Retrospective analysis of treatment outcome in 315 patients with oligodendroglial brain tumors

Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is considered to be well tolerated, side effects frequently lead to dose reduction or even discontinuation of treatment of oligodendroglial brain tumors. The primary objective of the analysis was to retrospectively compare progression-free survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side effects). Patients were retrospectively identified from a database containing our patients between 1990 and 2003. For the selected cases, all histopathology reports were re-evaluated by a local neuropathologist. Based on the updated histology data, patients were included in the study if they had at least one histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n = 61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate analysis adjusting for prognostic imbalances favouring the PC group showed a minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95% confidence interval 0.53–1.25; p = 0.346). Younger age (< 50 y) was a statistically significant predictor of longer PFS. Significant advantages in terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus oligoastrocytomas (p = 0.002), and WHO°II vs. °III (p < 0.001). Three risk groups regarding OS were identified. Findings support the hypothesis that PC may be as effective as PCV chemotherapy, while avoiding the additonal risks of vincristine. Younger age, lower tumor grade and histology of an oligodendroglioma were identified to be favorable prognostic factors.     

Mycorrhizal fungi enhance accumulation and tolerance of chromium in sunflower (Helianthus annuus)

Chromium (Cr) is a heavy metal risk to human health, and a contaminant found in agricultural soils and industrial sites. Phytoremediation, which relies on phytoextraction of Cr with biological organisms, is an important alternative to costly physical and chemical methods of treating contaminated sites. The ability of the arbuscular mycorrhizal fungus (AM),Glomus intraradices, to enhance Cr uptake and plant tolerance was tested on the growth and gas exchange of sunflower (Helianthus annuus L.). Mycorrhizal-colonized (AM) and non-inoculated (Non-AM) sunflower plants were subjected to two Cr species [trivalent cation (Cr³⁺) Cr(III) , and divalent dichromate anion (Cr₂O₇⁻) Cr(VI) ]. Both Cr species depressed plant growth, decreased net photosynthesis (A) and increased the vapor pressure difference; however, Cr(VI) was more toxic. Chromium accumulation was greatest in roots, intermediate in stems and leaves, and lowest in flowers. Greater Cr accumulation occurred with Cr(VI) than Cr(III). AM enhanced the ability of sunflower plants to tolerate and hyperaccumulate Cr. At higher Cr levels greater mycorrhizal dependency occurred, as indicated by proportionally greater growth, higherA and reduced visual symptoms of stress, compared to Non-AM plants. AM plants had greater Cr-accumulating ability than Non-AM plants at the highest concentrations of Cr(III) and Cr(VI), as indicated by the greater Cr phytoextraction coefficient. Mycorrhizal colonization (arbuscule, vesicle, and hyphae formation) was more adversely affected by Cr(VI) than Cr(III), however high levels of colonization still occurred at even the most toxic levels. Arbuscules, which play an important role in mineral ion exchange in root cortical cells, had the greatest sensitivity to Cr toxicity. Higher levels of both Cr species reduced leaf tissue phosphorus (P). While tissue P was higher in AM plants at the highest Cr(III) level, tissue P did not account for mycorrhizal benefits observed with Cr(VI) plants.     

Genomic signatures of population bottleneck and recovery in Northwest Atlantic pinnipeds

Population increases over the past several decades provide natural settings in which to study the evolutionary processes that occur during bottleneck, growth, and spatial expansion. We used parallel natural experiments of historical decline and subsequent recovery in two sympatric pinniped species in the Northwest Atlantic, the gray seal (Halichoerus grypus atlantica) and harbor seal (Phoca vitulina vitulina), to study the impact of recent demographic change in genomic diversity. Using restriction site‐associated DNA sequencing, we assessed genomic diversity at over 8,700 polymorphic gray seal loci and 3,700 polymorphic harbor seal loci in samples from multiple cohorts collected throughout recovery over the past half‐century. Despite significant differences in the degree of genetic diversity assessed in the two species, we found signatures of historical bottlenecks in the contemporary genomes of both gray and harbor seals. We evaluated temporal trends in diversity across cohorts, as well as compared samples from sites at both the center and edge of a recent gray seal range expansion, but found no significant change in genomewide diversity following recovery. We did, however, find that the variance and degree of allele frequency change measured over the past several decades were significantly different from neutral expectations of drift under population growth. These two cases of well‐described demographic history provide opportunities for critical evaluation of current approaches to simulating and understanding the genetic effects of historical demographic change in natural populations.     

The Infectious Molecular Clone and Pseudotyped Virus Models of Human Immunodeficiency Virus Type 1 Exhibit Significant Differences in Virion Composition with Only Moderate Differences in Infectivity and Inhibition Sensitivity

Two frequently employed methods for generating well-characterized, genetically defined infectious human immunodeficiency virus type 1 in vitro include the use of infectious molecular clones (IMCs) and pseudoviruses (PVs) competent for single-round infection. We compared six matched pairs of IMCs and PVs. The relative amounts of Env incorporated and efficiency of cleavage differed substantially between the two systems. Altering the ratio of proviral genome and env expression plasmids can produce pseudovirions that are structurally more similar to the matched IMCs. Differences in Env incorporation and cleavage translated into moderate differences in assays infectivity and sensitivity to neutralizing antibodies and entry inhibitors.In 2005, the Global Vaccine Enterprise called for the standardization of assays and put forth a strong suggestion for the use of pseudovirus (PV)-based assays (16). While there are a number of important advantages provided by the PV system (16) and significant efforts have gone into optimization and standardization (5, 8, 13, 16, 18, 23), the report highlighted a number of key areas that were in need of further study. One area was the careful comparison of replication-competent viruses and PVs with respect to envelope (Env) processing and incorporation and the effects that any differences may have on the outcome of assays.The creation of an infectious molecular clone (IMC) that represents the full proviral genome of a human immunodeficiency virus (HIV) variant allows the precise characterization and genetic manipulation of an isolate (1). In the IMC, the HIV long terminal repeat is used as a promoter to drive expression of the genome, and mRNA quantity and splicing are therefore the same as in native virions. The creation of IMCs can be technically challenging and therefore represents a substantial bottleneck in fully characterizing the numerous variants present within an individual. The PV system provides a more manageable alternative wherein the env gene is on a separate expression vector from the rest of the genome and is expressed with an exogenous constitutive promoter, most frequently that of the cytomegalovirus immediate-early 1 gene (6).Although previous reports have begun to compare IMCs and PVs (11, 12, 15, 20), the data remain inconclusive. To address areas where an extensive comparison has not yet been made, this study analyzed six matched pairs of HIV type 1 (HIV-1) IMCs and PVs that contain identical genomes. The study focused on four key parameters known to influence HIV-1 function and infectivity: Env cleavage into gp120 and gp41, total Env incorporated into the virion, viral infectivity, and sensitivity to inhibitors that target different steps in viral entry.To directly compare virions produced from the IMC and PV systems, we used the env sequences of six previously described maternal primary HIV-1 isolates (22, 27). This sample set comprised three clade A isolates (208.A3, 505.H3, and 505.C2), two C/D recombinants (184.G3 and 184.E4), and one D/A recombinant (535.B1). Q23Δenv (14, 21) was used at a by-mass 20:1 backbone/env ratio (except where noted otherwise) to complement the env expression plasmids and create PV, as previously described (4). To generate proviral chimeras for making IMCs, the same Q23-17 plasmid was engineered to have an XhoI restriction site in nef at position 8360 and an XhoI site was removed from the 3′ polylinker, allowing the native env gene to be excised with the restriction enzymes SmaI and XhoI. Therefore, vpu, rev, and env were isolate specific, while the remaining genome was derived from the Q23 backbone. The Q23 derivative Q23XhoΔXho (E. M. Long and J. Overbaugh, unpublished data) was used to create IMCs by directly ligating in the env gene of interest at the SmaI/XhoI sites. Full env sequencing was performed to verify the presence of the appropriate env gene. All virus preparations were generated by transfection of the same commonly used cell line, HEK293T cells.Purified virions were analyzed for Env incorporation and Env cleavage (amount of gp120 relative to that of unprocessed gp160). A compilation of quantitative Western blot assays is shown in Fig. ​Fig.1A1A and shows representative data, obtained as previously described (4), for each matched pair. The observed variation in Env mobility between isolates is consistent with the expected sizes of the Env proteins based on the numbers of amino acids and potential N-linked glycosylation sites. A double banding pattern was present in the uncleaved gp160 form of some variants, an observation that has been consistently reported by others and is believed to represent a highly sialylated form of Env (2, 9, 11, 17, 19). The low Env expression level of PVs 184.G3, 184.E4, and 505.H3 required the exposure intensity to be optimized for each virus pair. Since the LI-COR Odyssey system has a wide linear range (25) and the calculated values rely upon the ratio of the bands within the same lane, this manipulation had no impact on the calculated values. All comparisons of matched data were analyzed on the same gel by using the same manipulations.Open in a separate windowFIG. 1.Env incorporation and cleavage of matched IMC-PV pairs. (A) Representative Western blot assays of six matched IMC-PV pairs. The gp160 and gp120 bands for each pair are indicated by arrowheads, as differences in variable loop length and carbohydrate numbers resulted in variations in band migration. Matched Gag p24 (p24) bands are shown along the bottom. The integrated intensity (i.i.) of each band was quantified from a minimum of three independent experiments. (B) Virion Env incorporation was calculated with the formula (gp120 i.i. + gp160 i.i.)/p24 i.i. For each variant, the IMC value was set at 1, PV was calculated relative to the matched IMC, and data were analyzed with a one-sample t test. (C) Percent cleavage was calculated with the formula gp120 i.i./(gp120 i.i. + gp160 i.i.). Matched IMC and PV values were compared by the Mann-Whitney test. An asterisk denotes P < 0.05, and error bars represent the standard error of the mean.Each IMC-PV pair exhibited relatively equivalent levels of p24 (Fig. ​(Fig.1A,1A, bottom), suggesting that the overall amounts of virions produced by the IMC and PV systems were similar (7). However, the amount of virion-associated Env differed between the two models (Fig. ​(Fig.1B)1B) and was frequently lower in the PV system. The relative percentage of cleaved Env also differed significantly between the matched IMC and PV, again revealing that the PV more frequently had lower levels of cleaved gp120 Env (Fig. ​(Fig.1C).1C). The most striking example of this was seen with variant 505.C2, where 90% of the total Env was in the cleaved (gp120) form in the IMC but only 24% was cleaved in the PV.In order to determine if the observed physical differences impact measurements of biological significance, we assayed matched pairs for infectivity and neutralization sensitivity. Virus titers were determined on Tzm-bl cells by a previously described method (4) wherein relative light units from the linear part of the curve are normalized to p24 values from the same preparation. All six matched pairs exhibited statistically significant variability in infectivity, though the nature of the differences varied in direction and magnitude (Fig. ​(Fig.2).2). Neither Env incorporation nor Env cleavage alone could completely account for the direction of the difference.Open in a separate windowFIG. 2.Infectivity of IMC and PV matched pairs. Matched IMC (gray bars) and PV (black bars) pairs are shown. Infectivity was calculated as relative light units (RLU) normalized to p24 integrated intensity. Each sample was analyzed a minimum of four times, and mean values ± the standard errors of the means are shown. All matched pairs are significantly different by the Mann-Whitney test (P < 0.05).Two matched pairs, 505.C2 and 208.A3, were further tested against four entry inhibitors by using the Tzm-bl neutralization assay as previously described (4, 27). These pairs were selected because the matched IMC and PV demonstrated marked differences in Env incorporation, Env cleavage, and viral infectivity while providing robust titers to perform neutralization assays. This analysis used monoclonal antibodies (MAbs) 4E10 and IgG1-b12 (b12), the fusion inhibitor T-20, and the CCR5 inhibitor TAK-779 to target different epitopes on Env and different stages of viral fusion to the target cell as previously described (3, 10, 24, 26).In both sets of data, the overall profile of neutralization/inhibition sensitivity was generally similar between the matched IMC and PV. The 50% inhibitory concentrations for all but one analysis were less than 2.5-fold different between IMC and PV, a benchmark frequently used to identify a significant difference in neutralization sensitivity. For isolate 505.C2, there was a modest though consistent trend for the PV to be more sensitive than the IMC to neutralization by all of the MAbs and entry inhibitors tested (Fig. ​(Fig.3).3). However, the most dramatic difference was seen with T-20, which required a concentration to neutralize the IMC that was fivefold higher than that required to neutralize the PV (50% inhibitory concentrations of 0.5 and 0.1 μg/ml, respectively), yet the difference only trended toward significance (P = 0.07, Mann-Whitney test). The 208.A3 matched pair did not exhibit any consistent patterns in sensitivity and showed an overall similar profile between the IMC and PV.Open in a separate windowFIG. 3.Neutralization sensitivity of matched pairs for 505.C2 and 208.A3. The matched IMC and PV for 505.C2 (left panels) and 208.A3 (right panels) were tested against MAb 4E10 (recognizes gp41), MAb b12 (recognizes CD4 binding site), the fusion inhibitor T-20, and the CCR5 inhibitor TAK-779, as indicated. The x axis is the log₂ concentration of MAb (nanograms per milliliter), T-20 (nanograms per milliliter), or TAK-779 (micromolar). The y axis denotes percent neutralization calculated with the formula (background-normalized virus only − background-normalized virus with entry inhibitor)/background-normalized virus only. Each curve represents the mean ± the standard error of the mean of at least three independent experiments. None of the matched pairs reached significance by the Mann-Whitney test (P < 0.05). Open symbols denote IMC, and closed symbols denote PV. The 50% inhibitory concentration is marked with a dashed line.Although little difference was observed between the neutralization/inhibition data obtained with either IMCs or PVs, there were unpredictable differences in infectivity combined with the marked differences in Env incorporation and cleavage. This result is likely based on the overexpression of Env in the PV system when the gene exists on a separate plasmid under the control of its own promoter, particularly a strong promoter such as that of the human cytomegalovirus immediate-early 1 gene.This led us to test if the amount of env plasmid present in the transfection system was responsible for the observed differences in virus outcome and to discern if the two systems could be made more congruent. A panel of PVs was created with various backbone/env plasmid ratios. The total amount of transfected DNA was held constant, while the relative amount of env plasmid was decreased. For each variant, PV reparations were made at backbone/env plasmid mass ratios of 1:1, 2:1, 10:1, 20:1, 40:1, and 80:1. The 505.C2 and 535.B1 isolates were used in this analysis.Not surprisingly, as the backbone-to-env plasmid ratio increased (and therefore the relative amount of env plasmid decreased), the amount of virion incorporated Env also decreased dramatically (Fig. ​(Fig.4A).4A). This was true for both 535.B1 and 505.C2. The total amount of p24 stayed relatively constant (Fig. ​(Fig.4A)4A) despite the increase in backbone plasmid. The net result was less Env per virion as determined by the formula (gp120 i.i. + gp160 i.i.)/p24 (Fig. ​(Fig.4B,4B, solid lines). Decreased amounts of env plasmid also corresponded to higher levels of Env cleavage in both of the isolates tested (Fig. ​(Fig.4B,4B, dashed lines). For variant 505.C2, PV produced with the lowest amount of env plasmid (80:1 ratio) approached the level of cleavage (90%) seen in the matched 505.C2 IMC (compare Fig. ​Fig.4B,4B, dashed line, to 1C). Likewise, the 535.B1 PV produced with the lowest amount of env plasmid (80:1 ratio) exceeded the level of cleavage seen with the matched IMC (51 and 39%, respectively, compare Fig. ​Fig.4B,4B, dashed line, to 1C). For both of the 505.C2 and 535.B1 variants, the lower amount of env plasmid (80:1 ratio), which corresponded to less Env incorporation and higher Env cleavage, also resulted in decreased infectivity (Fig. ​(Fig.4C)4C) spanning 2 log orders of magnitude. This lower infectivity in the PVs at the 80:1 ratio for both 535.B1 and 505.C2 is consistent with lower infectivity of the IMCs in these pairs (Fig. ​(Fig.22).Open in a separate windowFIG. 4.PV comparisons of Env incorporation, Env cleavage, and viral infectivity. A panel of PVs was created from isolates 535.B1 (left side) and 505.C2 (right side). The total amount of transfected plasmid DNA was held constant, while the relative amounts of backbone and env plasmids were varied (1:1 had equal amounts of both plasmids, while 80:1 had 80 times more backbone plasmid than env plasmid). (A) Quantitative Western blots were probed for uncleaved Env (gp160), cleaved Env (gp120), and Gag p24. (B) Env incorporation (determined with the formula [gp160 i.i. + gp120 i.i.]/p24 i.i., where i.i. is integrated intensity) is shown as a solid line, while Env cleavage (determined with the equation gp120 i.i./[gp160 i.i. + gp120 i.i.]) is shown as a dashed line. (C) Infectivity was calculated as relative light units (RLU) normalized to the number of picograms of p24. Complete analyses were repeated a minimum of two times, and representative data are shown.In light of the need for a thorough comparison of the PV and IMC systems, this study presents a systematic analysis of four key areas in which the two systems of virus production may vary biochemically and/or phenotypically: Env virion incorporation, Env cleavage, viral infectivity, and sensitivity to entry inhibitors. This provides a direct comparison of the IMC and PV systems when virions are produced from the same frequently used producer cell line, HEK293T cells. A central finding of this study is that matched IMCs and PVs do not produce physically equivalent virions when constructed in the manner described. We found equal or significantly greater Env processing in the IMC for all six samples. The total Env incorporation was more variable; both the PV and IMC exhibited greater incorporation, depending on the isolate. Additionally, all six pairs exhibited statistically significant differences in infectivity with a range of magnitudes and directions. Despite these differences, previous work by Louder et al. (15) demonstrated no difference in neutralization sensitivity in three clade B viruses. Our study corroborates this finding with two clade A viruses, providing further validation of the PV system for determination of neutralization and inhibition sensitivity. For the characteristics in which the IMC and PV do exhibit differences, our study demonstrates a simple technique for reconciling these differences by varying the backbone/env ratio, allowing the use of the PV for biochemical analyses.     

Characterization of the genetic diversity of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> in São Paulo city,Brazil

Background

Tuberculosis is a major health problem in São Paulo, Brazil, which is the most populous and one of the most cosmopolitan cities in South America. To characterize the genetic diversity of Mycobacterium tuberculosis in the population of this city, the genotyping techniques of spoligotyping and MIRU were applied to 93 isolates collected in two consecutive years from 93 different tuberculosis patients residing in São Paulo city and attending the Clemente Ferreira Institute (the reference clinic for the treatment of tuberculosis).

Findings

Spoligotyping generated 53 different spoligotype patterns. Fifty-one isolates (54.8%) were grouped into 13 spoligotyping clusters. Seventy- two strains (77.4%) showed spoligotypes described in the international databases (SpolDB4, SITVIT), and 21 (22.6%) showed unidentified patterns. The most frequent spoligotype families were Latin American Mediterranean (LAM) (26 isolates), followed by the T family (24 isolates) and Haarlem (H) (11 isolates), which together accounted for 65.4% of all the isolates. These three families represent the major genotypes found in Africa, Central America, South America and Europe. Six Spoligo-International-types (designated SITs by the database) comprised 51.8% (37/72) of all the identified spoligotypes (SIT53, SIT50, SIT42, SIT60, SIT17 and SIT1). Other SITs found in this study indicated the great genetic diversity of M. tuberculosis, reflecting the remarkable ethnic diversity of São Paulo city inhabitants. The MIRU technique was more discriminatory and did not identify any genetic clusters with 100% similarity among the 93 isolates. The allelic analysis showed that MIRU loci 26, 40, 23 and 10 were the most discriminatory. When MIRU and spoligotyping techniques were combined, all isolates grouped in the 13 spoligotyping clusters were separated.

Conclusions

Our data indicated the genomic stability of over 50% of spoligotypes identified in São Paulo and the great genetic diversity of M. tuberculosis isolates in the remaining SITs, reflecting the large ethnic mix of the São Paulo city inhabitants. The results also indicated that in this city, M. tuberculosis isolates acquired drug resistance independently of genotype and that resistance was more dependent on the selective pressure of treatment failure and the environmental circumstances of patients.

     

Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy?

Introduction

Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy.

Methods

Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients'' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls.

Results

At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values.

Conclusions

Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.     

The response to oestrogen deprivation of the cartilage collagen degradation marker, CTX-II, is unique compared with other markers of collagen turnover

Introduction  

The urinary level of the type II collagen degradation marker CTX-II is increased in postmenopausal women and in ovariectomised rats, suggesting that oestrogen deprivation induces cartilage breakdown. Here we investigate whether this response to oestrogen is also true for other type II collagen turnover markers known to be affected in osteoarthritis, and whether it relates to its presence in specific areas of cartilage tissue.     

Enhanced myogenic tone in cerebral arteries from a rabbit model of subarachnoid hemorrhage

Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Currently, little is known regarding the impact of SAH on small diameter (100-200 microm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. With the use of a rabbit SAH model and in vitro video microscopy, cerebral artery diameter was measured in response to elevations in intravascular pressure. Cerebral arteries from SAH animals constricted more (approximately twofold) to pressure within the physiological range of 60-100 mmHg compared with control or sham-operated animals. Pressure-induced constriction (myogenic tone) was also enhanced in arteries from control animals organ cultured in the presence of oxyhemoglobin, an effect independent of the vascular endothelium or nitric oxide synthesis. Finally, arteries from both control and SAH animals dilated as intravascular pressure was elevated above 140 mmHg. This study provides evidence for a role of oxyhemoglobin in impaired autoregulation (i.e., enhanced myogenic tone) in small diameter cerebral arteries during SAH. Furthermore, therapeutic strategies that improve clinical outcome in SAH patients (e.g., supraphysiological intravascular pressure) are effective in dilating small diameter cerebral arteries isolated from SAH animals.     

Evolutionary optimization of classifiers and features for single-trial EEG Discrimination

Background  

State-of-the-art signal processing methods are known to detect information in single-trial event-related EEG data, a crucial aspect in development of real-time applications such as brain computer interfaces. This paper investigates one such novel approach, evaluating how individual classifier and feature subset tailoring affects classification of single-trial EEG finger movements. The discrete wavelet transform was used to extract signal features that were classified using linear regression and non-linear neural network models, which were trained and architecturally optimized with evolutionary algorithms. The input feature subsets were also allowed to evolve, thus performing feature selection in a wrapper fashion. Filter approaches were implemented as well by limiting the degree of optimization.