Dynamic range and sensitivity adaptation in a silicon spikingneuron

We propose an adaptive procedure that enables a spiking neuron, whether artificial or biological, to make optimal use of its dynamic range and gain. We discuss an analog electronic circuit implementation of this algorithm using a biologically realistic artificial "silicon" neuron. The adaptation procedure adapts the neuron's firing threshold and the sensitivity (or gain) of its current-frequency relationship to match the DC offset (or mean) and the dynamic range (or variance) of the time-varying somatic input current. The neuron extracts the minimum and maximum levels of the reconstructed somatic current signals from the cell's own spike trains. These are used to regulate the somatic leak conductance in order to shift the somatic current-frequency relation and to adjust a calcium-activated potassium conductance to change the dynamic range of the cell's somatic current-frequency relationship. We report experimental data from a test neuron-built using analog subthreshold CMOS VLSI technology-that shows the expected behavior.     

Influence of patient age and co-morbidity on outcome of a collaborative care pathway after radical prostatectomy and cystoprostatectomy

PURPOSE: We determined whether standardized care patterns developed with a collaborative care methodology can be applied successfully across all patient groups with favorable effects on cost and quality. MATERIALS AND METHODS: We retrospectively analyzed financial and clinical outcomes in 109 radical retropubic prostatectomy and 47 radical cystectomy cases. Patients older than 70 years and/or with an American Society of Anethesiology status of 3 or greater were compared to younger, healthier patients undergoing these procedures. RESULTS: Standardized care patterns resulted in favorable financial and clinical outcomes in high and low risk patient groups. The only apparent difference was an increased need for rehospitalization after discharge for patients undergoing radical prostatectomy with a high American Society of Anesthesiology status. CONCLUSIONS: Standardized care patterns developed with a collaborative care methodology provide a high quality, cost-efficient approach to medical care. This methodology is applicable to all patient groups and is highly compatible with current medical practice.     

Highly-efficient gene transfer with retroviral vectors into human T lymphocytes on fibronectin

Genetically modified lymphocytes have been successfully used for correction of ADA deficiency in children and in controlling graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation. Low transduction efficiencies are, however, limiting for gene therapeutic strategies based on lymphocytes. In this study we compared protocols for highly efficient gene transfer into human T cells using retroviral vector-containing supernatant. We showed that infection of both human primary T cells and CD4+ Jurkat cells is most efficient on the matrix component fibronectin. Transduction was carried out with a retroviral vector encoding both the human intracytoplasmatically truncated low-affinity nerve growth factor receptor (deltaLNGFR) as a gene transfer marker and the Herpes simplex virus thymidine kinase for negative selection. Based on LNGFR expression genetically modified cells were enriched to near purity by magnetic cell sorting (MACS). Enriched cells could be shown to be highly sensitive to ganciclovir.     

Is image selection a useful strategy to decrease the transmission time in teleradiology? A study using 100 emergency cranial CTs

This study examines the suitability of working with a selection of images in a teleradiology consulting system in neurological or neurosurgical emergency situations. The teleradiology system was based on IBM-compatible personal computers, video digitization for data acquisition, and data transmission by Integrated System Digital Network. Forty normal and 60 abnormal emergency cranial computed tomograms were shown to a radiologist on call who presented all cases he regarded as pathologic to a neuroradiologic expert by teleradiology. To reduce transmission time, only a selection of images from the CT study was presented (up to four images per case). For each case the on-call radiologist's diagnosis (D(on-call)), the expert's diagnosis on the teleradiology screen (D(monitor)), and the expert's diagnosis on the original film (D(original)) was documented, together with an estimation of the agreement between those diagnoses. There was clinically relevant disagreement between the on-call radiologist's diagnosis and the neuroradiologist's diagnosis based on the image selection on the teleradiology monitor in 23% of cases. A clinically important discrepancy between the neuroradiologist's diagnosis based on the image selection and his diagnosis using the original films was found in 30% of cases. This was due to the presence of clinically relevant information on images not transferred by the on-call radiologist. Image quality of the transferred images was sufficient in all cases. Drastic selection of images from a complete CT study leads to a high rate of incorrect diagnoses and is not appropriate to reduce transmission time in teleradiology.     

Response of V79 cells to low doses of X-rays and negative pi-mesons: clonogenic survival and DNA strand breaks

Mammalian cells are hypersensitive to very low doses of X-rays (< 0.2 Gy), a response which is followed by increased radioresistance up to 1 Gy. Increased radioresistance is postulated to be a response to DNA damage, possibly single-strand breaks, and it appears to be a characteristic of low linear energy transfer (LET) radiation. Here we demonstrate a correspondence between the extent of the increased radioresistance and linear energy transfer of 250 kVp X-rays and plateau and Bragg peak negative pi-mesons. The results support our hypothesis since the size of the increased radioresistant response appears to correspond to the number of radiation induced single-strand breaks. Furthermore, since survival prior to the increased radioresistant response (< 0.2 Gy) was LET-independent, these data support the notion that the increased radioresistant response may dictate the overall survival response to higher doses. However, while these data provide further circumstantial evidence for the involvement of DNA strand breaks in the triggering of increased radioresistance, more direct conclusions cannot be made. The data are not accurate enough to detect structure in the single-strand break profiles, the production of single-strand breaks being apparently linear with dose.     

Processing of the Borna disease virus glycoprotein gp94 by the subtilisin-like endoprotease furin

Open reading frame IV (ORF-IV) of Borna disease virus (BDV) encodes a protein with a calculated molecular mass of ca. 57 kDa (p57), which increases after N glycosylation to 94 kDa (gp94). The unglycosylated and glycosylated proteins are proteolytically cleaved by the subtilisin-like protease furin. Furin most likely recognizes one of three potential cleavage sites, namely, an arginine at position 249 of the ORF-IV gene product. The furin inhibitor decRVKRcmk decreases the production of infectious BDV significantly, indicating that proteolytic cleavage of the gp94 precursor molecule is necessary for the full biological activity of the BDV glycoprotein.     

Pantoprazole does not interact with the pharmacokinetics of carbamazepine

OBJECTIVE: Pantoprazole is a H+/K+-ATPase inhibitor with a minimized potential of interaction with the cytochrome P450 system. Imidazole derivatives such as cimetidine and omeprazole have been shown to markedly interact with carbamazepine, a major anticonvulsant with a narrow therapeutic range. Therefore, the influence of steady-state pantoprazole on the pharmacokinetics of carbamazepine was investigated. SUBJECTS AND METHODS: N = 20 healthy volunteers (12 male/8 female) completed a double-blind, placebo-controlled, randomized crossover study. During the test period they received 40 mg pantoprazole p.o. once daily for 11 days and concomitantly a single oral dose of 400 mg carbamazepine on day 5. In the reference period placebo was administered instead of pantoprazole. RESULTS: Serum concentrations of carbamazepine and its active metabolite carbamazepine-10,11-epoxide were measured until day 11. Geometric means of AUC (extent characteristic) and Cmax/AUC (rate characteristic) of carbamazepine were 292 and 287 mgxh/l, and 0.0150 and 0.0144 l/h (reference and test), respectively. Point estimates and 90% confidence intervals of the ratios were 0.98 (0.95, 1.01) for AUC, and 0.96 (0.92, 1.00) for Cmax/AUC, respectively. Since the 90% confidence intervals of the primary characteristics, AUC and Cmax/AUC were entirely within the predefined equivalence range of 0.80 - 1.25, lack of interaction of pantoprazole with the pharmacokinetics of carbamazepine was demonstrated. Equivalence was also demonstrated for carbamazepine-10,11-epoxide using the characteristics AUC and Cmax. CONCLUSION: No dose adjustment of carbamazepine is therefore required during concomitant treatment with pantoprazole.     

Parameter estimates for direct, maternal, and grandmaternal genetic effects for birth weight and weaning weight in Hereford cattle

Birth and weaning weights adjusted for age of dam from four lines of Hereford cattle were analyzed to determine the relationships among grandmaternal, maternal, and direct genetic effects. Three lines were selected for 1) weaning weight (WWL), 2) yearling weight (YWL), and 3) an index of yearling weight and muscle score (IXL). The fourth line was an unselected control line (CTL). Numbers of observations ranged from 1,699 (CTL) to 2,811 (WWL), and number of animals in the pedigree file ranged from 2,266 to 3,192. Two animal models were used to obtain estimates by REML using an average information method. Model 1 included random direct and maternal genetic, permanent maternal environmental, and residual environmental effects, and fixed sex x year effects. Model 2 additionally included random grandmaternal genetic and permanent grandmaternal environmental effects. For birth weight, Models 1 and 2 gave almost identical estimates for direct and maternal heritability, and for the fraction of variance that was due to maternal permanent environmental effects. Estimates for grandmaternal heritability could be obtained only for IXL (.03) and CTL (.01). For weaning weight, estimates for direct heritability were similar from both models. Estimates for maternal heritability from Model 1 were .18, .20, .13, and .20, and corresponding estimates from Model 2 were .34, .31, .13, and .34 for WWL, YWL, IXL, and CTL, respectively. For IXL, estimates for variances that were due to grandmaternal genetic and grandmaternal permanent environmental variances could not be obtained and were set to zero. Grandmaternal heritability estimates for WWL, YWL, and CTL were .05, .09, and .12. Estimates of correlations between direct and maternal genetic effects were -.13, -.44, -.11, and -.26 for WWL, YWL, IXL, and CTL. Estimates of correlations between direct and grandmaternal genetic effects were .21, .83, and .55, and those between maternal and grandmaternal genetic effects were -.99, -.84, and -.76 for WWL, YWL, and CTL, respectively. These results indicate that grandmaternal effects may be important for weaning weight and that maternal heritability may be underestimated if grandmaternal effects are not included in the model.     

Flexible sigmoidoscopy training program for internal medicine residents

We examined the possibility of an association between the bacterial genotype of Escherichia coli O157:H7 and the likelihood of progression to neurological complications in childhood gastroenteritis-associated haemolytic uraemic syndrome (D+HUS). Bacterial stool isolates were available from 51 patients with HUS; 11 of these patients suffered a neurological complication. Bacteria were assessed for plasmid content, verotoxin (Shiga-like toxin) profile, verotoxin 2 subtype, and presence of the eaeA (effacement and attachment) marker. No association of bacterial genotype with central nervous system (CNS) manifestations was observed. Whilst the cause of CNS manifestations may be multifactorial, there is no evidence at present to implicate specific bacterial traits.