Handwriting analysis for diagnosis and prognosis of Parkinson’s disease
Rüdiger W. Brause
- At present, there are no quantitative, objective methods for diagnosing the Parkinson disease. Existing methods of quantitative analysis by myograms suffer by inaccuracy and patient strain; electronic tablet analysis is limited to the visible drawing, not including the writing forces and hand movements. In our paper we show how handwriting analysis can be obtained by a new electronic pen and new features of the recorded signals. This gives good results for diagnostics. Keywords: Parkinson diagnosis, electronic pen, automatic handwriting analysis
The performance of approximating ordinary differential equations by neural nets
Rüdiger W. Brause
- The dynamics of many systems are described by ordinary differential equations (ODE). Solving ODEs with standard methods (i.e. numerical integration) needs a high amount of computing time but only a small amount of storage memory. For some applications, e.g. short time weather forecast or real time robot control, long computation times are prohibitive. Is there a method which uses less computing time (but has drawbacks in other aspects, e.g. memory), so that the computation of ODEs gets faster? We will try to discuss this question for the assumption that the alternative computation method is a neural network which was trained on ODE dynamics and compare both methods using the same approximation error. This comparison is done with two different errors. First, we use the standard error that measures the difference between the approximation and the solution of the ODE which is hard to characterize. But in many cases, as for physics engines used in computer games, the shape of the approximation curve is important and not the exact values of the approximation. Therefore, we introduce a subjective error based on the Total Least Square Error (TLSE) which gives more consistent results. For the final performance comparison, we calculate the optimal resource usage for the neural network and evaluate it depending on the resolution of the interpolation points and the inter-point distance. Our conclusion gives a method to evaluate where neural nets are advantageous over numerical ODE integration and where this is not the case. Index Terms—ODE, neural nets, Euler method, approximation complexity, storage optimization.
Evidence regarding clinical use of microvolt T-wave alternans
Stefan H. Hohnloser
Richard J. Cohen
- Background: Microvolt T-wave alternans (MTWA) testing in many studies has proven to be a highly accurate predictor of ventricular tachyarrhythmic events (VTEs) in patients with risk factors for sudden cardiac death (SCD) but without a prior history of sustained VTEs (primary prevention patients). In some recent studies involving primary prevention patients with prophylactically implanted cardioverter-defibrillators (ICDs), MTWA has not performed as well. Objective: This study examined the hypothesis that MTWA is an accurate predictor of VTEs in primary prevention patients without implanted ICDs, but not of appropriate ICD therapy in such patients with implanted ICDs. Methods: This study identified prospective clinical trials evaluating MTWA measured using the spectral analytic method in primary prevention populations and analyzed studies in which: (1) few patients had implanted ICDs and as a result none or a small fraction (≤15%) of the reported end point VTEs were appropriate ICD therapies (low ICD group), or (2) many of the patients had implanted ICDs and the majority of the reported end point VTEs were appropriate ICD therapies (high ICD group). Results: In the low ICD group comprising 3,682 patients, the hazard ratio associated with a nonnegative versus negative MTWA test was 13.6 (95% confidence interval [CI] 8.5 to 30.4) and the annual event rate among the MTWA-negative patients was 0.3% (95% CI: 0.1% to 0.5%). In contrast, in the high ICD group comprising 2,234 patients, the hazard ratio was only 1.6 (95% CI: 1.2 to 2.1) and the annual event rate among the MTWA-negative patients was elevated to 5.4% (95% CI: 4.1% to 6.7%). In support of these findings, we analyzed published data from the Multicenter Automatic Defibrillator Trial II (MADIT II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trials and determined that in those trials only 32% of patients who received appropriate ICD therapy averted an SCD. Conclusion: This study found that MTWA testing using the spectral analytic method provides an accurate means of predicting VTEs in primary prevention patients without implanted ICDs; in particular, the event rate is very low among such patients with a negative MTWA test. In prospective trials of ICD therapy, the number of patients receiving appropriate ICD therapy greatly exceeds the number of patients who avert SCD as a result of ICD therapy. In trials involving patients with implanted ICDs, these excess appropriate ICD therapies seem to distribute randomly between MTWA-negative and MTWA-nonnegative patients, obscuring the predictive accuracy of MTWA for SCD. Appropriate ICD therapy is an unreliable surrogate end point for SCD. Key words: Arrhythmia; Sudden cardiac death; Cardiac arrest; ICD; T-wave alternans; Surrogate endpoint; Ventricular tachyarrhythmic event; Primary prevention
Über den Widerspruch von religiöser Hoffnung und politischer Analyse in Adam Smith Theorie des freien Marktes
- Die zentrale These des vorliegenden Aufsatzes ist es, dass es ein Adam Smith-Problem im traditionellen Sinne nicht gibt, aber sehr wohl einen Selbstwiderspruch in Adam Smith ökonomischer Theorie.
Der Aufsatz behandelt zunächst die enge systematische Verbindung von Smith ökonomischer und ethischer Theorie. Die Verbindung beruht auf der Annahme eines höchsten Wesens und einer daraus gefolgerten prästabilisierenden Harmonie Dem religiösen Vertrauen auf eine natürliche Ordnung korresponiert der Glaube an die Gerechtigkeit des Marktes. Smith weitere politische Analyse produziert allerdings einen Selbstwiderspruch. Smith zeigt auf, dass die unternehmerischen Eigeninteressen dem Allgemeininteresse der Gesellschaft widersprechen und die Unternehmer zudem virtuoser und erfolgreicher beim Durchsetzen ihrer eigenen Interessen agieren als andere Marktakteure. Dennoch hält Smith an der Annahme fest, der Markt entfalte eine harmonisierende und den allseitigen Wohlstand fördernde Wirkung. Diese Annahme mutiert bei seinen Epigonen zu einer ontologischen Gewissheit.
Integer point sets minimizing average pairwise L1 distance: What is the optimal shape of a town?
Erik D. Demaine
Sándor P. Fekete
- An n-town, n[is an element of]N , is a group of n buildings, each occupying a distinct position on a 2-dimensional integer grid. If we measure the distance between two buildings along the axis-parallel street grid, then an n-town has optimal shape if the sum of all pairwise Manhattan distances is minimized. This problem has been studied for cities, i.e., the limiting case of very large n. For cities, it is known that the optimal shape can be described by a differential equation, for which no closed-form solution is known. We show that optimal n-towns can be computed in O(n[superscript 7.5]) time. This is also practically useful, as it allows us to compute optimal solutions up to n=80.
Ultrasound-guided intramural inoculation of orthotopic bladder cancer xenografts: a novel high-precision approach
Kilian M. Gust
Alan I. So
Joachim W. Thüroff
Peter C. Black
- Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23–37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice.
Longitudinal fluid-dynamics for ultrarelativistic heavy-ion collisions
Leonid M. Satarov
Igor N. Mishustin
- We develop a 1+1 dimensional hydrodynamical model for central heavy-ion collisions at ultrarelativistic energies. Deviations from Bjorken's scaling are taken into account by implementing finite-size profiles for the initial energy density. The calculated rapidity distributions of pions, kaons and antiprotons in central Au+Au collisions at the c.m. energy 200 AGeV are compared with experimental data of the BRAHMS Collaboration. The sensitivity of the results to the choice of the equation of state, the parameters of initial state and the freeze-out conditions is investigated. The best fit of experimental data is obtained for a soft equation of state and Gaussian-like initial profiles of the energy density.
Signatures for black hole production from hadronic observables at the Large Hadron Collider
Thomas J. Humanic
- The concept of Large Extra Dimensions (LED) provides a way of solving the Hierarchy Problem which concerns the weakness of gravity compared with the strong and electro-weak forces. A consequence of LED is that miniature Black Holes (mini-BHs) may be produced at the Large Hadron Collider in p+p collisions. The present work uses the CHARYBDIS mini-BH generator code to simulate the hadronic signal which might be expected in a mid-rapidity particle tracking detector from the decay of these exotic objects if indeed they are produced. An estimate is also given for Pb+Pb collisions.
Energy and system size dependence of chemical freeze-out in relativistic nuclear collisions
- We present a detailed study of chemical freeze-out in p-p, C-C, Si-Si and Pb-Pb collisions at beam momenta of 158A GeV as well as Pb-Pb collisions at beam momenta of 20A, 30A, 40A and 80A GeV. By analyzing hadronic multiplicities within the statistical hadronization model, we have studied the parameters of the source as a function of the number of the participating nucleons and the beam energy. We observe a nice smooth behaviour of temperature, baryon chemical potential and strangeness under-saturation parameter as a function of energy and nucleus size. Interpolating formulas are provided which allow to predict the chemical freeze-out parameters in central collisions at centre-of-mass energies > 4.5 GeV and for any colliding ions. Specific discrepancies between data and model emerge in particle ratios in Pb-Pb collisions at SPS between 20A and 40A GeV of beam energy which cannot be accounted for in the considered model schemes.
Transparency, mixing and reflection of initial flows in relativistic nuclear collisions
Mark I. Gorenstein
- We propose to use the hadron number fluctuations in the limited momentum regions to study the evolution of initial flows in high energy nuclear collisions. In this method by a proper preparation of a collision sample the projectile and target initial flows are marked in fluctuations in the number of colliding nucleons. We discuss three limiting cases of the evolution of flows, transparency, mixing and reflection, and present for them quantitative predictions obtained within several models. Finally, we apply the method to the NA49 results on fluctuations of the negatively charged hadron multiplicity in Pb+Pb interactions at 158A GeV and conclude that the data favor a hydrodynamical model with a significant degree of mixing of the initial flows at the early stage of collisions.