A novel method for the identification of synchronization effects in multichannel ECoG with an application to epilepsy.

In this paper, we present a novel method for the identification of synchronization effects in multichannel electrocorticograms (ECoG). Based on autoregressive modeling, we define a dependency measure termed extrinsic-to-intrinsic power ratio (EIPR) which quantifies directed coupling effects in the time domain. Hereby, a dynamic input channel selection algorithm assures the estimation of the model parameters despite the strong spatial correlation among the high number of involved ECoG channels. We compare EIPR to the partial directed coherence, show its ability to indicate Granger causality and successfully validate a signal model. Applying EIPR to ictal ECoG data of patients suffering from temporal lobe epilepsy allows us to identify the electrodes of the seizure onset zone. The results obtained by the proposed method are in good accordance with the clinical findings.

Structural parameters affecting the kinetics of RNA hairpin formation.

There is little experimental knowledge on the sequence dependent rate of hairpin formation in RNA. We have therefore designed RNA sequences that can fold into either of two mutually exclusive hairpins and have determined the ratio of folding of the two conformations, using structure probing. This folding ratio reflects their respective folding rates. Changing one of the two loop sequences from a purine- to a pyrimidine-rich loop did increase its folding rate, which corresponds well with similar observations in DNA hairpins. However, neither changing one of the loops from a regular non-GNRA tetra-loop into a stable GNRA tetra-loop, nor increasing the loop size from 4 to 6 nt did affect the folding rate. The folding kinetics of these RNAs have also been simulated with the program 'Kinfold'. These simulations were in agreement with the experimental results if the additional stabilization energies for stable tetra-loops were not taken into account. Despite the high stability of the stable tetra-loops, they apparently do not affect folding kinetics of these RNA hairpins. These results show that it is possible to experimentally determine relative folding rates of hairpins and to use these data to improve the computer-assisted simulation of the folding kinetics of stem-loop structures.

[Intraocular pressure after cyclophotocoagulation with the diode laser]. / Tensionsverlauf nach Zyklophotokoagulation mit dem Diodenlaser.

BACKGROUND: The reduction of intraocular pressure (IOP) following a single cyclophotocoagulation (CPC) procedure with a diode laser was investigated retrospectively. METHOD: CPC was performed on 150 eyes with a diode laser using standard parameters. The decrease of IOP between the 1st and 3rd day after surgery, after 6 months and after 1 year was investigated for different types of glaucoma and complications were documented. RESULTS: Overall and also in the individual groups the mean reduction of IOP within the first 3 days postoperation was 35%. The main effect, however, occurred within the 1st day after CPC. In the long-term results for 6 months and 1 year, the mean pressure values remained relatively stable but with a high standard deviation. A postoperative inflammatory reaction in the anterior chamber was observed in 15 eyes, 1 eye showed a temporary hypotension and 2 eyes a phthisis. Success of CPC was almost identical in all treatment groups with a 38% decrease of IOP after the 1st year. Additionally IOP was stable at a low level during the 1st year after CPC. After 1 year 42% of all eyes were still successfully treated: 38% of eyes needed further CPC treatment. CONCLUSIONS: CPC is an effective procedure for surgical reduction of intraocular pressure. The initial pressure-reducing effect of CPC was not related to the type of glaucoma. The individual predictability of the effect of CPC, however, is difficult because of the high interindividual differences. The rate of complications is low.

Epoetin treatment of anemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials.

Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95% confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95% CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.

Design of multistable RNA molecules.

We show that the problem of designing RNA sequences that can fold into multiple stable secondary structures can be transformed into a combinatorial optimization problem that can be solved by means of simple heuristics. Hence it is feasible to design RNA switches with prescribed structural alternatives. We discuss the theoretical background and present an efficient tool that allows the design of various types of switches. We argue that both the general properties of the sequence structure map of RNA secondary structures and the ease with which our design tool finds bistable RNAs strongly indicates that RNA switches are easily accessible in evolution. Thus conformational switches are yet another function for which RNA can be employed.

Influence of temperature and time on thermally induced forces in corneal collagen and the effect on laser thermokeratoplasty.

PURPOSE: To investigate thermomechanical aspects of corneal collagen denaturation as a function of temperature and time and the effect of the induced forces on refractive changes with laser thermokeratoplasty (LTK). SETTING: Medical Laser Center Lübeck, Lübeck, Germany. METHODS: In a material-test setup, porcine corneal strips were denatured in paraffin oil at various constant temperatures for 10 and 500 seconds, and the temporal course of the contractive forces was studied under isometric conditions. Typical LTK lesions were performed in porcine eyes in vitro with a continuous-wave infrared laser diode at a wavelength of 1.87 microm for 10 and 60 seconds. The laser power was chosen to achieve comparable denatured volumes at both irradiation times. The refractive changes were measured and analyzed by histologic evaluations and temperature calculations. RESULTS: The time course of the induced forces was characterized by a maximal force, which increased almost linearly with temperature, and a residual lower force. After 500 seconds of heating, the highest force was achieved with a temperature of 75 degrees C. With a limited heating period of only 10 seconds, the forces steadily increased with temperature over the entire observation period. Laser thermokeratoplasty produced less refractive change after 10 seconds of irradiation than after 60 seconds, although the laser power was 25% higher in the short heating period. Polarization light microscopy of LTK lesions revealed different stages of thermal damage. CONCLUSION: The course of the contractive forces during and after heating is a complicated function of the spatial time/temperature profile. Laser thermokeratoplasty lesions produced with 2 irradiation times showed different stages of denaturation and induced refractive change.

RNA folding at elementary step resolution.

We study the stochastic folding kinetics of RNA sequences into secondary structures with a new algorithm based on the formation, dissociation, and the shifting of individual base pairs. We discuss folding mechanisms and the correlation between the barrier structure of the conformational landscape and the folding kinetics for a number of examples based on artificial and natural sequences, including the influence of base modification in tRNAs.

Automatic detection of conserved RNA structure elements in complete RNA virus genomes.

We propose a new method for detecting conserved RNA secondary structures in a family of related RNA sequences. Our method is based on a combination of thermodynamic structure prediction and phylogenetic comparison. In contrast to purely phylogenetic methods, our algorithm can be used for small data sets of approximately 10 sequences, efficiently exploiting the information contained in the sequence variability. The procedure constructs a prediction only for those parts of sequences that are consistent with a single conserved structure. Our implementation produces reasonable consensus structures without user interference. As an example we have analysed the complete HIV-1 and hepatitis C virus (HCV) genomes as well as the small segment of hantavirus. Our method confirms the known structures in HIV-1 and predicts previously unknown conserved RNA secondary structures in HCV.

Secondary structure of the 3'-noncoding region of flavivirus genomes: comparative analysis of base pairing probabilities.

The prediction of the complete matrix of base pairing probabilities was applied to the 3' noncoding region (NCR) of flavivirus genomes. This approach identifies not only well-defined secondary structure elements, but also regions of high structural flexibility. Flaviviruses, many of which are important human pathogens, have a common genomic organization, but exhibit a significant degree of RNA sequence diversity in the functionally important 3'-NCR. We demonstrate the presence of secondary structures shared by all flaviviruses, as well as structural features that are characteristic for groups of viruses within the genus reflecting the established classification scheme. The significance of most of the predicted structures is corroborated by compensatory mutations. The availability of infectious clones for several flaviviruses will allow the assessment of these structural elements in processes of the viral life cycle, such as replication and assembly.

Density of states, metastable states, and saddle points exploring the energy landscape of an RNA molecule.

Detailed knowledge of the energy landscape of a biopolymer molecule is a prerequisite for understanding its folding kinetics and its final spatial structure. In the case of RNA we consider the energy landscape defined on the set of all secondary structures that can be formed by a given sequence. We show that the exploration of this energy landscapes is computationally feasible. For this purpose we present a recursive algorithm for computing the complete density of states and discuss its application to tRNA sequences. For shorter sequences a more detailed analysis of the energy surface is possible using a complete list of all secondary structures. In this case we identify metastable states and the saddle points that connect them.

[Surgery in patients over 80 years of age--a retrospective analysis of 642 general surgery patients]. / Chirurgie bei über 80-jährigen--eine retrospektive Analyse an 642 allgemeinchirurgischen Patienten.

We evaluated the data on 642 patients over 80 years of age who underwent general surgery within the preceding 10 years. Lethality in elective surgery was higher compared to younger patients and showed a threefold increase in emergency procedures. Preexisting co-diseases strongly determined survival, which emphasises the fact that a thorough preoperative risk-assessment is essential for elective surgery. Age itself is not a contraindication for elective surgery.

Effects of etomidate on the adrenocortical and metabolic adaptation of the neonate.

The effects of etomidate on corticosteroid synthesis were compared with those of methohexitone. We studied 40 neonates, 22 delivered by elective and 18 by emergency Caesarean section. Apgar scores, blood sugar and plasma concentrations of cortisol and etomidate were evaluated at birth and 2 and 6 h postpartum. There was no difference in Apgar scores attributable to the induction agent. The median cortisol concentrations in cord blood were small (136 nmol litre-1; range 47-478 nmol litre-1, and 259 nmol litre-1; range 58-1504 nmol litre-1 after elective and emergency sections, respectively). During the study, cortisol concentrations increased in the infants in the methohexitone groups and decreased in those in the etomidate groups; this effect was most evident 2 h after delivery (methohexitone groups 245 nmol litre-1, range 70-959 nmol litre-1; etomidate groups 121 nmol litre-1, range 56-320 nmol litre-1). There was no difference at 6 h postpartum (methohexitone groups 183 nmol litre-1, range 25-756 nmol litre-1; etomidate groups 190 nmol litre-1, range 33-628 nmol litre-1). The concentration changes during the study period differed significantly (P < 0.005) with respect to the induction agent. Blood glucose concentrations were small (mean (SD) in all 40 neonates 2 h postpartum was 2.64 (0.77) mmol litre-1), and did not differ between the groups. There were 17 cases of moderate to severe hypoglycaemia (blood glucose concentrations less than 2.5 mmol litre-1): nine in the etomidate group and eight in the methohexitone group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of Wilms' tumor (author's transl)]. / Therapie des Wilms-Tumors.

Uniform treatment based on the therapeutic approach of the 1st and 2nd US National Wilms' Tumor Study was decided on in March 1976 by paediatricians, surgeons, urologists and radiotherapists in Austria. Wilms' tumour was diagnosed in 34 children between 1 january 1976 an 29 february 1980 (stage I: n = 11, stage II: n = 8, stage III: n = 8, stage IV: n = 7). Parents of two children refused treatments; both children have since died of metastases. Of the remaining 32 children 29 (90.6%) are alive, 10 for more than 4, 15 for more than 3 and 19 for more than 2 years after diagnosis. 21 children are without need of treatment. Three children have died, one due to postoperative complications, one due to haemorrhagic chickenpox, but free of tumour, and one after insufficient treatment. Two of the five children with a recurrence between 2 1/4 to 15 months after diagnosis had been treated inadequately in the initial phase. The tumour free survival rate in 74.2%. Two children with early occurring or recurrent lung metastases have survived for 53 1/2 and 54 months up to now.