Integrating support vector machines and neural networks.

Support vector machines (SVMs) are a powerful technique developed in the last decade to effectively tackle classification and regression problems. In this paper we describe how support vector machines and artificial neural networks can be integrated in order to classify objects correctly. This technique has been successfully applied to the problem of determining the quality of tiles. Using an optical reader system, some features are automatically extracted, then a subset of the features is determined and the tiles are classified based on this subset.     

Reference and target region modeling of [11C]-(R)-PK11195 brain studies.

PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo imaging of microglial activation in the human brain. In this work we devised a supervised clustering procedure and a new quantification methodology capable of producing binding potential (BP) estimates quantitatively comparable with those derived from plasma input with robust quantitative implementation at the pixel level. METHODS: The new methodology uses predefined kinetic classes to extract a gray matter reference tissue without specific tracer binding and devoid of spurious signals (in particular, blood pool and muscle). Kinetic classes were derived from an historical database of 12 healthy control subjects and from 3 patients with Huntington's disease. BP estimates were obtained using rank-shaping exponential spectral analysis (RS-ESA) (both plasma and reference input) and the simplified reference tissue model (SRTM). Comparison between plasma- derived BPs and those produced with the new reference methodology was performed using 6 additional healthy control subjects. Reliability of the new methodology was performed on 4 test-retest studies of patients with Alzheimer's disease. RESULTS: The new algorithm selected reference voxels in gray matter tissue avoiding regions with specific binding located, in particular, in the venous and arterial circulation. Using the new reference, BP values obtained using a plasma input and a reference input were in excellent agreement and highly correlated (r = 0.811, P < 10(-5)) when calculated with RS-ESA and less so (r = 0.507, P < 0.005) when SRTM was used. In the production of parametric maps, SRTM was used with the new reference extraction, resulting in test-retest variability (10.6%; mean ICC = 0.878) that was superior to that obtained using the previous unsupervised clustering approach (mean ICC = 0.596). CONCLUSION: Reference region modeling combined with supervised reference tissue extraction produces a robust and reproducible quantitative assessment of [(11)C]-(R)-PK11195 studies in the human brain.     

Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents

Aim  

The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence.     

Transmitter Release Associated with Long-term Synaptic Depression in Rat Corticostriatal Slices

Using a corticostriatal slice preparation, we have recently shown that tetanic stimulation of the corticostriatal pathway produces long-term depression (LTD) of striatal excitatory synaptic transmission. In the present study we have analysed the relationship between LTD and the striatal release of different endogenous transmitters. Samples of perfusate were collected via a small cannula placed just above the surface of the striatal slice close to the recording electrode, and were analysed by HPLC. The high-frequency stimulation (100 Hz, three trains, 3 s duration, 20 s intervals) used to induce LTD caused a significant but transient increase in the release of both excitatory (aspartate and glutamate) and inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also produced a significant, but transient increase in the release of endogenous dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway is able to induce a large but transient release of excitatory amino acids and of dopamine, whose participation in the induction of striatal LTD has been demonstrated previously. Moreover, the maintenance of this form of synaptic plasticity does not seem to require a sustained change in transmitter release.     

Spontaneous reporting of adverse drug reactions in an Italian region: Six years of analysis and observations

Pharmacovigilance started in Italy in 1965, and from 1987 reporting of ADRs has been mandatory. Doctors have to send the filled forms on suspected ADRs to the Local Health Districts which transmit biannually all the reports to the Health Department. In a Northern Italian Region (Veneto) spontaneous reporting of adverse drug reactions (ADRs) has been studied during the period 1988–1993. This Region contributes a substantial percentage of the total Italian reports. The total number of reports was 3700, most of these (54 per cent) coming from GPs. A great variability in the reporting rate among the 36 districts of Veneto Region (range: 0–8.8 per 10,000 inhabitants per year) and an important under-reporting have been evident. Underreporting is also emphasized by the fact that in 1993 the Veneto doctors who sent at least one report were only 2.7 per cent. On the whole about 35 per cent of reports concerned minor reactions caused by drugs which have a well known toxicological profile. Comparison between reports coming from Veneto and the UK in some cases show a similar safety profile (omeprazole and simvastatin), whereas in other cases (e.g. terfenadine, glafenine, fluoxetine) no correspondence can be found. This article reveals the limits of the actual spontaneous reporting in Italy and suggests some possible measures for improving it.     

Prognostic role of immunosuppressive acidic protein in advanced ovarian cancer

OBJECTIVE: Our purpose was to investigate immunosuppressive acidic protein in the prognostic characterization of advanced ovarian cancer. STUDY DESIGN: Serum levels of immunosuppressive protein were prospectively measured in 80 patients with untreated ovarian carcinoma. To evaluate the prognostic significance of immunosuppressive acidic protein levels, cutoff points were studied every 50 μg/ml between 450 and 1350 μg/ml. RESULTS: Pretreatment immunosuppressive acidic protein levels were not significantly associated with stage, histotype, grade of differentiation, postoperative residual tumor, and response to chemotherapy. The most significant association with survival was observed at a cutoff value of 1100 μg/ml (p = 0.0089). In the univariate analysis for overall survival, International Federation of Gynecology and Obstetrics stage and immunosuppressive acidic protein status were found to have a role in predicting ovarian cancer prognosis. In the multivariate analysis only immunosuppressive acidic protein status was significantly associated with survival. A statistical correlation was found between serum levels and overall survival (p = 0.0104, χ² 6.56), including immunosuppressive acidic protein as a continuous variable. CONCLUSION: Our data suggest that immunosuppressive acidic protein assay is a potentially useful tool in the prognostic characterization of advanced ovarian cancer. (Am J Obstet Gynecol 1996;175:1606-10.)     

The effects of self-generated comparison targets, BMI, and social comparison tendencies on body image appraisal

Previous studies examining the association between social comparison processes and body image dissatisfaction have yielded inconsistent findings. This study examined whether such discrepancies are due to either the use of identical comparison targets for all subjects or variability in body mass. Specifically, 216 subjects were randomly assigned to one of three experimental conditions: self-generated upward comparison group, self-generated downward comparison group, or control group. Dependent variables were measures of body image. Results indicated that increasing body mass and trait comparison tendencies were associated with increased body dissatisfaction. However, the experimental manipulation did not affect body image ratings. Results suggest that social comparison processes may operate similarly over a range of body mass index (BMI) values.     

Influence of anesthesia on the threshold of pacing-induced ischemia.

Increased myocardial oxygen demand, induced by increased heart rate, may cause myocardial ischemia in the presence of significant coronary artery disease. Alterations in anesthetic depth or technique might put at risk or protect myocardium with compromised blood flow. In 20 dogs with critical left anterior descending coronary artery (LAD) stenosis, atrial pacing rates from 100 to 160 beats/min were achieved, with end-tidal halothane 0.7% (LowH) and 1.1% (HighH), end-tidal isoflurane 1.1% (LowI) and 1.5% (HighI), as well as with continuous fentanyl plus midazolam (FM) infusion anesthesia. Despite significantly different mean arterial and coronary perfusion pressures, rate-pressure product, and left ventricular dP/dtmax, the pacing rate at which systolic shortening decreased below the lower limit of the physiologic response, indicating regional dysfunction, was the same in all investigated anesthesia conditions (LowH: 127 +/- 4 beats/min; HighH: 128 +/- 5 beats/min; LowI: 125 +/- 4 beats/min; HighI: 122 +/- 5 beats/min; FM: 124 +/- 4 beats/min [mean +/- SEM], P greater than 0.05). None of the investigated anesthesia conditions either increased ischemia tolerance or showed a detrimental effect on myocardium with compromised coronary blood flow.