angiogenesis mediated by angiostatin K1–3, K1–4 and K1–4.5
Authors: Chen Ya-Huey , Wu Hua-Lin , Li Ching , Huang Yi-Hsien , Chiang Chi-Wu , Wu Ming-Ping , Wu Li-Wha
Published: March 2006

The molecular mechanism mediated by multiple forms of angiostatin via acting on proliferating vascular endothelium remains elusive. To address whether three forms of angiostatin, K1-3, K1-4 or K1-4.5, utilized similar or distinct pathways to mediate anti-angiogenesis, we adopted an adenoviral expression system to express secretable angiostatin molecules for CM collection. The anti-angiogenic activity of K1-3, K1-4 or K1-4.5 was confirmed by using proliferation, migration, tube formation and apoptotic assays of human endothelial cells. These angiostatin molecules at comparable expression level inhibited various in vitro angiogenesis assays with some variations. Furthermore, K1-3, K1-4 or K1-4.5 increased the expression of p53 protein and its downstream effectors, enhanced FasL-mediated signaling pathways, and decreased activation of AKT. At least three different receptors, Fas, integrin αvβ3 and ATP synthase, were involved in the anti-angiogenic action of angiostatin molecules. Besides, the expression of 189 genes at mRNA level was significantly altered by K1-3, K1-4 or K1-4.5. More than 70% of these genes participate in growth, inflammation, apoptosis, migration and extracellular matrix. Taken together, K1-3, K1-4 and K1-4.5, regardless of the number of kringles in the angiostatin molecules, mediated anti-angiogenesis via mostly similar pathways. We are the first to demonstrate the involvement of DAPK1 in the mediation of anti-angiogenesis by angiostatin.
Analysis of SAGE data in human platelets: Features of the transcriptome in an anucleate cell
Authors: Dittrich Marcus , Birschmann Ingvild , Pfrang Julia , Herterich Sabine , Smolenski Albert , Walter Ulrich , Dandekar Thomas
Published: March 2006

A comprehensive SAGE (serial analysis of gene expression) library of purified human platelets was established. Twenty-five thousand (25,000) tags were sequenced, and after removal of mitochondrial tags, 12,609 (51%) non-mitochondrial-derived tags remained, corresponding to 2,300 different transcripts with expression levels of up to 30,000 tags per million. This new, highly purified SAGE library of platelets is enriched in specific transcripts.The complexity in terms of tag distribution is similar to cells that are still able to replenish their mRNA pool by transcription.We show that our SAGE data are consistent with recently published microarray data but show further details of the platelet transcriptome, including (i) longer UTR regions and more stable folding in the enriched mRNAs, (ii) biologically interesting new candidate mRNAs that show regulatory elements, including elements for RNA stabilization or for translational control, and (iii) significant enrichment of specific, highly transcribed mRNAs compared to a battery of SAGE libraries from other tissues. Among several regulatory mRNA elements known to be involved in mRNA localization and translational control, CPE elements are in particular enriched in the platelet transcriptome. mRNAs previously reported to be translationally regulated were found to be present in the library and were validated by real-time PCR. Furthermore, specific molecular functions such as signal transduction activity were found to be significantly enriched in the platelet transcriptome.These findings emphasize the richness and diversity of the platelet transcriptome.
Prothrombotic activity is associated with the anatomical as well as the functional severity of peripheral arterial occlusive disease
Authors: Kroese Andries , Stranden Einar , Morken Britt , Sandbæk Gunnar , Lindahl Anne , Arnesen Harald , Seljeflot Ingebjørg , Nylænde Marthe
Published: March 2006

The importance of prothrombotic activity in cardiovascular disease has been well established. However, limited data exist on the relationship between prothrombotic activity and the severity of peripheral arterial occlusive disease (PAD).The objective of the present study was to investigate the relationship between markers of haemostasis and the diagnostic measures of PAD: ankle-brachial-index (ABI), maximum treadmill walking distance and angiographic score. In a cross-sectional study of 127 patients (mean age 66 years; 64% males) with angiographically verified PAD, fasting blood samples were drawn, and citrated plasma was obtained for determination of selected haemostatic variables: von Willebrand factor (vWF), thrombomodulin (sTM), thrombin-antithrombin complex (TAT), soluble tissue factor (sTF), tPA antigen (tPAag) and D-dimer were all significantly correlated with the angiographic score (p<0.05 for all). D-dimer, tPAag and fibrinogen were inversely correlated with the maximum treadmill walking distance, (p<0.0001, p<0.04 and p<0.05, respectively), whereas fibrinogen was the only variable correlating to ABI (r = –0.223, p<0.05). After adjustment for relevant covariates, D-dimer and TAT remained statistically significantly associated with the angiographic score (p<0.001), and fibrinogen was, independent of other risk factors, inversely related with both the maximum treadmill walking distance and the ABI (p<0.01 for both).This rather large study in patients with PAD showed that plasma levels of D-dimer, TAT and fibrinogen significantly predicted the extent of atherosclerosis, evaluated by angiographic score, maximum treadmill walking distance and ABI, respectively. These findings demonstrate a prothrombotic state in PAD patients, which might be of importance in future diagnosis and treatment of the disease.
One‐Dimensional Visco‐Elastoplastic Constitutive Model for Asphalt Concrete
Authors: Giunta Marinella , Angela Pisano Aurora
Published: March 2006

This paper proposes a new visco‐elastoplastic constitutive model for asphalt concretes able to reproduce the non linear time‐dependent behaviour of such materials.The constitutive model has been developed with the aim of making it fit specific experimental features previously observed. Moreover the proposed formulation will be demonstrated to be fully consistent with general thermodynamic requirements. Apart from a rigorous analytical formulation; a corresponding rheological sketch of the model is also given. From this representation, it can be shown that the model is essentially a combination of a generalized Maxwell model and a hardening visco‐plastic element.
Momentum‐Dependent Symmetries and Non‐Noether Conserved Quantities for Nonconservative Hamilton Systems
Authors: Fu Jing‐li , Chen Li‐qun , Chen Xiang‐wei
Published: March 2006

In this letter, based on the infinitesimal transformations with respect to the generalized coordinates and generalized momentums, we obtain the definition, determining equations and structure equation of the momentum‐dependent symmetry for the systems. This study directly leads to the non‐ Noether type conserved quantity for the systems. Further we also give the inverse issue of the momentum‐dependent symmetries of the systems. However, a theory of momentum‐dependent symmetries of the nonconservative Hamiltonian systems is established. Finally, an example is discussed to illustrate the results.
On the Quasi‐Static Boundary Value Problems in the Theory of Swelling Porous Elastic Soils
Authors: Gales C.
Published: March 2006

Quasi‐static boundary value problems are formulated for the isothermal linear theory of swelling porous elastic soils in the case that the fluid is incompressible. First, some general theorems (uniqueness, reciprocal and continuous dependence) are established in the general case. Then, in the case that solid matrix is saturated with fluid and occupies a semi‐infinite cylinder of smooth cross section, a time‐weighted cross‐sectional area measure is used in order to establish spatial decay estimates for the quasi‐static solutions.
Rheological‐Dynamical Theory of Visco‐Elasto‐Plasticity and Fatigue: Part 2
Authors: Milasinovic Dragan D.
Published: March 2006

The paper deals with the rheological‐dynamical analogy in which the three‐dimensional stress‐strain relations are defined under cyclic variation of stress for Hencky’s total strain theory. In many practical visco‐elasto‐plastic problems, like as multiaxial fatigue under loading at constant stress amplitude and constant stress ratio, the load‐carrying members are subjected to proportional loading. The classical Hencky’s theory has the advantage of mathematical convenience but its disadvantage is that the deformations predicted for the volume element are independent of the loading path. The existing formulations of the constitutive models for metals are mainly based on the Prandtl‐Reuss incremental theory of elasto‐plasticity, slip theory of plasticity or continuum damage mechanics. They have been shown capable of reproducing satisfactorily most experimental results available for metallic specimens. However, from the theoretical viewpoint little has been said about how these formulations relate to realistic predicting many different inelastic and time dependent problems of two‐ or threedimensional solids, such as fatigue, discontinuous plastic deformation etc. In this paper, fundamentally new aspect of isochronous constitutive relations for Hencky’s theory, which are dependent of the each loading path, is achieved by systematically introducing RDA concept into the continuum framework. Specific inelastic and fatigue formulation of triaxial state of stress is developed and discussed within the new theoretical tool and related to von Mises plasticity..
Reproducibility of Seasonal Land Surface Climate
Authors: Phillips Thomas J.
Published: March 2006

In this study, the sensitivity of the continental seasonal climate to initial conditions is estimated from an ensemble of decadal simulations of an atmospheric general circulation model with the same specifications of radiative forcings and monthly ocean boundary conditions, but with different initial states of atmosphere and land. As measures of the “reproducibility” of continental climate for different initial conditions, spatiotemporal correlations are computed across paired realizations of 11 model land surface variables in which the seasonal cycle is either included or excluded—the former case being pertinent to climate simulation and the latter to seasonal prediction.

It is found that the land surface variables that include the seasonal cycle are impacted only marginally by changes in initial conditions; moreover, their seasonal climatologies exhibit high spatial reproducibility. In contrast, the reproducibility of a seasonal land surface anomaly is generally low, although it is substantially higher in the Tropics; its spatial reproducibility also markedly fluctuates in tandem with warm and cold phases of the El Niño–Southern Oscillation. However, the overall degree of reproducibility depends on the particular land surface anomaly considered. It is also shown that the predictability of a land surface anomaly implied by its reproducibility statistics is consistent with what is inferred from more conventional predictability metrics. Implications of these results for climate model intercomparison projects and for operational forecasts of seasonal continental climate also are elaborated.
Impact of an Exponential Profile of Saturated Hydraulic Conductivity within the ISBA LSM: Simulations over the Rhône Basin
Authors: Decharme B. , Douville H. , Boone A. , Habets F. , Noilhan J.
Published: March 2006

This study focuses on the influence of an exponential profile of saturated hydraulic conductivity, ksat, with soil depth on the water budget simulated by the Interaction Soil Biosphere Atmosphere (ISBA) land surface model over the French Rhône River basin. With this exponential profile, the saturated hydraulic conductivity at the surface increases by approximately a factor of 10, and its mean value increases in the root zone and decreases in the deeper region of the soil in comparison with the values given by Clapp and Hornberger. This new version of ISBA is compared to the original version in offline simulations using the Rhône-Aggregation high-resolution database. Low-resolution simulations, where all atmospheric data and surface parameters have been aggregated, are also performed to test the impact of the modified ksat profile at the typical scale of a climate model. The simulated discharges are compared to observations from a dense network consisting of 88 gauging stations.

Results of the high-resolution experiments show that the exponential profile of ksat globally improves the simulated discharges and that the assumption of an increase in saturated hydraulic conductivity from the soil surface to a depth close to the rooting depth in comparison with values given by Clapp and Hornberger is reasonable. Results of the scaling experiments indicate that this parameterization is also suitable for large-scale hydrological applications. Nevertheless, low-resolution simulations with both model versions overestimate evapotranspiration (especially from the plant transpiration and the wet fraction of the canopy) to the detriment of total runoff, which emphasizes the need for implementing subgrid distribution of precipitation and land surface properties in large-scale hydrological applications.
The Human Resource Development function: the ambiguity of its status within the UK public service
Authors: Auluck Randhir K.
Published: March 2006

Improving performance through better employee development practice is a recurrent theme within the UK public sector. Human Resource Development (HRD) is seen as playing a pivotal role in this process. This article will review the role, structure and status of HRD within the UK public service. It will consider the apparent paradox that exists. On the one hand, the HRD function is reported to have a vital role in the development of those working within public service organizations. On the other hand, some hold the view that the reshaping of the function is diminishing its status and influence. The article draws on the findings of the first phase of a study examining the role, structure and status of the HRD function in UK public sector organizations. Findings suggest that how the HRD function is presented and represented is problematic.
Managing trust and relationships in PPPs: some Australian experiences
Authors: Teicher Julian , Alam Quamrul , Gramberg Bernadine Van
Published: March 2006

Governments in Australia increasingly rely on private sector service providers to improve efficiency in public service delivery and have entered into a range of business partnerships with those providers. This article considers the effectiveness of public-private partnership models used in delivering public services and suggests that some partnership initiatives have increased efficiency at the micro management level but have not been able to establish trust. The concept of public value, too, has not been used as a useful way of setting out public service goals. Other models have focused more on community participation in policy formulation and in building trust among the clients and the providers and these may point the way to the future of such initiatives. These tentative conclusions rest on an examination of two cases where partnerships have affected operating and management practices, Job Network and Best Value in Victorian Local Government.
International Human Rights and Local Justice in Guatemala
Authors: Dill Kathleen
Published: March 2006

This article is an ethnographic account of the various stages of a trial of local army collaborators accused of perpetrating massacres of civilians. The defendants were municipal-level paramilitaries; the complainants were survivors, and the prosecution was conducted by the state. International human rights lawyers used evidence from these cases to build a national-level case for the prosecution of the intellectual authors of state violence, but did not provide assistance for the prosecution of the local-level material authors. The case is used to highlight some of the tensions between the interests of communities and the practitioners of international human rights law, in the context of both groups’ efforts to hold a criminal state accountable. The author argues that, in some cases, local-level trials are an essential component to postwar community reconstruction and that these cases should receive support from the international human rights community.
Epidemiology of jellyfish stings reported to poison centers in Texas
Authors: Forrester M B
Published: March 2006

This study examined the relationship between selected factors and all human exposures involving jellyfish stings reported to Texas poison centers. Cases were obtained retrospectively from calls to poison centers in Texas and included all reported human exposures during 1998-2004 involving jellyfish stings. The distribution of cases was determined for a variety of demographic and clinical parameters. There were 423 total cases. Among the cases with a known patient age, 19.8% were<6 years of age, 53.5% were age 6-19 years, and 26.7% were > 19 years of age. Males accounted for 52% of the cases. Of the 118 cases with a known clinical outcome, 0.8% had no effect, 80.5% had minor effects, and 18.6% had moderate effects. Counties along the Gulf Coast accounted for 72.3% of the calls. This information can be used to identify those portions of the population most at need of education regarding the prevention and treatment of jellyfish stings.
Preliminary survey of ochratoxin A in millet, maize, rice and peanuts in Côte d'Ivoire from 1998 to 2002
Authors: Sangare-Tigori B , Dem A A , Kouadio H J , Betbeder A-M , Dano D S , Moukha S , Creppy E E
Published: March 2006

In a preliminary study, samples of millet (n=33) maize (n=41), rice (n=10) and peanuts (n=10) from Côte d'Ivoire were analysed for ochratoxin A (OTA) by HPLC with fluorimetric detection, followed by confirmation by cleavage of the OTA molecule using carboxypeptidase with HPLC separation and fluorimetric quantification of the released ochratoxin alpha (OTα). With the exception of four samples of peanuts, all samples showed OTA contamination, ranging from 3 to 1738 μg/kg. All cereals were contaminated and the OTA concentrations were in the range of 17-204 μg/kg for millet, 3-1738 μg/kg for maize, 9-92 μg/kg for rice and 0.6-64 μg/kg for peanuts, depending on the year of harvest.

Most of the samples would not be accepted according to the EU regulatory limits for this mycotoxin. Following this survey, research for other mycotoxins and the evaluation of the exposure of the population is under-way.
Calcium gluconate and sodium succinate for therapy of sodium fluoroacetate experimental intoxication in cats: clinical and electrocardiographic evaluation
Authors: Collicchio-Zuanaze R C , Sakate M , Schwartz D S , Trezza E , Crocci A J
Published: March 2006

Sodium fluoroacetate (SFAC) or Compound 1080 is a potent rodenticide, largely used after 1946 for rodent and home pest control. The toxic effects of SFAC are caused by fluorocitrate action, a toxic metabolite, which has a competitive action with aconitase enzyme, leading to citrate accumulation and resulting in interference in energy production by Krebs cycle blockade. In the present study, domestic cats were intoxicated with oral doses of fluoroacetate (0.45 mg/kg). The intoxicated animals presented emesis, diarrhea with abdominal pain posture and an abdominal palpation, tachypnea, bilateral midriasis, hypothermia, hyperexcitability and convulsions. Blood gas analysis indicated decreased pH and bicarbonate levels. Serum ionized calcium was also decreased. ECG showed non–specific changes in ventricular repolarization and ventricular arrhythmias. The survival rate was 75% in the treated group with calcium gluconate and sodium succinate and 37.5% in the nontreated group.
The influence of tobacco smoke and nicotine on antidepressant and memory-improving effects of venlafaxine
Authors: Nowakowska Elżbieta , Kus Krzysztof , Florek Ewa , Czubak Anna , Jodynis-Liebert Jadwiga
Published: March 2006

In experimental and clinical studies, central nicotinic systems have been shown to play an important role in cognitive function. Nicotinic acetylcholine receptors also mediate the reinforcing properties of nicotine (NIC) in tobacco products. A variety of studies have shown that acute treatment with NIC or nicotinic agonists can improve working memory function. Moreover, it is known that the monoaminergic system plays an important role in memory function. And there is evidence suggesting that prolonged use of NIC may exert antidepressant action via nicotinic receptors. The purpose of this study was to investigate the interactions between a novel antidepressant, venlafaxine (VEN), a blocker of noradrenaline and 5–hydroxytryptamine reuptake sites, and pure NIC in the context of antidepressant and memory function in tobacco smoke exposed and nonexposed rats. The animals were subjected to Porsolt's test for testing antidepressant activity and their memory function (spatial memory) was evaluated in the Morris Water Maze Test. In tobacco smoke non–exposed and exposed rats both single and chronic administration of VEN (20 mg/kg po) shortened immobility time. NIC (0.2 mg/kg sc) significantly reduced immobility time on the 1st, 7th and 14th test days in both non–exposed and exposed rats. Combined VEN–NIC treatment in tobacco smoke non–exposed rats reduced immobility too. This effect of the combination of drugs was significantly stronger as compared to the effects obtained after individual administration of VEN or NIC. In the group exposed to tobacco smoke, joint administration of VEN–NIC induced a significant reduction of immobility as compared to the control and NIC groups. In the Morris Water Maze Test single and chronic administration of VEN, lower values of escape latencies and lower numbers of crossed quadrants were noted in both exposed and non–exposed rats, which indicates improved performance. After administering NIC we could observe improvement of spatial memory in both the exposed and non–exposed group. A similar effect of improvement of spatial memory was observed after joint administration of VEN and NIC. The study results support the involvement of nicotinic systems in memory processes in rats. Memory improvement and antidepressant effects following joint administration of VEN and NIC may depend on nicotinic interactions with monoaminergic systems and VEN may represent a new therapeutic approach to smoking cessation.
Demographical, aetiological and clinical characteristics of poisonings in Mersin, Turkey
Authors: Mert Ertan , Bilgin Nursel Gamsiz
Published: March 2006

Background: As acute poisoning continues to be an important public health problem, and represents a frequent cause of admission in emergency departments, there is a constant need to have up to date information about it. The aim of this retrospective study was to evaluate the demographical, aetiological and clinical characteristics of acute poisonings who were admitted to a university hospital in the south part of Turkey. Methods: The data of 195 acute poisoning patients who were admitted to the Emergency Department of Mersin University were retrospectively studied. Results: Most poisonings occurred in the age range 0–6 years (57.5%) for children and 17–25 year (46.7%) for adults. The overall female to male ratio was 1.26. Drugs were the most common cause of poisonings (55.4%). Among the drug poisonings, psychotropics (41.7%) were the most frequent agent, followed by analgesics (20.4%). 67.7% of the cases presented to the emergency department within 3 hours of poisoning and the procedures for elimination of poison were performed in most of them. The clinical status of the patients on arrival was generally good. 69.2% of the patients were hospitalized. The mean duration of hospitalization was 2.49±2.8 days. 41.8% of the suicidal cases had a history of psychiatric disorders; 92.8% of the patients were discharged home after toxicological treatment; 2.6% of the cases died. Conclusion: Further studies are necessary to collect more data and these data will be helpful not only for determining risk factors of acute poisonings but also for developing education and prevention programmes.
Neuroprotective effect of Acorus calamus against middle cerebral artery occlusion–induced ischaemia in rat
Authors: Shukla Pradeep K , Khanna Vinay K , Ali M Mohd , Maurya Rakesh , Khan M Y , Srimal Rikhab C
Published: March 2006

The neuroprotective potential of ethanol:water (1:1) extract of rhizomes of Acorus calamus (AC–002) has been investigated in middle cerebral artery occlusion (MCAO)–induced ischaemia in rats. A significant behavioural impairment in Rota–Rod performance and grid walking was observed in rats, 72 hours after MCAO as compared to sham–operated animals. These rats also exhibited an increase in lipid peroxidation (cortex / 157%, corpus striatum – 58%) and a decrease in glutathione levels (cortex – 59%, corpus striatum – 34%) and superoxide dismutase (SOD) activity (cortex – 64%, corpus striatum – 32%) as compared to sham–operated animals. Ischaemic rats treated with AC–002 (25 mg/kg, p.o.) exhibited a significant improvement in neurobehavioural performance viz. Rota–Rod performance and grid walking as compared to the MCAO group. Interestingly, treatment with AC–002 in MCAO rats significantly decreased malonaldialdehyde levels in cortex as compared to ischaemic rats. A significant increase in reduced glutathione levels and SOD activity was also observed both in cortex and corpus striatum in MCAO rats treated with AC–002 in comparison to MCAO rats. Treatment with AC–002 in MCAO rats also reduced the contralateral cortical infarct area (19%) as compared to MCAO rats (33%). Neurological function score was improved in the AC–002–treated rats as compared to the MCAO group. The results of the present study indicate the neuroprotective efficacy of A. calamus in the rat model of ischaemia.
Methodologic issues in the design and analysis of epidemiologic studies of pregnancy outcome
Authors: Savitz David A , Dole Nancy , Herring Amy H
Published: March 2006

Using epidemiology to elucidate the causes of adverse pregnancy outcomes offers unique opportunities and poses distinctive challenges. The context of pregnancy includes contraception and planning, medical interventions altering the natural history, and the tendency for selective participation in demanding research protocols. Several key pervasive issues are considered in detail: 1) the close temporal proximity of determinants and outcomes, which makes separation of causes and effects difficult and introduces the real possibility of reverse causality; 2) non-random allocation of exposure, often done consciously in response to concerns about having a healthy pregnancy or to the health of the pregnancy itself, making confounding a major concern; 3) heterogeneity of pregnancy outcomes, with endpoints such as pregnancy loss and preterm birth arising through diverse pathways that are not easily identified and if grouped, could diminish the magnitude of observed associations; and 4) racial and ethnic disparities, which pose a public health challenge in the USA and offer a potentially important opportunity for identifying preventable causes of adverse pregnancy outcome. Sophisticated biological and statistical methods are needed to advance epidemiologic research in this area.
Analysis of repeated pregnancy outcomes
Authors: Louis Germaine Buck , Dukic Vanja , Heagerty Patrick J , Louis Thomas A , Lynch Courtney D , Ryan Louise M , Schisterman Enrique F , Trumble Ann ,   Pregnancy Modeling Working Group
Published: March 2006

Women tend to repeat reproductive outcomes, with past history of an adverse outcome being associated with an approximate two-fold increase in subsequent risk. These observations support the need for statistical designs and analyses that address this clustering. Failure to do so may mask effects, result in inaccurate variance estimators, produce biased or inefficient estimates of exposure effects. We review and evaluate basic analytic approaches for analysing reproductive outcomes, including ignoring reproductive history, treating it as a covariate or avoiding the clustering problem by analysing only one pregnancy per woman, and contrast these to more modern approaches such as generalized estimating equations with robust standard errors and mixed models with various correlation structures. We illustrate the issues by analysing a sample from the Collaborative Perinatal Project dataset, demonstrating how the statistical model impacts summary statistics and inferences when assessing etiologic determinants of birth weight.
Design and analysis of time-to-pregnancy
Authors: Scheike Thomas H , Keiding Niels
Published: March 2006

Time-to-pregnancy(TTP), the duration that a couple waits from initiating attempts to conceive until conception occurs, is regarded as one of the direct measures of natural fecundity. Statistical tools for designing and analysing TTP studies belong to the general area of survival analysis, but several special features have been developed: it is customary to work in discrete time, and random heterogeneity between couples has always played a prominent role. This review works on this background with focus on how to perform valid analyses, under various prospective, retrospective and cross-sectional sampling frames. We illustrate using examples from our own experience.
Heterogeneity in fecundability studies: issues and modelling
Authors: Ecochard René
Published: March 2006

Modelization of fecundability stepped recently from demography and population-based contexts to reproductive biology and treatment of infertility. This created a strong call for flexibility and robustness. Indeed, explained and unexplained heterogeneities are non-negligible sources of bias that result in false conclusions as to the determinants of fertility or to the success rates of reproductive techniques, among other examples. There are two main sources of heterogeneity: biological heterogeneity and heterogeneity of sexual behaviour. A uniform presentation of time-to-pregnancy and Barrett-Marshall models is proposed to enlighten their similarities and differences in modelling heterogeneity of fecundability. Mixed models for fecundability studies are presented as tools to allow for unexplained heterogeneity and to quantify heterogeneity of the effect of observed factors and variability of size of this unexplained heterogeneity between subpopulations. Some criteria for the modelling strategy in fecundability studies are suggested with emphasis on the unit-treatment additivity criterion. The strong and complex selection process resulting from heterogeneity is described as well as the selection and cross-selection processes of observed and unobserved fecundability factors. Consequences regarding data collection and statistical inference are discussed. In the current context, a consensus setting general rules for data collection and statistical analysis would be useful to compare the results and increase the reliability of these results in medical practice.
Cervical mucus symptom and daily fecundability: first results from a new database
Authors: Colombo Bernardo , Mion Arianna , Passarin Katia , Scarpa Bruno
Published: March 2006

With the collaboration of Italian centres providing services on natural family planning, a prospective study collected data on 2755 menstrual cycles of 193 women. A database was constructed using information on the daily characteristics of cervical mucus and episodes of intercourse. Taking the day of peak mucus as a conventional marker of ovulation, the database identified the length (12 days) and location of a ‘window’ of potential fertility, the highest level of conception probability being confined to the central five to six days. Univariate analysis provided evidence of the impact on fecundability of the woman’s age and the basic infertile pattern of a cycle. Several analytical approaches highlighted the relationship between daily mucus characteristics and levels of fecundability.
Statistical models for human fecundability
Authors: Zhou Haibo
Published: March 2006

Statistical models for fertility studies play a critical role in understanding the biology for conception and in identifying potential environmental factors that may negatively affect human reproduction. Aided with improved computing capability, statistical modeling for fertility data has made a remarkable progress in the past decade. The author provides an overview of the historic and current developments for fecundability models.