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Predictors of reading skill development in children with early cochlear implantation.

OBJECTIVE: The present study sought to document the word reading and comprehension levels attained by children who were implanted by 5 yr of age. It was hypothesized that the improved speech perception abilities acquired with cochlear implantation would promote phonological coding skills and facilitate the acquisition of beginning reading skills. DESIGN: Three subtests from diagnostic reading assessment batteries standardized on hearing children were administered to 181 children between 8 yr 0 mo and 9 yr 11 mo of age who had 4 to 6 yr of implant experience. In addition, a battery of processing measures was administered including a lexical decision task, a rhyme task and the digit span subtest of the Wechsler Intelligence Scale for Children. RESULTS: Over half of the children scored within the average range for their age compared with the normative data for hearing children. Reading competence was associated with higher nonverbal intelligence, higher family socio-economic status, female gender and later onset of deafness (between birth and 36 mo). After variance due to these child and family characteristics was removed, reading competence was associated with mainstream educational placement, use of an updated implant speech processor with a wide dynamic range, and speech processing characteristics that included longer memory span and use of phonological coding strategies. Reading outcome was most highly predicted by linguistic competence and, secondarily, by speech production skill. CONCLUSION: Children who experience severe to profound deafness early in their development have a better prognosis for normal literacy development than ever before. To the extent that use of a cochlear implant is associated with greater use of phonological coding strategies for decoding print, longer working memory spans for short-term storage of phonemes, words and sentences and accelerated language development for reading comprehension, it should have a facilitative effect on the acquisition of literacy.

Canada↗

[High-frequency dental surgery near metal reconstructions].

Dental electrosurgery carries the risk of incidental contact between the active electrode and metallic restorations. So far, on-line measurements of basic physical parameters during dental electrosurgery have not been performed under realistic conditions. The aim of our experimental study in pig jaws was to describe the physical phenomena more closely. 86 teeth in the jaws of freshly slaughtered pigs received occlusal amalgam fillings. Using 3 different units electrosurgical procedures were performed adjacent to the fillings. Voltage, current, impedance and power output were registered using a computer-controlled measuring system with high temporal resolution and broad dynamic range. The impedances of the amalgam fillings ranged from 0.5 to 9 k omega, with half of them being in the lower range of 0.5 to 1.5 k omega. During contact to amalgam fillings the dental electrosurgical unit had a high power output. Contact to fillings with low impedance yielded a power output up to 50 W. The other two electrosurgical units were equipped with different power output control systems thus preventing high power output during contact to metallic restorations. In conclusion, dental electrosurgery should be improved by units with dynamic power output control.

Animals↗

On the square root intensity coding at the level of cone photoreceptors.

In psychophysics as well as in sensory physiology, the response amplitude R is often a power function of the stimulus intensity S over a wide range of S (i.e. R = aSk; a = constant). In vision, there is a recent report that such a power relationship ("square root intensity coding" if k = 0.5) may arise as early as at the cone photoreceptor level if the stimulus is a narrow slit of light. A simple model is presented here to account for this finding: strong electrical coupling with several neighboring cones can act to expand the dynamic range of the impaled cone in such a way as to produce a square root coding region for the responses to fine visual objects such as small spots and narrow slits.

Dose-Response Relationship, Radiation↗

Sympathetic burst activity: characteristics and significance.

1. The activity recorded from mammalian sympathetic nerves comes in bursts, which result from large numbers of fibres firing synchronously. 2. Human sympathetic nerve activity behaves similarly to that in animals, although burst rates may be lower. 3. Vasomotor, cardiac and sudomotor nerve fibres all fire in bursts. Whether other sympathetic pathways do so is unknown. 4. Sympathetic activity is intrinsically 'bursty' but not intrinsically regular. 5. Bursting is a population phenomenon, not usually evident in the firing of individual neurons. 6. Bursts in post-ganglionic nerves are driven by synchronously firing preganglionic neurons. 7. The origin of bursts remains controversial. Preganglionic neuron properties are likely to be important in at least shaping bursts. 8. Burst amplitude, which reflects the number of fibres firing together, and burst probability are controlled independently. 9. Baroreceptors affect burst probability over a wide range, but have less effect on mean burst amplitude. How they affect burst timing within the cardiac cycle is discussed. 10. Burst probability is determined 'downstream' of the rostral ventrolateral medulla, implicating either the spinal cord or recurrent brainstem connections in burst generation. 11. Neuroeffector responses are too slow to follow individual bursts. However, bursting will promote spatial facilitation at both ganglionic and effector levels, which may increase the dynamic range of neural control.

Animals↗

Frequency division multiplexed multichannel high-speed fluorescence confocal microscope.

In this article, we report a new type of fluorescence confocal microscope: frequency division multiplexed multichannel fluorescence confocal microscope, in which we encode the spatial location information into the frequency domain. In this microscope, the exciting laser beam is first split into multiple beams and each beam is modulated at a different frequency. These multiple beams are focused at different locations of the target to form multiple focal points, which further generate multiple fluorescent emission spots. The fluorescent emissions from different focal points are also modulated at different frequencies, because the exciting beams are modulated at different frequencies (or difference carrier frequency). Then, all the fluorescent emissions (modulated at different frequencies) are collected together and detected by a highly sensitive, large-dynamic-range photomultiplier tube. By demodulating the detected signal (i.e., via the Fourier transform), we can distinguish the fluorescent light emitted from the different locations by the corresponding carrier frequencies. The major advantage of this unique fluorescence confocal microscope is that it not only has a high sensitivity because of the use of photomultiplier tube but also can get multiple-point data simultaneously, which is crucial to study the dynamic behavior of many biological process. As an initial step, to verify the feasibility of the proposed multichannel confocal microscope, we have developed a two-channel confocal fluorescence microscope and applied it to study the dynamic behavior of the changes of the calcium ion concentration during the single cardiac myocyte contraction. Our preliminary experimental results demonstrated that we could indeed realize multichannel confocal fluorescence microscopy by utilizing the frequency division multiplexed microscope, which could become an effective tool to study the dynamic behavior of many biological processes.

Animals↗

Evaluation of different nucleic acid stains for sensitive double-stranded DNA analysis with capillary electrophoretic separation.

This paper outlines the first use of SYTOX Orange, SYTO 82 and SYTO 25 nucleic acid stains for on-column staining of double-stranded DNA (dsDNA) fragments separated by capillary electrophoresis (CE). Low-viscosity, replaceable poly(vinylpyrrolidone) (PVP) polymer solution was used as the sieving matrix on an uncoated fused-silica capillary. The effects of PVP concentration, electric field strength, and incorporated nucleic acid stain concentrations on separation efficiency were examined for a wide range of DNA fragment sizes. Our study was focused on using nucleic acid stains efficiently excitable at a wavelength of 532 nm. Among the five tested nucleic acid stains, SYTOX Orange stain was shown to have the best sensitivity for dsDNA detection by CE. About a 500-fold lower detection limit was obtained compared to commonly used ethidium bromide and propidium iodide. SYTOX Orange stain also provided a wide linear dynamic range for direct DNA quantitation with on-line CE detection. Use of SYTOX Orange stain can greatly improve the measurement of DNA fragments by CE, which will enable an expanded set of applications in genomics and diagnostics.

Coloring Agents↗

Differences between the tactile sensitivity on the anterior torso of normal individuals and those having suffered complete transection of the spinal cord.

Using the method of limits and a magnitude estimation procedure, the sense of touch was examined at multiple sites on the anterior torso of normal subjects. Their performance was compared with the performance of individuals having experienced a functionally complete spinal cord transection more than 6 months prior to the tests. Near the insentient regions of the spinal cord-injured patients there was a zone wherein the threshold for light touch was elevated and variable. Within this same transition zone, estimates of the magnitude of a brushing stimulus increased as a linear function of distance from the border for approximately 12 cm away from insentient skin. Throughout the rest of the thorax, spinal cord-injured patients displayed touch thresholds 67% higher than normals and, at the same test sites, spinal cord-injured patients offered estimates of the intensity of the brushing stimulus that averaged 62% higher than normal subjects. The greater intensity of the sensations experienced by spinal cord-injured patients with even very weak stimuli and the smaller range within which they were able to scale stimulus intensity, produced a situation wherein the patients made frequent errors of judgement even on skin regions far from the body parts affected by the lesion. These observations support the hypothesis that spinal cord lesions interrupt tonic modulatory mechanisms having global influences on the sense of touch. This loss produces an elevation of the touch threshold and a reduction of the normal dynamic range of tactile sensory perception for all skin surfaces on the anterior torso.

Abdomen↗

Fluorescence sensor using a molecularly imprinted polymer as a recognition receptor for the detection of aluminium ions in aqueous media.

This paper describes the investigation of a molecularly imprinted polymer (MIP) as a sensing receptor for Al(3+) ion detection by using an optical approach. Al(3+) ion was adopted as the template molecule and 8-hydroxyquinoline sulfonic acid ligand as the fluorescence tag. The polymer was synthesised using acrylamide as monomer, 2-hydroxyethyl methacrylate as co-monomer and ethylene glycol dimethracylate as cross-linker. The free radical polymerisation was performed in methanol and initiated by 2,2'-azobisisobutyronitrile at 70 degrees C. The imprinted polymer was fluorometrically characterised using a fibre optic attachment in a self-designed flow-cell. NaF was used to leach the Al(3+) ion from the MIP. The optimum pH for the rebinding of Al(3+) ion with the leached polymer was found to be pH 5 and the fluorescence response was found to be stable within the buffer strength range of 0.05-0.10 M. The fluorescence intensity during Al(3+) ion rebinding was inversely dependent on temperature, and a low interference response (<3%) toward metal ions except for Cu(2+) and Zn(2+) ions was observed. The polymer rebinding repeatability study conducted over 9 cycles with Al(3+) ion (0.8 x 10(-4) M) was found to give an RSD value of 2.82% with a standard deviation of 0.53. The dynamic range of the system was found to be linear up to 1.0 x 10(-4) M Al(3+) ion with a limit of detection of 3.62 microM.

Aluminum↗

A rapid fluorometric enzyme immunoassay for the determination of neonatal TSH from blood spots.

We describe a novel method for the detection of thyrotropin from dried blood spots using a horseradish peroxidase-labelled sandwich enzyme immunoassay with fluorometric detection. The detection limit of the present assay is 1.25 mIU/l with within-run and between-run imprecision being in the range 5.2 to 11.4%. The results of the assay correlate well with two commercial methods: an enzyme immunoassay (r = 0.93) and a time-resolved fluorescence assay (r = 0.90). The blood spot values also show a good correlation (r = 0.93) with respective values obtained from plasma using a commercial immunoradiometric method. The assay may also be performed colorimetrically with sensitivity similar to the fluorometric assay. However, the latter provides a wider dynamic range with an upper limit of 400 mIU/l while the colorimetric method reaches a plateau at 25 mIU/l. Due to its simplicity and rapid performance (3 h), the fluorometric assay is suitable for the routine screening of congenital hypothyroidism.

Antibodies↗

The use of proteomics for the assessment of clinical samples in research.

Proteomics, the analysis of expressed proteins, has been an important developing area of research for the past two decades [Anderson, NG, Anderson, NL. Twenty years of two-dimensional electrophoresis: past, present and future. Electrophoresis 1996;17:443-453]. Advances in technology have led to a rapid increase in applications to a wide range of samples; from initial experiments using cell lines, more complex tissues and biological fluids are now being assessed to establish changes in protein expression. A primary aim of clinical proteomics is the identification of biomarkers for diagnosis and therapeutic intervention of disease, by comparing the proteomic profiles of control and disease, and differing physiological states. This expansion into clinical samples has not been without difficulties owing to the complexity and dynamic range in plasma and human tissues including tissue biopsies. The most widely used techniques for analysis of clinical samples are surface-enhanced laser desorption/ionisation mass spectrometry (SELDI-MS) and 2-dimensional gel electrophoresis (2-DE) coupled to matrix-assisted laser desorption ionisation [Person, MD, Monks, TJ, Lau, SS. An integrated approach to identifying chemically induced posttranslational modifications using comparative MALDI-MS and targeted HPLC-ESI-MS/MS. Chem. Res. Toxicol. 2003;16:598-608]-mass spectroscopy (MALDI-MS). This review aims to summarise the findings of studies that have used proteomic research methods to analyse samples from clinical studies and to assess the impact that proteomic techniques have had in assessing clinical samples.

Biomarkers↗

A dissociative change in the efficacy of supraspinal versus spinal morphine in the neuropathic rat.

The efficacy of spinally versus supraspinally administered morphine was studied in rats with a spinal nerve ligation-induced neuropathy. Behavioural assessment indicated that the effect of intrathecally administered morphine on pain-related responses was attenuated when compared with unoperated controls. The decreased efficacy of spinal morphine was associated with neuropathic symptoms, since sham ligation or nerve ligation without accompanying tactile allodynia did not lead to spinal inefficacy of morphine. In contrast, the pain attenuating effect of morphine in the periaqueductal gray (PAG) was enhanced in neuropathic animals. The effect of systemically administered morphine on pain-related behavior of neuropathic rats was in the same range as in controls or decreased, depending on the test. Coadministration of lidocaine or MK-801, a N-methyl-D-aspartate (NMDA) receptor antagonist, into the rostroventromedial medulla enhanced the tactile antiallodynic but not the thermal antinociceptive effect of intrathecally administered morphine in neuropathic animals. Supraspinal administration of MK-801 or lidocaine did not influence efficacy of spinal morphine in sham-operated animals. Electrophysiological recordings of nociceptive wide-dynamic range (WDR) neurons in the deep spinal dorsal horn of pentobarbitone-anesthetized animals corresponded to a large extent with behavioral results. The inhibitory effect of spinally and systemically administered morphine on WDR neuron responses was attenuated whereas that induced by morphine in the PAG was enhanced in neuropathic animals. The results indicate that in spinal nerve ligation-induced neuropathy the efficacy of spinal morphine is decreased whereas that of supraspinal morphine is increased. Descending influence from brainstem-spinal pathways, involving NMDA receptors in the rostroventromedial medulla, may contribute to the selective reduction in tactile antiallodynic efficacy of spinal morphine.

Analgesics, Opioid↗

Development of immunosensors for the analysis of 1-naphthol in organic media.

Immunosensor systems have been developed for the rapid determination of 1-naphthol. In this work, the comparison of performance of immunosensors working in aqueous and organic media was done. Direct, indirect and capture formats were studied. Immunoreagents were immobilized on controlled pore glass (CPG), hidroxysuccinimide agarose gel or on azlactone Protein A/G supports. The Protein A/G-based sensor showed the best performance. In aqueous media, a LOD of 16.2 microg l(-1) and a DR of 33.7-586.6 microg l(-1) were achieved employing Tween 20 at a concentration ranging from 0.01 to 0.05% v/v. Maximum sensitivity was reached with 0.025% of surfactant. Binary mixtures of methanol or acetonitrile with aqueous buffer and ternary mixtures of methanol/isopropanol or ethyl acetate/methanol with the same buffer were studied as organic media. The mixture 50% MeOH-50% 20 mM sodium phosphate, pH 8, with 0.05% (v/v) Tween 20 resulted to be the best. A detection limit of 12.0 microg l(-1) and a dynamic range of 53.6-17,756.0 microg l(-1) were reached. The recycling of Protein A/G-based sensor working in this media was about 300 assays. Preconcentration factors around 250 were achieved using methanol as extracting solvent. It has been demonstrated that the technique can be successful in carrying out the analysis of low solubility in water analytes, such as 1-naphthol. The sensors developed can use higher concentrations of organic solvent (up to 50% methanol) compared to ELISA. On the other hand, the advantage of preconcentration can also be taken for the use of the same procedure as recommended for standard sample treatments.

Biosensing Techniques↗

Constraining inverse-curvature gravity with supernovae.

We show that models of generalized modified gravity, with inverse powers of the curvature, can explain the current accelerated expansion of the Universe without resorting to dark energy and without conflicting with solar system experiments. We have solved the Friedmann equations for the full dynamical range of the evolution of the Universe and performed a detailed analysis of supernovae data in the context of such models that results in an excellent fit. If we further include constraints on the current expansion of the Universe and on its age, we obtain that the matter content of the Universe is 0.07<or=omegam<or=0.21 (95% C.L.). Hence the inverse-curvature gravity models considered cannot explain the dynamics of the Universe just with a baryonic matter component.

Journal Article↗

Dynamic image-adaptive x-ray beam limiters.

The imaging capability of the dynamic spatial reconstructor (DSR), a fast (60/second), synchronous, multislice (up to 240) computed x-ray tomography scanner, has been limited by the suboptimal match of the dynamic range of the x-ray projection images with that of the image-intensified charge-coupled device (CCD) video sensors. Effective blockage of the "raw" beam component of the projection images by fixed shutters is generally impossible because of the rapid change in the multiple angles of view that result from the 15 RPM rotation of the scanner assembly about the object of study. For this reason a programmable, dynamic, image-adaptive x-ray beam shutter system has been developed to reduce the "raw" beam component of the x-ray image without degrading the image in the region of interest. This system is designed to dynamically position 28 shutters (two for each of 14 x-ray sources) continuously and independently, as a function of the angle of view, so as to selectively obscure any unattenuated "raw" x-ray beam passing alongside the object of study at all angles of view for each x-ray source.

Equipment Design↗

Tailored UPRE2 variants for dynamic gene regulation in yeast.

Genetic elements are foundational in synthetic biology serving as vital building blocks. They enable programming host cells for efficient production of valuable chemicals and recombinant proteins. The unfolded protein response (UPR) is a stress pathway in which the transcription factor Hac1 interacts with the upstream unfolded protein response element (UPRE) of the promoter to restore endoplasmic reticulum (ER) homeostasis. Here, we created a UPRE2 mutant (UPRE2m) library. Several rounds of screening identified many elements with enhanced responsiveness and a wider dynamic range. The most active element m84 displayed a response activity 3.72 times higher than the native UPRE2. These potent elements are versatile and compatible with various promoters. Overexpression of HAC1 enhanced stress signal transduction, expanding the signal output range of UPRE2m. Through molecular modeling and site-directed mutagenesis, we pinpointed the DNA-binding residue Lys60 in Hac1(Hac1-K60). We also confirmed that UPRE2m exhibited a higher binding affinity to Hac1. This shed light on the mechanism underlying the Hac1-UPRE2m interaction. Importantly, applying UPRE2m for target gene regulation effectively increased both recombinant protein production and natural product synthesis. These genetic elements provide valuable tools for dynamically regulating gene expression in yeast cell factories.

Saccharomyces cerevisiae↗

Multicenter comparison of first- and second-generation IMx tacrolimus microparticle enzyme immunoassays in liver and kidney transplantation.

Tacrolimus is a potent immunosuppressive drug successfully used for baseline and rescue immunosuppression in patients after liver and kidney transplantation. Data from several clinical trials have demonstrated the efficacy of tacrolimus in the prevention of allograft rejection, even at lower concentrations in the therapeutic range (5-15 microg/L). In fact, some patients with tacrolimus levels at less than 5 microg/L have excellent hepatic or kidney function. The limit of detection of the IMx Tacrolimus I assay (TAC I; Abbott Laboratories, IL) is only 5 microg/L and that of the lower tacrolimus calibrator is 10 microg/L. The second-generation assay uses the same monoclonal antibody and the same IMx technology but offers improved sensitivity, with a dynamic range from 0 microg/L to 30 microg/L (lower calibrator, 3 microg/L). The aim of this multicenter study was to evaluate the new IMx Tacrolimus II assay (TAC II) by assessing its precision, sensitivity, performance, and correlation degree relative to the IMx TAC I assay. The study was performed at three centers in Spain. The within-run coefficients of variation (CVs) obtained for the new assay, using each of the trilevel controls in replicates of 20 during 3 consecutive days, were 8.06%, 4.38% and 5.09% at 5 microg/L, 11 microg/L, and 22 microg/L, respectively. The corresponding between-run CVs obtained measuring each of the three controls in duplicate on 10 consecutive days were 9.54%, 6.38% and 5.75%. The limit of detection, with 97.5% confidence, was 1.22 microg/L. TAC II results (Y) were compared with those from the original TAC I assay (X) analyzing 293 whole blood samples from liver (n=145) and kidney (n=148) transplant recipients. The correlation study with patient samples (using the Passing-Bablock method) was y=1.056, x + 0.017, r=0.927. No statistically significant differences were observed between assays (TAC I versus TAC II) in the mean values obtained for total patients (9.89+/-5.42 microg/L versus 10.49+/-5.63 microg/L), liver patients (9.16+/-4.79 microg/L versus 10.00+/-5.20 microg/L), and kidney patients (10.62+/-5.87 micro g/L versus 10.98+/-5.99 microg/L). The new IMx TAC II assay demonstrated the same precision and accuracy that characterized the original assay but showed improved sensitivity to the demands of tacrolimus monitoring in the lower therapeutic range of drug concentrations.

Antibodies, Monoclonal↗

Performance with the 20 + 2L lateral wall cochlear implant.

OBJECTIVE: The purpose of this study was to investigate the operating characteristics of the Nucleus 20 + 2L lateral wall cochlear implant including speech recognition results. STUDY DESIGN: This was a prospective randomized study involving five different modes of stimulation. SETTING: This study was carried out in an academic, tertiary referral center. PATIENTS: The patients included in this study were adult cochlear implant candidates ages 44-74 years. Length of deafness ranged from 1 to 58 years with a variety of etiologies. INTERVENTIONS: All patients were implanted with a 20 + 2L implant, which includes an intrascalar electrode array and an apically placed extracochlear, titanium encased ball electrode in contact with the endosteum of the apical turn. All patients underwent psychophysical and speech recognition testing in five different modes of electrode configuration. MAIN OUTCOME MEASURE(S): The main outcome measures included thresholds, comfort levels, dynamic ranges, and speech recognition results obtained in five electrode configuration modes. RESULTS: Thresholds were significantly lower (repeated measures ANOVA) in both monopolar conditions when compared to bipolar mode of stimulation. A binomial statistical analysis indicated that in five of nine patients activated in all five modes of stimulation, the monopolar modes of stimulation resulted in improved speech recognition scores. CONCLUSIONS: The results of the study demonstrate the feasibility of the use of an apical lateral cochlear wall electrode in conjunction with an intrascalar electrode array. It further demonstrated the superiority of monopolar stimulation in selected patients.

Adult↗

Monitoring spatio-temporal regulation of Ras and Rho GTPase with GFP-based FRET probes.

GFP-based fluorescence resonance energy transfer (FRET) probes that visualize local activity-changes of Ras and Rho GTPases in living cells are now available for examining the spatio-temporal regulation of these proteins. This article describes principles and strategies to develop intramolecular FRET probes for Ras- and Rho-family GTPases. The procedure for characterizing candidate probes, and image acquisition and processing are also explained. An optimal FRET probe should have (i) a wide dynamic range (which means a high sensitivity), (ii) a high fluorescence intensity, (iii) target specificity, and (iv) a minimal perturbation to endogenous signaling cascades. Although an improvement of FRET probes should be executed in a trial-and-error manner, practical tips for optimization are provided here. In addition, we illustrate some applications of FRET probes for neuronal cells, which are composed of diverse subcellular compartments with different functions; thus, tools to decipher the dynamics of GTPase activity in each compartment have long been desired.

Animals↗