Use of a Decision Support Tool on Prognosis of Work Ability in Work Disability Assessments: An Experimental Study Among Insurance Physicians.

Purpose Assessment of prognosis of work disability is a challenging task for occupational health professionals. An evidence-based decision support tool, based on a prediction model, could aid professionals in the decision-making process. This study aimed to evaluate the efficacy of such a tool on Dutch insurance physicians' (IPs) prognosis of work ability and their prognostic confidence, and assess IPs' attitudes towards use of the tool. Methods We conducted an experimental study including six case vignettes among 29 IPs. For each vignette, IPs first specified their own prognosis of future work ability and prognostic confidence. Next, IPs were informed about the outcome of the prediction model and asked whether this changed their initial prognosis and prognostic confidence. Finally, respondents reported their attitude towards use of the tool in real practice. Results The concordance between IPs' prognosis and the outcome of the prediction model was low: IPs' prognosis was more positive in 72 (41%) and more negative in 20 (11%) cases. Using the decision support tool, IPs changed their prognosis in only 13% of the cases. IPs prognostic confidence decreased when prognosis was discordant, and remained unchanged when it was concordant. Concerning attitudes towards use, the wish to know more about the tool was considered as the main barrier. Conclusion The efficacy of the tool on IPs' prognosis of work ability and their prognostic confidence was low. Although the perceived barriers were overall limited, only a minority of the IPs indicated that they would be willing to use the tool in practice.

Multicentre randomized clinical trial to investigate the cost-effectiveness of an allogeneic single-donor fibrin sealant after coronary artery bypass grafting (FIBER Study).

BACKGROUND: Reduction of blood transfusion in cardiac surgery is an important target. The aim of this study was to investigate the cost-effectiveness of the use of CryoSeal®, an allogeneic single-donor fibrin sealant, in patients undergoing coronary artery bypass grafting (CABG). METHODS: This randomized clinical study involved seven cardiac surgery centres in the Netherlands. Patients undergoing elective isolated CABG with the use of at least one internal thoracic artery (ITA) graft were assigned randomly to receive either CryoSeal® (5 ml per ITA bed) or no CryoSeal®. Primary efficacy endpoints were units of transfused red blood cells, fresh frozen plasma and platelet concentrates, and duration of intensive care unit stay. Secondary efficacy endpoints were 48-h blood loss, reoperation for bleeding, mediastinitis, 30-day mortality and duration of hospital stay. RESULTS: Between March 2009 and January 2012, 1445 patients were randomized. The intention-to-treat (ITT) population comprised 1436 patients; the per-protocol (PP) population 1292. In both the ITT and the PP analysis, no significant difference between the treatment groups was observed for any of the primary and secondary efficacy endpoints. In addition, no significant difference between the groups was seen in the proportion of transfused patients. Estimated CryoSeal® costs were €822 (95 per cent c.i. €808 to €836) per patient, which translated to €72,000 per avoided transfusion (unbounded 95 per cent c.i.). CONCLUSION: The use of the fibrin sealant CryoSeal® did not result in health benefits. Combined with the high cost per avoided transfusion, this study does not support the implementation of routine CryoSeal® use in elective isolated CABG. REGISTRATION NUMBER: NTR1386 ( http://www.trialregister.nl).

Visuomotor coordination is different for different directions in three-dimensional space.

In most visuomotor tasks in which subjects have to reach to visual targets or move the hand along a particular trajectory, eye movements have been shown to lead hand movements. Because the dynamics of vergence eye movements is different from that of smooth pursuit and saccades, we have investigated the lead time of gaze relative to the hand for the depth component (vergence) and in the frontal plane (smooth pursuit and saccades) in a tracking task and in a tracing task in which human subjects were instructed to move the finger along a 3D path. For tracking, gaze leads finger position on average by 28 ± 6 ms (mean ± SE) for the components in the frontal plane but lags finger position by 95 ± 39 ms for the depth dimension. For tracing, gaze leads finger position by 151 ± 36 ms for the depth dimension. For the frontal plane, the mean lead time of gaze relative to the hand is 287 ± 13 ms. However, we found that the lead time in the frontal plane was inversely related to the tangential velocity of finger. This inverse relation for movements in the frontal plane could be explained by assuming that gaze leads the finger by a constant distance of ∼ 2.6 cm (range of 1.5-3.6 cm across subjects).

Inability of single resting arterial blood gas to predict significant hypoxaemia in chronic obstructive pulmonary disease.

BACKGROUND: While point measurement of resting arterial partial pressure of oxygen (P(a)O(2)) is the traditional gold-standard for assessment of oxygenation in chronic obstructive pulmonary disease (COPD), 24-h oximetry may identify further patients with clinically significant hypoxaemia. We aimed to describe the relationship between these two parameters and identify other correlated variables. METHODS: All patients registered with the Barwon Health Hospital Admission Risk Program from 1 March to 31 October 2008 for the diagnosis of COPD were identified. The main inclusion criteria were obstructive spirometry, clinical stability and moderate resting hypoxaemia (P(a)O(2) 56-70 mmHg). All patients underwent 24-h oximetry, arterial blood gas, spirometry, anthropometry and telephone questionnaire, and 23 patients also completed polysomnography. RESULTS: Inclusion criteria were met in 35 of 287 patients. Mean recording time was 23.5 h, representing 97% of intended oximetry time. Nineteen patients (54%) spent greater than 30% of recorded oximetry time below 90%. There was a moderate inverse correlation between time below 90% saturations and P(a)O(2) (r=-0.40, P= 0.02), with body mass index (BMI) the only other independent predictor of the primary outcome identified (r= 0.39, P= 0.02). Correlations were similar for waking hours considered separately. However, for sleeping oximetry, BMI and age were the only independent predictors of time below 90%. Polysomnography demonstrated a high prevalence of rapid eye movement-related hypoventilation and obstructive sleep apnoea syndrome. CONCLUSIONS: Many patients with moderate hypoxaemia on resting P(a)O(2) desaturate significantly on ambulatory oximetry. The correlation between P(a)O(2) and proportion of saturations below 90% is moderate and similar to BMI, but this pattern does not hold during sleeping hours.

Asymmetry in pulse-coupled oscillators with delay.

We studied the dynamics of synchronization in asymmetrically coupled neural oscillators with time delay. Stability analysis revealed that symmetric excitatory coupling results in synchrony at multiple phase relations. Asymmetry yields two saddle-node bifurcations of the stable states when coupling is asymmetric. By contrast, with inhibitory coupling only in phase or antiphase is stable as long as coupling is symmetric. Otherwise, these stable states shift or even vanish. The reduced bistability range suggests the beneficial role of asymmetric coupling for reliable neural information transfer.

Local induction of pacemaking activity in a monolayer of electrically coupled quiescent NRK fibroblasts.

Cultures of normal rat kidney (NRK) fibroblasts may display spontaneous calcium action potentials which propagate throughout the cellular monolayer. Pacemaking activity of NRK cells was studied by patch clamp electrophysiology and vital calcium imaging, using a new experimental approach in which a ring was placed on the monolayer in order to physically separate pacemakers within or under the ring and follower cells outside the ring. Stimulation of cells inside the ring with IP(3)-generating hormones such as prostaglandin F(2alpha) (PGF(2alpha)) resulted in the induction of periodic action potentials outside the ring, which were abolished when the L-type calcium channel blocker nifedipine was added outside the ring, but not inside the ring. PGF(2alpha)-treated cells displayed asynchronous IP(3)-mediated calcium oscillations of variable frequency, while follower cells outside the ring showed synchronous calcium transients which coincided with the propagating action potential. Mathematical modelling indicated that addition of PGF(2alpha) inside the ring induced both a membrane potential gradient and an intracellular IP(3) gradient, both of which are essential for the induction of pacemaking activity under the ring. These data show that intercellular coupling between PGF(2alpha)-treated and non-treated cells is essential for the generation of a functional pacemaker area whereby synchronization of calcium oscillations occurs by activation of L-type calcium channels.

[Churg-Strauss syndrome in a patient with asthma treated with montelukast]. / Syndroom van Churg-Strauss bij een astmapatiënt onder behandeling met montelukast.

A 75-year-old woman with a history of asthma, rhinitis and nasal polyps was admitted due to petechial lesions on the lower left leg and weakness of the right foot. Six weeks prior to admission, she had started treatment with montelukast 10 mg daily. Based on the asthma, eosinophilia, mononeuritis of the right leg and a skin biopsy showing small vessel vasculitis with eosinophilic granulocytes, the patient was diagnosed with Churg-Strauss syndrome (CSS). After consulting with the pulmonologist, montelukast therapy was discontinued and replaced with a combined preparation of a parasympatholytic and a P2-sympathomimetic. The patient was also given prednisone 60 mg daily, which resulted in prompt clinical improvement and resolution of the eosinophilia. Development of CSS has been associated with the use of montelukast and should be considered in patients with asthma who develop new symptoms, such as neuritis, vasculitis of the skin or pulmonary infiltrates with an increase in eosinophilia during montelukast therapy. In these patients, treatment with montelukast should be discontinued, although whether a causal relationship exists between montelukast and CSS continues to be debated in the literature.

Microbial processes as key drivers for metal (im)mobilization along a redox gradient in the saturated zone.

Two sites representing different aquifer types, i.e., Dommel (sandy) and Flémalle (gravelly loam) along the Meuse River, have been selected to conduct microcosm experiments. Various conditions ranging from aerobic over nitrate- to sulphate reducing were imposed. For the sandy aquifer, nitrate reducing conditions predominated, which specifically in the presence of a carbon source led to pH increases and enhanced Zn removal. For the calcareous gravelly loam, sulphate reduction was dominant resulting in immobilization of both Zn and Cd. For both aquifer types and almost all redox conditions, higher arsenic concentrations were measured in the groundwater. Analyses of different specific microbial populations by polymerase chain reaction (PCR) revealed the dominance of denitrifiers for the Dommel site, while sulfate reducing bacteria (SRB) were the prevailing population for all redox conditions in the Flémalle samples.

Interactions between self-motion and depth perception in the processing of optic flow.

Moving and acting in a 3D environment requires the perception of its 3D structure. Vision is known to play a crucial role in the control of self-motion, particularly through the changes in the retinal image subsequent to movements of the observer. Reciprocally, signals related to self-motion can also influence our visual perception of 3D space. These interactions between 3D visual perception and self-motion, as demonstrated behaviourally, are now better understood thanks to the development of computational models for processing moving images. They also bear a particular interest in the context of the recent intensive exploration of the inferior parietal lobe (IPL) by neurophysiologists. The IPL is now firmly established as one site of interaction between 3D visual perception and motor control. The parallel between behaviour and neurophysiology leads to a set of crucial, yet unanswered, questions.

Coordination of arm muscles during flexion and supination: application of the tensor analysis approach.

In order to obtain a good understanding of the coordination of the motor system several problems have to be solved. Two major issues are: (1) that muscles do not form an orthogonal coordinate system, and (2) that the number of muscles that may contribute to a movement in general exceeds the number of degrees of freedom of the movement. The latter allows the movement to be executed by an infinite variety of muscle activations. A theoretical solution to these problems has been elaborated by Pellionisz and Llinás. However, convincing experimental support for this theory is still lacking. In this paper the theory has been applied to the activation of arm muscles which contribute to flexion/extension and supination/pronation of the arm. Motor unit activity was recorded with fine wire electrodes. As reported in previous papers, the recruitment threshold of motor units in arm muscles during isometric contraction depends on a combination of forces in flexion and supination directions. This dependence is characteristic for motor units in a single muscle, but is very different for motor units in different muscles. The theoretical results are in good agreement with the behavior of the recruitment threshold for flexion, which decreases (such as m. biceps brachii), or increases (such as for m. brachialis and m. brachioradialis) with force in supination direction. The theory also correctly predicts how the recruitment threshold for motor units changes as a function of the angle between forearm and upper arm. These results give firm support to the hypothesis that the central nervous system uses a tensorial approach for the activation of the motor system, as originally proposed by Pellionisz and Llinás.

Intrinsic and afferent components in apparent muscle stiffness in man.

The subject was asked to bring his lower arm to a prescribed position against an applied torque. He was instructed not to intervene when the torque was unexpectedly changed and this resulted in a movement to a new position. During these experiments motor unit activity of m. biceps or triceps brachii was recorded. It was found that changes in the torque are compensated by reflex-induced recruitment of motor units and variations in their firing frequency. Recordings of motor unit activity revealed that in the range investigated the firing frequency of the motoneurones varied approximately linearly with the applied torque. From the results, it is concluded that afferent input plays a more important role in position control than intrinsic muscle properties. It is argued that the afferent feedback is controlled by central activation of the gamma-motoneurones.

New aspects of human muscle coordination as revealed by motor-unit studies.

Increasing evidence has become available against the view that individual muscles should be regarded as functional units in the control of force by the motor apparatus. The relative contribution of various motoneurone pools (belonging to a single muscle) to muscle force appears to depend on the direction of torque exerted by the corresponding limb. This clearly indicates the presence of more than one control or activation parameter for the total motoneurone pool of a single muscle. Windhorst et al. (1989) have even proposed a combined sensory and neuromuscular partitioning, such that segmental control mechanisms are based on subdivisions of motoneurone pool--muscle complexes. Size-related recruitment occurs within these subdivisions rather than in the motoneurone pool as a whole. Moreover, motoneurones can operate in various modes (different relative contributions of the recruitment mechanism and the firing frequency mechanism to muscle force) related either to movement or to force. This indicates that muscle coordination is organised differently in force tasks and in movement tasks. These properties of motoneurone activation mentioned above are difficult to incorporate in existing models on sensorimotor organisation. Some of these discrepancies will be reviewed in order to highlight future directions for modelling.

Sauvagine regulates Ca2+ oscillations and electrical membrane activity of melanotrope cells of Xenopus laevis.

Ca2+ oscillations regulate secretion of the hormone alpha-melanphore-stimulating hormone (alpha-MSH) by the neuroendocrine pituitary melanotrope cells of the amphibian Xenopus laevis. These Ca2+ oscillations are built up by discrete increments in the intracellular Ca2+ concentration, the Ca2+ steps, which are generated by electrical membrane bursting firing activity. It has been demonstrated that the patterns of Ca2+ oscillations and kinetics of the Ca2+ steps can be modulated by changing the degree of intracellular Ca2+ buffering. We hypothesized that neurotransmitters known to regulate alpha-MSH secretion also modulate the pattern of Ca2+ oscillations and related electrical membrane activity. In this study, we tested this hypothesis for the secretagogue sauvagine. Using high temporal-resolution Ca2+ imaging, we show that sauvagine modulated the pattern of Ca2+ signalling by increasing the frequency of Ca2+ oscillations and inducing a broadening of the oscillations through its effect on various Ca2+ step parameters. Second, we demonstrate that sauvagine caused a small but significant decrease in K+ currents measured in the whole-cell voltage-clamp, whereas Ca2+ currents remained unchanged. Third, in the cell-attached patch-clamp mode, a stimulatory effect of sauvagine on action current firing was observed. Moreover, sauvagine changed the shape of individual action currents. These results support the hypothesis that the secretagogue sauvagine stimulates the frequency of Ca2+ oscillations in Xenopus melanotropes by altering Ca2+ step parameters, an action that likely is evoked by an inhibition of K+ currents.

The effect of isoluminant and isochromatic stimuli on latency and amplitude of saccades.

When two stimuli are presented in different positions successively at short time intervals saccadic eye movements are usually directed at intermediate positions. This phenomenon of "averaging" of saccadic eye movements has been studied in responses to double-step target displacements in different stimulus conditions. In these conditions isoluminant and isochromatic stimuli were used with variable contrast and at different background luminances. Although the critical duration of temporal summation differed considerably in these stimulus conditions the duration of the phenomenon of "averaging" remained the same in all conditions. This indicates that temporal properties of the sensory system are not the prime cause of "averaging". Moreover, the onset time of "averaging" relative to the second target displacement turned out to be highly correlated with the mean latency of saccades in the different conditions. The implications of the results for models of oculomotor control are discussed.

Perception of three-dimensional shape from ego- and object-motion: comparison between small- and large-field stimuli.

We compare the performance in the detection of the shape of concave, planar and convex surfaces for small-field (8 deg) and large-field (90 deg) stimuli. Shape is perceived from head translations, object translations and object rotations. We find large differences between small-field and large-field stimulation. For small-field stimulation performance is best for object rotation, intermediate for self-motion and worst for object translation. For large-field stimulation performance is similar across conditions. Few errors on the sign of the curvature are found for self-motion for both field sizes, indicating that self-motion information disambiguates the curvature sign. For object rotation with small-field stimulation, the concave-convex ambiguity is strong with many apparent deformations. In contrast, large-field curvature signs are always accurately reported, suggesting that the weight of the rigidity hypothesis depends on field size.

An alternative three-dimensional interpretation of Hering's equal-innervation law for version and vergence eye movements.

In the context of Hering's equal-innervation law, this paper discusses the problem of how the three-dimensional positions of the two eyes, each expressed by a rotation vector, can be separated into contributions of the version and vergence system. As proposed by Van Rijn and Van den Berg [(1993) Vision Research, 33, 691-708], this can be done by taking the sum and difference of the position rotation vectors of each eye. In our alternative procedure the vergence signal is defined as the rotation which transforms the left eye position into the right eye position and the version signal is the common factor in both eye positions that remains after removing the vergence signal. The version and vergence contributions, defined in this way, can be interpreted straightforwardly as rotations. When Van Rijn and Van den Berg applied their definitions to their own data, they obtained the interesting result that the reconstructed version and vergence contributions were effectively limited to two dimensions (2D). The version signal was confined to Listing's plane (no torsion) whereas the vergence signal remained within a horizontal-torsional plane (no vertical vergence). They showed theoretically that a model based on 2D version/2D vergence control will indeed produce the torsional eye positions in near fixations found in their experiments. This model cannot account for a second set of data in the literature [Mok, Ro, Cadera, Crawford & Vilis (1992) Vision Research, 32, 2055-2064]. With our definitions, we found that the simple 2D version/2D vergence control strategy cannot account for the Van Rijn and Van den Berg (1993) data but is nicely compatible with the considerably smaller amount of cyclotorsion in the data collected by Mok et al. (1992). We also show that, in such a system, having 2D vergence control is compatible with minimization of torsional disparity and provides the cyclovergence signals suitable for stabilizing the eyes in the non-Listing positions caused by a vertical saccade in near vision.

Remapping of neural activity in the motor colliculus: a neural network study.

Neurophysiological studies have shown that the deeper layers of the superior colliculus (SC) contain a topographical neural map representing the ocular vectorial displacement required for foveation of the target (motor error). It is known that the location of the active area in this neural map can be updated, not only following changes in retinal error, but also by efference-copy signals representing a change in eye position. Since it can be shown that a two-layer feedforward network cannot perform this task, we have simulated this system by training a three-layered neural network with access to retinal error and efference copy information about eye position. The network was taught to code motor error topographically (as in the collicular motor map) by generating population activity at the appropriate location in its output layer for different combinations of visual and efference copy signals. After the network had learned the required remapping transformation with sufficient precision (error of one deg over an 80 x 80 deg working range), the properties of the trained network were analyzed. From an investigation of the activity patterns of the hidden units in the trained network it appeared that information about target location relative to the head, implicitly present at the level of input signals, is no longer available at the level of the hidden layer. More detailed inspection of the properties of these units revealed that they code motor error. Their movement field is a monotonic function of motor error amplitude, and shows broad direction tuning specific for each unit. Finally, simulations were made with a four layered network with an architecture and access to input signals closely mimicking Robinson's model of the saccadic system. Again, the network was trained to represent motor error topographically in its output layer. The model shows, for the first time, how the computation of the topographical motor error map in the SC from retinal and eye position signals may proceed in two steps, involving a stage where target location is coded in a distributed fashion in craniotopic coordinates and a subsequent supracollicular stage, where radial motor error is represented in a firing-rate code in units with broad tuning characteristics. These two stages in the model show interesting similarities with the characteristics of neuron populations shown neurophysiologically in area 7a and parietal region LIP, respectively.

A model for the peripheral auditory nervous system of the grassfrog.

A model is presented which incorporates several data from the literature on isolated parts of the peripheral auditory nervous system into a coherent model. The usefulness of the model lies in the fact that it describes the functional properties of eighth nerve fibres and dorsal medullary nucleus neurons in response to monaural stimuli. The components are: a middle ear filter, transduction and tuning of the haircell, short-term adaptation, event generation with refractory properties, and coincidence detection. In a previous paper [Van Stokkum (1987), Hear. Res. 29, 223-235] a class of dorsal medullary nucleus neurons was described, which preferred fast intensity changes. Using a coincidence detection mechanism the proposed model reproduces the same preference. Variation of the parameters of the model successfully reproduces the range of response patterns which have been obtained from eighth nerve fibres and dorsal medullary nucleus neurons. With one set of parameters the output of the model in response to a set of spectrally and temporally structured stimuli qualitatively resembles the response of a single neuron. In this way the responses to the different stimuli are synthesized into a framework, which functionally describes the neuron.

The relative activation of elbow-flexor muscles in isometric flexion and in flexion/extension movements.

Coordination studies of multi-joint movements suggest that the central nervous system uses some constraints to reduce the large number of degrees of freedom of the arm. To gain insight into how the net joint torque is distributed among the muscles, intramuscular EMG recordings were made to determine the relative activation of five major elbow-flexor muscles during isometric, shortening, and lengthening contractions at three elbow joint angles. A regularization procedure was used to evaluate the effect of two different approaches used to calculate the relative contribution of elbow-flexor muscles to joint torque from intramuscular EMG recordings. The results demonstrate a significant increase of the relative contribution of the biarticular muscles for more extended elbow joint angles and for isotonic tasks relative to isometric tasks.

Estimating the contribution of muscles to joint torque based on motor-unit activity.

Because most joints in the human arm are crossed by a number of muscles which exceeds the number of degrees of freedom for those joints, the motor system can use a variety of muscle activation patterns for the same torque in each joint. We have developed a mode to estimate the contribution of individual muscles to the total torque in a joint based on intramuscular EMG recordings. EMG activity recorded with surface electrodes may be contaminated with cross-talk from other muscles. Moreover, it may not be representative for the activation of a muscle when there are several subpopulations of motor units in the muscle. We derive a relation between the recruitment threshold of a motor unit in a subpopulation for force in various directions and the relative contribution by that subpopulation to joint torque. A set of linear equations can then be constructed which relates the contribution of each subpopulation (and therefore of each muscle) to the total joint torque. If the activition of individual subpopulations is modulated differently for forces in various directions, the relative contribution of the individual subpopulations to the total joint torque can be estimated.