Sub-Riemannian geodesics on nested principal bundles

We study the interplay between geodesics on two non-holono\-mic systems that are related by the action of a Lie group on them. After some geometric preliminaries, we use the Hamiltonian formalism to write the parametric form of geodesics. We present several geometric examples, including a non-holonomic structure on the Gromoll-Meyer exotic sphere and twistor space.Comment: 10 page

Standardizing effect size from linear regression models with log-transformed variables for meta-analysis

Background: Meta-analysis is very useful to summarize the effect of a treatment or a risk factor for a given disease. Often studies report results based on log-transformed variables in order to achieve the principal assumptions of a linear regression model. If this is the case for some, but not all studies, the effects need to be homogenized. Methods: We derived a set of formulae to transform absolute changes into relative ones, and vice versa, to allow including all results in a meta-analysis. We applied our procedure to all possible combinations of log-transformed independent or dependent variables. We also evaluated it in a simulation based on two variables either normally or asymmetrically distributed. Results: In all the scenarios, and based on different change criteria, the effect size estimated by the derived set of formulae was equivalent to the real effect size. To avoid biased estimates of the effect, this procedure should be used with caution in the case of independent variables with asymmetric distributions that significantly differ from the normal distribution. We illustrate an application of this procedure by an application to a meta-analysis on the potential effects on neurodevelopment in children exposed to arsenic and manganese. Conclusions: The procedure proposed has been shown to be valid and capable of expressing the effect size of a linear regression model based on different change criteria in the variables. Homogenizing the results from different studies beforehand allows them to be combined in a meta-analysis, independently of whether the transformations had been performed on the dependent and/or independent variables

Cost-effectiveness of exercise therapy versus general practitioner care for osteoarthritis of the hip: design of a randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is the most common joint disease, causing pain and functional impairments. According to international guidelines, exercise therapy has a short-term effect in reducing pain/functional impairments in knee OA and is therefore also generally recommended for hip OA. Because of its high prevalence and clinical implications, OA is associated with considerable (healthcare) costs. However, studies evaluating cost-effectiveness of common exercise therapy in hip OA are lacking. Therefore, this randomised controlled trial is designed to investigate the cost-effectiveness of exercise therapy in conjunction with the general practitioner's (GP) care, compared to GP care alone, for patients with hip OA.</p> <p>Methods/Design</p> <p>Patients aged ≥ 45 years with OA of the hip, who consulted the GP during the past year for hip complaints and who comply with the American College of Rheumatology criteria, are included. Patients are randomly assigned to either exercise therapy in addition to GP care, or to GP care alone. Exercise therapy consists of (maximally) 12 treatment sessions with a physiotherapist, and home exercises. These are followed by three additional treatment sessions in the 5th, 7th and 9th month after the first treatment session. GP care consists of usual care for hip OA, such as general advice or prescribing pain medication. Primary outcomes are hip pain and hip-related activity limitations (measured with the Hip disability Osteoarthritis Outcome Score [HOOS]), direct costs, and productivity costs (measured with the PROductivity and DISease Questionnaire). These parameters are measured at baseline, at 6 weeks, and at 3, 6, 9 and 12 months follow-up. To detect a 25% clinical difference in the HOOS pain score, with a power of 80% and an alpha 5%, 210 patients are required. Data are analysed according to the intention-to-treat principle. Effectiveness is evaluated using linear regression models with repeated measurements. An incremental cost-effectiveness analysis and an incremental cost-utility analysis will also be performed.</p> <p>Discussion</p> <p>The results of this trial will provide insight into the cost-effectiveness of adding exercise therapy to GPs' care in the treatment of OA of the hip. This trial is registered in the Dutch trial registry <url>http://www.trialregister.nl</url>: trial number <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1462">NTR1462</a>.</p

Quantitative Analysis of Vasodilatory Action of Quercetin on Intramural Coronary Resistance Arteries of the Rat In Vitro

Background: Dietary quercetin improves cardiovascular health, relaxes some vascular smooth muscle and has been demonstrated to serve as a substrate for the cyclooxygenase enzyme. Aims: 1. To test quantitatively a potential direct vasodilatory effect on intramural coronary resistance artery segments, in different concentrations. 2. To scale vasorelaxation at different intraluminal pressure loads on such vessels of different size. 3. To test the potential role of prostanoids in vasodilatation induced by quercetin. Methods: Coronary arterioles (70-240 mu m) were prepared from 24 rats and pressurized in PSS, using a pressure microangiometer. Results: The spontaneous tone that developed at 50 mmHg was relaxed by quercetin in the 10(-9) moles/lit concentration (p<0.05), while 10(-5) moles/lit caused full relaxation. Significant relaxation was observed at all pressure levels (10-100 mmHg) at 10(-7) moles/lit concentration of quercetin. The cyclooxygenase blocker indomethacin (10(-5) moles/lit) induced no relaxation but contraction when physiological concentrations of quercetin were present in the tissue bath (p<0.02 with Anova), this contraction being more prominent in smaller vessels and in the higher pressure range (p<0.05, Pearson correlation). A further 2-8% contraction could be elicited by the NO blocker L-NAME (10(-4) moles/lit). Conclusion: These results demonstrate that circulating levels of quercetin (10(-7) moles/lit) exhibit a substantial coronary vasodilatory effect. The extent of it is commeasurable with that of several other physiological mechanisms of coronary blood flow control. At least part of this relaxation is the result of an altered balance toward the production of endogenous vasodilatory prostanoids in the coronary arteriole wall

P300 amplitude is insensitive to working memory load in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Working memory (WM) tasks usually elicit a P300 ERP component, whose amplitude decreases with increasing WM load. So far, this effect has not been studied in schizophrenics (SZs), a group that is considered to have an aberrant brain connectivity and impairments in WM capacity. The aim of this study was to determine the dependency of the P300 component on WM load in a sample of SZ subjects.</p> <p>Methods</p> <p>We recorded 26 subjects (13 SZ patients and their matched controls) with an 80-channel electroencephalogram. Subjects performed an N-back task, a WM paradigm that manipulates the number of items to be stored in memory.</p> <p>Results</p> <p>In healthy subjects, P300 amplitude was highest in the low WM load condition, and lowest in both the attentional control condition and the high WM load condition. In contrast, SZs evidenced low P300 amplitude in all conditions. A significant between group difference in P300 amplitude was evidenced only at the low WM load condition (1 -back), being smaller in SZs.</p> <p>Conclusions</p> <p>SZ subjects display a lower than normal P300 amplitude, which does not vary as a function of memory load. These results are consistent with a general impairment in WM capacity in these patients.</p

Targeting the Neurokinin Receptor 1 with Aprepitant: A Novel Antipruritic Strategy

Chronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment with e.g. antihistamines. Therefore antipruritic therapies which target physiological mechanisms of pruritus need to be developed. Substance P (SP) is a major mediator of pruritus. As it binds to the neurokinin receptor 1 (NKR1), we evaluated if the application of a NKR1 antagonist would significantly decrease chronic pruritus.Twenty hitherto untreatable patients with chronic pruritus (12 female, 8 male; mean age, 66.7 years) were treated with the NKR1 antagonist aprepitant 80 mg for one week. 16 of 20 patients (80%) experienced a considerable reduction of itch intensity, as assessed by the visual analog scale (VAS, range 0 to 10). Considering all patients, the mean value of pruritus intensity was significantly reduced from 8.4 VAS points (SD +/-1.7) before treatment to 4.9 VAS points (SD +/-3.2) (p<0.001, CI 1.913-5.187). Patients with dermatological diseases (e.g. atopic diathesis, prurigo nodularis) had the best profit from the treatment. Side-effects were mild (nausea, vertigo, and drowsiness) and only occurred in three patients.The high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur