A benchmark test for a quantitative assessment of simple neuron models

Several methods and algorithms have recently been proposed that allow for the systematic evaluation of simple neuron models from intracellular or extracellular recordings. Models built in this way generate good quantitative predictions of the future activity of neurons under temporally structured current injection. It is, however, difficult to compare the advantages of various models and algorithms since each model is designed for a different set of data. Here, we report about one of the first attempts to establish a benchmark test that permits a systematic comparison of methods and performances in predicting the activity of rat cortical pyramidal neurons. We present early submissions to the benchmark test and discuss implications for the design of future tests and simple neurons models

Phase-sensitive dual-inversion recovery for accelerated carotid vessel wall imaging.

OBJECTIVES: Dual-inversion recovery (DIR) is widely used for magnetic resonance vessel wall imaging. However, optimal contrast may be difficult to obtain and is subject to RR variability. Furthermore, DIR imaging is time-inefficient and multislice acquisitions may lead to prolonged scanning times. Therefore, an extension of phase-sensitive (PS) DIR is proposed for carotid vessel wall imaging. METHODS: The statistical distribution of the phase signal after DIR is probed to segment carotid lumens and suppress their residual blood signal. The proposed PS-DIR technique was characterized over a broad range of inversion times. Multislice imaging was then implemented by interleaving the acquisition of 3 slices after DIR. Quantitative evaluation was then performed in healthy adult subjects and compared with conventional DIR imaging. RESULTS: Single-slice PS-DIR provided effective blood-signal suppression over a wide range of inversion times, enhancing wall-lumen contrast and vessel wall conspicuity for carotid arteries. Multislice PS-DIR imaging with effective blood-signal suppression is enabled. CONCLUSIONS: A variant of the PS-DIR method has successfully been implemented and tested for carotid vessel wall imaging. This technique removes timing constraints related to inversion recovery, enhances wall-lumen contrast, and enables a 3-fold increase in volumetric coverage at no extra cost in scanning time.

Iowa Pore Index Test, MLR-80-2, 1980

The objective of the investigation was the development of a test that would readily identify the potential of an aggregate to cause D-cracking because of its susceptivity to critical saturation. A Press-Ur-Meter was modified by replacing the air chamber with a one-inch diameter plastic tube calibrated in milli-. It was concluded that the pore index was sufficiently reliable to determine the D-cracking potential of limestone aggregates in all but a few cases where marginal results were obtained. Consistently poor or good results were always in agreement with established service records or concrete durability testing. In those instances where marginal results are obtained, the results of concrete durability testing should be considered when making the final determination of the D-cracking susceptibility of the aggregate in question. The following applications for the pore index test have been recommended for consideration: concrete durability testing be discontinued in the evaluation process of new aggregate sources with pore index results between 0-20 (Class 2 durability) and over 35 (Class 1) durability; composite aggregates with intermediate pore index results of 20-35 be tested on each stone type to facilitate the possible removal of low durability stone from the production process; and additional investigation should be made to evaluate the possibility of using the test to monitor and upgrade the acceptance of aggregate from sources associated with D-cracking.

Evaluation of the Argentine Nondestructive Test for Determining Concrete Compressive Strength, R-269 and MLR-75-2, 1975

The compressive strength of concrete is an important factor in the design of concrete structures and pavements. To assure the quality of the concrete placed at the project, concrete compressive cylinders are made at the jobsite. These cylinders undergo a destructive test to determine their compressive strength. However, the determination of concrete compressive strength of the concrete actually in the structure or pavement is frequently desirable. For this reason, a nondestructive test of the concrete is required. A nondestructive test of concrete compressive strength should be economical, easily performed by field personnel, and capable of producing accurate, reproducible results. The nondestructive test should be capable of detecting the extent of poor concrete in a pavement or structure due to improper handling, placement, or variations in mixing or materials.

Improvement of cardiovascular risk prediction: time to review current knowledge, debates, and fundamentals on how to assess test characteristics.

Cardiovascular risk assessment might be improved with the addition of emerging, new tests derived from atherosclerosis imaging, laboratory tests or functional tests. This article reviews relative risk, odds ratios, receiver-operating curves, posttest risk calculations based on likelihood ratios, the net reclassification improvement and integrated discrimination. This serves to determine whether a new test has an added clinical value on top of conventional risk testing and how this can be verified statistically. Two clinically meaningful examples serve to illustrate novel approaches. This work serves as a review and basic work for the development of new guidelines on cardiovascular risk prediction, taking into account emerging tests, to be proposed by members of the 'Taskforce on Vascular Risk Prediction' under the auspices of the Working Group 'Swiss Atherosclerosis' of the Swiss Society of Cardiology in the future.

Two Signatures For A New Blood-Based Test For Colorectal Cancer Screening

Background: Detection rates for adenoma and early colorectal cancer (CRC) are unsatisfactory due to low compliance towards invasive screening procedures such as colonoscopy. There is a large unmet screening need calling for an accurate, non-invasive and cost-effective test to screen for early neoplastic and pre-neoplastic lesions. Our goal is to identify effective biomarker combinations to develop a screening test aimed at detecting precancerous lesions and early CRC stages, based on a multigene assay performed on peripheral blood mononuclear cells (PBMC).Methods: A pilot study was conducted on 92 subjects. Colonoscopy revealed 21 CRC, 30 adenomas larger than 1 cm and 41 healthy controls. A panel of 103 biomarkers was selected by two approaches: a candidate gene approach based on literature review and whole transcriptome analysis of a subset of this cohort by Illumina TAG profiling. Blood samples were taken from each patient and PBMC purified. Total RNA was extracted and the 103 biomarkers were tested by multiplex RT-qPCR on the cohort. Different univariate and multivariate statistical methods were applied on the PCR data and 60 biomarkers, with significant p-value (< 0.01) for most of the methods, were selected.Results: The 60 biomarkers are involved in several different biological functions, such as cell adhesion, cell motility, cell signaling, cell proliferation, development and cancer. Two distinct molecular signatures derived from the biomarker combinations were established based on penalized logistic regression to separate patients without lesion from those with CRC or adenoma. These signatures were validated using bootstrapping method, leading to a separation of patients without lesion from those with CRC (Se 67%, Sp 93%, AUC 0.87) and from those with adenoma larger than 1cm (Se 63%, Sp 83%, AUC 0.77). In addition, the organ and disease specificity of these signatures was confirmed by means of patients with other cancer types and inflammatory bowel diseases.Conclusions: The two defined biomarker combinations effectively detect the presence of CRC and adenomas larger than 1 cm with high sensitivity and specificity. A prospective, multicentric, pivotal study is underway in order to validate these results in a larger cohort.

Development of a Conductometric Test for Frost Resistance of Concrete, HR-272, 1988

Research is described that was aimed at developing a test method which can be reasonably and rapidly performed in the laboratory and in the field to predict, with a high degree of certainty, the behavior of concrete subjected to the action of alternate freezing and thawing. The conductometric evaluation of concrete durability was explored with 3 different test methods: conductometric evaluation of the resistance of concrete to rapid freezing and thawing; conductomtric evaluation of the resistance of concrete to natural freezing and thawing, and conductometric evaluation of the pore size distribution of concrete and its correlation to concrete durability. The study showed that conductance could be used as a viable method for determining the durability of portland cement concrete. This would also allow the continuous monitoring of concrete durability without the removal twice per week from the freeze/thaw chamber. Recommendations for the continued development of these test methods are also included.

Test result-based sampling: an efficient design for estimating the accuracy of patient safety indicators.

OBJECTIVE: Accuracy studies of Patient Safety Indicators (PSIs) are critical but limited by the large samples required due to low occurrence of most events. We tested a sampling design based on test results (verification-biased sampling [VBS]) that minimizes the number of subjects to be verified. METHODS: We considered 3 real PSIs, whose rates were calculated using 3 years of discharge data from a university hospital and a hypothetical screen of very rare events. Sample size estimates, based on the expected sensitivity and precision, were compared across 4 study designs: random and VBS, with and without constraints on the size of the population to be screened. RESULTS: Over sensitivities ranging from 0.3 to 0.7 and PSI prevalence levels ranging from 0.02 to 0.2, the optimal VBS strategy makes it possible to reduce sample size by up to 60% in comparison with simple random sampling. For PSI prevalence levels below 1%, the minimal sample size required was still over 5000. CONCLUSIONS: Verification-biased sampling permits substantial savings in the required sample size for PSI validation studies. However, sample sizes still need to be very large for many of the rarer PSIs.

Hyperactivation of retina by light in mice leads to photoreceptor cell death mediated by VEGF and retinal pigment epithelium permeability.

Light toxicity is suspected to enhance certain retinal degenerative processes such as age-related macular degeneration. Death of photoreceptors can be induced by their exposure to the visible light, and although cellular processes within photoreceptors have been characterized extensively, the role of the retinal pigment epithelium (RPE) in this model is less well understood. We demonstrate that exposition to intense light causes the immediate breakdown of the outer blood-retinal barrier (BRB). In a molecular level, we observed the slackening of adherens junctions tying up the RPE and massive leakage of albumin into the neural retina. Retinal pigment epithelial cells normally secrete vascular endothelial growth factor (VEGF) at their basolateral side; light damage in contrast leads to VEGF increase on the apical side - that is, in the neuroretina. Blocking VEGF, by means of lentiviral gene transfer to express an anti-VEGF antibody in RPE cells, inhibits outer BRB breakdown and retinal degeneration, as illustrated by functional, behavioral and morphometric analysis. Our data show that exposure to high levels of visible light induces hyperpermeability of the RPE, likely involving VEGF signaling. The resulting retinal edema contributes to irreversible damage to photoreceptors. These data suggest that anti-VEGF compounds are of therapeutic interest when the outer BRB is altered by retinal stresses.

Innovative Leak Test for Pavement Joint Seals, Progress Report, HR-318, 1993

Premature failure of concrete pavement contraction joint seals is an ongoing and costly problem for the Iowa Department of Transportation. Several joint seal test sections consisting of variations in sawing methods, joint cleaning techniques, sealant installation, and sealant types have been established over the past few years. Laboratory analysis and field inspections were done as a part of the tests, and core samples were taken for laboratory adhesion pull tests. Such methods often cover specifically small areas and may not expose hidden failures. Some tests are also labor-intensive and destructive, especially that of coring. An innovative, nondestructive, broad coverage joint seal tester that yields quick results has been designed and developed for evaluation of pavement joint seal performance. The Iowa vacuum joint seal tester (IA-VAC) applies a low vacuum above a joint seal that has been spray-covered with a foaming water solution. Any unsealed area or leak that exists along the joint will become quickly and clearly visible by the development of bubbles at the leak point. By analyzing the results from the IA-VAC tests, information on the number and types of leaks can be obtained; such information will help identify the source of the problem and direct efforts toward a solution.

A Study of the Reliability of the ASTM C-666 Freeze-Thaw Test, MLR-72-01 and R-252, 1972

The Iowa State Highway Commission purchased a Conrad automatic freeze and thaw machine and placed it in operation during October 1961. There were a few problems, but considering, the many electrical and mechanical devices used in the automatic system it has always functioned quite well. Rapid freezing and thawing of 4"x4"xl8" concrete beams has been conducted primarily in accordance with ASTM C-29l (now ASTM C-666 procedure B) at the rate of one beam per day. Over 4000 beams have been tested since 1961, with determination of the resulting durability factors. Various methods of curing were used and a standard 90 day moist cure was selected. This cure seemed to yield durability factors that correlated very well with ratings of coarse aggregates based on service records. Some concrete beams had been made using the same coarse aggregate and the durability factors compared relatively well with previous tests. Durability factors seemed to yield reasonable results until large variations in durability factors were noted from beams of identical concrete mix proportions in research projects R-234 and R-247. This then presents the question "How reliable is the durability as determined by ASTM C-666?" This question became increasingly more important when a specification requiring a minimum durability factor for P.C. concrete made from coarse aggregates was incorporated into the 1972 Standard Specification for coarse aggregates for concrete.

Which anatomical sites should be sampled for screening of methicillin-resistant Staphylococcus aureus carriage by culture or by rapid PCR test?

The nose is the anatomical site usually recommended for methicillin-resistant Staphylococcus aureus (MRSA) screening. Other sites are also recommended, but are more controversial. We showed that the sensitivities of MRSA detection from nasal swabs alone were 48% and 62% by culture or by rapid PCR test, respectively. These percentages increased to 79% and 92% with the addition of groin swabs, and to 96% and 99% with the addition of groin and throat swabs. In conclusion, neither by culture nor by rapid PCR test is nose sampling alone sufficient for MRSA detection. Additional anatomical sites should include at least the groin and throat.

Evaluation of the Chemical Durability of Iowa Fly Ash Concretes, HR-327, 1993

The major objective of this research project was to investigate how Iowa fly ashes influenced the chemical durability of portland cement based materials. Chemical durability has become an area of uncertainty because of the winter application of deicer salts (rock salts) that contain a significant amount of sulfate impurities. The sulfate durability testing program consisted of monitoring portland cement-fly ash paste, mortar and concrete test specimens that had been subjected to aqueous solutions containing various concentrations of salts (both sulfate and chloride). The paste and mortar specimens were monitored for length as a function of time. The concrete test specimens were monitored for length, relative dynamic modulus and mass as a function of time. The alkali-aggregate reactivity testing program consisted of monitoring the expansion of ASTM C311 mortar bar specimens that contained three different aggregates (Pyrex glass, Oreapolis and standard Ottawa sand). The results of the sulfate durability study indicated that the paste and concrete test specimens tended to exhibit surface spalling but only very slow expansive tendencies. This suggested that the permeability of the test specimens was controlling the rate of deterioration. Concrete specimens are still being monitored because the majority of the test specimens have expanded less than 0.05%; hence, this makes it difficult to estimate the service life of the concrete test specimens or to quantify the performance of the different fly ashes that were used in the study. The results of the mortar bar studies indicated that the chemical composition of the various fly ashes did have an influence on their sulfate resistance. Typically, Clinton and Louisa fly ashes performed the best, followed by the Ottumwa, Neal 4 and then Council Bluffs fly ashes. Council Bluffs fly ash was the only fly ash that consistently reduced the sulfate resistance of the many different mortar specimens that were investigated during this study. None of the trends that were observed in the mortar bar studies have yet become evident in the concrete phase of this project. The results of the alkali-aggregate study indicated that the Oreapolis aggregate is not very sensitive to alkali attack. Two of the fly ashes, Council Bluffs and Ottumwa, tended to increase the expansion of mortar bar specimens that contained the Oreapolis aggregate. However, it was not clear if the additional expansion was due to the alkali content of the fly ash, the periclase content of the fly ash or the cristobalite content of the fly ash, since all three of these factors have been found to influence the test results.

Effects of prior repeated-sprints with different recovery duration on oxygen uptake kinetics during subsequent heavy-exercise

Introduction: Prior repeated-sprints (6) has become an interesting method to resolve the debate surrounding the principal factors that limits the oxygen uptake (V'O2) kinetics at the onset of exercise [i.e., muscle O2 delivery (5) or metabolic inertia (3)]. The aim of this study was to compare the effects of two repeated-sprints sets of 6x6s separated by different recovery duration between the sprints on V'O2 and muscular de-oxygenation [HHb] kinetics during a subsequent heavy-intensity exercise. Methods: 10 male subjects performed a 6-min constant-load cycling test (T50) at intensity corresponding to half of the difference between V'O2max and the ventilatory threshold. Then, they performed two repeated-sprints sets of 6x6s all-out separated by different recovery duration between the sprints (S1:30s and S2:3min) followed, after 7-min-recovery, by the T50 (S1T50 and S2T50, respectively). V'O2, [HHb] of the vastus lateralis (VL) and surface electromyography activity [i.e., root-mean-square (RMS) and the median frequency of the power density spectrum (MDF)] from VL and vastus medialis (VM) were recorded throughout T50. Models using a bi-exponential function for the overall T50 and a mono-exponential for the first 90s of T50 were used to define V'O2 and [HHb] kinetics respectively. Results: V'O2 mean value was higher in S1 (2.9±0.3l.min-1) than in S2 (1.2±0.3l.min-1); (p<0.001). The peripheral blood flow was increased after sprints as attested by a higher basal heart rate (HRbaseline) (S1T50: +22%; S2T50: +17%; p≤0.008). Time delay [HHb] was shorter for S1T50 and S2T50 than for T50 (-22% for both; p≤0.007) whereas the mean response time of V'O2 was accelerated only after S1 (S1T50: 32.3±2.5s; S2T50: 34.4±2.6s; T50: 35.7±5.4s; p=0.031). There were no significant differences in RMS between the three conditions (p>0.05). MDF of VM was higher during the first 3-min in S1T50 than in T50 (+6%; p≤0.05). Conclusion: The study show that V'O2 kinetics was speeded by prior repeated-sprints with a short (30s) but not a long (3min) inter-sprints-recovery even though the [HHb] kinetics was accelerated and the peripheral blood flow was enhanced after both sprints. S1, inducing a greater PCr depletion (1) and change in the pattern of the fibres recruitment (increase in MDF) compared with S2, may decrease metabolic inertia (2), stimulate the oxidative phosphorylation activation (4) and accelerate V'O2 kinetics at the beginning of the subsequent high-intensity exercise.