Is this scaling nonlinear?

One of the most celebrated findings in complex systems in the last decade is that different indexes y (e.g. patents) scale nonlinearly with the population x of the cities in which they appear, i.e. y∼x (ß) ,ß≠1. More recently, the generality of this finding has been questioned in studies that used new databases and different definitions of city boundaries. In this paper, we investigate the existence of nonlinear scaling, using a probabilistic framework in which fluctuations are accounted for explicitly. In particular, we show that this allows not only to (i) estimate ß and confidence intervals, but also to (ii) quantify the evidence in favour of ß≠1 and (iii) test the hypothesis that the observations are compatible with the nonlinear scaling. We employ this framework to compare five different models to 15 different datasets and we find that the answers to points (i)-(iii) crucially depend on the fluctuations contained in the data, on how they are modelled, and on the fact that the city sizes are heavy-tailed distributed.

Searching chaotic saddles in high dimensions.

We propose new methods to numerically approximate non-attracting sets governing transiently chaotic systems. Trajectories starting in a vicinity Ω of these sets escape Ω in a finite time τ and the problem is to find initial conditions x∈Ω with increasingly large τ=τ(x). We search points x' with τ(x')>τ(x) in a search domain in Ω. Our first method considers a search domain with size that decreases exponentially in τ, with an exponent proportional to the largest Lyapunov exponent λ1. Our second method considers anisotropic search domains in the tangent unstable manifold, where each direction scales as the inverse of the corresponding expanding singular value of the Jacobian matrix of the iterated map. We show that both methods outperform the state-of-the-art Stagger-and-Step method [Sweet et al., Phys. Rev. Lett. 86, 2261 (2001)] but that only the anisotropic method achieves an efficiency independent of τ for the case of high-dimensional systems with multiple positive Lyapunov exponents. We perform simulations in a chain of coupled Hénon maps in up to 24 dimensions (12 positive Lyapunov exponents). This suggests the possibility of characterizing also non-attracting sets in spatio-temporal systems.

Characterizing weak chaos using time series of Lyapunov exponents.

We investigate chaos in mixed-phase-space Hamiltonian systems using time series of the finite-time Lyapunov exponents. The methodology we propose uses the number of Lyapunov exponents close to zero to define regimes of ordered (stickiness), semiordered (or semichaotic), and strongly chaotic motion. The dynamics is then investigated looking at the consecutive time spent in each regime, the transition between different regimes, and the regions in the phase space associated to them. Applying our methodology to a chain of coupled standard maps we obtain (i) that it allows for an improved numerical characterization of stickiness in high-dimensional Hamiltonian systems, when compared to the previous analyses based on the distribution of recurrence times; (ii) that the transition probabilities between different regimes are determined by the phase-space volume associated to the corresponding regions; and (iii) the dependence of the Lyapunov exponents with the coupling strength.

Prevalence of marginally unstable periodic orbits in chaotic billiards.

The dynamics of chaotic billiards is significantly influenced by coexisting regions of regular motion. Here we investigate the prevalence of a different fundamental structure, which is formed by marginally unstable periodic orbits and stands apart from the regular regions. We show that these structures both exist and strongly influence the dynamics of locally perturbed billiards, which include a large class of widely studied systems. We demonstrate the impact of these structures in the quantum regime using microwave experiments in annular billiards.

Nontwist non-Hamiltonian systems.

We show that the nontwist phenomena previously observed in Hamiltonian systems exist also in time-reversible non-Hamiltonian systems. In particular, we study the two standard collision-reconnection scenarios and we compute the parameter space breakup diagram of the shearless torus. Besides the Hamiltonian routes, the breakup may occur due to the onset of attractors. We study these phenomena in coupled phase oscillators and in non-area-preserving maps.

Distinct factors correlating with adverse cardiac events after major vascular surgery.

INTRODUCTION: Cardiovascular complications remain the principal cause of both morbidity and mortality after major vascular surgery. The well-known coincidence between vascular disease and coronary artery disease provided the rationale for a detailed analysis of major perioperative cardiovascular complications in their relation to preoperative and intraoperative parameter METHODS AND PATIENTS: 90 patients scheduled to undergo either femoral-popliteal bypass (n = 74) or repair of an infrarenal aortic aneurysm (n = 16) were prospectively included in the study. All patients had no signs of unstable cardiac disease and required no cardiac testing. Both preoperative and intraoperative parameter were correlated to adverse cardiac events (cardiac death and myocardial infarction -MI). RESULTS: Univariate analysis identified the following parameter to be significantly related to cardiac complications: prior MI and intraoperative hypertension (systolic blood pressure above 200 mmHg). In contrast perioperative betablocker therapy was revealed to be protective. In multivariate analysis the history of MI and intraoperative hypertension correlated with poor cardiac outcome. CONCLUSIONS: Our results underline the importance of the individual history in predicting perioperative risk and corroborate the beneficial effects of long-standing beta-blocker therapy. Additionally the significance of stable intraoperative hemodynamic parameter is demonstrated.

Microcirculation and tolerability following i.v. infusion of PGE1 and iloprost: a randomized cross-over study in patients with critical limb ischemia.

In a randomized cross-over study, the effect of PGE(1) and iloprost on microcirculation as well as the tolerability was investigated in 36 patients with peripheral arterial occlusive disease stage III and IV according to Fontaine. Patients received PGE(1) and iloprost by single 3-h i.v. infusions on two different days at doses recommended by the manufacturers or in previous studies (PGE(1): first hour 20 microg, next 2h 30 microg each. Iloprost: first hour 0.5 ng/kg/min, next 2h 1.0 ng/kg/min). Transcutaneous oxygen pressure (tcPO(2)) values increased much more with PGE(1). Median tcPO(2) increase over baseline 30 min after the end of infusion was 9 and 2 mmHg for PGE(1) and iloprost, respectively, corresponding to median AUC differences from baseline of 1050 and 210 min mmHg. Because of its exploratory character, the study was not powered to test for significance. Adverse effects occurred in 19.4% (PGE(1)) and 30.6% (iloprost) of patients. Dose reduction was required in 3 patients receiving iloprost (hypotension, nausea, irritation of the infused vein), and in none receiving PGE(1).

[DRG-based cost analysis of inpatient conservative treatment of stage III/IV peripheral arterial occlusive disease]. / DRG-basierte Kostenanalyse zur stationären konservativen Behandlung der PAVK Stadium III/IV.

UNLABELLED: DRG-based cost analysis of inpatient conservative treatment of PAD stage III/IV BACKGROUND: In a prospective study carried out by the German Society of Angiology and the DRG Competence Center, Munich, the question was investigated whether the costs of conservative treatment of patients with PAOD stage III/IV (DRG F65) are adequately represented within the current G-DRG system. METHODS UND PATIENTS: Between September 1 and December 16, 2002, a total of 704 patients with DRG F65 (peripheral vascular diseases) were evaluated at 8 angiologic centers in Germany. Apart from the length of hospital stay, the total costs (cost equivalents) were calculated using a method developed by the DRG Research Group at the University of Münster. Moreover, the study population was compared with a German calculation sample for the DRGs F65A/B, as published by InEK. RESULTS: As it turned out, conservatively treated patients with PAOD stage III or IV (DRGs F65A/B) cause significantly (p < 0.001) higher costs and have significantly (p < 0.001) greater lengths of hospital stay than patients who were also assigned to DRG F65 because of other vascular diseases. At the same time it became clear that angiologic centers treat twice as many patients with critical limb ischemia in comparison with the German average. The reimbursement hitherto estimated by InEK covers not even half the cost actually produced by conservative treatment of PAD stage III/IV. CONCLUSION: To ensure a performance-related reimbursement, a new basis DRG for patients with PAD stage III/IV has to be created, as has ben proposed by the German Society of Angiology. Otherwise, adequate conservative therapy in accordance with existing guidelines, of patients who cannot be treated surgically or interventionally will not be possible any more in the future.

Differences in treatment and outcome of patients with acute myocardial infarction admitted to hospitals with compared to without departments of cardiology; results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA 1+2) Registries and the Myocardial Infarction Registry (MIR).

AIMS: The specialty of the admitting physician may influence treatment and outcome in patients with acute myocardial infarction. METHODS AND RESULTS: The pooled data of three German acute myocardial infarction registries: the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) 1+2 studies and the Myocardial Infarction Registry (MIR) were analysed. Patients admitted to hospitals with departments of cardiology were compared to hospitals without such departments. A total of 24 814 acute myocardial infarction patients were included, 9020 (36%) patients at 91 (29.8%) hospitals with departments of cardiology and 15 794 (64%) at 214 (70.2%) hospitals without cardiology departments. There were only minor differences in patient characteristics and prevalence of concomitant diseases between the two types of hospital. The first electrocardiogram was more often diagnostic at hospitals with cardiology departments (71.8% vs 66.5%, P<0.001). Reperfusion therapy and adjunctive medical therapy, such as aspirin, beta-blockers and ACE-inhibitors were used more often at cardiology departments (all P -values <0.001), even after adjustment for confounding parameters. Treatment improved at both types of hospital over time. Admission to a hospital with a department of cardiology was independently associated with a lower hospital mortality (14.2% vs 15.4%, adjusted OR=0.91; 95%CI: 0.83-0.99). Additional logistic regression models showed that the higher use of reperfusion therapy and recommended concomitant medical therapy was responsible for most of the survival benefit at such hospitals. CONCLUSION: Treatment of acute myocardial infarction patients at hospitals with departments of cardiology was independently associated with a higher use of recommended therapy and a lower hospital mortality compared to hospitals without such departments.

Impact of prehospital delay on mortality in patients with acute myocardial infarction treated with primary angioplasty and intravenous thrombolysis.

BACKGROUND: In patients with acute myocardial infarction treated with thrombolysis, longer times to treatment are associated with increasingly worse clinical outcome. This relation may be different for treatment with primary angioplasty. METHODS: We analyzed the pooled data of the German acute myocardial infarction registries Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) and Myocardial Infarction Registry (MIR) to determine the influence of prehospital delays on hospital mortality rates. Primary angioplasty was performed in 1063 patients and thrombolysis in 7552 patients. RESULTS: In patients treated with thrombolysis, in-hospital time to treatment was constantly 30 minutes median. In patients treated with primary angioplasty, in-hospital time to treatment increased from 60 minutes median up to 87 minutes median with increasing prehospital delay. Hospital mortality rates slightly decreased with increasing prehospital delays in patients treated with primary angioplasty (P for trend =.02). However, in patients treated with thrombolysis, mortality rate was nonsignificantly increased (P for trend =.11). Logistic regression analysis showed no significant difference in mortality rates between primary angioplasty and thrombolysis for prehospital delays of <3 hours. However, when prehospital delay was >3 hours, thrombolysis was independently associated with a higher mortality rate compared with primary angioplasty. CONCLUSIONS: Compared with thrombolysis, primary angioplasty is independently associated with a lower mortality rate in prehospital delays of >3 hours. The reason for this may be a time-dependent loss of efficacy to achieve reperfusion for thrombolysis but not for primary angioplasty.

Primary angioplasty versus no reperfusion therapy in patients with acute myocardial infarction and a pre-hospital delay of > 12-24 hours: results from the pooled data of the maximal individual therapy in acute myocardial infarction (MITRA) registry and the myocardial infarction registry (MIR).

OBJECTIVE: In patients with acute myocardial infarction (AMI), treatment with thrombolysis is superior to no reperfusion therapy only up to 12 hours after the onset of symptoms. There are no data addressing whether this time limit is also justified for treatment with primary angioplasty. DESIGN: The pooled data of two German ST-segment elevation AMI registries, the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study and the Myocardial Infarction Registry (MIR), were analyzed. PATIENTS: Out of 22,749 patients, eight hundred and forty-eight with a pre-hospital delay of > 12 hours and < or = 24 hours were treated with either primary angioplasty (94/848; 11.1%) or no reperfusion therapy (754/848; 88.9%). RESULTS: Patients treated with primary angioplasty were 10 years younger (59 years versus 69 years; p = 0.001), more often male [72.3% versus 59.9%; odds ratio (OR) = 0.57; 95% confidence interval (CI) = 0.36-0.92] and less likely to be diabetics (17% versus 27.2%; OR = 0.55; 95% CI = 0.31-0.97). Hospital mortality was 8.5% in patients treated with primary angioplasty compared to 17.1% in patients with no reperfusion therapy (OR = 0.45; 95% CI = 0.21-0.95; p = 0.033) and the combined endpoint (death, reinfarction or stroke) occurred significantly less often (11.7% versus 20.3%; OR = 0.52; 95% CI =0.27-1; p = 0.045). However, multiple logistic regression showed only a non-significant trend for lower mortality (OR = 0.54; 95% CI =0.20-1.23) and the combined endpoint (OR = 0.65; 95% CI = 0.29-1.31) in patients treated with primary angioplasty. CONCLUSIONS: These data show the possibility of a benefit of primary angioplasty over conservative treatment in patients with pre-hospital delays of > 12 up to 24 hours, although multiple logistic regression analysis failed to find significant differences between treatments. This might be due to inadequate study power or a selection bias. These findings encourage further investigation of this subject.

Primary angioplasty versus intravenous thrombolysis in acute myocardial infarction: can we define subgroups of patients benefiting most from primary angioplasty? Results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction Registry and the Myocardial Infarction Registry.

OBJECTIVES: We sought to determine the effectiveness of primary angioplasty compared with thrombolysis in clinical practice. BACKGROUND: In clinical practice, primary angioplasty for the treatment of acute myocardial infarction (AMI) has not yet been proven more effective than intravenous thrombolysis, nor have subgroups of patients been identified who would perhaps benefit from primary angioplasty. METHODS: The pooled data of two AMI registries--the Maximal Individual TheRapy in Acute myocardial infarction (MITRA) study and the Myocardial Infarction Registry (MIR)--were analyzed. A total of 9,906 lytic-eligible patients with AMI, with a pre-hospital delay of < or =12 h, were treated with either primary angioplasty (n = 1,327) or thrombolysis (n = 8,579). RESULTS: Despite differences in the patients' characteristics and concomitant diseases between the two groups, the prevalence of adverse risk factors was balanced. Univariate analysis of hospital mortality showed a more favorable course for patients treated with primary angioplasty: 6.4% versus 11.3% (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.43 to 0.67). This was confirmed by logistic regression analysis (multivariate OR 0.58, 95% CI 0.44 to 0.77). Primary angioplasty was associated with a lower mortality in all subgroups analyzed. We observed a significant correlation between mortality and absolute risk reduction (r = 0.82, p < 0.0001) in the different subgroups: as mortality increased, there was an increase in absolute benefit of primary angioplasty compared with thrombolysis. CONCLUSIONS: These large registry data showed the effect of primary angioplasty to be more favorable than thrombolysis for the treatment of patients with AMI in clinical practice. This effect was not restricted to special subgroups of patients. As mortality increased, the absolute benefit of primary angioplasty also increased.

7-Pyrrolidinyl- and 7-piperidinyl-5-aryl-pyrrolo[2,3-d]pyrimidines--potent inhibitors of the tyrosine kinase c-Src.

7-Heterocyclyl-5-aryl-pyrrolo[2,3-d]pyrimidines represent a new class of highly potent and selective inhibitors of the tyrosine kinase pp60(c-Src).

7-Alkyl- and 7-cycloalkyl-5-aryl-pyrrolo[2,3-d]pyrimidines--potent inhibitors of the tyrosine kinase c-Src.

7-Substituted-5-aryl-pyrrolo[2,3-d]pyrimidines have been prepared starting from alpha-bromoacetophenones. These compounds represent a novel class of potent inhibitors of the tyrosine kinase pp60(c-Src) with good specificity towards other tyrosine kinases (EGF-R, v-Abl).

Effect of preinfarction angina pectoris on outcome in patients with acute myocardial infarction treated with primary angioplasty (results from the Myocardial Infarction Registry.

Preinfarction angina is associated with better clinical outcome in patients with acute myocardial infarction (AMI) who receive intravenous thrombolysis. This has not been proved in patients with AMI treated with primary angioplasty. We analyzed the data of the prospective multicenter Myocardial Infarction Registry (MIR). Of 14,440 patients with AMI, 774 with a prehospital delay of < or =12 hours were treated with primary angioplasty. Five hundred thirty-two patients (68.7%) had preinfarction angina. Patients with preinfarction angina were slightly older than patients without (63 vs 62 years, p = 0.042), prehospital delay was 1 hour longer (180 vs 120 minutes, p = 0.001), and arterial hypertension was more prevalent (47.6% vs 32.2%, odds ratio [OR] 1.91, 95% confidence intervals [CI] 1.39 to 2.62). There was no significant difference in hospital mortality (5.6% vs 3.3%, OR 1.75, 95% CI 0.79 to 3.87), reinfarction, stroke, or the combined end point of death, reinfarction, or stroke between the 2 groups. Logistic regression analysis showed no association of preinfarction angina with the occurrence of either death (OR 2.21, 95% CI 0.91 to 6.08) or the combined end points (OR 1.10, 95% CI 0.55 to 2.31). There was also no significant difference in mortality (6% vs 5.1%, OR 1.19, 95% CI 0.56 to 2.52), reinfarction, stroke, postinfarction angina, or the combined end points between patients with preinfarction angina within 48 hours compared with patients with preinfarction angina between 49 hours and 4 weeks before the AMI. Thus, the MIR data showed no protective effects of preinfarction angina in patients with AMI treated with primary angioplasty.

[Initial manifestation of thromboangiitis obliterans as necrotizing colitis]. / Erstmanifestation einer Thrombangiitis obliterans als nekrotisierende Kolitis.

Necrotizing colitis as primary manifestation of Buerger's disease. We report the disease process of a 41 year old woman, who was referred to our clinic with intermittent claudication of the leg. She has been an excessive smoker since early youth. Three years ago a hemicolectomy was carried out because of a necrotizing colitis. The clinical, angiographic and histologic findings are presented. Finally the frequency of intestinal Buerger's disease and the types of clinical course are discussed.

Decreasing hospital mortality between 1994 and 1998 in patients with acute myocardial infarction treated with primary angioplasty but not in patients treated with intravenous thrombolysis. Results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Registry and the Myocardial Infarction Registry (MIR).

OBJECTIVES: We investigated changes in the clinical outcome of primary angioplasty and thrombolysis for the treatment of acute myocardial infarction (AMI) from 1994 to 1998. BACKGROUND: Primary angioplasty for the treatment of AMI is a sophisticated technical procedure that requires experienced personnel and optimized hospital logistics. Growing experience with primary angioplasty in clinical routine and new adjunctive therapies may have improved the outcome over the years. METHODS: The pooled data of two German AMI registries: the Maximal Individual Therapy in AMI (MITRA) study and the Myocardial Infarction Registry (MIR) were analyzed. RESULTS: Of 10,118 lytic eligible patients with AMI, 1,385 (13.7%) were treated with primary angioplasty, and 8,733 (86.3%) received intravenous thrombolysis. Patients characteristics were quite balanced between the two treatment groups, but there was a higher proportion of patients with a prehospital delay of >6 h in those treated with primary angioplasty. The proportion of an in-hospital delay of more than 90 min significantly decreased in patients treated with primary angioplasty over the years (p for trend = 0.015, multivariate odds ratio [OR] for each year of the observation period = 0.84, 95% confidence interval [CI]: 0.73-0.96) but did not change significantly in patients treated with thrombolysis. Hospital mortality decreased significantly in the primary angioplasty group (p = 0.003 for trend; multivariate OR for each year = 0.73, 95% CI: 0.58-0.93). However, for patients treated with thrombolysis, hospital mortality did not change significantly (p for trend 0.175, multivariate OR for each year: 1.02, 95% CI: 0.94- 1.11). CONCLUSIONS: Compared with thrombolysis the clinical results of primary angioplasty for the treatment of AMI improved from 1994 to 1998. This indicates a beneficial effect of the growing experience and optimized hospital logistics of this technique over the years.

Safety and efficacy of eptifibatide vs placebo in patients receiving thrombolytic therapy with streptokinase for acute myocardial infarction; a phase II dose escalation, randomized, double-blind study.

AIMS: Thrombolytic therapy restores coronary patency in patients with acute myocardial infarction, although normal perfusion (TIMI 3 flow) is not achieved in all patients. In an attempt to improve TIMI 3 flow, a combination of full-dose streptokinase, aspirin and escalating dosages of a platelet glycoprotein IIb/IIIa receptor blocker, eptifibatide, vs placebo were tested. METHODS AND RESULTS: A bolus of 180 microg. kg(-1)of eptifibatide was administered in each group, followed by a 72 h continuous infusion of 0.75 (44 patients), 1.33 (n=45) and 2.00 microg. kg(-1). min(-1)(n = 30); 62 patients received placebo. Normal perfusion (TIMI 3 flow) at 90 min was observed in 31% of placebo patients compared to 46, 42 and 45% in the ascending eptifibatide groups (44% for combined eptifibatide groups, P = 0.07). Patency (TIMI 2 and 3 flow combined) increased from 61% (placebo) to 78% for the combined eptifibatide groups (P = 0.02). Reocclusion was infrequent. No differences were observed in TIMI flow grades among eptifibatide groups. Major and minor bleeding was increased and occurred mainly at the arterial puncture site. CONCLUSION: A combination of full dose streptokinase with different eptifibatide regimens enhanced coronary perfusion, but bleeding risk was excessive. Additional trials are needed with different dosage regimens to determine the optimal combination of fibrinolytic agents and platelet glycoprotein IIb/IIIa receptor blockers.

Substituted 5,7-diphenyl-pyrrolo[2,3d]pyrimidines: potent inhibitors of the tyrosine kinase c-Src.

5,7-Diphenyl-pyrrolo[2,3d]pyrimidines represent a new class of highly potent inhibitors of the tyrosine kinase c-Src (IC50 < 50 nM) with specificity against a panel of different tyrosine kinases. The substitution pattern on the two phenyl rings determines potency and specificity and provides a means to modulate cellular activity.

Transfer of patients with acute myocardial infarction for primary or acute angioplasty from hospitals without the facilities to perform angioplasty. Results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Registry and the Myocardial Infarction Registry (MIR).

In patients with acute myocardial infarction (AMI) admitted at hospitals without angioplasty facilities there are some subgroups of patients which seem to profit from a transfer to primary or acute angioplasty. However, current clinical practice at such hospitals is unknown. We analyzed the pooled data of the German acute myocardial infarction registries MITRA and the MIR. Angioplasty was not available at 221/271 hospitals (81.5%). Out of 14,487 patients with acute myocardial infarction admitted to these hospitals, 50.1% (7,259/14,487) received thrombolysis at the initial hospital and 3.6% (523/14,487) were transferred. Out of the transferred patients, 55.3% (289/523) were treated with primary angioplasty and 44.7% (234/523) received a combination of thrombolysis and angioplasty. The proportion of transferred patients increased from 1.1% in 1994 to 5.5% in 1998 (p for trend = 0.001). One hundred and four hospitals (47.1%) never transferred patients. Patients transferred for primary angioplasty (289 patients) were compared to patients treated with thrombolysis at the initial hospitals (7,259 patients). Multivariate analysis showed the following independent predictors for transfer of patients for primary angioplasty: contraindications for thrombolysis (OR = 17.9), a non-diagnostic first ECG (OR = 4.0), pre-hospital delay > 6 hours (OR = 2.5), unknown symptom onset of the acute myocardial infarction (OR = 2.0) and anterior wall acute myocardial infarction (OR = 1.6). Heart failure at admission was the only independent predictor not to transfer patients (OR = 0.40). In Germany only 47.1% of hospitals without angioplasty facilities transfer patients with acute myocardial infarction to primary or acute angioplasty. The proportion of transferred patients increased from 1.1% in 1994 to 5.5% in 1998. Contraindications for thrombolysis were the strongest predictor to transfer patients to primary angioplasty.