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PubMed1995

Age-related changes in open-loop and closed-loop postural control mechanisms.

In an earlier posturographic investigation (Collins and De Luca 1993) it was proposed that open-loop and closed-loop control mechanisms are involved in the regulation of undisturbed, upright stance. In this study, stabilogram-diffusion analysis was used to examine how the natural aging process affects the operational characteristics of these control mechanisms. Stabilogram-diffusion analysis leads to the extraction of repeatable center-of-pressure (COP) parameters that can be directly related to the steady-state behavior and functional interaction of the neuromuscular mechanisms underlying the maintenance of erect posture. Twenty-five healthy young males (aged 19-30 years) and twenty-five elderly males (aged 71-80 years) who were free of major gait and postural disorders were included in the study. An instrumented force platform was used to measure the time-varying displacements of the COP under each subject's feet during quiet standing. The COP trajectories were analyzed as one-dimensional and two-dimensional random walks, according to stabilogram-diffusion analysis. Using this technique, it was demonstrated cross-sectionally that healthy aging is associated with significant changes in the 'quasi-static' dynamics of the postural control system. (It was also shown that more traditional posturographic analyses, i.e., summary statistics, were not sensitive enough to detect these age-related differences.) It was found that the steady-state behavior of the open-loop postural control mechanisms in the elderly is more positively correlated and therefore perhaps more unstable, i.e., the output of the overall system has a greater tendency to move or drift away from a relative equilibrium point over the short term. In contrast with this result, it was also found that the steady-state behavior of the closed-loop postural control mechanisms in the elderly is more negatively correlated and therefore perhaps more stable, i.e., over the longer term, there is an increased probability that movements away from a relative equilibrium point will be offset by corrective adjustments back towards the equilibrium position. In addition, it was demonstrated that the elderly utilize open-loop control schemes for longer time intervals and correspondingly larger COP displacements during periods of undisturbed stance. This result suggests that in the elderly there is a greater delay, on average, before closed-loop feedback mechanisms are called into play. Finally, it was shown that there is an increased heterogeneity of postural control abilities in healthy older adults.

Adult↗
PubMed2002

Value of central analysis of leucocyte depletion quality control data within the National Blood Service, England.

BACKGROUND AND OBJECTIVES: The results of quality monitoring leucocyte counts were analysed nationally for the first 2 years of universal leucocyte depletion (LD), spanning the time-period before and after standardization of the counting and LD methods. The objectives were twofold: first to determine whether the implementation strategy was effective in achieving the LD specification (< 5 x 10(6) leucocytes in 99% of components with 95% statistical confidence); and second, whether quality monitoring was able to detect potential non-conformance. MATERIALS AND METHODS: Residual leucocytes were counted using Beckman Coulter or Becton Dickinson (BD) flow cytometers and reagents. Data were collected into standardized analysis software (NWA Quality Analyst) for local trend analysis and checks for conformance to process specification, and collated centrally. Analysis was performed for six time-periods between January 1999 and March 2001. Specification failures were analysed to determine the likelihood of extreme failure. Statistical process monitoring was adjusted to suit LD processes. RESULTS: Data from red cells in optimal additive solution (OAS), filtered either as whole blood or red cell concentrates, and platelet pools improved significantly over the 2-year period with specification failures falling from 0.35%, 0.48% and 0.56%, respectively, in January-June 1999 to 0.06%, 0.01% and 0.04% in January-March 2001. Specification failures in red cells in OAS LD for the period January-December 2000 showed only 0.02% with a leucocyte count of > 30 x 10(6)/unit. Extreme failures are now very rare. Monitoring methods have been effective in detecting process change and drift. CONCLUSION: LD performance varies between different LD systems, but monitoring has proved sufficiently robust to detect processes that perform poorly. The chosen specification has been both achievable and appropriate to the systems in use. Standardization of the counting method is central to the ability to monitor and analyse results effectively across the whole service.

Blood Banks↗
PubMed2002

Colour and luminance interactions in the visual perception of motion.

We sought to determine the extent to which red-green, colour-opponent mechanisms in the human visual system play a role in the perception of drifting luminance-modulated targets. Contrast sensitivity for the directional discrimination of drifting luminance-modulated (yellow-black) test sinusoids was measured following adaptation to isoluminant red-green sinusoids drifting in either the same or opposite direction. When the test and adapt stimuli drifted in the same direction, large sensitivity losses were evident at all test temporal frequencies employed (1-16 Hz). The magnitude of the loss was independent of temporal frequency. When adapt and test stimuli drifted in opposing directions, large sensitivity losses were evident at lower temporal frequencies (1-4 Hz) and declined with increasing temporal frequency. Control studies showed that this temporal-frequency-dependent effect could not reflect the activity of achromatic units. Our results provide evidence that chromatic mechanisms contribute to the perception of luminance-modulated motion targets drifting at speeds of up to at least 32 degrees s(-1). We argue that such mechanisms most probably lie within a parvocellular-dominated cortical visual pathway, sensitive to both chromatic and luminance modulation, but only weakly selective for the direction of stimulus motion.

Adaptation, Ocular↗
PubMed2005

Characterization of arm-gun movement during air pistol aiming phase.

AIM: Air pistol shooting is a sport requiring extreme movement precision. The purpose of our study is to collect and analyze kinematic data of arm/gun complex during the pointing phase in order to characterize movement and between segment coordination by means of time and frequency domain analysis techniques. METHODS: Thirteen air pistol athletes participated to the recording sessions held at the 10 m shooting range. Kinematic data of neck, shoulder, elbow, wrist and gun were collected during the aiming phase using an optoelectronic motion capture system. Displacement series were split up in slow drift and tremor components. Amplitude of the movement of each segment and strength of the relationship between adjacent segments were estimated in time domain respectively by means of standard deviation and coefficient of regression. Moreover, coherence and phase spectral functions were calculated to assess between-segment coupling at different frequencies. RESULTS: Significantly larger movements were seen for slow drift component with respect to tremor one for all segments especially for lateral movements. Higher between segment correlation were found for lateral direction and for slow drift component. The coherence calculated on vertical series of tremor component showed significant coupling at 1.5 Hz and 5-7 Hz with phase opposition between wrist and gun motion at 5-7 Hz. CONCLUSIONS: Slow drift motion appears to affect mainly lateral movements and all the segments were equally involved indicating a probable origin in postural body sway. Vertical displacements could be referred to shoulder and wrist motion with features typical of physiological tremor. Quantitative characterization of segments displacements during aiming phase may serve as a basis for scientific evaluation and training in competitive precision shooting.

Adolescent↗
PubMed1988

Synthetic peptides in the study of the interaction of rabies virus and the acetylcholine receptor.

The neurotropism of some viruses may be explained in part by the attachment of these viruses to host cell receptors that are present on or even largely restricted to neurons. Rabies virus is an RNA virus that, after a period of replication in muscle, gains access to the central nervous system, where it selectively infects certain neuronal populations. The nicotinic acetylcholine receptor occurs in high density at the neuromuscular junction and is present in the central nervous system. Although several different cell surface constituents may act as attachment determinants for rabies, direct binding of radioactively labeled virus to affinity-purified acetylcholine receptor has been demonstrated. Binding of virus to the receptor was saturable and inhibited by up to 50% by alpha-bungarotoxin, a snake venom neurotoxin that binds at or near the acetylcholine binding site on the receptor. The molecular basis for the virus-receptor interaction may lie in an amino acid sequence similarity between the snake venom neurotoxins and a segment of the rabies virus glycoprotein. Two peptides (10 and 13 residues) of the rabies virus glycoprotein and homologous bungarotoxin peptides were synthesized and tested for ability to compete with labeled alpha-bungarotoxin for binding to the acetylcholine receptor. The peptides were found to compete with toxin binding with affinities comparable to those of the cholinergic ligands d-tubocurarine and nicotine. These findings indicate that a segment of the rabies virus glycoprotein interacts with the acetylcholine receptor at or near the acetylcholine binding site of the receptor. The similarity between the virus glycoprotein and the neurotoxin was further evidenced by the cross reaction of antibody raised against the virus 10-mer with the bungarotoxin 10-mer. Binding of rabies virus to the acetylcholine receptor or to other neuronal bungarotoxin-binding proteins may be related to the neurotropism of this virus. In addition, knowledge of both the region of the virus involved in binding and the binding domain on the receptor may be helpful in developing new strategies for treatment, especially for viruses that infect the central nervous system or evade the immune response through genetic drift. These strategies include development of antiviral agents that cross the blood-brain barrier and inhibit viral binding and the utilization as immunogens the regions of viruses, such as their binding domains, that are highly conserved among different strains.

Animals↗
PubMed1997

Computational parallels between the biological olfactory pathway and its analogue 'the electronic nose': Part II. Sensor-based machine olfaction.

Over the last fifteen years, we have witnessed a rapid expansion in the development of artificial odour sensing systems, or so called 'electronic nose' systems. Whilst the power of this approach to flavour has undoubtedly been demonstrated by its recent application to various complex odours, it will be argued that the original research programme, aimed at developing a comparative model of the biological olfactory pathway, has degenerated into an attempt to obtain an ad hoc workable system, based around readily available sensor and pattern recognition (PARC) technologies. At the time, the first 'model' nose system reflected the limited understanding of sensory information processing carried out within the biological olfactory pathway. We are now presented with an opportunity to evaluate and re-assess the architecture for an electronic nose, in view of the recent advances in understanding the key processing principals exploited by the olfactory bulb and cortex in the identification and characterisation of molecular stimuli. In Part II of this paper, we examine the parallels that exist between the biological olfactory system and the electronic nose. It is shown that the two systems share many similarities in their architectures and other properties, such as odour delivery, nonspecific sensor/receptor response, sensor/receptor preprocessing and content addressable memory (CAM) function. Of particular importance, both systems need to overcome similar operating problems, such as sensor/receptor drift, degeneration and poisoning, limited sensor/receptor sensitivity, discrimination of odour quality invariant of intensity and also the identification of particular odour components within a mixture of background odours. Finally, a number of opportunities for improving the biological plausibility of electronic nose systems are suggested that may yield an improvement in performance.

Animals↗
PubMed2005

Trends and issues in the international drug control system--Vienna 2003.

The April, 2003 meeting of the Commission on Narcotic Drugs, and the meetings and other efforts to influence it sponsored by interested parties before and around the Commission meeting, are described and analyzed. The 2003 meeting was seen as significant because it was the occasion for assessments of progress on the process goals set out in the United National General Assembly Special Session on drugs in 1998. Debate and discussion of the text of resolutions in the Commission meetings are analyzed in terms of the major points of conflict in 2003 between national delegations--cannabis policies, harm reduction, substitution therapy, and preferences for dramatizing or matter-of-fact language. Also discussed are the drift toward a crime rubric for the drug control system, and the increasing distance between the focus of the system on policing and the focus of most Western European governments on drugs as welfare or health issues. It is concluded that the system seems to be at a stalemate.

Drug and Narcotic Control↗
PubMed2006

Concordant genetic estimators of migration reveal anthropogenically enhanced source-sink population structure in the river sculpin, Cottus gobio.

River systems are vulnerable to natural and anthropogenic habitat fragmentation and will often harbor populations deviating markedly from simplified theoretical models. We investigated fine-scale population structure in the sedentary river fish Cottus gobio using microsatellites and compared migration estimates from three FST estimators, a coalescent maximum-likelihood method and Bayesian recent migration analyses. Source-sink structure was evident via asymmetry in migration and genetic diversity with smaller upstream locations emigration biased and larger downstream subpopulations immigration biased. Patterns of isolation by distance suggested that the system was largely, but not entirely, in migration-drift equilibrium, with headwater populations harboring a signal of past colonizations and in some cases also recent population bottlenecks. Up- vs. downstream asymmetry in population structure was partly attributable to the effects of flow direction, but was enhanced by weirs prohibiting compensatory upstream migration. Estimators of migration showed strong correspondence, at least in relative terms, especially if pairwise FST was used as an indirect index of relative gene flow rather than being translated to Nm. Since true parameter values are unknown in natural systems, comparisons among estimators are important, both to determine confidence in estimates of migration and to validate the performance of different methods.

Animal Migration↗
PubMed2004

Design and evaluation of an ultrasound-based bladder volume monitor.

Ultrasonic bladder volume monitors have successfully been used in the diagnosis and treatment of various urological disorders. Ultrasonic bladder monitors have been developed but they have either been too bulky or too simple and inaccurate. A new, wearable ultrasonic bladder volume monitor has been designed for urological patients. The instrument consists of seven phased-array ultrasonic transducers ergonomically arranged in a circular pattern to optimise detection of the bladder walls perpendicular to the abdominal wall. A Bluetooth radio link was used to transmit data to a laptop computer, where the main signal processing was performed. After detection of bladder surface points, a three-dimensional convex hull representing the bladder was generated, and the volume was estimated. Accuracy, precision, drift over time, temperature dependency and dynamic performance were evaluated using ultrasound phantoms. Furthermore, the system was tested on one volunteer using magnetic resonance imaging (MRI) as reference. The apparatus showed no significant drift, systematic error or temperature effects. Percentage error during static volume measurements had a 95% central prediction interval of +/-7.5% and mean absolute percentage error of 2.9%. The dynamic performance analysis showed linearity in the analysed volume interval. The in vivo study showed a high degree of correlation (R2= 0.99) between the volume measured using MRI and that measured with the apparatus.

Diagnosis, Computer-Assisted↗
PubMed1990

Evaluation of a fiberoptic intracranial pressure monitor.

The fiberoptic device is a relatively new type of intracranial pressure (ICP) monitor which appears to offer certain advantages over conventional monitoring systems, particularly its ability to measure brain parenchymal pressures. This study was undertaken to analyze the accuracy and drift characteristics of the fiberoptic device and to compare pressures in the subdural, intraparenchymal, and intraventricular compartments. The device was accurate to +/- 3 mm Hg over a 0- to 30-mm Hg range in vitro. The maximum daily drift was +/- 2.5 mm Hg, with an average daily drift of +/- 0.6 mm Hg and an average drift over a 5-day period of +/- 2.1 mm Hg. In vivo, the pressures and waveform characteristics obtained with the fiberoptic device and with a strain-gauge transducer connected to a ventriculostomy were very similar. Alterations in ICP were induced by various therapeutic and pathological manipulations, and the pressures in the three intracranial compartments were compared. Changes in ICP appeared to be reflected simultaneously and equally in all three compartments. Furthermore, changes in ICP secondary to a unilateral mass lesion were identical in both supratentorial parenchymal compartments when measured simultaneously. It is concluded that the fiberoptic device is an accurate and reliable system for ICP monitoring; the pressures recorded in the subdural, intraparenchymal, and intraventricular compartments paralleled each other in all of the physiological and pathological states tested. Although the drift associated with this device is less than that reported for previously available systems, its maximal cumulative drift over a 5-day period of +/- 6 mm Hg is significant. Since the fiberoptic device cannot be recalibrated in situ, it is suggested that the device be replaced if monitoring is to be continued for periods longer than 5 days.

Animals↗
PubMed1987

Simulating evolution by gene duplication.

By considering the recent finding that unequal crossing over and other molecular interactions are contributing to the evolution of multigene families, a model of the origin of repetitive genes was studied by Monte Carlo simulations. Starting from a single gene copy, how genetic systems evolve was examined under unequal crossing over, random drift and natural selection. Both beneficial and deteriorating mutations were incorporated, and the latter were assumed to occur ten times more frequently than the former. Positive natural selection favors those chromosomes with more beneficial mutations in redundant copies than others in the population, but accumulation of deteriorating mutations (pseudogenes) have no effect on fitness so long as there remains a functional gene. The results imply the following: Positive natural selection is needed in order to acquire gene families with new functions. Without it, too many pseudogenes accumulate before attaining a functional gene family. There is a large fluctuation in the outcome even if parameters are the same. When unequal crossing over occurs more frequently, the system evolves more rapidly. It was also shown, under realistic values of parameters, that the genetic load for acquiring a new gene is not as large as J.B.S. Haldane suggested, but not so small as in a model in which a system for selection started from already redundant genes.

Alleles↗
PubMed2003

Evaluation of Cobas Integra 800 under simulated routine conditions in six laboratories.

The new selective access analyser Cobas Integra 800 from Roche Diagnostics was evaluated in an international multicentre study at six sites. Routine simulation experiments showed good performance and full functionality of the instrument and provocation of anomalous situations generated no problems. The new features on Cobas Integra 800, namely clot detection and dispensing control, worked according to specifications. The imprecision of Cobas Integra 800 fulfilled the proposed quality specifications regarding imprecision of analytical systems for clinical chemistry with few exceptions. Claims for linearity, drift, and carry-over were all within the defined specifications, except urea linearity. Interference exists in some cases, as could be expected due to the chemistries applied. Accuracy met the proposed quality specifications, except in some special cases. Method comparisons with Cobas Integra 700 showed good agreement; comparisons with other analysis systems yielded in several cases explicable deviations. Practicability of Cobas Integra 800 met or exceeded the requirements for more than 95% of all attributes rated. The strong points of the new analysis system were reagent handling, long stability of calibration curves, high number of tests on board, compatibility of the sample carrier to other Roche systems, and the sample integrity check for more reliable analytical results. The improvement of the workflow offered by the 5-position rack and STAT handling like on Cobas Integra 800 makes the instrument attractive for further consolidation in the medium-sized laboratory, for dedicated use of special analytes, and/or as back-up in the large routine laboratory.

Blood Proteins↗
PubMed1988

Effects of temporal frequency on the contrast sensitivity of the human accommodation system.

Contrast thresholds were determined for the initiation of accommodative responses to drifting sine-wave stimuli (4.1 c/deg) over a range of temporal frequencies (0-14.0 Hz). Accommodation was monitored with a dynamic infrared optometer. Psychophysical detection thresholds were also determined for the same stimuli. A comparison of the contrast thresholds for detection with those for the initiation of accommodation indicates that these two tasks are mediated by mechanisms of comparable sensitivity. Examination of the effects of temporal frequency on the contrast sensitivity of these two visual tasks reveals modest differences in the tuning properties of the underlying sensory mechanisms. Transient mechanisms tuned to intermediate temporal frequencies appear to have a greater role in the initiation of accommodative responses to grating stimuli than in the detection of such stimuli.

Accommodation, Ocular↗
PubMedDate not supplied

Nocturnal hypoglycaemia in type 1 diabetes--consequences and assessment.

Hypoglycaemia is inevitable when striving for low HbA1c values. Nocturnal hypoglycaemia often occurs without symptoms, but results in diminished next day well-being and hypoglycaemia unawareness. Frequency of nocturnal hypoglycaemia was first assessed in research ward settings, but suffered from insufficient glucose sampling frequency. This may have resulted in overestimation of the duration of hypoglycaemic episodes. The advent of the first continuous glucose sensor, the needle-type MedtronicMiniMed Continuous Glucose Measurement System, revolutionized the assessment of glucose values. However, on scrutiny, the first version of this sensor showed a drift into the hypoglycaemic area and delayed recovery from hypoglycaemia. Using the microdialysis-based GlucoDay system, our group reported a lower frequency of nocturnal hypoglycaemia in type 1 diabetes patients using an insulin pump, than that expected from the existing literature. Today, more than 80 years after the introduction of insulin for the treatment of type 1 diabetes, the associated frequency of nocturnal hypoglycaemia still awaits its definitive assessment.

Circadian Rhythm↗
PubMed1982

Polycythemia vera: studies of hemopoiesis in continuous long-term culture of human marrow.

Long-term cultures of marrow cells from ten normal subjects and three patients with polycythemia vera were established to compare normal and neoplastic hemopoiesis in vitro. Suspended cells were removed periodically from the cultures and assayed from their content of various colony-forming cells, including erythroid colony- and burst-forming cells (CFU-E and BFU-E), granulocyte/macrophage colony-forming (CFU-C), and "mixed cell" colony progenitors (CFU-GEMM). To determine if mixed cell colonies arise from a single progenitor, we used the cellular mosaicism conferred by X-chromosome inactivation. The isoenzymes of glucose-6-phosphate dehydrogenase (G-6-PD) were used as markers of the mosaicism. Preliminary results suggest that these colonies are clonal only at low plating densities. The G-6-PD system was also used to determine whether selection or "drift" occurs in continuous long-term cultures. The ratios of G-6-PD isoenzyme types in pooled colonies from cultures of two normal heterozygotes remained similar, indicating stable cultures. Long-term cultures of normal marrow and marrow from the patients with polycythemia vera maintained BFU-E for a mean of 8.7 (+/- 0.6) and 12.5 (+/- 0.5) weeks (P = 0.03), respectively. The fractions of total BFU-E detected as endogenous erythroid colonies remained similar over the culture period. These results demonstrate that 1) hemopoiesis in polycythemia vera can be analyzed in long-term culture; 2) polycythemia vera marrow grows as well or better than normal in long-term culture; and 3) the proportion of the neoplastic clone in polycythemia vera represented by endogenous erythroid colony growth is unchanged over time, suggesting no reemergence of normal stem cell progeny in this system.

Bone Marrow↗
PubMedDate not supplied

Linkage equilibrium and disequilibrium in human population studies.

It is suggested that in such genetic systems as HLA, characterized by sets of alleles at several closely linked loci, the existence of a state of linkage disequilibrium in a population indicates that this population is the result of recent hybridization between two or more populations, which may previously each have been in a state of equilibrium. Disequilibrium may, however, be modified by natural selection and by genetic drift. Examples of disequilibrium in the Rh, MNSs and HLA systems are discussed.

Alleles↗
PubMed1994

A fiber optic system for measuring dynamic mechanical properties of embryonic tissues.

Dynamic mechanical properties of embryonic tissues, including viscoelasticity and active motility, play a major role in morphogenesis. Mechanical abnormalities resulting from altered cytoskeletal chemistry presumably contribute to spina bifida and other birth defects, but research in this area has been limited by inadequate mechanical measurement techniques. This paper discusses aspects of embryo tissues that make them difficult to measure and describes a versatile new system developed and used to study the biomechanics of morphogenesis in amphibian embryos. It incorporates a flexible optical-fiber probe driven by piezoceramic elements to impose and measure feedback-controlled, two-dimensional, time-varying patterns of stress or strain in the tissue. Compression, tension, and shear geometries are possible. Capacitive displacement sensors provide the precision and low drift rates required for these measurements. Software control permits the system to perform both standard and customized rheological tests, including interactive ones in which test parameters change in response to measured tissue behavior. Sample size range is 50 microns to 5 mm. Displacement range is 60 microns with a resolution of 0.1 microns. Force range is 10 microN with a resolution of 0.02 microN. Frequency range is DC to 20 Hz.

Amphibians↗
PubMed2004

Investigation of noncovalent interactions in deprotonated peptides: structural and energetic competition between aggregation and hydration.

Noncovalent peptide-peptide and peptide-water interactions in small model systems were examined using an electrospray mass spectrometer equipped with a high-pressure drift cell. The results of these aggregation and hydration experiments were interpreted with the aid of molecular mechanics (MM) and density functional theory (DFT) calculations. The systems investigated include bare deprotonated monomers and dimers [P(1,2)-H](-) and hydrated deprotonated monomers and dimers [P(1,2)-H](-).(H(2)O)(n)() for the peptides dialanine (P = AA) and diglycine (P = GG). Mass spectra indicated that both peptides AA and GG form exclusively dimer ions in the electrospray process. Monomeric ions were generated by high-energy injection of the dimers into the drift cell. Temperature-dependent hydration equilibrium experiments carried out in the drift cell yielded water binding energies ranging from 11.7 (first water molecule) to 7.1 kcal/mol (fourth water) for [AA-H](-) and 11.0 to 7.4 kcal/mol for [GG-H](-). The first water molecule adding to the dimer ions [AA-H](-).(AA) and [GG-H](-).(GG) is bound by 8.4 and 7.5 kcal/mol, respectively. The hydration mass spectra for the monomers and dimers provide a means to compare the ability of water and a neutral peptide to solvate a deprotonated peptide [P-H](-). The data indicate that a similar degree of solvation is achieved by four water molecules, [P-H](-).(H(2)O)(4), or one neutral peptide, [P-H](-).(P). Temperature-dependent kinetics experiments yielded activation energies for dissociation of the dimers [AA-H](-).(AA) and [GG-H](-).(GG) of 34.9 and 32.2 kcal/mol, respectively. MM and DFT calculations carried out for the dialanine system indicated that the dimer binding energy is 24.3 kcal/mol, when the [AA-H](-) and AA products are relaxed to their global minimum structures. However, a value of 38.9 kcal/mol is obtained if [AA-H](-) and AA dissociate but retain the structures of the moieties in the dimer, suggesting the transition state occurs early in the dissociation process. Similar results were found for the diglycine dimer.

Dipeptides↗