Implications of the choice of distance-based measures in assessing and investigating tumble turn performance.

Although the tumble turn in swimming has been studied extensively, no consensus exists about which measure is best suited to capture its performance. The aim of this study was to better understand the implications of choosing a particular distance-based performance measure for assessing and investigating tumble turn performance in freestyle swimming. To this end, a large set of retrospective turn data consisting of 2,813 turns performed by 160 swimmers was analyzed statistically in three steps. First, a mixed-effects model was derived for the entire data set, which showed that both performance level and sex had clear effects on the distance-based performance measures and performance determining variables studied in the literature. Second, repeated measures correlations were calculated for the entire data set and four performance level- and sex-based subgroups to determine the level of association between the performance measures. This analysis revealed that the performance measures were strongly correlated (r > 0.84 and p < 0.05 for all possible pairs), largely independent of performance level and sex. This finding implies that the choice of performance measure is not very critical when one is interested solely in the overall performance. In the third and last step, mixed-effects models were derived for the performance measures of interest to establish the importance of different turn-related actions for each measure, again for both the entire data set and the four subgroups separately. The results of this analysis revealed that performance measures with short(er) distances are more sensitive to changes in the adaptation time and reflect the wall contact time better than performance measures with long(er) distances, which in contrast are more useful if the focus is on the approach speed prior to the turn. In this final analysis, various effects of performance level and sex were found on the technical execution of the tumble turn.

Improving tumble turn performance in swimming-the impact of wall contact time and tuck index.

Race time can be shortened by improving turn performance in competitive swimming, but this requires insight into the optimal turn technique. The aim of the present study was to examine the effect of Wall Contact Time (WCT) and Tuck Index on tumble turn performance and their interrelations by experimentally manipulating both variables, which has not been done in previous research. Eighteen Dutch national level swimmers (FINA points 552 ± 122) performed tumble turns with three different WCTs (shorter, preferred, longer) and three different Tuck Indices (higher, preferred, lower), which were recorded by four underwater cameras and a wall-mounted force plate. Linear kinematic and kinetic variables, including the approach velocity (Vin), wall adaptation time (Tadapt), percentage of active WCT (aWCT), peak push-off force (FPeak) and exit velocity (Vexit), were extracted from the recordings and analyzed statistically, using the 5 m round trip time (5mRTT) as performance measure. The results indicated that the WCT should be sufficiently long to generate a high push-off force at the end of wall contact when the body is in a streamlined position. This led to a significantly shorter 5mRTT than a shorter or longer WCT. A linear mixed effect model yielded negative significant effects of WCT (-4.22, p < 0.001), FPeak (-2.18, p = 0.04), Vin (-4.83, p = 0.02), Tadapt (-2.68, p = 0.002), and Vexit (-9.52, p < 0.001) on the 5mRTT. The best overall turning performance was achieved with a Tuck Index of 0.7, which suggests that some of the participating swimmers could benefit from adapting their distance to the wall while turning, as was exemplified by calculating the optimal Tuck Index for individual swimmers. These results underscore the importance of WCT and Tuck Index vis-à-vis tumble turn performance, as well as their interrelations with other performance determining variables in this regard.

End-to-end security for personal telehealth.

Personal telehealth is in rapid development with innovative emerging applications like disease management. With personal telehealth people participate in their own care supported by an open distributed system with health services. This poses new end-to-end security and privacy challenges. In this paper we introduce new end-to-end security requirements and present a design for consent management in the context of the Continua Health Alliance architecture. Thus, we empower patients to control how their health information is shared and used in a personal telehealth eco-system.

Emergency access to protected health records.

Digital Rights Management (DRM) schemes are receiving increased attention in the healthcare domain for the protection of sensitive health records as they offer security against insider attacks and advance protection features such as usage control. However, to be accepted by health care providers, a DRM solution has to fulfill specific healthcare requirements including emergency access. In this paper, we propose such DRM solution that can be deployed in highly distributed environments of electronic or personal health record infrastructures.

Antithrombotic potential of GW813893: a novel, orally active, active-site directed factor Xa inhibitor.

BACKGROUND: Factor Xa (FXa) has been a target of considerable interest for drug development efforts aimed at suppressing thrombosis. In this report, a new orally active, small molecule, active-site directed FXa inhibitor, GW813893, has been profiled in a succession of in vitro and in vivo assays involved in its preclinical characterization as a potential antithrombotic therapeutic. METHODS: In vitro profiling of GW813893 consisted of assessing its inhibitory potential against FXa and a broad panel of related and unrelated enzymes and receptors. Additionally, the FXa inhibition potential of GW813893 was assessed in prothrombinase and plasma-based clotting assays. In vivo characterization of GW813893 consisted of thrombosis studies in a rat inferior vena cava model, a rat carotid artery thrombosis model, and a rabbit jugular thrombosis model. Bleeding studies were conducted in a rat tail transection model. Ex vivo determinations of compound effects on FX and clotting activity were also undertaken. RESULTS: GW813893 was more than 90-fold selective over all enzymes tested, and it inhibited FXa and prothrombinase activity with a Ki of 4.0 nM and 9.7 nM, respectively. In vivo, GW813893 concentration-dependently suppressed thrombotic activity in all models tested. The antithrombotic activity correlated with the suppression of plasma-based clotting activity and the inhibition of plasma FX activity (P < 0.02). Over the antithrombotic dose-range, an increased bleeding diathesis was not observed. CONCLUSION: These experiments demonstrate that GW813893 is a potent, selective, orally active inhibitor of FXa. The data suggest that GW813893 has robust antithrombotic potential at doses that have no detectable hemostasis liability. Collectively, the profile suggests that GW813893 has the preclinical pharmacology underpinnings of an oral antithrombotic therapeutic.

Reliable personal health records.

A number of applications based on personal health records (PHRs) are emerging in the field of health care and wellness. PHRs empower patients by giving them control over their health data. Health data for PHRs can be supplied by patients, wellness providers and health care providers. Health care providers may use the PHRs to provide medical care. Unfortunately, the quality of the health data in PHRs cannot be guaranteed in all cases. For example, consider cases where non-professionals such as patients and wellness providers supply data. To address this problem, we present in this paper a system that provides health care professionals with an indication of the quality of health data in a PHR. This indication is based on the reputation of the supplier and on metadata provided by measurement devices. The proposed reputation system mimics the way in which trust in health data and their suppliers is built in the real world. The system introduces minimal overhead for health care providers and patients.

A practical method to estimate the benefits of improved road network reliability: an application to departing air passengers.

This paper develops and applies a practical method to estimate the benefits of improved reliability of road networks. We present a general methodology to estimate the scheduling costs due to travel time variability for car travel. In contrast to existing practical methods, we explicitly consider the effect of travel time variability on departure time choices. We focus on situations when only mean delays are known, which is typically the case when standard transport models are used. We first show how travel time variability can be predicted from mean delays. We then estimate the scheduling costs of travellers, taking into account their optimal departure time choice given the estimated travel time variability. We illustrate the methodology for air passengers traveling by car to Amsterdam Schiphol Airport. We find that on average planned improvements in network reliability only lead to a small reduction in access costs per trip in absolute terms, mainly because most air passengers drive to the airport outside peak hours, when travel time variability tends to be low. However, in relative terms the reduction in access costs due to the improvements in network reliability is substantial. In our case we find that for every 1 Euro reduction in travel time costs, there is an additional cost reduction of 0.7 Euro due to lower travel time variability, and hence lower scheduling costs. Ignoring the benefits from improved reliability may therefore lead to a severe underestimation of the total benefits of infrastructure improvements.

L-Carnitine intake and high trimethylamine N-oxide plasma levels correlate with low aortic lesions in ApoE(-/-) transgenic mice expressing CETP.

OBJECTIVE: Dietary l-carnitine can be metabolized by intestinal microbiota to trimethylamine, which is absorbed by the gut and further oxidized to trimethylamine N-oxide (TMAO) in the liver. TMAO plasma levels have been associated with atherosclerosis development in ApoE(-/-) mice. To better understand the mechanisms behind this association, we conducted in vitro and in vivo studies looking at the effect of TMAO on different steps of atherosclerotic disease progression. METHODS: J774 mouse macrophage cells were used to evaluate the effect of TMAO on foam cell formation. Male ApoE(-/-) mice transfected with human cholesteryl ester transfer protein (hCETP) were fed l-carnitine and/or methimazole, a flavin monooxygenase 3 (FMO3) inhibitor that prevents the formation of TMAO. Following 12 week treatment, l-carnitine and TMAO plasma levels, aortic lesion development, and lipid profiles were determined. RESULTS: TMAO at concentrations up to 10-fold the Cmax reported in humans did not affect in vitro foam cell formation. In ApoE(-/-)mice expressing hCETP, high doses of l-carnitine resulted in a significant increase in plasma TMAO levels. Surprisingly, and independently from treatment group, TMAO levels inversely correlated with aortic lesion size in both aortic root and thoracic aorta. High TMAO levels were found to significantly correlate with smaller aortic lesion area. Plasma lipid and lipoprotein levels did not change with treatment nor with TMAO levels, suggesting that the observed effects on lesion area were independent from lipid changes. CONCLUSION: These findings suggest that TMAO slows aortic lesion formation in this mouse model and may have a protective effect against atherosclerosis development in humans.

Inhibition of factor IX(a) is protective in a rat model of thromboembolic stroke.

BACKGROUND AND PURPOSE: Although used clinically to prevent stroke, there are few examples of anticoagulant investigations in the treatment of acute thromboembolic stroke in animal models. The treatment of thromboembolic stroke in experimental models has been investigated almost exclusively around the use of tissue plasminogen activator (tPA). In this study, using a rat thromboembolic stroke model, we investigated the use of an inhibitory anti-factor IX(a) monoclonal antibody (SB 249417) for the treatment of thromboembolic stroke and compared its efficacy to that of tPA. METHODS: Stroke was initiated by delivering 6 clots into the internal carotid artery. After 2, 4, or 6 hours, rats received either intravenous vehicle, 10.0 mg/kg tPA, or 1.0, 2.0, or 3.0 mg/kg SB 249417. At 24 hours after stroke, infarct volumes and neurological deficits were assessed. RESULTS: Treatment with tPA 2, 4, or 6 hours after stroke reduced infarct volumes by 35% (P=NS), 45%, and 39%, respectively. tPA treatment did not improve neurological deficits at any time point. Treatment with SB 249417 (3.0 mg/kg) 2, 4, or 6 hours after stroke reduced infarct volumes by 44%, 50%, and 13% (P=NS), respectively. Neurological deficits were reduced by 49%, 42%, and 13% (P=NS), respectively. Neither mortality nor hemorrhage was affected by either treatment. CONCLUSIONS: The data indicate that the inhibition of factor IX(a) within 4 hours of thromboembolic stroke produced a more favorable outcome than tPA. When treatment was initiated 6 hours after stroke, the benefits of factor IX(a) inhibition were lost, whereas tPA continued to suppress lesion development, albeit without a corresponding improvement in functional deficits. This study suggests that cerebral ischemia and the resultant perfusion deficit are exacerbated by the activation of blood coagulation and that anticoagulants like SB 249417 may find utility in the treatment of ischemic stroke.

The antithrombotic efficacy of lotrafiban (SB 214857) in canine models of acute coronary thrombosis.

In patients with acute coronary syndromes, inhibition of platelet aggregation with parenteral alpha(IIb)/beta(III) antagonists has proven effective at preventing nonfatal myocardial infarction and repeat percutaneous coronary interventions. Paradoxically, the efficacy observed for acute indications and parenteral agents has not extended to oral agents and chronic prevention of secondary thrombotic events, despite robust antithrombotic properties in preclinical thrombosis models. This report documents the preclinical data of Lotrafiban, an oral alpha(IIb)/beta(III) antagonist that recently failed in a phase III clinical trial (BRAVO) for the prevention of secondary thrombosis. Lotrafiban was characterized in a dog circumflex artery electrical injury model, and a cyclic flow reduction model ("Folts"). The data demonstrate that both oral (1.0-50.0 mg/kg) and intravenous (0.1-0.8ug/kg/min) administration of lotrafiban produced dose-related inhibition (45%-95%) of ex vivo platelet aggregation. In the electrical injury model, the dose-related inhibition correlated with a significant reduction in the frequency of coronary occlusion, size of the developing thrombus, and the extent of left ventricular ischemic damage. Effects on blood flow and bleeding time were also dose related. The combination of low dose lotrafiban (0.1ug/kg/min) and aspirin (5.0 mg/kg) generated additive antithrombotic effects, approximating the antithrombotic efficacy of a 2-4 fold higher dose of lotrafiban while only modestly prolonging the bleeding time. For purposes of comparison, the ADP receptor antagonist clopidogrel was also assessed in the electrical injury model. Clopidogrel (5.0-10.0 mg/kg, iv.) significantly reduced the resulting left ventricular infarct areas, but lacked the overall efficacy of lotrafiban. In the "Folts" model, lotrafiban inhibited cyclic blood flow reductions (CFR's) by 100% in animals insensitive to the antithrombotic effects of aspirin. Overall, the preclinical data demonstrated that alpha(IIb)/beta(III) antagonism with lotrafiban was a well tolerated and effective strategy for attenuating acute arterial thrombosis. The lack of a correlation between these preclinical data and the outcome of the clinical trial BRAVO are unexplained. However, the combined evidence suggests that these acute canine thrombosis studies may not completely capture the pathology reflected in chronic human atherothrombotic disease.