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PubMed2006

Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel.

Potassium channels share a common selectivity filter that determines the conduction characteristics of the pore. Diversity in K+ channels is given by how they are gated open. TASK-2, TALK-1, and TALK-2 are two-pore region (2P) KCNK K+ channels gated open by extracellular alkalinization. We have explored the mechanism for this alkalinization-dependent gating using molecular simulation and site-directed mutagenesis followed by functional assay. We show that the side chain of a single arginine residue (R224) near the pore senses pH in TASK-2 with an unusual pKa of 8.0, a shift likely due to its hydrophobic environment. R224 would block the channel through an electrostatic effect on the pore, a situation relieved by its deprotonation by alkalinization. A lysine residue in TALK-2 fulfills the same role but with a largely unchanged pKa, which correlates with an environment that stabilizes its positive charge. In addition to suggesting unified alkaline pH-gating mechanisms within the TALK subfamily of channels, our results illustrate in a physiological context the principle that hydrophobic environment can drastically modulate the pKa of charged amino acids within a protein.

Amino Acid Sequence↗

PubMed2003

A head and neck cancer patient dies! Why perform an autopsy: for the relatives, for the clinicians or for the pathologists?

It is no secret that autopsy rates at most hospitals worldwide--both teaching and community hospitals--have declined precipitously in recent decades, but is this a desirable state of affairs? This article explores this issue from three viewpoints: that of the family members who grant permission for autopsies; that of the clinicians who seek permission for the autopsy to be carried out; and that of the pathologists who actually perform the post-mortem examination. Family concerns about (the sometimes tangential) matter of organ retention following autopsy have recently been highlighted in Europe, with an accompanying negative overall impression of the autopsy being conveyed by many outlets of the popular media. Clinicians will often concede that they feel somewhat distanced from the whole process of autopsy, and so do not hold it in such high esteem as their predecessors once did decades ago. Pathologists at present often perform autopsies as "additional duties" to be fitted in around their central functions, and so do not see them as a primary task to be accomplished. However, there are reasons why this may be detrimental to patient care, including in particular the fact that clinical/radiographic diagnoses are sometimes not confirmed by the results of a complete autopsy. Suggestions for improving the autopsy rate--in particular amongst head and neck cancer patients--are discussed, and include performance of a more rapid limited autopsy and the designation of specialist pathologists in head and neck cancer to carry out autopsies of these patients as an extension of their clinical duties. One conclusion seems inescapable: to increase autopsy rates, the status of the procedure will necessarily have to be upgraded from that of "afterthought/perfunctory task" to that of "consultation", with all of the shifts in attitude such a modification would entail.

Attitude of Health Personnel↗

PubMed1997

Anticipatory postural adjustments in the back and leg lift.

This study examined anticipatory postural adjustments in a dynamic multi-joint action in which a relatively fast voluntary movement is being executed while balance is maintained in the field of gravity. In a bi-manual whole body lifting task, the pickup of the load induces a forward shift in the position of the center of mass, challenging the dynamic balance regulation while simultaneously impeding the ongoing extension movement. We investigated whether anticipatory postural adjustments are an addition to a voluntary motor command or an inherent component of this command. Using a global mechanical analysis of the movement, we found that anticipatory postural adjustments are present in bimanual lifting, both in back lifting and leg lifting, and that lifting technique had a significant influence on the pattern of the adjustments. If the mass of the object was reduced unexpectedly, balance was disturbed in 92% of the mass-reduced trials. These findings suggest that the anticipatory postural adjustments to be performed are specified in advance such that the expected changes in the mechanical interaction with the environment are taken into account. The observations lend support to the hypothesis that the control of the observed anticipatory postural adjustments is an integral part of the control of the lifting movement itself. Consequently, the strict dichotomy in the control of posture and movement is being questioned.

Adult↗

PubMedDate not supplied

Posttraining sleep enhances automaticity in perceptual discrimination.

Perceptual learning can develop over extended periods, with slow, at times sleep-dependent, improvement seen several days after training. As a result, performance can become more automatic, that is, less dependent on voluntary attention. This study investigates whether the brain correlates of this enhancement of automaticity are sleep-dependent. Event-related potentials produced in response to complex auditory stimuli were recorded while subjects' attention was focused elsewhere. We report here that following training on an auditory discrimination task, performance continued to improve, without significant further training, for 72 hr. At the same time, several event-related potential components became evident 48-72 hr after training. Posttraining sleep deprivation prevented neither the continued performance improvement nor the slow development of cortical dynamics related to an enhanced familiarity with the task. However, those brain responses associated with the automatic shift of attention to unexpected stimuli failed to develop. Thus, in this auditory learning paradigm, posttraining sleep appears to reduce the voluntary attentional effort required for successful perceptual discrimination by facilitating the intrusion of a potentially meaningful stimulus into one's focus of attention for further evaluation.

Adult↗

PubMed2004

Impaired neuropsychological functioning in lead-exposed children.

Neuropsychological functions were assessed in 174 children participating in a longitudinal study of low-level lead exposure. At age 5 1/2 years, children were administered the Working Memory and Planning Battery of the Cambridge Neuropsychological Testing Automated Battery. Measures of sociodemographic characteristics of the family, prenatal and perinatal risk, quality of caregiving and crowding in the home, and maternal and child intelligence were used as covariates to test the hypothesis that children with higher lifetime average blood lead concentrations would perform more poorly on tests of working memory, attentional flexibility, and planning and problem solving. The lifetime average blood lead level in this sample was 7.2 micrograms per deciliter (mug/dL; range: 0-20 mug/dL). Children with greater exposure performed more poorly on tests of executive processes. In both bivariate and multivariate analyses, children with higher lifetime average blood lead concentrations showed impaired performance on the tests of spatial working memory, spatial memory span, intradimensional and extradimensional shifts, and an analog of the Tower of London task. Many of the significant associations remained after controlling for children's intelligence test scores, in addition to the other covariates. These findings indicate that the effects of pediatric lead exposure are not restricted to global indexes of general intellectual functioning, and executive processes may be at particular risk of lead-induced neurotoxicity.

Attention↗

PubMed1992

Persistence and problem-solving skills in young male alcoholics.

This study compares the level of persistence between 31 inpatient alcoholic males and 31 abstinent or light social drinking males matched on age, education, socioeconomic status and estimated premorbid IQ. An unsolvable anagram and diagram were selected as measures of persistence. Results indicated that alcoholics persisted for significantly shorter periods of time on both measures than their matched controls. However, there were no significant group differences on two measures from the Wisconsin Card Sorting Test (set shifting and set maintenance). Persistence measures from the unsolvable tasks were not significantly correlated with the set maintenance score of the Wisconsin Card Sorting Test. Possible explanations are considered for these findings of persistence deficits without problem-solving impairments among young alcoholics.

Adult↗

PubMed2001

Choices between positive and negative reinforcement during treatment for escape-maintained behavior.

Positive reinforcement was more effective than negative reinforcement in promoting compliance and reducing escape-maintained problem behavior for a child with autism. Escape extinction was then added while the child was given a choice between positive or negative reinforcement for compliance and the reinforcement schedule was thinned. When the reinforcement requirement reached 10 consecutive tasks, the treatment effects became inconsistent and reinforcer selection shifted from a strong preference for positive reinforcement to an unstable selection pattern.

Autistic Disorder↗

PubMed2006

Effects of forced-choice runway variations on rats' T-maze serial pattern learning.

Rats learned an ordered RNR/RNN serial pattern task in a T-maze where they were shifted to a different runway on Trial 3 only in the RNR series (shift-win/stay-lose group) or only in the RNN series (stay-win/shift-lose group). The shift-win/stay-lose group developed faster speeds on Trial 3 of the RNR than on Trial 3 of the RNN series more easily than the stay-win/shift-lose group. This difference occurred whether all rats were forced onto the same runway on the first two trials (Experiment 1) or onto a different runway on Trial 2 from that on Trial 1 in each series (Experiment 2). Posttraining probe tests revealed that the shift-win/stay-lose group in each experiment relied on the runway shift event in Trial 3 or on the series position to anticipate the second reward within a series. Such reward expectancies were greater when the runway shift occurred in the same series position as during training. These probe tests revealed that the stay-win/shift-lose group relied only on the series position in Experiment 2. Our findings do not support predictions based on an associative predictive validity model. Rather, they reflect rats' predisposition to spontaneously alternate choices in the T-maze, a tendency corresponding to their inherent win-shift foraging strategy. Rats in each group also reduced their speeds less on the nonrewarded Trial 2 when it preceded a rewarded rather than a nonrewarded Trial 3. This effect suggests that rats were able to determine which series contained a second rewarded trial. We discuss the theoretical implications of this Trial 2 speed effect in terms of rats' uncertainty about where this second rewarded trial might occur in the RNR series.

Animals↗

PubMed2000

Attention switching in depth using random-dot autostereograms: attention gradient asymmetries.

Random-dot autostereograms (RDASs) were used to investigate attention shifts along the sagittal plane in distractor-free tasks of high perceptual load. In three experiments using a same/different comparison task, the shape of the gradient over five different depths was examined and the conditions under which the gradient is and is not observed were compared. When the target set consisted of five similar objects, a robust asymmetric depth gradient was observed. When the target set consisted of two dissimilar objects, no gradient was observed. The results support a hypothesis of a viewer-centered asymmetric attention gradient in the depth plane that is dependent on perceptual or attentional load defined by target-set discriminability.

Attention↗

PubMed1975

The effects of stimulus complexity and sensory modality on reaction time in normal and retarded readers.

Intra- and crossmodal performance of normal and retarded readers was compared in a reaction-time task. Both reading groups showed slower crossmodal than intramodal shifting. This effect occurred equally for both reading groups. Differences between the two groups occurred, however, when a complex visual stimulus was present. The complex stimulus resulted in the retarded readers showing slower reaction times to other stimuli in that setting. This effect occurred for stimuli both within and across modalities. The results suggested that the demands of stimulus complexity within the visual modality rather than the demands of crossmodal shifting were related to reading ability.

Achievement↗

PubMedDate not supplied

[Occupational fitness of workers with fibromyalgia syndrome].

Fibromyalgia is a syndrome characterized by widespread musculoskeletal chronic pain and by other clinical manifestations such as stiffness, fatigue, sleep disturbances, anxiety and depression. The disorder has a considerable impact on the ability to perform work and daily living activities, often reducing workforce participation. Fitness to work, in relation to biomechanically taxing tasks execution, vibration exposure, environmental microclimatic conditions and night shift, is discussed.

Fatigue Syndrome, Chronic↗

PubMed2006

Virtual exclusion and telework: barriers and opportunities of technocentric workplace accommodation policy.

Teleworking, a restructuring of the manner in which work occurs, based on information communication technologies (ICTs), is a promising way of further integrating people with disabilities into the workplace. In contrast to telecommuting, in which the work is primarily shifted in locale, telework is a restructuring of the tasks to be accomplished within the larger work setting which could result in "work" being done remotely, or collaboratively with coworkers (remotely or not) using ICTs. Drawing upon a review of the literature, this paper explores the relationship between telework and people with disabilities. While the advent of telecommuting and subsequently "teleworking" might open increased opportunities for the hiring of people with disabilities, it may also place severe constraints on the type of work, workplace environment and interactions, and accumulation of social capital for people with disabilities. Whereas much of the prevailing literature on telework and disability is often proscriptive in nature and is written with an audience of employers in mind, it is just as important to consider policy options from the standpoint of the employee as well. This paper proposes a number of policy approaches for the creation of an inclusive work environment for teleworkers with disabilities that can minimize, as much as possible, the social isolation faced by teleworkers with disabilities while maximizing their participation within the workplace community. Policy objectives for enhancing telework for people with disabilities fall into three general categories: 1) research, 2) outreach, and 3) interventions.

Persons with Disabilities↗

PubMedDate not supplied

[Repetitive movements of the upper limbs: results of exposure evaluation and clinical investigation during the sorting and packaging of apples].

In the fruit industry, workers sorting and packing apples perform a job that is characterised by repetitive actions, that require them to remain in an upright position for prolonged periods of time and, occasionally, to manually lift loads of apples. The aim of the study was to detect and provide a preliminary quantification of any possible risks for the musculo-skeletal system, as well as any disorders present among the workers. A risk analysis for WMSDs was performed in an apple packing plant, using video recordings of the job cycles associated with two different tasks (semi-automatic sorting and manual packing). A clinical and anamnestic investigation was carried out in nine plants; a standard questionnaire was distributed to 180 employees, with the purpose of detecting disorders and diseases of the locomotor system. An initial evaluation of the risks for WMSDs indicated that the routine tasks performed by the female apple workers featured a very high frequency of actions, also in view of the fact that the repetitive tasks lasted for the duration of the entire work shift. In the situation examined, the action frequency limits were greatly exceeded; moreover, the recovery times were inadequate in terms both of their duration and distribution. Regarding clinical and anamnestic examination, an overall analysis of the results shows a very high prevalence of spinal and hand-arm disorders. Given these preliminary findings, the authors suggest that the sample population of fruit sorters should undergo clinical and instrumental testing to evaluate the condition of the spine and upper limbs, and that a specific health surveillance programme should be adopted across the industry.

Adult↗

PubMed1992

Immediate colour constancy.

Colour constancy is traditionally interpreted as the stable appearance of the colour of a surface despite changes in the spectral composition of the illumination. When colour constancy has been assessed quantitatively, however, by observers making matches between surfaces illuminated by different sources, its completeness has been found to be poor. An alternative operational approach to colour constancy may be taken which concentrates instead on detecting the underlying chromatic relationship between the parts of a surface under changes in the illuminant. Experimentally the observer's task was to determine whether a change in the appearance of a surface was due to a change in its reflecting properties or to a change in the incident light. Observers viewed computer simulations of a row of three Mondrian patterns of Munsell chips. The centre pattern was a reference pattern illuminated by a simulated, spatially uniform daylight; one of the outer patterns was identical but illuminated by a different daylight; and the other outer pattern was equivalent but not obtainable from the centre pattern by such a change in illuminant. Different patterns and different shifts in daylight were generated in each experimental trial. The task of the observer was to identify which of the outer patterns was the result of an illuminant change. Observers made reliable discriminations of the patterns with displays of durations from several seconds to less than 200 ms, and, for one observer, with displays of 1 ms. By these measures, human observers appear capable of colour constancy that is extremely rapid, and probably preattentive in origin.

Color Perception↗

PubMed1999

Temporal properties of attention sharing consequent to disturbed balance.

The time course and extent of attentional shifts associated with compensatory balancing reactions were explored using a novel dual-task paradigm. Seated subjects performed a continuous visuomotor tracking task with the hand while the feet simultaneously balanced an inverted pendulum. The pendulum was randomly perturbed, evoking compensatory balance reactions. Changes in tracking performance were held to reflect attentional shifts. Discrete deviation in visuomotor tracking, typically a pause in tracking, began on average 235 ms after the onset of the balance reaction (TA EMG; average latency 90 ms). Such pauses lasted on average 600 ms, although additional errors in tracking lasted up to 9 s following the perturbation. The findings reveal evidence of dynamic shifts in attention associated with distinct phases of compensatory balance control. The initial phase appears to be triggered automatically, whereas later phases involve varying degrees of attentional resources.

Adult↗

PubMed2006

Frontal regions involved in learning of motor skill--A functional NIRS study.

To investigate cerebral mechanisms underlying learning of motor skill, we assessed serial changes of cortical activation patterns during a pursuit rotor (PR) task in 18 right-handed, healthy subjects using a functional near-infrared spectroscopy (fNIRS) system. Subjects performed the task with the right hand for 30 s alternated with 30-s rest for 8 repetitions (cycle1 to 8). Gains in motor skill were evaluated by time for keeping the stylus on the target (max 30 s), surface EMG patterns and trajectories of the arm. Performance improved with repetitions of the task cycles (12.9/17.1/19.3/20.0/21.1/22.2/23.6/23.9 s on average) and reached plateau at the 7th cycle. Reciprocal EMG patterns and steady trajectories were associated with acquisition of the motor skill. Task-related increases of oxygenated hemoglobin (oxyHb) were observed in the channels covering the sensorimotor cortex (SMC), premotor and prefrontal regions. There were also task-related decreases of deoxygenated hemoglobin (deoxyHb) in these areas although the changes were smaller compared with those of oxyHb. The center of task-related increases of oxyHb was initially located in the presupplementary motor area (preSMA) and shifted caudally to the supplementary motor area (SMA) with cycle repetitions. The ratios of oxyHb changes in preSMA to SMA significantly decreased with task repetitions. DeoxyHb changes confirmed the activation patterns. These data suggest that preSMA plays an important role in the early phase of motor learning while the SMA might be more involved in the late learning phase of the motor skill.

Adult↗

PubMed2004

Single neurons in posterior parietal cortex of monkeys encode cognitive set.

The primate posterior parietal cortex (PPC), part of the dorsal visual pathway, is best known for its role in encoding salient spatial information. Yet there are indications that neural activity in the PPC can also be modulated by nonspatial task-related information. In this study, we tested whether neurons in the PPC encode signals related to cognitive set, that is, the preparation to perform a particular task. Cognitive set has previously been associated with the frontal cortex but not the PPC. In this study, monkeys performed a cognitive set shifting paradigm in which they were cued in advance to apply one of two different task rules to the subsequent stimulus on every trial. Here we show that a subset of neurons in the PPC, concentrated in the lateral bank of the intraparietal sulcus and on the angular gyrus, responds selectively to cues for different task rules.

Analysis of Variance↗

PubMed2001

Comparing performance on a simulated 12 hour shift rotation in young and older subjects.

OBJECTIVES: To simulate a 12 hour shift rotation and measure the difference in performance if any, between older and younger subjects. Significant reductions in neurobehavioural performance during shift work and particularly night work have long been recognised. There are conflicting reports of the effects of 12 hour shifts on performance, alertness, and safety. Furthermore, research suggests that older shift workers have more sleep disruption and maladaption to shift work. When this is combined with longer hours at work there may be considerable reductions in performance for older compared with younger workers. METHODS: Thirty two subjects were allocated to groups according to age. Group one had 16 subjects with a mean (SD) age of 21.2 (2.7) years, and group two had 16 subjects with a mean (SD) age of 43.9 (6.8) years. Subjects came to the laboratory for six consecutive days and completed a simulated 12 hour shift rotation consisting of two 12 hour day shifts (0700-1900), followed by two 12 hour night shifts (1900-0700). During the work period subjects completed a computer administered neurobehavioural performance task every hour. RESULTS: Performance for the older subjects was consistently lower than for the younger subjects. There was a significant difference in performance across the shift between older and younger subjects. There was a significant change in performance across the shifts in the older subjects, such that performance significantly increased across the day shifts and decreased across the night shifts. By contrast, the younger subjects were able to maintain performance across both day shifts and the second night shift. CONCLUSIONS: There are significant differences in performance of older and younger subjects during a simulated 12 hour shift rotation. Future studies both in the field and the laboratory would be useful in determining whether this is typical and if there are any important consequences for the older worker on 12 hour shifts.

Adolescent↗