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An exploratory prospective observational study of environmental factors exacerbating atopic eczema in children.

BACKGROUND: Possible exacerbating factors are a major concern of parents of children with atopic eczema (AE). However, there is minimal evidence for their direct role in leading to disease flares. OBJECTIVES: To assess the association between 'trigger factors' and disease flares in AE. METHODS: Twenty-five children with AE were recruited. Participants completed diaries, recording severity and exposure to potential exacerbating factors (18 variables) over 28 days. Severity was assessed at baseline and study completion. The relationship between severity and exposures was assessed. RESULTS: At episode level, on the day of exposure (lag 0), hot weather correlated to increased scratch scores (P=0.043). At a lag of 2 days after exposure, damp weather was associated with raised scratch scores (P=0.027). At lag 3 days, elevated scratch scores were associated with sweating and stress (P=0.029 and 0.019, respectively). Outside damp was associated with elevated scores (P=0.001) at lag 4. Multivariate analysis of all significant variables showed that only damp at lag 4 was significantly associated with flares (P=0.039). CONCLUSIONS: This study suggests association between stress, damp and heat and disease flares. These findings need to be studied over a longer period, using objective exposure measures.

Adolescent↗

Error-prone and inefficient replication across 8-hydroxyguanine (8-oxoguanine) in human and mouse ras gene fragments by DNA polymerase kappa.

Using fragments of human c-Ha-ras and mouse Ha-ras1 genes containing 8-hydroxyguanine (8-OH-G) in hypermutagenic codon 12, we analyzed the kinetics of DNA synthesis catalyzed by human Polkappa. This translesion DNA polymerase, belonging to the Y-family, was found to be moderately inhibited by the presence of 8-OH-G on either mouse or human templates. From our previous results, inhibition of various polymerases by 8-OH-G increases in the following order: Poleta < Polkappa < Polbeta < Polalpha, showing that major replicative and repair polymerases are more sensitive to this lesion than enzymes belonging to the Y-family. In the direct mutagenesis experiments, Polkappa was found to be more mutagenic than Poleta studied previously: it inserted dAMP more efficiently than dCMP opposite 8-OH-G. Polkappa was also able to cause indirect mispair ('action-at-a-distance' mutagenesis), this effect being more distinct on mouse templates. Two adjacent 8-OH-G residues in codon 12 inhibited Polkappa moderately and induced misincorporation of dAMP. However, this effect was not comparable to the strong relaxation of the enzyme specificity, observed previously in the case of Poleta. Polkappa catalyzed incorporation (and misincorporation of dAMP) much more efficiently on mouse templates, human DNA fragments being distinctly worse substrates. Interestingly, in direct mutagenesis systems, the preference for dAMP over dCMP was nearly the same on mouse and human templates.

Animals↗

Attention deficits and clumsiness in Swedish 7-year-old children.

A population study of 409 seven-year-old children in a middle-sized Swedish town was performed. All children were examined by the same doctor and evaluated by means of parent interview, motor examinations, and teacher reports on behaviour in the classroom. Follow-up was carried out 8 months later. The rate of severe problems in the fields of attention deficit-hyperactivity disorder (ADHD), developmental coordination disorder (DCD), and deficits in attention, motor control, and perception (DAMP) (the combination of ADHD and DCD) was 6.1%, with boys being affected more frequently than girls. There was considerable overlap between ADHD and DCD, with about half of each diagnostic group also meeting criteria for the other diagnosis. Attention deficits at diagnosis strongly predicted attention deficits at follow-up. If parents had noted attention deficits in the home setting, then teachers almost always independently agreed that there were similar problems in the classroom. However, the reverse did not always apply. Clumsiness also showed striking stability over time. The diagnosis of DAMP, particularly severe DAMP, had a stronger association with classroom dysfunction and with high Conners scores than did diagnoses of ADHD or DCD. It is concluded that DAMP may be a clinically valid diagnostic construct.

Attention Deficit Disorder with Hyperactivity↗

Muscarinic receptor subtypes in the submandibular gland and the urinary bladder of the rabbit: in vivo and in vitro functional comparisons of receptor antagonists.

1. In pentobarbitone-anaesthetized rabbits, the inhibitory effects of muscarinic receptor antagonists with different selectivity profiles were examined on carbachol-evoked submandibular secretion and urinary bladder contractions, and on parasympathetically nerve-evoked secretion. On isolated submandibular gland fragments, the inhibitory effects of the antagonists were studied on carbachol-evoked release of potassium and on the overflow of tritium in response to electrical field stimulation. 2. In vivo, 4-DAMP equipotently inhibited simultaneously carbachol-evoked submandibular secretory and contractile responses of the urinary bladder, while pirenzepine was found to be four times as potent in inhibiting the secretory response compared with the contractile response. 3. The inhibition of carbachol-evoked salivation caused by atropine, 4-DAMP and pirenzepine was as great as their inhibition of parasympathetic nerve-evoked salivation. Methoctramine exerted less inhibitory effect on nerve-evoked salivation than on carbachol-evoked, thus seemingly causing greater presynaptic inhibition. 4. In vitro, pirenzepine was only 30 times less potent in inhibiting carbachol-evoked potassium release than 4-DAMP (pA2, 9.58 vs 8.10). Whereas atropine, 4-DAMP and pirenzepine abolished the overflow of tritium from isolated glands in response to electrical field stimulation, methoctramine increased it. 5. It is concluded that the muscarinic secretory response in the rabbit submandibular gland is exerted via both muscarinic M1 and M3 receptors, while the contractile response of the urinary bladder to muscarinic agonists is exerted via muscarinic M3 receptors. The release of acetylcholine from nerve terminals in the gland can be inhibited via M2 autoreceptors in rabbits.

Animals↗

Effects of chain-length and unsaturation on affinity and selectivity at muscarinic receptors.

1. Lengthening the chain in diphenylacetylcholine decreases affinity for muscarinic cholinoceptors in guinea-pig ileum. Diphenylacetoxypropyldimethylamine and its quaternary trimethylammonium salt are roughly equiactive: the dimethylamine and the piperidine have some selectivity for ileum compared with atria, but are not as active nor as selective as 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methobromide (MeBr). With the weaker diphenylacetoxybutyl compounds the base is more active than the quaternary salt. 2. The diphenylacetoxybutyl-, cis-butenyl and trans-butenyl compounds have similar affinities. The quaternary salts are less active than the tertiary bases, but they are less selective than the butynyl analogues studied in earlier work. 3. 1,1-Diphenyl-1-hydroxy-2,4-hexadiynyl dimethylamine and its trimethylammonium salt are inactive in concentrations below 100 microM, as are the (+)-camphor-sulphonyl ester of 4-hydroxy-N-methyl piperidine and its methiodide. The (+/-)-phenylcyclopentylacetyl ester of 4-hydroxy-N-methylpiperidine methobromide is more active than its cyclohexyl analogue and than 4-DAMP MeBr but it is less selective than 4-DAMP MeBr. 4. The high selectivity of p-fluoro-hexahydrosila-diphenidol is confirmed but this compound has relatively low affinity (for ileum log K = 7.8). 5. The results indicate steric constraints to binding at muscarinic receptors which could be used to check molecular modelling of the receptor based on its known amino acid sequence. The group binding the charged nitrogen is probably at the mouth of a cavity which can accommodate two large rings (as in 4-DAMP MeBr) but with a depth less than about 7 A so that the rod-like hexadiynes cannot fit. Differences between types of receptor may only involve small changes in geometry secondary to differences in amino acids not directly involved in binding and the production of selectivity depends upon finding substituents which interfere with binding more at one type of receptor than at another.

Animals↗

Functional characterization of muscarinic receptors in murine airways.

1. The effects of muscarinic receptor antagonists considered to be selective for M1 receptors (pirenzepine; PZ), M2 receptors (AFDX-116), and for M3 receptors (4-diphenyl acetoxy N-methyl-piperidine (4-DAMP)) were used to investigate the existence of muscarinic receptors subtypes in murine airways. Atropine was used as a nonselective antagonist. The effects of these antagonists were studied upon tracheal contractions induced either by EFS (electric field stimulation) or by application of an exogenous cholinoceptor agonist (arecoline). 2. The muscarinic receptor antagonists tested inhibited arecoline-induced tracheal contractions with the following rank order of potency: 4-DAMP = atropine > pirenzepine = AFDX-116. The rank order of potency of the muscarinic antagonists used in inhibiting EFS-induced tracheal contractions was: 4-DAMP = atropine > PZ > AFDX-116. The pA2 values for these antagonists were similar when compared to the pA2 values determined in guinea-pig and bovine airway smooth muscle. 3. In addition to in vitro studies, the effects of inhalation of the different muscarinic antagonists on lung function parameters in vivo were investigated. Inhalation of 4-DAMP induced a decrease in airway resistance and an increase in lung compliance. In contrast, inhalation of AFDX-116 induced an increase in airway resistance and almost no change in lung compliance. Apart from some minor effects of atropine on airway resistance, atropine, PZ, and pilocarpine failed to induce changes in lung mechanics as determined by in vivo lung function measurements. 4. The results provide evidence for the existence of M3 receptors on murine tracheae that are involved in the contraction of tracheal smooth muscle. This is in agreement with other animal species such as the guinea-pig and bovine. In vivo experiments also demonstrated that in the mouse, M3 receptors play an important role in bronchial smooth muscle contraction and thus in bronchoconstriction. Interestingly we have also demonstrated that M2 receptors can play a role in bronchodilatation. Inhalation of an M2 receptor antagonist induced an increase in airway resistance whereas inhalation of an M3 receptor antagonist induced a decrease in airway resistance. It is therefore likely that an M3/M2 receptor balance plays an important role in the regulation of airway function.

Administration, Inhalation↗

Muscarinic excitatory and inhibitory mechanisms involved in afferent fibre-evoked depolarization of motoneurones in the neonatal rat spinal cord.

1. The involvement of acetylcholine and muscarinic receptors in spinal synaptic responses evoked by electrical and noxious sensory stimuli was investigated in the neonatal rat spinal cord in vitro. 2. Potentials were recorded extracellularly from a ventral root (L3-L5) of the isolated spinal cord, spinal cord-cutaneous nerve, and spinal cord-skin preparations of 1- to 4-day-old rats. Spinal reflexes were elicited by electrical stimulation of the ipsilateral dorsal root or the cutaneous saphenous nerve, or by noxious skin stimulation. 3. Single shock stimulation of supramaximum intensity of a dorsal root induced a mono-synaptic reflex in the corresponding ventral root. Bath-application of the muscarinic agonists, muscarine (0.3-30 microM) and (+)-cis-dioxolane (0.1-100 microM), produced an inhibition of the mono-synaptic reflex and a depolarization of motoneurones. Other muscarinic agonists, arecoline (10 nM-10 microM) and oxotremorine (10 nM-1 microM), inhibited the mono-synaptic reflex with little or no depolarization of motoneurones. Repetitive stimulation of the saphenous nerve at C-fibre strength induced a slow depolarizing response lasting about 30 s of the L3 ventral root. This slow ventral root potential (VRP) was also inhibited by arecoline (10 nM-10 microM) and oxotremorine (10 nM-1 microM). 4. In the spinal cord-saphenous nerve-skin preparation, a slow VRP was evoked by application of capsaicin (0.5 microM), bradykinin (3 microM), or noxious heat (47 degrees C) to skin. This slow VRP was depressed by the muscarinic agonists, arecoline (3 microM) and oxotremorine (1 microM). 5. Of the (+)-cis-dioxolane-induced inhibition of mono-synaptic reflex and motoneurone depolarization, the M2 antagonists, AF-DX 116 (0.1-1 microM) and methoctramine (100-300 nM), preferentially blocked the former response, whereas the M3 antagonists, 4-DAMP (3-10 nM) and p-F-HHSiD (0.3-3 microM), preferentially blocked the latter response. AF-DX 116 (0.1-1 microM) and methoctramine (100-300 nM) also effectively antagonized the arecoline- and oxotremorine-induced inhibition of the slow VRP. The pA2 values of AF-DX 116 and methoctramine against the arecoline-induced inhibition of the mono-synaptic reflex were both 6.79, and that of 4-DAMP against the (+)-cis-dioxolane-induced motoneurone depolarization was 8.16. 6. In the spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow VRP was augmented by the anticholinesterase, edrophonium (5 microM). AF-DX 116 (1 microM) and methoctramine (100 nM) also potentiated the slow VRP, whereas 4-DAMP (10 nM) depressed the response. 4-DAMP(5-10 nM) depressed the capsaicin-induced slow VRP in the spinal cord-skin preparation.7. Oxotremorine (0.3 microM) and arecoline (1 AM) markedly depressed the depolarization of motoneurones evoked by application of capsaicin (3 9AM) to the spinal cord, whereas they depressed only slightly the depolarization induced by substance P (10 nM).8. The present study suggests that both excitatory (via M3-type receptors) and inhibitory (via M2-type receptors) muscarinic mechanisms are involved in afferent fibre-evoked nociceptive transmissions in the neonatal rat spinal cord.

Animals↗

Mediation by M3-muscarinic receptors of both endothelium-dependent contraction and relaxation to acetylcholine in the aorta of the spontaneously hypertensive rat.

1. Experiments were designed to characterize the subtype(s) of endothelial muscarinic receptor that mediate(s) endothelium-dependent relaxation and contraction in the aorta of spontaneously hypertensive rats (SHR). 2. Rings of SHR aorta with endothelium were suspended in organ baths for the measurement of isometric force. Ecothiopate (an inhibitor of acetylcholinesterase) was present throughout the experiments. Endothelium-dependent contraction to acetylcholine was studied in quiescent aortic rings in the presence of NG-nitro-L-arginine (to prevent the formation of nitric oxide). Endothelium-dependent relaxation to acetylcholine was obtained during contraction to phenylephrine and in the presence of indomethacin (to inhibit cyclo-oxygenase activity). Responses to acetylcholine were assessed against the non-preferential muscarinic receptor antagonist, atropine, and the preferential antagonists pirenzepine (M1), methoctramine (M2) and 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP; M3). 3. The potency of acetylcholine in inducing endothelium-dependent contraction was 6.54 +/- 0.07 (EC50). Atropine, pirenzepine, methoctramine and 4-DAMP displayed competitive antagonism towards the endothelium-dependent contraction to acetylcholine. The pA2 values for these muscarinic receptor antagonists were estimated from Arunlakshana-Schild plots to be (-log M) 9.48 +/- 0.07, 6.74 +/- 0.22, 6.30 +/- 0.20 and 9.39 +/- 0.22 respectively. The potency of acetylcholine in inducing endothelium-dependent relaxation was 7.82 +/- 0.09 (IC50). Atropine, pirenzepine and 4-DAMP displayed competitive antagonism towards the endothelium-dependent relaxation to acetylcholine but methoctramine had no effect. The pA2 values for atropine and 4-DAMP for the relaxation to acetylcholine were estimated from Arunlakshana-Schild plots to be (-log M) 9.15 +/- 0.23 and 9.63 +/- 0.28, respectively. These results suggest that the muscarinic M3 receptor subtype mediates both endothelium-dependent relaxation and contraction to acetylcholine in SHR aorta.

Acetylcholine↗

Day care center characteristics and children's respiratory health.

UNLABELLED: Day care centers provide an important exposure arena with potential harmful health effects for children. This study has linked health effect data from a survey among 942 3-5-year-old Oslo children with information on day care center characteristics collected during inspection of the 175 day care centers these children attended. The aim of the study was to estimate associations between dampness problems and other building characteristics and several respiratory health outcomes. Dampness problems (sign of molds, water leakage, damage to floor/wall) were observed in 51% of the day care centers. In multiple logistic regression analyses none of the studied symptoms and diseases (nightly cough, blocked or runny nose without common cold, wheeze, heavy breathing or chest tightness, the common cold, tonsillitis/pharyngitis, otitis media, bronchitis, pneumonia, asthma, and allergic rhinitis) were systematically associated with dampness problems or type of ventilation in day care centers. None of the studied indicators of day care center exposures were found to have a clear effect on day care children's respiratory health. Even so this study does not rule out negative health effects of day care center exposures. The study demonstrates that population-based studies of these relations are demanding with regard to assessment of exposure and health outcomes. PRACTICAL IMPLICATIONS: Simple and easy-to-register indicators of exposures like dampness problems and type of ventilation assessed in 175 day care centers were not related to respiratory health among 3-5-year-old Norwegian children attending the day care centers. The study does not rule out negative health effects of day care center exposures, but demonstrates methodological challenges needed to be addressed in studies of health effects of the day care environment.

Air Pollution, Indoor↗

Muscarinic receptor agonist-antagonist interaction in the rat rectum: are there ways of activating the same receptors?

The interaction between the muscarinic receptor agonists, carbachol, acetylcholine (ACh) and methacholine, and antagonists, atropine, gallamine, 4-DAMP and pirenzepine, was studied on the rat isolated rectum preparation. ACh (1.93 X 10(-8)-1.95 X 10(-6) M), methacholine (8.7 X 10(-8)-1.1 X 10(-6) M) and carbachol (1.1 X 10(-7)-3.5 X 10(-6) M) induced contractions that were reversibly antagonized by atropine (1.9 X 10(-9)-4.8 X 10(-8) M), 4-DAMP (1.5 X 10(-8)-2.86 X 10(-7) M) gallamine (1.12 X 10(-6)-1.12 X 10(-4) M) and pirenzepine (2.8 X 10(-7)-7.0 X 10(-6) M). The pA2 values were atropine: 8.99 +/- 0.28, 9.29 +/- 0.14 and 8.86 +/- 0.05; 4-DAMP: 8.39 +/- 0.10, 8.66 +/- 0.15 and 8.26 +/- 0.30, gallamine: 5.85 +/- 0.23, 5.73 +/- 0.25 and 5.96 +/- 0.10 and pirenzepine: 6.85 +/- 0.44, 7.17 +/- 0.13 and 7.21 +/- 0.03 against ACh, methacholine and carbachol, respectively. The experimental dose-ratio (atropine + gallamine) was greater than the expected dose-ratio (as predicted by the Paton & Rang rule) for ACh and methacholine while the experimental dose-ratio closely approximates the expected dose-ratio for carbachol. It is suggested that atropine, 4-DAMP pirenzepine and gallamine act on the same receptors but gallamine allosterically altered the binding of the agonists and antagonists to varying extents.

Acetylcholine↗

The role of cholinergic and peptidergic pathways in the regulation of pancreatic exocrine function during postnatal development in pigs.

The aim of this study was to investigate the role of the parasympathetic (cholinergic and peptidergic) nervous system in the regulation of exocrine pancreas function in piglets during their early postnatal development. The cholinergic and peptidergic regulatory pathways of exocrine pancreatic function were tested by the specific muscarinic receptor blocker 4-diphenylacetoxy-N-methylpiperidine-methiodide (4-DAMP) and bombesin, respectively. At the age of 2 weeks, piglets were surgically fitted with a chronic pancreatic duct catheter, a duodenal re-entrant cannula and a jugular vein catheter. The experiments comprised a pre-weaning period, and a post-weaning period that commenced at the beginning of the 5th week of age. Intravenous infusion of 4-DAMP (100 pmol x kg(-1) x h(-1)) reduced the outflow of pancreatic juice, the output of total protein and the activity of trypsin, chymotrypsin, carboxyl ester hydrolase and amylase during preprandial and postprandial pancreatic secretion, in both the pre- and post-weaning periods. However, the inhibitory effect of 4-DAMP during postprandial secretion was significantly greater (P < 0.05) in suckling piglets. The infusion of bombesin (10, 100 and 1000 pmol x kg(-1) x h(-1)) stimulated exocrine pancreatic secretion in a dose-dependent manner during both the pre- and post-weaning periods. However, the stimulatory effect of 1000 pmol x kg(-1) x h(-1) bombesin on total protein output and the activities of trypsin, chymotrypsin and amylase were significantly higher (P < 0.05) in suckling piglets. In summary, our study showed that cholinergic and peptidergic mechanisms are involved in the regulation of exocrine pancreas function in piglets in both the pre- and post-weaning stages. 4-DAMP had a greater inhibitory effect on exocrine pancreatic secretion in piglets during the pre-weaning period. Thus, these observations suggest that the parasympathetic nervous system plays a dominant role in the functioning of the exocrine pancreas at this time. The action of bombesin suggests that it is a potent secretagogue for the exocrine pancreas in pigs during their postnatal development.

Amylases↗

On muscarinic control of neurogenic mucus secretion in ferret trachea.

1. Muscarinic receptor subtypes mediating neurogenic mucus secretion in ferret trachea were characterized in vitro and in vivo using 35SO4 as a label for secreted mucus, and the muscarinic receptor antagonists telenzepine for the M1 receptor subtype, methoctramine for the M2 subtype and 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) for the M3 receptor. We also performed receptor binding and mapping studies. 2. Each muscarinic antagonist displaced [N-methyl-3H]scopolamine binding with high-affinity binding constant (KH) values of 1.9, 2.7 and 5.0 nM for telenzepine, methoctramine and 4-DAMP, respectively. Muscarinic M1 and M3 receptors localized to submucosal glands, whereas M2 receptors did not. 3. In vitro, electrical stimulation (50 V, 10 Hz, 0.5 ms for 5 min) increased 35SO4 output by 160%. Telenzepine did not inhibit the neurogenic secretory response at concentrations two-or twentyfold its KH value, nor did it inhibit secretion induced by acetylcholine (ACh). 4-DAMP inhibited neurogenic secretion by 80 and 95%, respectively, at concentrations two-and twentyfold its KH value, and also inhibited ACh-induced secretion. Methoctramine potentiated neurogenic secretion induced at 2.5 Hz (50 V, 0.5 ms for 5 min) in a dose-related (5.4-100 nM) manner with increases of 33-451% above electrically stimulated values. Methoctramine did not potentiate secretion induced at 10 Hz and did not have any effect on ACh-induced secretion. 4. In vivo, vagal stimulation (10 V, 10 Hz, 2 ms for 8 min) increased output of 35SO4 by approximately 120%. Telenzepine had no significant effect on neurogenic secretion. Methoctramine approximately doubled the stimulated response, whereas 4-DAMP abolished the stimulated secretory response. 5. We conclude that in ferret trachea, cholinergic nerve stimulation increases mucus secretion via muscarinic M3 receptors on the submucosal glands. The magnitude of the secretory response is regulated by neuronal M2 muscarinic receptors. The muscarinic M1 receptors localized to the submucosal glands do not appear to be involved with mucus secretion.

Animals↗

Modeling the dynamic characteristics of pneumatic muscle.

A pneumatic muscle (PM) system was studied to determine whether a three-element model could describe its dynamics. As far as the authors are aware, this model has not been used to describe the dynamics of PM. A new phenomenological model consists of a contractile (force-generating) element, spring element, and damping element in parallel. The PM system was investigated using an apparatus that allowed precise and accurate actuation pressure (P) control by a linear servo-valve. Length change of the PM was measured by a linear potentiometer. Spring and damping element functions of P were determined by a static perturbation method at several constant P values. These results indicate that at constant P, PM behaves as a spring and damper in parallel. The contractile element function of P was determined by the response to a step input in P, using values of spring and damping elements from the perturbation study. The study showed that the resulting coefficient functions of the three-element model describe the dynamic response to the step input of P accurately, indicating that the static perturbation results can be applied to the dynamic case. This model is further validated by accurately predicting the contraction response to a triangular P waveform. All three elements have pressure-dependent coefficients for pressure P in the range 207 < or = P < or = 621 kPa (30 < or = P < or = 90 psi). Studies with a step decrease in P (relaxation of the PM) indicate that the damping element coefficient is smaller during relaxation than contraction.

Air Pressure↗

Quantification analysis for saccadic eye movements.

Traditional parameters, such as latency and peak velocity, have been used for quantitative analysis of saccade dynamics. However, saccades of equal magnitude which differ substantially in dynamics may still have the same peak velocity. This lack of selectivity might degrade the efficacy of the peak velocity measurement in discriminating patients from normal subjects. In this study, an alternative parameter, the damping ratio of a second-order response, is proposed to concisely and accurately describe saccadic dynamics. A measurement of damping ratio is made by considering the response curve of saccade as the step response of a second-order transfer function. Using the least-mean-square algorithm, the second-order function has been optimized to fit the response of the saccade dynamics with the latency removed. Nineteen normal subjects (ten young and nine older) and 16 patients of Parkinson's disease (eight mildly affected and eight advanced affected) were tested for eye movements in response to pseudorandom saccadic stimuli. While the traditional peak velocity had difficulties in differentiating between the saccadic dynamics of normal and Parkinson subjects, the damping ratio is sensitive enough not only to highlight the difference between a group of patients mildly affected with Parkinson's disease and an age-matched normal group (p<0.01; abnormal versus normal), but also to distinguish between groups at different ages (p<0.01; younger versus older). It is proposed that the damping ratio could be a useful parameter in analyzing saccadic dynamics.

Adult↗

One-dimensional computer analysis of oscillatory flow in rigid tubes.

The dynamic characteristics of catheter-transducer systems using rigid tubes with compliance lumped in the transducer and oscillatory flow of fluid in rigid tubes were analyzed. A digital computer model based on one dimensional laminar oscillatory flow was developed and verified by exact solution of the Navier-Stokes Equation. Experimental results indicated that the damping ratio and resistance is much higher at higher frequencies of oscillation than predicted by the one dimensional model. An empirical correction factor was developed and incorporated into the computer model to correct the model to the experimental data. Amplitude of oscillation was found to have no effect on damping ratio so it was concluded that the increased damping ratio and resistance at higher frequencies was not due to turbulence but to two dimensional flow effects. Graphs and equations were developed to calculate damping ratio and undamped natural frequency of a catheter-transducer system from system parameters. Graphs and equations were also developed to calculate resistance and inertance for oscillatory flow in rigid tubes from system parameters and frequency of oscillation.

Blood Flow Velocity↗

Wave reflection and transmission reduction using a piezoelectric semipassive nonlinear technique.

This study addresses the problem of noise reduction using piezoelements. The nonlinear technique, synchronized switch damping (SSD), is implemented. The device is a pulse-tube termination equipped with piezoelements, which allows performant damping of the vibration resulting from an incident acoustic wave. Due to this damping, both reflected and transmitted wave are reduced. In the semipassive damping approach proposed in this paper, energy degradation is strongly enhanced when the piezoelements are continuously switched from open to short circuit synchronously to the strain. This technique has been developed following two strategies. The first is SSD on a short circuit in which the piezoelement is always in open circuit, except for a very brief period at each strain extremum where it is short-circuited. The second approach is SSD on an inductor. The process is very similar, except that instead of forcing the voltage to zero, the voltage is exactly reversed using a controlled oscillating discharge of the piezoelement capacitor on an inductor during switch drive. Due to this switching mechanism, a phase shift appears between the strain and the resulting voltage, thus creating energy dissipation. Following SSD on an piezoelement, attenuations of 15 dB in reflection and 7 dB in transmission were obtained.

Journal Article↗

Material identification of real impact sounds: effects of size variation in steel, glass, wood, and plexiglass plates.

Identification of the material of struck objects of variable size was investigated. Previous studies on this issue assumed recognition to be based on acoustical measures of damping. This assumption was tested, comparing the power of a damping measure in explaining identification data with that of several other acoustical descriptors. Listeners' performance was perfect with respect to gross material categories (steel-glass and wood-plexiglass) comprising materials of vastly different mechanical properties. Impaired performance was observed for materials within the same gross category, identification being based on the size of the objects alone. The damping descriptor accounted for the identification of the gross categories. However other descriptors such as signal duration explained the results equally well. Materials within the same gross category were identified mainly on the basis of signal frequency. Overall poor support for the relevance of damping to material perception was found. An analysis of the acoustical support for perfect material identification was carried out. Sufficient acoustical information for perfect performance was found. Thus, procedural biases for the origin of the effects of size could be discarded, pointing toward their cognitive, rather than methodological nature. Identification performance was explained in terms of the regularities of the everyday acoustical environment.

Adult↗

Analyses of Mössbauer mechanical measurements indicate that the cochlea is mechanically active.

Using the results of Mössbauer measurements, mechanical activity in the cochlea was tested for by comparing the measured basilar membrane (BM) transverse velocity amplitude with that calculated for a lossless mechanically passive system, derived from the measured BM velocity phase. If the cochlea is considered to be a lossless mechanically passive system, then the transverse velocity amplitude can be calculated from the group velocity and the relative variation of stiffness along the BM. The group velocity can be derived from the Mössbauer phase measurements, and the relative variation of stiffness along the BM can be derived from the frequency map of the cochlea. Making some general assumptions, the actual transverse velocity amplitudes are then compared from the Mössbauer amplitude data with those derived from the Mössbauer phase data, to determine if there is a significant transverse velocity gain. This operation was performed on several sets of Mössbauer data. From Mössbauer data showing sharp tuning, differences were found of up to 40 dB between the actual transverse velocity amplitude and the calculated lossless passive transverse velocity amplitude derived from the phase data. Examination of the assumptions made during the calculation of the lossless passive transverse velocity amplitude showed that none could account for a 40-dB transverse velocity gain. Thus, it is concluded that this transverse velocity gain can only be accounted for by the contribution to the amplitude of the transverse BM velocity by mechanically active elements along the cochlear duct. From Mössbauer data showing much less sharp tuning, it was found that the actual transverse velocity amplitude was approximately equal to the calculated lossless passive transverse velocity amplitude, basal to the characteristic place. This result is attributed to the disabling of the mechanically active elements along the cochlear duct. Apical to the characteristic place, the actual transverse velocity amplitude is shown to behave in a manner that suggests that the effective damping increases markedly in this region. This increase in effective damping is not necessarily due to an increase in viscous damping but could be due to any mechanism removing energy from the BM traveling wave. As an example, this paper discusses how this effective damping could be accounted for the transfer of energy to another mode of vibration at the characteristic place.

Acoustic Stimulation↗