bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity of three accelerometers during treadmill walking and motor vehicle travel
Authors: Maddocks Matthew , Petrou Andrea , Skipper Lindsay , Wilcock Andrew 
Published: August 2008

ObjectiveTo determine the relative accuracy during treadmill walking and motor vehicle travel of the ActivPAL, PALlite and Digi-Walker accelerometers.MethodsForty healthy volunteers wearing all accelerometers undertook either five treadmill walks (n=20) at speeds ranging between 0.6 and 1.4 m/s or a 15 min motor vehicle journey (n=20). Step counts recorded by each accelerometer were compared with the actual step count determined by video analysis (treadmill walking) or with an actual step count of zero (motor vehicle). Mean percentage measurement error was calculated and compared between devices by one-way ANOVA and Student t test.ResultsFor treadmill walking, the measurement error was lowest for the ActivPAL, with no significant differences between the ActivPAL and the PALlite monitors. The measurement error was significantly higher for the Digi-Walker at speeds of ≤1 m/s. During vehicle travel erroneous steps were recorded by the PALlite (254 steps) and Digi-Walker (25 steps), but not the ActivPAL monitor (0 steps).ConclusionsThe ActivPAL accelerometer accurately measures step count over a range of walking speeds and, unlike the other accelerometers tested, is not falsely triggered by motor vehicle travel.
Interspecies differences in coagulation profile
Authors: Siller-Matula Jolanta M. , Plasenzotti Roberto , Spiel Alexander , Quehenberger Peter , Jilma Bernd 
Published: August 2008

SummaryMany animals are used in research on blood coagulation and fibrinolysis, but the relevance of animal models to human health is often questioned because of differences between species. The objective was to find an appropriate animal species
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which mimics the coagulation profile in humans most adequately. Species differences in the coagulation profile with and without thrombin stimulation in vitro were assessed in whole blood by Rotation Thromboelastometry (ROTEM). Endogenous thrombin generation was measured in platelet-poor plasma. Measurements were performed in blood from five different species: humans, rats, pigs, sheep and rabbits. In humans and sheep, the clotting time (ROTEM) was in the same range with or without thrombin stimulation and a 100-fold lower dose of thrombin (0.002 IU) was required to cause a shortening in the clotting time as compared to rats, pigs and rabbits (0.2 IU) (p<0.05).Similarly, the endogenous thrombin potential (ETP) was in the same range in humans and sheep. The maximum clot firmness with or without thrombin stimulation was similar in rabbits and humans. The maximum lysis with or without thrombin stimulation was similar in humans and pigs. Significant species differences exist in the coagulation profile with or without thrombin stimulation. Most importantly, sheep had a clotting time most similar to humans and could thus be a suitable species for translational coagulation studies. Moreover, our findings confirm the potential usefulness of pigs as an experimental species to study fibrinolytic pathway and support the usefulness of rabbits as a species for examining platelets.
Predicting recurrences or major bleeding in cancer patients with venous thromboembolism
Authors: Trujillo-Santos Javier , Nieto José , Tiberio Gregorio , Piccioli Andrea , Micco Pierpaolo , Prandoni Paolo , Monreal Manuel 
Published: August 2008

SummaryCancer patients with acute venous thromboembolism (VTE) have an increased incidence of recurrences and bleeding complications while on anticoagulant therapy. Methods RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for recurrent pulmonary embolism (PE), deep vein thrombosis (DVT) or major bleeding. Up to May 2007, 3, 805 cancer patients had been enrolled in RIETE. During the first three months of follow-up after the acute, index VTE event, 90 (2.4%) patients developed recurrent PE, 100 (2.6%) recurrent DVT, 156 (4.1%) had major bleeding. Forty patients (44%) died of the recurrent PE,46 (29%) of bleeding. On multivariate analysis, patients aged <65 years (odds ratio [OR]: 3.0; 95% confidence interval [CI]: 1.9–4.9), with PE at entry (OR: 1.9; 95% CI: 1.2–3.1), or with <3 months from cancer diagnosis to VTE (OR: 2.0; 95% CI: 1.2–3.2) had an increased incidence of recurrent PE. Those aged <65 years (OR: 1.6; 95% CI: 1.0–2.4) or with <3 months from cancer diagnosis (OR: 2.4; 95% CI: 1.5–3.6) had an increased incidence of recurrent DVT. Finally, patients with immobility (OR: 1.8; 95% CI: 1.2–2.7), metastases (OR: 1.6; 95% CI: 1.1–2.3), recent bleeding (OR: 2.4; 95% CI: 1.1–5.1), or with creatinine clearance <30 ml/ min (OR: 2.2; 95% CI: 1.5–3.4), had an increased incidence of major bleeding. With some variables available at entry we may identify those cancer patients withVTE at a higher risk for recurrences or major bleeding.
Evaluation of liposomal dose in recombinant factor VIII reconstituted with pegylated liposomes for the treatment of patients with severe haemophilia A
Authors: Plyushch Olga P. , Andreeva Tatyana A. , Khametova Rosa N. , Spira Jack 
Published: August 2008

SummaryPatients with haemophilia A treated prophylactically require frequent factor VIII (FVIII) infusions for bleed protection. Recombinant sucrose-formulated FVIII (rFVIII-FS) with pegylated liposomes (PEGLip-rFVIII-FS) was previously shown to extend the bleed-free period after prophylactic infusion versus rFVIII-FS using two doses of FVIII with a fixed amount of liposomal diluent. This randomised, subject-blinded, four-way crossover study evaluated the efficacy and safety of PEGLip-rFVIII-FS using various quantities of pegylated liposomes with a fixed FVIII dose. Adults with severe haemophilia A were randomised to one of four treatment arms. Each arm had four treatment segments, with each segment consisting of a prophylactic infusion followed by on-demand infusions. The prophylactic infusions used a fixed dose of 35 IU/kg rFVIII-FS, but varied in the amount of pegylated liposomes used for reconstitution (4.2, 12.6, or 22.1 mg/kg of body weight or water as a control). On-demand infusions all used 35 IU/kg rFVIII-FS. After treatment of spontaneous bleeds and a wash-out, subjects crossed to another treatment segment (i.e. another PEGLip-rFVIII-FS dose or control).Sixteen subjects enrolled in and completed the study. Mean number of bleed-free days after prophylactic infusion increased from 7.8 days for control rFVIII-FS to 8.7, 10.8, and 10.9 days for PEGLip-rFVIII-FS reconstituted in 4.2, 12.6, and 22.1 mg/kg of pegylated liposomes, respectively. The difference in bleed-free days approached but did not achieve statistical significance in this small study population. No drug-related adverse events or inhibitors were reported. This study helps establish the optimal concentration of liposomes in PEGLip-rFVIII-FS to prolong the post-infusion bleed-free period.
Heparin-induced antibodies and cardiovascular risk in patients on dialysis
Authors: Segal Jodi B. , Plantinga Laura C. , Fink Nancy E. , Kerman Jonathan S. , Kickler Thomas S. , Coresh Josef , Gardner Lawrence B. , Asmis Lars M. 
Published: August 2008

SummaryThe clinical relevance of heparin-induced antibodies (HIA) in the absence of thrombocytopenia remains to be defined. The aims of this study were (i) to determine the prevalence of HIA in patients treated by dialysis, (ii) to determine the prevalence of thrombocytopenia and heparin-induced thrombocytopenia (HIT), and (iii) to test whether HIA are associated with adverse outcomes. Sera from 740 patients treated by hemodialysis (HD, n=596) and peritoneal dialysis (PD, n=144) were tested for HIA (IgG, IgA or IgM) by masked investigators at approximately six months after enrolment in the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) study. We assessed, with time-to-event Cox proportional hazards models, whether the presence of HIA predicted any of four clinical outcomes: arterial cardiovascular events, venous thromboembolism, vascular access occlusion and mortality. HIA prevalence was 10.3% overall. HIA positivity did not predict development of thrombocytopenia or any of the four clinical outcomes over a mean follow-up of 3.6 years, with hazard ratios for arterial cardiovascular events of 0.98 (95% confidence interval 0.70–1.37), venous thromboembolism 1.39 (0.17–11.5), vascular access occlusion 0.82 (0.40–1.71), and mortality 1.18 (0.85–1.64). Chronic intermittent heparin exposure was associated with a high seroprevalence of HIA. In dialysis patients these antibodies were not an independent risk factor for cardiovascular events and mortality. Our data do not suggest that dialysis patients should be monitored for HIA antibodies in the absence of thrombocytopenia.
Serpin-independent anticoagulant activity of a fucosylated chondroitin sulfate
Authors: Glauser Bianca F. , Pereira Mariana S. , Monteiro Robson Q. , Mourão Paulo A. S. 
Published: August 2008

SummaryFucosylated chondroitin sulfate is a glycosaminoglycan from sea cucumber composed of a chondroitin sulfate-like core with branches of sulfated fucose. This glycosaminoglycan has high anticoagulant and antithrombotic activities. Its serpin-dependent anticoagulant activity is mostly due to activating thrombin inhibition by heparin cofactor II. Here, we evaluated the anticoagulant activity of fucosylated chondroitin sulfate using antithrom-bin- and heparin cofactor II-free plasmas. In contrast to mammalian heparin, the invertebrate glycosaminoglycan is still able to prolong coagulation time and delay thrombin and factor Xa generation in serpin-free plasmas. These observations suggest that fucosylated chondroitin sulfate has a serpin-independent anticoagulant effect. We further investigated this effect using purified blood coagulation proteins. Clearly, fucosylated chondroitin sulfate inhibits the intrinsic tenase and prothrombinase complexes, which are critical for thrombin generation. It is possiblethat the invertebrate chondroitin sulfate inhibits interactions between cofactor Va and factor Xa. We also employed chemically modified polysaccharides in order to trace a structure versus activity relationship. Removal of the sulfated fucose branches, but not reduction of the glucuronic acid residues to glucose, abolished its activity. In conclusion, fucosylated chondroitin sulfate has broader effects on the coagulation system than mammalian glycosaminoglycans. In addition to its serpin-dependent inhibition of coagulation protease, it also inhibits the generation of factor Xa and thrombin by the tenase and prothrombinase complexes, respectively. In plasma systems, the serpin-independent anticoagulant effect of fucosylated chondroitin sulfate predominates over its serpin-dependent action. This glycosaminoglycan opens new avenues for the development of antithrombotic agents.
Simplified recombinant plasmin: Production and functional comparison of a novel thrombolytic molecule with plasma-derived plasmin
Authors: Hunt Jennifer , Petteway Stephen , Scuderi Philip , Novokhatny Valery 
Published: August 2008

SummaryA simplified and fully functional deletion mutant of plasminogen was created in which the middle portion of the molecule was removed, resulting in kringle 1 attachment to the serine protease domain. This recombinant plasminogen deletion mutant, Δ(K2-K5)Pg, was produced in the form of inclusion bodies at the yield of up to 200 mg/l in an Escherichia coliT7 expression system. Following protein refolding and purification on lysine-Sepharose, the conversion of the recombinant molecule Δ(K2-K5)Pg to the active enzyme mutant Δ(K2-K5)Pm by plasminogen activators was evaluated, and functional characteristics of the simplified plasmin were studied. Properties of Δ(K2-K5)Pg were similar to native, human plasma-derived plasminogen. Δ(K2-K5)Pg effectively bound ε-aminocaproic acid (Kd = 1 1.3 ± 2.3 μ. M) and fibrin (C50 ≈ 0.3 μM).The plasminogen activators streptokinase, urokinase, and tissue plasminogen activator effectively converted the recombinant zymogen Δ(K2-K5)Pg to the active recombinant enzyme, Δ(K2-K5)Pm. Additionally, Δ[K2-K5]Pm was rapidly inhibited by α2-antiplas-min(1.1±0.1x107M−1s−1)andα2-macroglobulin(7.6±0.6x105 M−1s−1). In an in-vitro model, Δ(K2-K5)Pm demonstrated fibrinolytic potency comparable to human plasma-derived plasmin. Because of their unique biochemistry, including fibrin-binding properties and rapid inhibition by α2-antiplasmin, both native plasmin and a simplified deletion mutant of plasmin are potentially safe and effective direct thrombolytic agents for various thrombotic conditions. Further studies evaluating the in-vivo pharmacologic safety and clinical efficacy of this simplified plasmin (i.e. Δ[K2-K5]Pm) are warranted.
Heparan sulfate proteoglycan is essential to thrombin-induced calcium transients and nitric oxide production in aortic endothelial cells
Authors: Kimura Chiwaka , Oike Masahiro 
Published: August 2008

SummaryThrombin induces Ca2+ transients and subsequent nitric oxide (NO) production in vascular endothelial cells. Thrombin cleaves protease-activated receptors, resulting in activation of intracellular signals, but it is not clarified how the extracellular thrombin stays around the cells to exert its enzyme activities. This study aimed to investigate the possible involvement of heparin sulfate proteoglycan (HSPG) in the effects of thrombin on vascular endothelium. Heparinase III completely removed the polysaccharide chain of HSPG in bovine aortic endothelial cells (BAECs).Thrombin induced Ca2+ transients in control BAECs, but not in heparinase III-treated BAECs. In contrast, ATP induced Ca2+ transients both in control and heparinase III-treated BAECs. Thrombin that was pre-incubated with heparin also failed to induced Ca2+ transients in BAECs. Furthermore, thrombin-induced NO production, as assessed with DAF-2 flu-orescence, was suppressed in heparinase III-treated BAECs and by the pre-incubation of thrombin with heparin. ATP-induced NO production was, however, not affected in heparinase III-treated BAECs. These results indicate that it is essential for thrombin to bind to the polysaccharide chain of HSPG for inducing Ca2+ transients and NO production in BAECs.
Neural Correlates of Subjective Awareness and Unconscious Processing: An ERP Study
Authors: Lamy Dominique , Salti Moti , Bar-Haim Yair 
Published: August 2008

Abstract
The aim of the present study was to dissociate the ERP (Event Related Potentials) correlates of subjective awareness from those of unconscious perception. In a backward masking paradigm, participants first produced a forced-choice response to the location of a liminal target presented for an individually calibrated duration, and then reported on their subjective awareness of the target's presence. We recorded (Event-Related Potentials) ERPs and compared the ERP waves when observers reported being aware vs. unaware of the target but localized it correctly, thereby isolating the neural correlates of subjective awareness while controlling for differences in objective performance. In addition, we compared the ERPs when participants were subjectively unaware of the target's presence and localized it correctly versus incorrectly, thereby isolating the neural correlates of unconscious perception. All conditions involved stimuli that were physically identical and were presented for the same duration. Both behavioral measures were associated with modulation of the amplitude of the P3 component of the ERP. Importantly, this modulation was widely spread across all scalp locations for subjective awareness, but was restricted to the parietal electrodes for unconscious perception. These results indicate that liminal stimuli that do not affect performance undergo considerable processing and that subjective awareness is associated with a late wave of activation with widely distributed topography.
Contribution of Prior Semantic Knowledge to New Episodic Learning in Amnesia
Authors: Kan Irene P. , Alexander Michael P. , Verfaellie Mieke 
Published: August 2008

Abstract
We evaluated whether prior semantic knowledge would enhance episodic learning in amnesia. Subjects studied prices that are either congruent or incongruent with prior price knowledge for grocery and household items and then performed a forced-choice recognition test for the studied prices. Consistent with a previous report, healthy controls' performance was enhanced by price knowledge congruency; however, only a subset of amnesic patients experienced the same benefit. Whereas patients with relatively intact semantic systems, as measured by an anatomical measure (i.e., lesion involvement of anterior and lateral temporal lobes), experienced a significant congruency benefit, patients with compromised semantic systems did not experience a congruency benefit. Our findings suggest that when prior knowledge structures are intact, they can support acquisition of new episodic information by providing frameworks into which such information can be incorporated.
Task-relevant Output Signals are Sent from Monkey Dorsolateral Prefrontal Cortex to the Superior Colliculus during a Visuospatial Working Memory Task
Authors: Johnston Kevin , Everling Stefan 
Published: August 2008

AbstractVisuospatial working memory is one of the most extensively investigated functions of the dorsolateral prefrontal cortex (DLPFC). Theories of prefrontal cortical function have suggested that this area exerts cognitive control by modulating the activity of structures to which it is connected. Here, we used the oculomotor system as a model in which to characterize the output signals sent from the DLPFC to a target structure during a classical spatial working memory task. We recorded the activity of identified DLPFC–superior colliculus (SC) projection neurons while monkeys performed a memory-guided saccade task in which they were required to generate saccades toward remembered stimulus locations. DLPFC neurons sent signals related to all aspects of the task to the SC, some of which were spatially tuned. These data provide the first direct evidence that the DLPFC sends task-relevant information to the SC during a spatial working memory task, and further support a role for the DLPFC in the direct modulation of other brain areas.
Don't Do It! Cortical Inhibition and Self-attribution during Action Observation
Authors: Schütz-Bosbach Simone , Avenanti Alessio , Aglioti Salvatore Maria , Haggard Patrick 
Published: August 2008

Abstract
Numerous studies suggest that both self-generated and observed actions of others activate overlapping neural networks, implying a shared, agent-neutral representation of self and other. Contrary to the shared representation hypothesis, we recently showed that the human motor system is not neutral with respect to the agent of an observed action [Schütz-Bosbach, S., Mancini, B., Aglioti, S. M., & Haggard, P. Self and other in the human motor system. Current Biology, 16, 1830–1834, 2006]. Observation of actions attributed to another agent facilitated the motor system, whereas observation of identical actions linked to the self did not. Here we investigate whether the absence of motor facilitation for observing one's own actions reflects a specific process of cortical inhibition associated with self-representation. We analyzed the duration of the silent period induced by transcranial magnetic stimulation of the motor cortex in active muscles as an indicator of motor inhibition. We manipulated whether an observed action was attributed to another agent, or to the subjects themselves, using a manipulation of body ownership on the basis of the rubber hand illusion. Observation of actions linked to the self led to longer silent periods than observation of a static hand, but the opposite effect occurred when observing identical actions attributed to another agent. This finding suggests a specific inhibition of the motor system associated with self-representation. Cortical suppression for actions linked to the self might prevent inappropriate perseveration within the motor system.
Posterior Beta and Anterior Gamma Oscillations Predict Cognitive Insight
Authors: Sheth Bhavin R. , Sandkühler Simone , Bhattacharya Joydeep 
Published: August 2008

AbstractPioneering neuroimaging studies on insight have revealed neural correlates of the emotional “Aha!” component of the insight process, but neural substrates of the cognitive component, such as problem restructuring (a key to transformative reasoning), remain a mystery. Here, multivariate electroencephalogram signals were recorded from human participants while they solved verbal puzzles that could create a small-scale experience of cognitive insight. Individuals responded as soon as they reached a solution and provided a rating of subjective insight. For unsolved puzzles, hints were provided after 60 to 90 sec. Spatio-temporal signatures of brain oscillations were analyzed using Morlet wavelet transform followed by exploratory parallel-factor analysis. A consistent reduction in beta power (15–25 Hz) was found over the parieto-occipital and centro-temporal electrode regions on all four conditions—(a) correct (vs. incorrect) solutions, (b) solutions without (vs. with) external hint, (c) successful (vs. unsuccessful) utilization of the external hint, and d) self-reported high (vs. low) insight. Gamma band (30–70 Hz) power was increased in right fronto-central and frontal electrode regions for conditions (a) and (c). The effects occurred several (up to 8) seconds before the behavioral response. Our findings indicate that insight is represented by distinct spectral, spatial, and temporal patterns of neural activity related to presolution cognitive processes that are intrinsic to the problem itself but not exclusively to one's subjective assessment of insight.
Multimodal Effects of Local Context on Target Detection: Evidence from P3b
Authors: Fogelson Noa , Wang Xue , Lewis Jeffrey B. , Kishiyama Mark M. , Ding Mingzhou , Knight Robert T. 
Published: August 2008

AbstractWe used the P300 component to investigate how changes in local context influenced the ability to detect target stimuli. Local context was defined as the occurrence of a short predictive series of stimuli before delivery of a target event. EEG was recorded in 12 subjects during auditory and visual sessions. Stimuli were presented in the center of the auditory and visual field and consisted of 15% targets (1000 Hz tone or downward facing triangle) and 85% of equal amounts of three types of standards (1500, 2000, and 2500 Hz tones or triangles facing left, upward, and right). Recording blocks consisted of targets preceded by either randomized sequences of standards or by sequences including a three-standard predictive sequence signaling the occurrence of a subsequent target event. Subjects pressed a button in response to targets. Peak target P300 (P3b) amplitude and latency were evaluated for targets after predictive and nonpredictive sequences using conventional averaging and a novel single-trial analysis procedure. Reaction times were shorter for predictable targets than for nonpredicted targets. P3b latency was shorter for predicted targets than for nonpredictive targets, and there were no significant P3b amplitude differences between predicted and random targets, as determined by both conventional averaging and single-trial analysis. Comparable effects on amplitude and latency were observed in both the auditory and visual modalities. The results indicate that local context has differential effects on P3b amplitude and latency, and exerts modality-independent effects on cognitive processing.