Predictive Modeling for Diagnostic Tests with High Specificity, but Low Sensitivity: A Study of the Glycerol Test in Patients with Suspected Menière’s Disease

A high specificity does not ensure that the expected benefit of a diagnostic test outweighs its cost. Problems arise, in particular, when the investigation is expensive, the prevalence of a positive test result is relatively small for the candidate patients, and the sensitivity of the test is low so that the information provided by a negative result is virtually negligible. The consequence may be that a potentially useful test does not gain broader acceptance. Here we show how predictive modeling can help to identify patients for whom the ratio of expected benefit and cost reaches an acceptable level so that testing these patients is reasonable even though testing all patients might be considered wasteful. Our application example is based on a retrospective study of the glycerol test, which is used to corroborate a suspected diagnosis of Menière’s disease. Using the pretest hearing thresholds at up to 10 frequencies, predictions were made by K-nearest neighbor classification or logistic regression. Both methods estimate, based on results from previous patients, the posterior probability that performing the considered test in a new patient will have a positive outcome. The quality of the prediction was evaluated using leave-one-out cross-validation, making various assumptions about the costs and benefits of testing. With reference to all 356 cases, the probability of a positive test result was almost 0.4. For subpopulations selected by K-nearest neighbor classification, which was clearly superior to logistic regression, this probability could be increased up to about 0.6. Thus, the odds of a positive test result were more than doubled

Amyotrophic lateral sclerosis weakens spinal recurrent inhibition and post-activation depression

Objectives: Amyotrophic lateral sclerosis (ALS) disrupts motoneurons that control movement and some vital functions, however, exact details of the neuronal circuits involved in ALS have yet to be fully endorsed. To contribute to our understanding of the responsible neuronal circuits, we aimed to investigate the spinal recurrent inhibition (RI) and post-activation depression (P-AD) in ALS patients. / Methods: In two groups of ALS patients, i.e. lumbar-affected (clinical signs in leg muscles) and nonlumbar-affected (clinical signs in arms or bulbar region but not in the legs), RI and P-AD on the soleus muscle were investigated using single motor units and amplitude changes of H-reflex in surface electromyography, respectively. The data were compared with healthy subjects. / Results: Compared to controls, P-AD of H-reflex was reduced severely in lumbar-affected patients and reduced to a certain degree in nonlumbar-affected patients. Similarly, a significant reduction in the duration of RI on firing motoneurons was found in lumbar-affected patients (11.5 ± 2.6 ms) but not in nonlumbar-affected patients (29.7 ± 12.4 ms, P<0.0001) compared to controls (30.8 ± 7.2 ms, P<0.0001). / Conclusion: The current study revealed that spinal inhibitory circuits are impaired in ALS. / Significance: These findings may provide insight for proposing new therapeutic approaches and following disease progression in humans

Thermodynamic Model of a Very High Efficiency Power Plant Based on a Biomass Gasifier, SOFCs, and a Gas Turbine

Thermodynamic calculations with a power plant based on a biomass gasifier, SOFCs and a gas turbine are presented. The SOFC anode off-gas which mainly consists of steam and carbon dioxides used as a gasifying agent leading to an allothermal gasification process for which heat is required. Implementation of heat pipes between the SOFC and the gasifier using two SOFC stacks and intercooling the fuel and the cathode streams in between them has shown to be a solution on one hand to drive the allothermal gasification process and on the other hand to cool down the SOFC. It is seen that this helps to reduce the exergy losses in the system significantly. With such a system, electrical efficiency around 73% is shown as achievable

Post-activation depression of primary afferents reevaluated in humans

Amplitude variation of Hoffmann Reflex (H-reflex) was used as a tool to investigate many neuronal networks. However, H-reflex itself is a subject to intrinsic changes including post-activation depression (P-AD). We aimed to investigate P-AD and its implication on motor control in humans. Upon tibial nerve stimulation in 23 healthy participants, peak-to-peak amplitude change of H-reflex was investigated using surface electromyography (SEMG) of soleus muscle. Variety of stimulus intensities, interstimulus intervals (ISIs), voluntary contraction levels/types and force recording were used to investigate the nature of P-AD. We have shown that P-AD was significantly stronger in the shorter ISIs. The only exception was the ISI of 200 msecs which had a weaker P-AD than some of the longer ISIs. Sudden muscle relaxation, on the other hand, further increased the effectiveness of the ongoing P-AD. Moreover, P-AD displayed its full effect with the first stimulus when there was no muscle contraction and was efficient to reduce the muscle force output by about 30%. These findings provide insight about the variations and mechanism of P-AD and could lead to improvements in diagnostic tools in neurological diseases

Effect of aging on H-reflex response to fatigue

Injury as a result of tripping is relatively common among older people. The risk of falling increases with fatigue and of importance is the ability to dorsiflex the foot through timely activation of the tibialis anterior (TA) muscle to ensure the foot clears the ground, or an obstacle, during the swing phase of walking. We, therefore, questioned whether the muscle spindle input to the motoneurons alters with ongoing fatigue in older people. We electrically stimulated the common peroneal nerve to assess the TA primary afferent efficacy using H-reflex before, immediately following and after a fatiguing maximal isometric contraction. M-response was kept unchanged throughout the experiment to ensure a similar stimulus intensity was delivered across time points. H-reflex increased significantly while the TA muscle was in a state of fatigue for the younger participants but tended to decrease with increasing age. The main contributor to the tonicity of TA muscle, i.e., excitatory synapses of spindle primary endings of motoneurons that innervate TA muscle, tend to lose their efficacy during fatigue in the older individuals but increased efficiency in the majority of the younger people. Since TA muscle is the main dorsiflexor of the foot and it needs to be active during the swing phase of stepping to prevent tripping, older individuals become more susceptible to falling when their muscles are fatigued. This finding may help improve devices/treatments to overcome the problem of tripping among older individuals

Analysis of motoneuron responses to composite synaptic volleys (computer simulation study)

This paper deals with the analysis of changes in motoneuron (MN) firing evoked by repetitively applied stimuli aimed toward extracting information about the underlying synaptic volleys. Spike trains were obtained from computer simulations based on a threshold-crossing model of tonically firing MN, subjected to stimulation producing postsynaptic potentials (PSPs) of various parameters. These trains were analyzed as experimental results, using the output measures that were previously shown to be most effective for this purpose: peristimulus time histogram, raster plot and peristimulus time intervalgram. The analysis started from the effects of single excitatory and inhibitory PSPs (EPSPs and IPSPs). The conclusions drawn from this analysis allowed the explanation of the results of more complex synaptic volleys, i.e., combinations of EPSPs and IPSPs, and the formulation of directions for decoding the results of human neurophysiological experiments in which the responses of tonically firing MNs to nerve stimulation are analyzed

Mimicking human neuronal pathways in silico: an emergent model on the effective connectivity

International audienceWe present a novel computational model that detects temporal configurations of a given human neuronal pathway and constructs its artificial replication. This poses a great challenge since direct recordings from individual neurons are impossible in the human central nervous system and therefore the underlying neuronal pathway has to be considered as a black box. For tackling this challenge, we used a branch of complex systems modeling called artificial self-organization in which large sets of software entities interacting locally give rise to bottom-up collective behaviors. The result is an emergent model where each software entity represents an integrate-and-fire neuron. We then applied the model to the reflex responses of single motor units obtained from conscious human subjects. Experimental results show that the model recovers functionality of real human neuronal pathways by comparing it to appropriate surrogate data. What makes the model promising is the fact that, to the best of our knowledge, it is the first realistic model to self-wire an artificial neuronal network by efficiently combining neuroscience with artificial self-organization. Although there is no evidence yet of the model's connectivity mapping onto the human connectivity, we anticipate this model will help neuroscientists to learn much more about human neuronal networks, and could also be used for predicting hypotheses to lead future experiments

Exploring the receptor origin of vibration-induced reflexes

STUDY DESIGN: An experimental design. OBJECTIVES: The aim of this study was to determine the latencies of vibration-induced reflexes in individuals with and without spinal cord injury (SCI), and to compare these latencies to identify differences in reflex circuitries. SETTING: A tertiary rehabilitation center in Istanbul. METHODS: Seventeen individuals with chronic SCI (SCI group) and 23 participants without SCI (Control group) were included in this study. Latency of tonic vibration reflex (TVR) and whole-body vibration-induced muscular reflex (WBV-IMR) of the left soleus muscle was tested for estimating the reflex origins. The local tendon vibration was applied at six different vibration frequencies (50, 85, 140, 185, 235, and 265 Hz), each lasting for 15 s with 3-s rest intervals. The WBV was applied at six different vibration frequencies (35, 37, 39, 41, 43, and 45 Hz), each lasting for 15 s with 3-s rest intervals. RESULTS: Mean (SD) TVR latency was 39.7 (5.3) ms in the SCI group and 35.9 (2.7) ms in the Control group with a mean (95% CI) difference of -3.8 (-6.7 to -0.9) ms. Mean (SD) WBV-IMR latency was 45.8 (7.4) ms in the SCI group and 43.3 (3.0) ms in the Control group with a mean (95% CI) difference of -2.5 (-6.5 to 1.4) ms. There were significant differences between TVR latency and WBV-IMR latency in both the groups (mean (95% CI) difference; -6.2 (-9.3 to -3.0) ms, p = 0.0001 for the SCI group and -7.4 (-9.3 to -5.6) ms, p = 0.011 for Control group). CONCLUSIONS: The results suggest that the receptor of origin of TVR and WBV-IMR may be different

Raman enhancement on a broadband meta-surface

Plasmonic metamaterials allow confinement of light to deep subwavelength dimensions, while allowing for the tailoring of dispersion and electromagnetic mode density to enhance specific photonic properties. Optical resonances of plasmonic molecules have been extensively investigated; however, benefits of strong coupling of dimers have been overlooked. Here, we construct a plasmonic meta-surface through coupling of diatomic plasmonic molecules which contain a heavy and light meta-atom. Presence and coupling of two distinct types of localized modes in the plasmonic molecule allow formation and engineering of a rich band structure in a seemingly simple and common geometry, resulting in a broadband and quasi-omni-directional meta-surface. Surface-enhanced Raman scattering benefits from the simultaneous presence of plasmonic resonances at the excitation and scattering frequencies, and by proper design of the band structure to satisfy this condition, highly repeatable and spatially uniform Raman enhancement is demonstrated. On the basis of calculations of the field enhancement distribution within a unit cell, spatial uniformity of the enhancement at the nanoscale is discussed. Raman scattering constitutes an example of nonlinear optical processes, where the wavelength conversion during scattering may be viewed as a photonic transition between the bands of the meta-material. © 2012 American Chemical Society