Optimal learning paths in information networks.

Each sphere of knowledge and information could be depicted as a complex mesh of correlated items. By properly exploiting these connections, innovative and more efficient navigation strategies could be defined, possibly leading to a faster learning process and an enduring retention of information. In this work we investigate how the topological structure embedding the items to be learned can affect the efficiency of the learning dynamics. To this end we introduce a general class of algorithms that simulate the exploration of knowledge/information networks standing on well-established findings on educational scheduling, namely the spacing and lag effects. While constructing their learning schedules, individuals move along connections, periodically revisiting some concepts, and sometimes jumping on very distant ones. In order to investigate the effect of networked information structures on the proposed learning dynamics we focused both on synthetic and real-world graphs such as subsections of Wikipedia and word-association graphs. We highlight the existence of optimal topological structures for the simulated learning dynamics whose efficiency is affected by the balance between hubs and the least connected items. Interestingly, the real-world graphs we considered lead naturally to almost optimal learning performances.

Corticospinal excitability during action observation in task-specific dystonia: a transcranial magnetic stimulation study.

Observation of actions performed by other individuals activates the onlooker's motor system in a way similar to real movement execution. The functioning of this mechanism in the pathological domain is not clear yet. The aim of this study was to explore whether action observation activates the motor system of patients affected by a task-specific form of dystonia, such as writer's cramp. Transcranial magnetic stimulation was applied over the primary motor cortex and motor evoked potentials were recorded from hand (FDI and ADM) and forearm (FCR) muscles at baseline and during observation of actions (grasping and writing) or images. Writing actions could be performed with healthy or dystonic movement patterns. Results showed a highly specific and reversed pattern of activation in the FDI muscle of the two groups. Differences between the two writing conditions were significantly opposite in the two groups: control subjects had higher activation during observation of the dystonic compared to the healthy action, whereas in patients observation of the healthy writing led to higher activation than the dystonic writing. This opposite corticospinal modulation might be explained by a different self-attribution of the observed actions in the two groups.

Plasmapheresis for treatment of pulmonary alveolar proteinosis.

Whole lung lavage (WLL) is currently the standard therapy for pulmonary alveolar proteinosis (PAP). Nevertheless, some PAP patients respond poorly to WLL or require it frequently. The present paper reports a patient with autoimmune PAP with persistent disease despite three WLL treatments over 10 months. Plasmapheresis with ten 1.5-L plasma exchanges was performed, which lowered the serum granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody level from 250 microg mL(-1) to 156 microg mL(-1) but did not improve respiratory impairment. Further WLL therapy was required and transiently effective. Serum GM-CSF autoantibody levels declined progressively, reaching a value of 56 microg mL(-1) 80 weeks after completion of plasmapheresis. However, this decrease was not accompanied by clinical improvement and the patient required additional WLL therapy. The results confirm that minor reductions in serum granulocyte-macrophage colony-stimulating factor autoantibody levels from plasmapheresis are not reflected in clinical improvement in the severity of lung disease in pulmonary alveolar proteinosis.

Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis.

Whole lung lavage (WLL) is still the gold-standard therapy for pulmonary alveolar proteinosis (PAP). The few studies on the duration of the effect of WLL, belonging to a rather remote period, show significant but transient benefits. In 21 patients with idiopathic PAP, the duration of any benefit and, in 16 of them, the time course of lung function improvement (at baseline, 1 week, 6 months, 1 yr and then every 2 yrs after WLL) were evaluated. The present WLL technique takes longer, is invasively monitored and partially modified with respect to past techniques. More than 70% of patients remained free from recurrent PAP at 7 yrs. The bulk of the improvement in spirometric results was almost completely gained in the immediate post-WLL period due to the efficient clearance of the alveoli. At a median of 5 yrs, recovery of diffusing capacity of the lung for carbon monoxide was incomplete (75 +/- 19% of the predicted value) and there were residual gas exchange abnormalities (alveolar to arterial oxygen tension difference 3.6 +/- 1.5 kPa (27 +/- 11 mmHg)) and exercise limitation, probably explained by engorgement of lymphatic vessels. In conclusion, whole lung lavage for idiopathic pulmonary alveolar proteinosis is currently a safe procedure in an experienced setting, and provides long-lasting benefits in the majority of patients.

Surfactant apoprotein A modulates interleukin-8 and monocyte chemotactic peptide-1 production.

Previous studies have shown that surfactant apoprotein A (SP-A) and natural or synthetic surfactant can modulate the release of pro-inflammatory cytokines from alveolar mononuclear phagocytes. The aim of this study was to assess whether SP-A or Surfactant (Surf) from patients with pulmonary alveolar proteinosis (PAP) can affect the release of two chemokines (interleukin (IL)-8 and monocyte chemtactic peptide (MCP)-1) from human monocytes and rat lung type-II cells. In addition IL-8 and MCP-1 levels were assessed in the brochoalveolar lavage fluid (BALF) of seven patients with PAP and compared with those in a group of control subjects (n=5). SP-A, tested over a wide range of concentrations, significantly increased IL-8 and MCP-1 release from monocytes. SP-A retained its activity after collagenase digestion, but was not active after heat treatment. The release of IL-8 by monocytes was also stimulated by Surf. Finally, median BALF IL-8 and MCP-1 levels in PAP patients were significantly higher than in controls (9.50 and 9.51 pg x mL(-1) in controls versus 151.95 and 563.70 pg x mL(-1) in PAP, respectively) and significantly correlated with SP-A concentrations in BALF. Overall the results of this study support the view that the high content of alveolar surfactant apoprotein A may contribute to the upregulation of chemokine release in pulmonary alveolar proteinosis, thus contributing to airway inflammation.

Usefulness of platelet glycoprotein IIb/IIIa inhibitors in coronary stenting for reconstruction of complex lesions: procedural and 30 day outcome.

BACKGROUND: Intracoronary stent implantation during percutaneous transluminal coronary angioplasty (PTCA) has shown favorable results, reducing acute complications associated with PTCA, such as coronary artery dissection and abrupt or threatened vessel closure. However, treatment of lesions with a complex morphology and diffuse disease, requiring long or multiple coronary stents, is still associated with a poorer outcome. We investigated the hypothesis that abciximab might lead to a different outcome in patients with complex coronary lesions, which require long or multiple stent implantation. METHODS: One hundred and six patients were randomized to receive either a combination of abciximab (bolus and 12 hour infusion) and weight-adjusted low-dose heparin or weight-adjusted heparin alone and followed up to 30 days. RESULTS: The procedural success rate was 100% in both groups of patients. In the control group a composite rate of major adverse events such as any death irrespective of cause, Q wave or non-Q wave myocardial infarction, acute or subacute stent thrombosis and urgent revascularization of 15.3% was shown at 30-day follow-up. The use of abciximab reduced the composite adverse event rate to 3.7% (76% absolute reduction, p < 0.05). CONCLUSIONS: The use of abciximab during high risk stenting is safe and reduces the risk of cardiac events at 30-day follow-up as compared to standard treatment with heparin. A longer follow-up period is warranted to confirm the beneficial effects observed at 30 days with abciximab in this setting.

Diagnostic value of exercise electrocardiography for predicting a positive scintigraphic test in patients with complete right bundle branch block.

BACKGROUND: The diagnostic value of exercise electrocardiography (ECG) in patients with complete right bundle block (cRBBB) remains controversial. The aim of this study was to investigate the diagnostic accuracy of exercise ECG for predicting ischemia in the presence of cRBBB. METHODS: From a series of 1300 consecutive patients attending for exercise ECG and 99mTc-tetrofosmin single photon emission computed tomography (SPECT), we identified 38 male patients with cRBBB and 38 matched controls with normal intraventricular conduction. Patients with left ventricular hypertrophy or previous revascularization were excluded. Exercise ECG (modified Bruce protocol) was considered positive at > or = 1 mm ST horizontal or downsloping depression in > or = 2 adjacent leads. SPECT imaging at rest and post-exercise was performed at least 48 hours apart. RESULTS: The odds ratio for ischemia comparing patients with positive and negative exercise ECGs was 11.0 (95% confidence interval 2.49-48.64, p = 0.002) in controls and 2.49 (95% confidence interval 0.64-9.08, p = 0.32) in cRBBB. The prior probability of ischemia was 0.37 in controls and 0.58 with cRBBB. The posterior probability after a positive test was 0.65 in controls and 0.68 in cRBBB. Thus, the utility of the test (posterior probability minus prior probability) was greater in controls (+0.28) than in cRBBB (+0.1). This difference was most pronounced in the anterior leads V1-V4 (controls +0.63 vs cRBBB +0.01) but less significant in the lateral leads V5-V6 (controls +0.26 vs cRBBB +0.21). Similar analysis also indicated reduced diagnostic value of negative exercise ECGs in cRBBB patients. CONCLUSIONS: The diagnostic value of exercise ECG is reduced in patients with cRBBB, although ST-segment changes in the lateral ECG territory provide superior predictive accuracy to those in the anterior leads. The use of SPECT as a first-line investigation may be justified in patients with cRBBB.

Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS.

Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs, limitation of airway pressure, allowing hypercapnia if necessary, is already used for ventilation of acute respiratory distress syndrome (ARDS). Whether a systematic and more drastic reduction is necessary is debatable. A multicenter randomized study was undertaken to compare a strategy aimed at limiting the end-inspiratory plateau pressure to 25 cm H2O, using tidal volume (VT) below 10 ml/kg of body weight, versus a more conventional ventilatory approach (with regard to current practice) using VT at 10 ml/kg or above and close to normal PaCO2. Both arms used a similar level of positive end-expiratory pressure. A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers. The two groups were similar at inclusion. Patients in the two arms were ventilated with different VT (7.1 +/- 1.3 versus 10.3 +/- 1.7 ml/kg at Day 1, p < 0.001) and plateau pressures (25.7 +/- 5. 0 versus 31.7 +/- 6.6 cm H2O at Day 1, p < 0.001), resulting in different PaCO2 (59.5 +/- 15.0 versus 41.3 +/- 7.6 mm Hg, p < 0.001) and pH (7.28 +/- 0.09 versus 7.4 +/- 0.09, p < 0.001), but a similar level of oxygenation. The new approach did not reduce mortality at Day 60 (46.6% versus 37.9% in control subjects, p = 0.38), the duration of mechanical ventilation (23.1 +/- 20.2 versus 21.4 +/- 16. 3 d, p = 0.85), the incidence of pneumothorax (14% versus 12%, p = 0. 78), or the secondary occurrence of multiple organ failure (41% versus 41%, p = 1). We conclude that no benefit could be observed with reduced VT titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H2O.

Bronchoalveolar lavage fluid composition in alveolar proteinosis. Early changes after therapeutic lavage.

In patients with idiopathic alveolar proteinosis, the alveoli are filled with materials rich in surfactant components, especially surfactant protein A (SP-A). The anomaly could be caused by either increased secretion, decreased clearance, or both. To clarify this point, we studied five patients who underwent therapeutic lavage and then were ventilated mechanically for 24 h. During the first 8 h of mechanical ventilation, a surfactant-depleted lung was lavaged at selected intervals, and the bronchoalveolar lavage fluid was analyzed. We observed that, after lavage, various surfactant components accumulated in the airways with different time courses. We also observed that SP-A increased until the second hour and then dropped rapidly, suggesting the existence of an efficient mechanism of removal. These findings suggest that idiopathic alveolar proteinosis might be caused by a primary defect in a slow mechanism of removal or by the presence of factor(s) that interfere with the clearance of surfactant and that can be removed by lavage. It seems clear, however, that an increased secretion rate is unlikely to be the major cause of idiopathic alveolar proteinosis.

Whole lung lavage.

Bronchoalveolar lavage is universally employed as a diagnostic procedure and also, both in the massive (whole lung) and limited forms, has important therapeutic applications. Since the second half of the century whole lung lavage (WLL) has been applied in patients with pulmonary alveolar proteinosis and has proved successful. The procedure has improved over the years in terms of safety and efficacy, whilst indications and methods for WLL are not yet completely defined and standardized. In this paper, we summarize the history of the development of WLL, and describe the procedure used eight times in five patients in our department.