Survival and confinement under quenched disorder.

We study the survival and confinement of random walkers under quenched disorder characterized by spatially-varying waiting times and decay rates. Spatial heterogeneity and segregation lead to a dynamic coupling between transport and reaction, resulting in history-dependent dynamics exhibiting long survivals and confinement. The survival probability decays as a power law, in contrast to the classical exponential law for decay at a homogeneous rate. The mean squared displacement shows dimension-dependent subdiffusive growth followed by localization, with stronger confinement in higher dimensions.

Reaction-diffusion with stochastic decay rates.

Understanding anomalous transport and reaction kinetics due to microscopic physical and chemical disorder is a long-standing goal in many fields including geophysics, biology, and engineering. We consider reaction-diffusion characterized by fluctuations in both transport times and decay rates. We introduce and analyze a model framework that explicitly connects microscopic fluctuations with the mescoscopic description. For broad distributions of transport and reaction time scales we compute the particle density and derive the equations governing its evolution, finding power-law decay of the survival probability, and spatially varying decay that leads to subdiffusion and an asymptotically stationary surviving-particle density. These anomalies are clearly attributable to non-Markovian effects that couple transport and chemical properties in both reaction and diffusion terms.

Evidence of NI-0101 pharmacological activity, an anti-TLR4 antibody, in a randomized phase I dose escalation study in healthy volunteers receiving LPS.

Toll-like receptor-4 (TLR4) pathways are major contributors to pathological inflammatory responses induced by tissue damage. NI-0101 is the first monoclonal antibody (mAb) blocking TLR4 signaling. This activity is independent of the ligand type and concentration, therefore, potentially blocking any TLR4 ligands. A phase I single ascending dose study was conducted in 73 healthy volunteers to evaluate NI-0101 tolerability, preliminary safety, pharmacokinetics (PKs), and pharmacodynamics (PDs), in absence and in presence of a systemic challenge with lipopolysaccharide (LPS), a TLR4 ligand. NI-0101 was well tolerated without safety concern. The PK profile was characterized by a half-life of ∼10 days at high concentrations and by a rapid elimination at low concentrations due to expected target-mediated drug disposition. NI-0101 prevented cytokine release following ex vivo and in vivo LPS administration and prevented the C-reactive protein (CRP) increase and the occurrence of flu-like symptoms expected following the in vivo administration of LPS.

Nonergodic subdiffusion from Brownian motion in an inhomogeneous medium.

Nonergodicity observed in single-particle tracking experiments is usually modeled by transient trapping rather than spatial disorder. We introduce models of a particle diffusing in a medium consisting of regions with random sizes and random diffusivities. The particle is never trapped but rather performs continuous Brownian motion with the local diffusion constant. Under simple assumptions on the distribution of the sizes and diffusivities, we find that the mean squared displacement displays subdiffusion due to nonergodicity for both annealed and quenched disorder. The model is formulated as a walk continuous in both time and space, similar to the Lévy walk.

Distribution of entanglement in large-scale quantum networks.

The concentration and distribution of quantum entanglement is an essential ingredient in emerging quantum information technologies. Much theoretical and experimental effort has been expended in understanding how to distribute entanglement in one-dimensional networks. However, as experimental techniques in quantum communication develop, protocols for multi-dimensional systems become essential. Here, we focus on recent theoretical developments in protocols for distributing entanglement in regular and complex networks, with particular attention to percolation theory and network-based error correction.

Comment on "Finding finite-time invariant manifolds in two-dimensional velocity fields" [Chaos 10, 99 (2000)].

This note serves as a commentary of the paper of Haller [Chaos 10, 99 (2000)] on techniques for detecting invariant manifolds. Here we show that the criterion of Haller can be improved in two ways. First, by using the strain basis reference frame, a more efficient version of theorem 1 of Haller (2000) allows to better detect the manifolds. Second, we emphasize the need to nondimensionalize the estimate of hyperbolic persistence. These statements are illustrated by the example of the Kida ellipse. (c) 2001 American Institute of Physics.

Coexisting left congenital diaphragmatic hernia and esophageal atresia with tracheoesophageal fistula: successful management in a premature neonate.

The combination of left congenital diaphragmatic hernia (CDH) with esophageal atresia (EA) and distal tracheoesophageal fistula (TEF) is extremely rare and is considered highly lethal. The authors describe a premature neonate with this association, who is alive at 6 1/2 years of age. Temporary banding of the gastroesophageal junction and gastrostomy was performed concurrently with hernia repair and prosthetic abdominoplasty to enlarge the abdominal cavity. A right thoracotomy for ligation of the fistula, using extracorporeal membrane oxygenation (ECMO), was performed 13 days later. Complete repair of the esophageal atresia was accomplished 7 weeks after birth. The methods that have been suggested in the literature are discussed. The institution of ECMO at birth could allow a primary complete surgical repair of EA and CDH. Nevertheless, surgical management with staged repair, as described herein, can be useful.

Pharmacodynamic effects of three doses of ORG 9426 used for endotracheal intubation in humans.

STUDY OBJECTIVE: To determine the pharmacodynamic characteristics of three incremental doses of ORG 9426 used for endotracheal intubation in patients. DESIGN: Double-blind, randomized administration of one of three doses of intravenous ORG 9426. SETTING: Inpatients requiring surgery at Georgetown University Medical Center. PATIENTS: Thirty-six patients, ages 18 to 65, ASA physical status I, II, and III, scheduled for general surgery. INTERVENTIONS: After Georgetown University Institutional Review Board approval and patient consent, patients were premedicated with midazolam or droperidol. Anesthesia was induced with thiopental sodium and fentanyl. Anesthesia was maintained with 60% nitrous oxide in oxygen. The ulnar nerve was stimulated supramaximally with a 2 Hz train-of-four (TOF) every 20 seconds. Thumb contractions were measured with a force transducer. When TOF and anesthesia were stable, 2, 2.5, or 3 times the ED95 of ORG 9426 (570 micrograms/kg, 710 micrograms/kg, or 850 micrograms/kg) was administered randomly. Tracheal intubation was attempted at maximal depression of the first TOF response (T1). MEASUREMENTS AND MAIN RESULTS: The following parameters were measured: time interval from the injection of ORG 9426 to 90% depression of T1 (T1 90% block), maximal T1 depression (onset time), intubating conditions, clinical duration (time for return of T1 to 25% of control), heart rate (HR), blood pressure (BP), and any adverse clinical experience. ORG 9426 provided adequate intubating conditions in all patients but two, independent of the dose used. Its onset time was rapid, but increasing the dose did not shorten the onset. T1 90% block was achieved rapidly (75 +/- 25 seconds to 78 +/- 18 seconds, means +/- SD). The clinical duration of ORG 9426 was relatively short and lengthened with increasing doses (from 36 +/- 18 minutes at 570 micrograms/kg to 42 +/- 10 minutes at 850 micrograms/kg. Spontaneous twitch recovery from 10% to 25% was similar in all dosage groups (5 +/- 1 minutes to 6 +/- 4 minutes). No clinically significant changes in HR and BP and no adverse clinical experiences were noted in any group. CONCLUSION: These findings warrant further clinical evaluation of ORG 9426 for induction and maintenance of muscle relaxation in humans.

[Cardiovascular tolerance to tianeptine]. / Acceptabilité cardiovasculaire de la tianeptine.

The cardiovascular effects of tianeptine were assessed by a specific placebo-controlled trial in healthy volunteers and by heart rate, blood pressure and electrocardiogram data analyses in five studies enrolling depressed patients. In two of these studies the effects of tianeptine were compared to those of amitriptyline. The three other studies were performed as open, long-term trials (up to one-year treatment) in large populations of patients (more than 3,300 patients). The findings show that tianeptine does not modify heart rate, blood pressure, conduction or ventricular function. Tianeptine was well tolerated in depressed patients and induced no significant changes at the current dosage in treatment periods from three-months to one-year even in elderly patients, patients with cardiovascular abnormalities or alcoholic patients. Fewer cases of orthostatic hypotension were observed than with other antidepressants. Suicide attempts with tianeptine overdosage did not lead to death due to cardiovascular complications.

[Early reocclusion after in situ coronary desobstruction either with streptokinase or angioplasty during the acute phase of myocardial infarction]. / Réocclusion précoce après désobstruction coronarienne in situ soit par streptokinase soit par angioplastie à la phase aiguë de l'infarctus du myocarde.

The aim of this study was to assess the incidence of early reocclusion after therapeutic reperfusion of coronary arteries in acute myocardial infarction. Seventy four patients underwent intracoronary thrombolysis and 133 patients had immediate coronary angioplasty. The success rates were 70 per cent and 86 per cent respectively (p less than 0.01) and the degree of residual stenosis was 77 +/- 13 percent and 25 +/- 15 per cent respectively (p less than 0.001). The patients in whom coronary reperfusion was successful, 52 after in situ thrombolysis, 48 after angioplasty alone, and 66 after combined angioplasty and intravenous thrombolysis, underwent coronary arteriography 24 to 36 hours later. Reocclusion was asymptomatic in 46 per cent of cases (13/28) and its prevalence was 16.9 per cent: 25.5 per cent for the right coronary compared with 12.8 per cent for the left anterior descending (p less than 0.05) and 11.7 per cent for the left circumflex artery; reocclusion occurred in 8.6 per cent of patients treated before the 3rd hour compared with 22.9 per cent of patients receiving treatment after the 3rd hour (p less than 0.05). The incidence of reocclusion was 17.3 per cent after intracoronary thrombolysis and 16.7 per cent after angioplasty (angioplasty alone 18.7 per cent; associated with thrombolysis 15.2%). The degree of residual stenosis was nil after intracoronary thrombolysis and 16.3 per cent after angioplasty when the stenosis was insignificant, and 20.5 per cent and 18.8 per cent respectively with stenotic lesions greater than 50 per cent.

[Contribution of perindopril to the treatment of chronic congestive cardiac insufficiency. Multicenter pilot double blind study versus placebo]. / Apport du perindopril au traitement de l'insuffisance cardiaque chronique congestive. Etude pilote multicentrique en double aveugle contre placebo.

Cardiac decompensation occurred in three patients of the placebo group, but not in the perindopril group. The effectiveness of perindopril in heart failure was demonstrated by the improvement observed in exercise test and severity score and by the decrease of cardiothoracic ratio. Changes in SAP, and serum creatinine levels, in particular, showed that the drug was well tolerated.

Isoflurane attenuates baroreflex control of heart rate in human neonates.

Clinical studies have suggested that baroreflex regulation of heart rate may be more affected by inhalational anesthetics in human neonates or young animals than in adults. To test this hypothesis, baroreceptor reflex control of heart rate was studied in eight neonates during administration of 1 MAC isoflurane. The neonates were hemodynamically stable and their lungs were mechanically ventilated. No other anesthetic was used. Mean (+/- SD) corrected gestational age was 39.4 +/- 2.0 weeks and mean weight was 2,710 +/- 430 g. The pressor response was tested with the use of phenylephrine and the depressor response with nitroglycerin. Changes in heart rate (R-R interval) were plotted against the changes in systolic arterial pressure, and the slope of the linear portion of this relationship was used to define the baroreflex response. Both baroresponses measured in awake neonates varied widely between patients. With administration of approximately 1 MAC isoflurane, the pretest mean systolic arterial pressure decreased by about 30% (P less than 0.001), whereas mean heart rate values remained unchanged compared with control awake values. During isoflurane administration, the mean (+/- SD) pressor response decreased to 23% of control awake values (11.2 +/- 7.7 ms/mmHg vs. 2.6 +/- 3.7 ms/mmHg; P less than 0.01) and the depressor response to 28% of control (4.3 +/- 3.2 ms/mmHg vs. 1.2 +/- 0.8 ms/mmHg; P less than 0.05). These changes can be attributed to a significant resetting of heart rate itself (calculated as the change in R-R interval at a constant pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Value of perindopril in the treatment of chronic congestive heart failure. Multicenter double-blind placebo-controlled study.

Right cardiac catheterization studies have demonstrated an improvement in cardiac hemodynamics in patients with heart failure following the administration of perindopril (per): reduction in ventricular filling pressures (pulmonary capillary wedge pressure, right atrial pressure) and systemic resistance and an increase in cardiac output. The intensity and duration of these modifications were frequently insufficient after 2 mg, but were significant over 24 hours after 4 mg. A randomized, double-blind multicenter study versus placebo (pla) was conducted for 3 months, following a preinclusion period of 15 days, in 103 heart failure patients (stages II and III of the NYHA classification) treated with diuretic +/- digitalis. The following parameters were evaluated before (be), after 1 month (1m) and after 3 months (3 m) treatment: duration of stress test (DST) (sec), clinical severity score (SS), cardiothoracic ratio (CTR), serum creatinine (Cr) (mumol/l), systolic blood pressure (SBP) (mm Hg) in the supine (s) and erect (e) positions. 50 patients received per and 53 received pla; 46 patients in each group completed the double-blind period. Perindopril was administered at doses of 2 mg (n = 6) and 4 mg (n = 40). The following results were obtained: (table; see text) Three cases of acute heart failure occurred in the placebo group compared with none in the peridopril group. The efficacy of perindopril in heart failure was demonstrated by the improvement in effort capacity and severity score and by the reduction in cardiothoracic ratio. The variation in SBP and serum creatinine, in particular, reflected the good safety.