Kinematic Calibration of Parallel Kinematic Machines on the Example of the Hexapod of Simple Design

The aim of using parallel kinematic motion systems as an alternative of conventional machine tools for precision machining has raised the demands made on the accuracy of identification of the geometric parameters that are necessary for the kinematic transformation of the motion variables. The accuracy of a parallel manipulator is not only dependent upon an accurate control of its actuators but also upon a good knowledge of its geometrical characteristics. As the platform's controller determines the length of the actuators according to the nominal model, the resulted pose of the platform is inaccurate. One way to enhance platform accuracy is by kinematic calibration, a process by which the actual kinematic parameters are identified and then implemented to modify the kinematic model used by the controller. The first and most general valuation criterion for the actual calibration approaches is the relative improvement of the motion accuracy, eclipsing the other aspects to pay for it. The calibration outlay has been underestimated or even neglected for a long time. The scientific value of the calibration procedure is not only in direct proportion to the achieved accuracy, but also to the calibration effort. These demands become particularly stringent in case of the calibration of hexapods of the so-called simple design. The objectives of the here proposed new calibration procedure are based on the deficits mentioned above under the special requirements due to the circumstances of the simple design-concept. The main goals of the procedure can be summarized in obtaining the basics for an automated kinematic calibration procedure which works efficiently, quickly, effectively and possibly low-cost, all-in-one economically applied to the parallel kinematic machines. The problem will be approached systematically and taking step by step the necessary conclu-sions and measurements through: Systematical analysis of the workspace to determine the optimal measuring procedure, measurements with automated data acquisition and evaluation, simulated measurements based on the kinematic model of the structure and identifying the kinematic parameters using efficient optimization algorithms. The presented calibration has been successfully implemented and tested on the hexapod of simple design `Felix' available at the IWM, TU Dresden. The obtained results encourage the application of the procedure to other hexapod structures

Relationship between nitrate headache and outcome in patients with acute stroke: results from the efficacy of nitric oxide in stroke (ENOS) trial

IntroductionNitrate-induced headache is common and may signify responsive cerebral vasculature. We assessed the relationship between nitrate-headache and outcome in patients with acute stroke.Materials and MethodsPatients were those randomised to glyceryl trinitrate (GTN) versus no GTN in the Efficacy of Nitric Oxide in Stroke trial. Development of headache by end of treatment (day 7), and functional outcome (modified Rankin Scale, mRS, primary outcome) at day 90, were assessed. Analyses are adjusted for baseline prognostic factors and give odds ratio (OR) and mean difference (MD) with 95% confidence intervals (95% CI).ResultsIn 4011 patients, headache was more common in GTN than control (360, 18.0% vs. 170, 8.5%; 2

Effect of glyceryl trinitrate on haemodynamics in acute stroke: data from the Efficacy of Nitric Oxide in Stroke trial

Background and Purpose: Increased blood pressure (BP), heart rate and their derivatives (variability, pulse pressure, rate-pressure product [RPP]) are associated with poor clinical outcome in acute stroke. We assessed the effects of glyceryl trinitrate (GTN) on haemodynamic parameters, and these on outcome in participants in the Efficacy of Nitric Oxide in Stroke trial.Methods: 4011 patients with acute stroke and raised BP were randomised within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral haemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as standard deviation) was assessed in quintiles. Functional outcome was assessed as modified Rankin Scale (mRS) and cognition as telephone mini-mental state examination (t-MMSE) at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference (MD) or odds ratios (OR) with 95% confidence intervals (CI).Results: Increased baseline BP (diastolic, variability), heart rate and RPP were each associated with unfavourable functional outcome at day 90. Increased between-visit systolic BP variability was associated with an unfavourable shift in mRS (highest quintile adjusted OR 1.65, 95% CI 1.37 to 1.99), worse cognitive scores (t-MMSE: highest quintile adjusted MD -2.03, 95% CI -2.84 to -1.22) and increased odds of death at day 90 (highest quintile adjusted OR 1.57, 95% CI 1.12 to 2.19). GTN lowered BP and RPP, and increased heart rate at day 1; and reduced between-visit systolic BP variability.Conclusions: Increased between-visit BP variability was associated with poor functional and cognitive outcomes and increased death 90 days after acute stroke. In addition to lowering BP and RPP, GTN reduced between-visit systolic BP variability. Agents that lower BP variability in acute stroke require further study

Central adjudication of serious adverse events did not affect trial's safety results: Data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial

Background and Purpose: Central adjudication of serious adverse events (SAEs) can be undertaken in clinical trials, especially for open-label studies where outcome assessment may be at risk of bias. This study explored the effect of central adjudication of SAEs on the safety results of the Efficacy of Nitric Oxide in Stroke (ENOS) Trial. Methods: ENOS assigned patients with acute stroke at random to receive either transdermal glyceryl trinitrate (GTN) or no GTN and to Stop or Continue previous antihypertensive treatment. SAEs were reported by local investigators who were not blinded to treatment allocation. Central adjudicators blinded to treatment allocation, reviewed the investigators reports and used evidence available to confirm or re-categorise the classification of event, likely causality, diagnosis and expectedness of event. Results: Of 4011 patients enrolled in ENOS, 1473 SAEs were reported by local investigators; this was reduced to 1444 after the review by adjudicators, with 29 re-classified as not an SAE. There was fair agreement between investigators and adjudicators regarding likely causality, with 808 agreements and 644 disagreements (56% crude agreement, weighted kappa, κ = 0.31). Agreement increased upon dichotomisation of the causality categories, with 1432 agreements and 20 disagreements (99% crude agreement, kappa = 0.54). Repeating the main trial safety analysis with investigator reported events showed that adjudication had no effect on the main trial safety conclusions. Conclusions: In a large trial, with many SAEs reported, central adjudication of these events did not affect trial conclusions. This suggests that adjudication of SAEs in a clinical trial where the intervention already has a well-established safety profile may not be necessary. Potential efficiency savings (financial, logistical) can be made through not adjudicating SAEs

Continuing versus stopping prestroke antihypertensive therapy in acute intracerebral hemorrhage: a subgroup analysis of the efficacy of nitric oxide in stroke trial

Background and purpose: More than 50% of patients with acute intracerebral haemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Methods: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life. Results: Blood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45- 1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events. Conclusions: Among patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily

Route of feeding as a proxy for dysphagia after stroke and the effect of transdermal glyceryl trinitrate: data from the efficacy of nitric oxide in stroke randomised controlled trial

Post-stroke dysphagia is common, associated with poor outcome and often requires non-oral feeding/fluids. The relationship between route of feeding and outcome, as well as treatment with glyceryl trinitrate (GTN), was studied prospectively. The Efficacy of Nitric Oxide in Stroke (ENOS) trial assessed transdermal GTN (5 mg versus none for 7 days) in 4011 patients with acute stroke and high blood pressure. Feeding route (oral = normal or soft diet; nonoral = nasogastric tube, percutaneous endoscopic gastrostomy tube, parenteral fluids, no fluids) was assessed at baseline and day 7. The primary outcome was the modified Rankin Scale (mRS) measured at day 90. At baseline, 1331 (33.2%) patients had non-oral feeding, were older, had more severe stroke and more were female, than 2680 (66.8%) patients with oral feeding. By day 7, 756 patients had improved from non-oral to oral feeding, and 119 had deteriorated. Non-oral feeding at baseline was associated with more impairment at day 7 (Scandinavian Stroke Scale 29.0 versus 43.7; 2p < 0.001), and worse mRS (4.0 versus 2.7; 2p < 0.001) and death (23.6 versus 6.8%; 2p = 0.014) at day 90. Although GTN did not modify route of feeding overall, randomisation ≤6 hours of stroke was associated with a move to more oral feeding at day 7 (odds ratio = 0.61, 95% confidence intervals 0.38, 0.98; 2p = 0.040). As a proxy for dysphagia, non-oral feeding is present in 33% of patients with acute stroke and associated with more impairment, dependency and death. GTN moved feeding route towards oral intake if given very early after stroke

It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis

Background There is concern that blood pressure (BP) lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis. We assessed the effect of glyceryl trinitrate (GTN) in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke (ENOS) Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP (140–220 mm Hg) to transdermal GTN or no GTN within 48 hours of onset. Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days. The primary outcome was the modified Rankin Scale (mRS) at day 90. Ipsilateral carotid stenosis was split

The prevalence of psychiatric symptoms before the diagnosis of Parkinson's disease in a nationwide cohort: A comparison to patients with cerebral infarction

Objectives Psychiatric symptoms (PS) can be non-motor features in Parkinson's disease (PD) which are common even in the prodromal, untreated phase of the disease. Some PS, especially depression and anxiety recently became known predictive markers for PD. Our objective was to explore retrospectively the prevalence of PS before the diagnosis of PD. Methods In the framework of the Hungarian Brain Research Program we created a database from medical and medication reports submitted for reimbursement purposes to the National Health Insurance Fund in Hungary, a country with 10 million inhabitants and a single payer health insurance system. We used record linkage to evaluate the prevalence of PS before the diagnosis of PD and compared that with patients with ischemic cerebrovascular lesion (ICL) in the period between 2004-2016 using ICD-10 codes of G20 for PD, I63-64 for ICL and F00-F99 for PS. We included only those patients who got their PD, ICL and psychiatric diagnosis at least twice. Results There were 79 795 patients with PD and 676 874 patients with ICL. Of the PD patients 16% whereas of those with ischemic cerebrovascular lesion 9.7% had a psychiatric diagnosis before the first appearance of PD or ICL (p<0.001) established in psychiatric care at least twice. The higher rate of PS in PD compared to ICL remained significant after controlling for age and gender in logistic regression analysis. The difference between PD and ICL was significant for Mood disorders (F30-F39), Organic, including symptomatic, mental disorders (F00-F09), Neurotic, stress-related and somatoform disorders (F40-F48) and Schizophrenia, schizotypal and delusional disorders (F20-F29) diagnosis categories (p<0.001, for all). Discussion The higher rate of psychiatric morbidity in the premotor phase of PD may reflect neurotransmitter changes in the early phase of PD

Baseline characteristics of the 4011 patients recruited into the 'Efficacy of Nitric Oxide in Stroke' (ENOS) trial

BACKGROUND: High blood pressure is common in acute stroke and associated with a worse functional outcome. Many patients who present with acute stroke are taking prescribed antihypertensive therapy before their stroke. AIMS: ENOS tested whether lowering blood pressure and continuing pre-stroke antihypertensive therapy are each safe and effective. METHODS: This study is an international multi-centre prospective randomized single-blind blinded-endpoint parallel-group partial-factorial controlled trial of transdermal glyceryl trinitrate(a nitric oxide donor, given for seven-days) vs. no glyceryl trinitrate, and of continuing vs. stopping (temporarily for seven-days) pre-stroke antihypertensive drugs if relevant, inpatients with acute ischaemic stroke or intracerebral haemorrhage and high systolic blood pressure (140–220 mmHg). RESULTS: Recruitment ran from July 2001 to October 2013. Four thousand eleven patients [2097 (52·3%) in the continue/stop arm] were recruited from 173 sites across 23 countries in 5 continents (Asia 14%, Continental Europe 16%, UK 64%). Baseline characteristics include: mean age 70 (standard deviation 12) years; male 57%; mean time from stroke to recruitment 26 (13) h; mean severity (Scandinavian Stroke Scale) 34(13) of 58; mean blood pressure 167 (19)/90 (13) mmHg; ischaemic stroke 83%; and intracerebral haemorrhage 16%. The main trial results will be presented in May 2014. The results will also be presented in updated Cochrane systematic reviews and included in individual patient data meta-analyses of all relevant randomized controlled trials. CONCLUSION: ENOS is a large completed international trial of blood pressure management in acute stroke and includes patients representative of many stroke services worldwide