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Sample records for auditory-nerve responses predict

  1. Auditory brainstem responses predict auditory nerve fiber thresholds and frequency selectivity in hearing impaired chinchillas.

    Science.gov (United States)

    Henry, Kenneth S; Kale, Sushrut; Scheidt, Ryan E; Heinz, Michael G

    2011-10-01

    Noninvasive auditory brainstem responses (ABRs) are commonly used to assess cochlear pathology in both clinical and research environments. In the current study, we evaluated the relationship between ABR characteristics and more direct measures of cochlear function. We recorded ABRs and auditory nerve (AN) single-unit responses in seven chinchillas with noise-induced hearing loss. ABRs were recorded for 1-8 kHz tone burst stimuli both before and several weeks after 4 h of exposure to a 115 dB SPL, 50 Hz band of noise with a center frequency of 2 kHz. Shifts in ABR characteristics (threshold, wave I amplitude, and wave I latency) following hearing loss were compared to AN-fiber tuning curve properties (threshold and frequency selectivity) in the same animals. As expected, noise exposure generally resulted in an increase in ABR threshold and decrease in wave I amplitude at equal SPL. Wave I amplitude at equal sensation level (SL), however, was similar before and after noise exposure. In addition, noise exposure resulted in decreases in ABR wave I latency at equal SL and, to a lesser extent, at equal SPL. The shifts in ABR characteristics were significantly related to AN-fiber tuning curve properties in the same animal at the same frequency. Larger shifts in ABR thresholds and ABR wave I amplitude at equal SPL were associated with greater AN threshold elevation. Larger reductions in ABR wave I latency at equal SL, on the other hand, were associated with greater loss of AN frequency selectivity. This result is consistent with linear systems theory, which predicts shorter time delays for broader peripheral frequency tuning. Taken together with other studies, our results affirm that ABR thresholds and wave I amplitude provide useful estimates of cochlear sensitivity. Furthermore, comparisons of ABR wave I latency to normative data at the same SL may prove useful for detecting and characterizing loss of cochlear frequency selectivity.

  2. Modeling auditory-nerve responses to electrical stimulation

    DEFF Research Database (Denmark)

    Joshi, Suyash Narendra; Dau, Torsten; Epp, Bastian

    2014-01-01

    Cochlear implants (CI) directly stimulate the auditory nerve (AN), bypassing the mechano-electrical transduction in the inner ear. Trains of biphasic, charge balanced pulses (anodic and cathodic) are used as stimuli to avoid damage of the tissue. The pulses of either polarity are capable of produ......Cochlear implants (CI) directly stimulate the auditory nerve (AN), bypassing the mechano-electrical transduction in the inner ear. Trains of biphasic, charge balanced pulses (anodic and cathodic) are used as stimuli to avoid damage of the tissue. The pulses of either polarity are capable......μs, which is large enough to affect the temporal coding of sounds and hence, potentially, the communication abilities of the CI listener. In the present study, two recently proposed models of electric stimulation of the AN [1,2] were considered in terms of their efficacy to predict the spike timing...... for anodic and cathodic stimulation of the AN of cat [3]. The models’ responses to the electrical pulses of various shapes [4,5,6] were also analyzed. It was found that, while the models can account for the firing rates in response to various biphasic pulse shapes, they fail to correctly describe the timing...

  3. A model of auditory nerve responses to electrical stimulation

    DEFF Research Database (Denmark)

    Joshi, Suyash Narendra; Dau, Torsten; Epp, Bastian

    to neutralize the charge induced during the cathodic phase. Single-neuron recordings in cat auditory nerve using monophasic electrical stimulation show, however, that both phases in isolation can generate an AP. The site of AP generation differs for both phases, being more central for the anodic phase and more...... perception of CI listeners, a model needs to incorporate the correct responsiveness of the AN to anodic and cathodic polarity. Previous models of electrical stimulation have been developed based on AN responses to symmetric biphasic stimulation or to monophasic cathodic stimulation. These models, however......, fail to correctly predict responses to anodic stimulation. This study presents a model that simulates AN responses to anodic and cathodic stimulation. The main goal was to account for the data obtained with monophasic electrical stimulation in cat AN. The model is based on an exponential integrate...

  4. Wiener-kernel analysis of responses to noise of chinchilla auditory-nerve fibers

    NARCIS (Netherlands)

    Recio-Spinoso, A; Temchin, AN; van Dijk, P; Fan, YH; Ruggero, MA

    2005-01-01

    Responses to broadband Gaussian white noise were recorded in auditory-nerve fibers of deeply anesthetized chinchillas and analyzed by computation of zeroth-, first-, and second-order Wiener kernels. The first- order kernels ( similar to reverse correlations or "revcors") of fibers with characteristi

  5. Wiener kernels of chinchilla auditory-nerve fibers : Verification using responses to tones, clicks, and noise and comparison with basilar-membrane vibrations

    NARCIS (Netherlands)

    Temchin, AN; Recio-Spinoso, A; van Dijk, P; Ruggero, MA

    2005-01-01

    Responses to tones, clicks, and noise were recorded from chinchilla auditory-nerve fibers (ANFs). The responses to noise were analyzed by computing the zeroth-, first-, and second-order Wiener kernels (h(0), h(1), and h(2)). The h(1) s correctly predicted the frequency tuning and phases of responses

  6. Changes across time in the temporal responses of auditory nerve fibers stimulated by electric pulse trains.

    Science.gov (United States)

    Miller, Charles A; Hu, Ning; Zhang, Fawen; Robinson, Barbara K; Abbas, Paul J

    2008-03-01

    Most auditory prostheses use modulated electric pulse trains to excite the auditory nerve. There are, however, scant data regarding the effects of pulse trains on auditory nerve fiber (ANF) responses across the duration of such stimuli. We examined how temporal ANF properties changed with level and pulse rate across 300-ms pulse trains. Four measures were examined: (1) first-spike latency, (2) interspike interval (ISI), (3) vector strength (VS), and (4) Fano factor (FF, an index of the temporal variability of responsiveness). Data were obtained using 250-, 1,000-, and 5,000-pulse/s stimuli. First-spike latency decreased with increasing spike rate, with relatively small decrements observed for 5,000-pulse/s trains, presumably reflecting integration. ISIs to low-rate (250 pulse/s) trains were strongly locked to the stimuli, whereas ISIs evoked with 5,000-pulse/s trains were dominated by refractory and adaptation effects. Across time, VS decreased for low-rate trains but not for 5,000-pulse/s stimuli. At relatively high spike rates (>200 spike/s), VS values for 5,000-pulse/s trains were lower than those obtained with 250-pulse/s stimuli (even after accounting for the smaller periods of the 5,000-pulse/s stimuli), indicating a desynchronizing effect of high-rate stimuli. FF measures also indicated a desynchronizing effect of high-rate trains. Across a wide range of response rates, FF underwent relatively fast increases (i.e., within 100 ms) for 5,000-pulse/s stimuli. With a few exceptions, ISI, VS, and FF measures approached asymptotic values within the 300-ms duration of the low- and high-rate trains. These findings may have implications for designs of cochlear implant stimulus protocols, understanding electrically evoked compound action potentials, and interpretation of neural measures obtained at central nuclei, which depend on understanding the output of the auditory nerve.

  7. Effects of Electrode Position on Spatiotemporal Auditory Nerve Fiber Responses: A 3D Computational Model Study

    Directory of Open Access Journals (Sweden)

    Soojin Kang

    2015-01-01

    Full Text Available A cochlear implant (CI is an auditory prosthesis that enables hearing by providing electrical stimuli through an electrode array. It has been previously established that the electrode position can influence CI performance. Thus, electrode position should be considered in order to achieve better CI results. This paper describes how the electrode position influences the auditory nerve fiber (ANF response to either a single pulse or low- (250 pulses/s and high-rate (5,000 pulses/s pulse-trains using a computational model. The field potential in the cochlea was calculated using a three-dimensional finite-element model, and the ANF response was simulated using a biophysical ANF model. The effects were evaluated in terms of the dynamic range, stochasticity, and spike excitation pattern. The relative spread, threshold, jitter, and initiated node were analyzed for single-pulse response; and the dynamic range, threshold, initiated node, and interspike interval were analyzed for pulse-train stimuli responses. Electrode position was found to significantly affect the spatiotemporal pattern of the ANF response, and this effect was significantly dependent on the stimulus rate. We believe that these modeling results can provide guidance regarding perimodiolar and lateral insertion of CIs in clinical settings and help understand CI performance.

  8. A Phenomenological Model of the Electrically Stimulated Auditory Nerve Fiber: Temporal and Biphasic Response Properties.

    Science.gov (United States)

    Horne, Colin D F; Sumner, Christian J; Seeber, Bernhard U

    2016-01-01

    We present a phenomenological model of electrically stimulated auditory nerve fibers (ANFs). The model reproduces the probabilistic and temporal properties of the ANF response to both monophasic and biphasic stimuli, in isolation. The main contribution of the model lies in its ability to reproduce statistics of the ANF response (mean latency, jitter, and firing probability) under both monophasic and cathodic-anodic biphasic stimulation, without changing the model's parameters. The response statistics of the model depend on stimulus level and duration of the stimulating pulse, reproducing trends observed in the ANF. In the case of biphasic stimulation, the model reproduces the effects of pseudomonophasic pulse shapes and also the dependence on the interphase gap (IPG) of the stimulus pulse, an effect that is quantitatively reproduced. The model is fitted to ANF data using a procedure that uniquely determines each model parameter. It is thus possible to rapidly parameterize a large population of neurons to reproduce a given set of response statistic distributions. Our work extends the stochastic leaky integrate and fire (SLIF) neuron, a well-studied phenomenological model of the electrically stimulated neuron. We extend the SLIF neuron so as to produce a realistic latency distribution by delaying the moment of spiking. During this delay, spiking may be abolished by anodic current. By this means, the probability of the model neuron responding to a stimulus is reduced when a trailing phase of opposite polarity is introduced. By introducing a minimum wait period that must elapse before a spike may be emitted, the model is able to reproduce the differences in the threshold level observed in the ANF for monophasic and biphasic stimuli. Thus, the ANF response to a large variety of pulse shapes are reproduced correctly by this model.

  9. Modeling the anti-masking effects of the olivocochlear reflex in auditory nerve responses to tones in sustained noise.

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    Chintanpalli, Ananthakrishna; Jennings, Skyler G; Heinz, Michael G; Strickland, Elizabeth A

    2012-04-01

    The medial olivocochlear reflex (MOCR) has been hypothesized to provide benefit for listening in noise. Strong physiological support for an anti-masking role for the MOCR has come from the observation that auditory nerve (AN) fibers exhibit reduced firing to sustained noise and increased sensitivity to tones when the MOCR is elicited. The present study extended a well-established computational model for normal-hearing and hearing-impaired AN responses to demonstrate that these anti-masking effects can be accounted for by reducing outer hair cell (OHC) gain, which is a primary effect of the MOCR. Tone responses in noise were examined systematically as a function of tone level, noise level, and OHC gain. Signal detection theory was used to predict detection and discrimination for different spontaneous rate fiber groups. Decreasing OHC gain decreased the sustained noise response and increased maximum discharge rate to the tone, thus modeling the ability of the MOCR to decompress AN fiber rate-level functions. Comparing the present modeling results with previous data from AN fibers in decerebrate cats suggests that the ipsilateral masking noise used in the physiological study may have elicited up to 20 dB of OHC gain reduction in addition to that inferred from the contralateral noise effects. Reducing OHC gain in the model also extended the dynamic range for discrimination over a wide range of background noise levels. For each masker level, an optimal OHC gain reduction was predicted (i.e., where maximum discrimination was achieved without increased detection threshold). These optimal gain reductions increased with masker level and were physiologically realistic. Thus, reducing OHC gain can improve tone-in-noise discrimination even though it may produce a “hearing loss” in quiet. Combining MOCR effects with the sensorineural hearing loss effects already captured by this computational AN model will be beneficial for exploring the implications of their interaction

  10. Directionality of auditory nerve fiber responses to pure tone stimuli in the grassfrog, Rana temporaria. I. Spike rate responses

    DEFF Research Database (Denmark)

    Jørgensen, M B; Christensen-Dalsgaard, J

    1997-01-01

    We studied the directionality of spike rate responses of auditory nerve fibers of the grassfrog, Rana temporaria, to pure tone stimuli. All auditory fibers showed spike rate directionality. The strongest directionality was seen at low frequencies (200-400 Hz), where the spike rate could change by...

  11. Directionality of auditory nerve fiber responses to pure tone stimuli in the grassfrog, Rana temporaria. II. Spike timing

    DEFF Research Database (Denmark)

    Jørgensen, M B; Christensen-Dalsgaard, J

    1997-01-01

    We studied the directionality of spike timing in the responses of single auditory nerve fibers of the grass frog, Rana temporaria, to tone burst stimulation. Both the latency of the first spike after stimulus onset and the preferred firing phase during the stimulus were studied. In addition, the ...

  12. Predicting dynamic range and intensity discrimination for electrical pulse-train stimuli using a stochastic auditory nerve model: the effects of stimulus noise.

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    Xu, Yifang; Collins, Leslie M

    2005-06-01

    This work investigates dynamic range and intensity discrimination for electrical pulse-train stimuli that are modulated by noise using a stochastic auditory nerve model. Based on a hypothesized monotonic relationship between loudness and the number of spikes elicited by a stimulus, theoretical prediction of the uncomfortable level has previously been determined by comparing spike counts to a fixed threshold, Nucl. However, no specific rule for determining Nucl has been suggested. Our work determines the uncomfortable level based on the excitation pattern of the neural response in a normal ear. The number of fibers corresponding to the portion of the basilar membrane driven by a stimulus at an uncomfortable level in a normal ear is related to Nucl at an uncomfortable level of the electrical stimulus. Intensity discrimination limens are predicted using signal detection theory via the probability mass function of the neural response and via experimental simulations. The results show that the uncomfortable level for pulse-train stimuli increases slightly as noise level increases. Combining this with our previous threshold predictions, we hypothesize that the dynamic range for noise-modulated pulse-train stimuli should increase with additive noise. However, since our predictions indicate that intensity discrimination under noise degrades, overall intensity coding performance may not improve significantly.

  13. Reverse correlation analysis of auditory-nerve fiber responses to broadband noise in a bird, the barn owl.

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    Fontaine, Bertrand; Köppl, Christine; Peña, Jose L

    2015-02-01

    While the barn owl has been extensively used as a model for sound localization and temporal coding, less is known about the mechanisms at its sensory organ, the basilar papilla (homologous to the mammalian cochlea). In this paper, we characterize, for the first time in the avian system, the auditory nerve fiber responses to broadband noise using reverse correlation. We use the derived impulse responses to study the processing of sounds in the cochlea of the barn owl. We characterize the frequency tuning, phase, instantaneous frequency, and relationship to input level of impulse responses. We show that, even features as complex as the phase dependence on input level, can still be consistent with simple linear filtering. Where possible, we compare our results with mammalian data. We identify salient differences between the barn owl and mammals, e.g., a much smaller frequency glide slope and a bimodal impulse response for the barn owl, and discuss what they might indicate about cochlear mechanics. While important for research on the avian auditory system, the results from this paper also allow us to examine hypotheses put forward for the mammalian cochlea.

  14. Predicting the threshold of pulse-train electrical stimuli using a stochastic auditory nerve model: the effects of stimulus noise.

    Science.gov (United States)

    Xu, Yifang; Collins, Leslie M

    2004-04-01

    The incorporation of low levels of noise into an electrical stimulus has been shown to improve auditory thresholds in some human subjects (Zeng et al., 2000). In this paper, thresholds for noise-modulated pulse-train stimuli are predicted utilizing a stochastic neural-behavioral model of ensemble fiber responses to bi-phasic stimuli. The neural refractory effect is described using a Markov model for a noise-free pulse-train stimulus and a closed-form solution for the steady-state neural response is provided. For noise-modulated pulse-train stimuli, a recursive method using the conditional probability is utilized to track the neural responses to each successive pulse. A neural spike count rule has been presented for both threshold and intensity discrimination under the assumption that auditory perception occurs via integration over a relatively long time period (Bruce et al., 1999). An alternative approach originates from the hypothesis of the multilook model (Viemeister and Wakefield, 1991), which argues that auditory perception is based on several shorter time integrations and may suggest an NofM model for prediction of pulse-train threshold. This motivates analyzing the neural response to each individual pulse within a pulse train, which is considered to be the brief look. A logarithmic rule is hypothesized for pulse-train threshold. Predictions from the multilook model are shown to match trends in psychophysical data for noise-free stimuli that are not always matched by the long-time integration rule. Theoretical predictions indicate that threshold decreases as noise variance increases. Theoretical models of the neural response to pulse-train stimuli not only reduce calculational overhead but also facilitate utilization of signal detection theory and are easily extended to multichannel psychophysical tasks.

  15. Tone and call responses of units in the auditory nerve and dorsal medullary nucleus of Xenopus laevis

    DEFF Research Database (Denmark)

    Elliott, Taffeta M.; Christensen-Dalsgaard, Jakob; Kelley, Darcy B.

    2007-01-01

    those in partially terrestrial anurans. Broad tuning exists across characteristic frequencies (CFs). Threshold minima are -101 dB re 1 mm/s at 675 Hz; -87 dB at 1,600 Hz; and -61 dB at 3,000 Hz (-90, -77, and -44 dB re 1 Pa, respectively), paralleling the peak frequency of vocalizations at 1.2-1.6 k......The clawed frog Xenopus laevis produces vocalizations consisting of distinct patterns of clicks. This study provides the first description of spontaneous, pure-tone and communication-signal evoked discharge properties of auditory nerve (n.VIII) fibers and dorsal medullary nucleus (DMN) cells...... in an obligatorily aquatic anuran. Responses of 297 n.VIII and 253 DMN units are analyzed for spontaneous rates (SR), frequency tuning, rate-intensity functions, and firing rate adaptation, with a view to how these basic characteristics shape responses to recorded call stimuli. Response properties generally resemble...

  16. Recovery characteristics of the electrically stimulated auditory nerve in deafened guinea pigs : Relation to neuronal status

    NARCIS (Netherlands)

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B.; Klis, Sjaak F L; Grolman, Wilko

    2015-01-01

    Successful cochlear implant performance requires adequate responsiveness of the auditory nerve to prolonged pulsatile electrical stimulation. Degeneration of the auditory nerve as a result of severe hair cell loss could considerably compromise this ability. The main objective of this study was to ch

  17. Horseradish peroxidase dye tracing and embryonic statoacoustic ganglion cell transplantation in the rat auditory nerve trunk.

    Science.gov (United States)

    Palmgren, Björn; Jin, Zhe; Jiao, Yu; Kostyszyn, Beata; Olivius, Petri

    2011-03-04

    At present severe damage to hair cells and sensory neurons in the inner ear results in non-treatable auditory disorders. Cell implantation is a potential treatment for various neurological disorders and has already been used in clinical practice. In the inner ear, delivery of therapeutic substances including neurotrophic factors and stem cells provide strategies that in the future may ameliorate or restore hearing impairment. In order to describe a surgical auditory nerve trunk approach, in the present paper we injected the neuronal tracer horseradish peroxidase (HRP) into the central part of the nerve by an intra cranial approach. We further evaluated the applicability of the present approach by implanting statoacoustic ganglion (SAG) cells into the same location of the auditory nerve in normal hearing rats or animals deafened by application of β-bungarotoxin to the round window niche. The HRP results illustrate labeling in the cochlear nucleus in the brain stem as well as peripherally in the spiral ganglion neurons in the cochlea. The transplanted SAGs were observed within the auditory nerve trunk but no more peripheral than the CNS-PNS transitional zone. Interestingly, the auditory nerve injection did not impair auditory function, as evidenced by the auditory brainstem response. The present findings illustrate that an auditory nerve trunk approach may well access the entire auditory nerve and does not compromise auditory function. We suggest that such an approach might compose a suitable route for cell transplantation into this sensory cranial nerve.

  18. Deafness in cochlear and auditory nerve disorders.

    Science.gov (United States)

    Hopkins, Kathryn

    2015-01-01

    Sensorineural hearing loss is the most common type of hearing impairment worldwide. It arises as a consequence of damage to the cochlea or auditory nerve, and several structures are often affected simultaneously. There are many causes, including genetic mutations affecting the structures of the inner ear, and environmental insults such as noise, ototoxic substances, and hypoxia. The prevalence increases dramatically with age. Clinical diagnosis is most commonly accomplished by measuring detection thresholds and comparing these to normative values to determine the degree of hearing loss. In addition to causing insensitivity to weak sounds, sensorineural hearing loss has a number of adverse perceptual consequences, including loudness recruitment, poor perception of pitch and auditory space, and difficulty understanding speech, particularly in the presence of background noise. The condition is usually incurable; treatment focuses on restoring the audibility of sounds made inaudible by hearing loss using either hearing aids or cochlear implants.

  19. Recovery characteristics of the electrically stimulated auditory nerve in deafened guinea pigs: relation to neuronal status.

    Science.gov (United States)

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B; Klis, Sjaak F L; Grolman, Wilko

    2015-03-01

    Successful cochlear implant performance requires adequate responsiveness of the auditory nerve to prolonged pulsatile electrical stimulation. Degeneration of the auditory nerve as a result of severe hair cell loss could considerably compromise this ability. The main objective of this study was to characterize the recovery of the electrically stimulated auditory nerve, as well as to evaluate possible changes caused by deafness-induced degeneration. To this end we studied temporal responsiveness of the auditory nerve in a guinea pig model of sensorineural hearing loss. Using masker-probe and pulse train paradigms we compared electrically evoked compound action potentials (eCAPs) in normal-hearing animals with those in animals with moderate (two weeks after ototoxic treatment) and severe (six weeks after ototoxic treatment) loss of spiral ganglion cells (SGCs). Masker-probe interval and pulse train inter-pulse interval was varied from 0.3 to 16 ms. Whereas recovery assessed with masker-probe was roughly similar for normal-hearing and both groups of deafened animals, it was considerably faster for six weeks deaf animals (τ ≈ 1.2 ms) than for two weeks deaf or normal-hearing animals (τ ≈ 3-4 ms) when 100-ms pulse trains were applied. Latency increased with decreasing inter-pulse intervals, and this was more pronounced with pulse trains than with masker-probe stimulation. With high frequency pulse train stimulation eCAP amplitudes were modulated for deafened animals, meaning that amplitudes for odd pulse numbers were larger than for even pulses. The relative refractory period (τ) and the modulation depth of the eCAP amplitude for pulse trains, as well as the latency increase for both paradigms significantly correlated with quantified measures of auditory nerve degeneration (size and packing density of SGCs). In addition to these findings, separate masker-probe recovery functions for the eCAP N1 and N2 peaks displayed a robust non-monotonic or shoulder

  20. Trauma-induced auditory nerve degeneration due to cerebellopontine(CP) angle manipulations:clinical and experimental experience

    Institute of Scientific and Technical Information of China (English)

    Tetsuji Sekiya

    2004-01-01

    In order to investigate the pathophysiologic mechanisms responsible for trauma-induced hearing disturbances due to auditory nerve degeneration, we established for the first time a rat experimental model in which auditory nerve degeneration due to compression injury of the cerebellopontine (CP) angle portion of the auditory nerve can be quantitatively evaluated. In this paper, Ⅰ demonstrate our clinical experience in CP angle surgery and some of the results of our experiments performed onthis rat experimental model. Trauma-induced hearing loss in CP angle operations has long been regarded as a sort of unavoidable "natural course"and therefore hopeless.I believe that this pessimistic view should be challenged and changed through new approaches in scientific research.

  1. Ion channel noise can explain firing correlation in auditory nerves.

    Science.gov (United States)

    Moezzi, Bahar; Iannella, Nicolangelo; McDonnell, Mark D

    2016-10-01

    Neural spike trains are commonly characterized as a Poisson point process. However, the Poisson assumption is a poor model for spiking in auditory nerve fibres because it is known that interspike intervals display positive correlation over long time scales and negative correlation over shorter time scales. We have therefore developed a biophysical model based on the well-known Meddis model of the peripheral auditory system, to produce simulated auditory nerve fibre spiking statistics that more closely match the firing correlations observed in empirical data. We achieve this by introducing biophysically realistic ion channel noise to an inner hair cell membrane potential model that includes fractal fast potassium channels and deterministic slow potassium channels. We succeed in producing simulated spike train statistics that match empirically observed firing correlations. Our model thus replicates macro-scale stochastic spiking statistics in the auditory nerve fibres due to modeling stochasticity at the micro-scale of potassium channels.

  2. Tinnitus suppression by electric stimulation of the auditory nerve

    Directory of Open Access Journals (Sweden)

    Janice Erica Chang

    2012-03-01

    Full Text Available Electric stimulation of the auditory nerve via a cochlear implant (CI has been observed to suppress tinnitus, but parameters of an effective electric stimulus remain unexplored. Here we used CI research processors to systematically vary pulse rate, electrode place, and current amplitude of electric stimuli, and measure their effects on tinnitus loudness and stimulus loudness as a function of stimulus duration. Thirteen tinnitus subjects who used CIs were tested, with 9 (70% being Responders who achieved greater than 30% tinnitus loudness reduction in response to at least one stimulation condition and the remaining 4 (30% being Non-Responders who had less than 30% tinnitus loudness reduction in response to any stimulus condition tested. Despite large individual variability, several interesting observations were made between stimulation parameters, tinnitus characteristics, and tinnitus suppression. If a subject’s tinnitus was suppressed by one stimulus, then it was more likely to be suppressed by another stimulus. If the tinnitus contained a pulsating component, then it would be more likely suppressed by a given combination of stimulus parameters than tinnitus without these components. There was also a disassociation between the subjects’ clinical speech processor and our research processor in terms of their effectiveness in tinnitus suppression. Finally, an interesting dichotomy was observed between loudness adaptation to electric stimuli and their effects on tinnitus loudness, with the Responders exhibiting higher degrees of loudness adaptation than the Non-Responders. Although the mechanisms underlying these observations remain to be resolved, their clinical implications are clear. When using a CI to manage tinnitus, the clinical processor that is optimized for speech perception needs to be customized for optimal tinnitus suppression.

  3. A model of electrical excitation of the mammalian auditory-nerve neuron.

    Science.gov (United States)

    Colombo, J; Parkins, C W

    1987-12-31

    A model of the mammalian auditory-nerve neuron has been developed based on the classical work of Frankenhauser and Huxley [(1964) J. Physiol. 171, 302-315], modified by McNeal [(1976) IEEE Trans. Biomed. Eng. BME-23, 329-336], and Reilly et al. [(1985) IEEE Trans. Biomed. Eng. BME-32, 1001-1011], and fine tuned to represent physiological data obtained from single auditory-nerve fiber experiments in squirrel monkeys. The model is capable of reproducing neural action potential waveforms due to electrical stimulation, and can reliably predict action potential thresholds and strength-duration curves. This paper explains the derivation of the mathematical model and the effects of varying certain independent parameters including fiber diameter, length of the nodes of Ranvier, internodal length, and myelin thickness. The model parameters were selected according to the anatomical findings of Liberman and Oliver [(1984) J. Comp. Neurol. 223, 163-176], and Liberman (Pers. Commun.). The length of the unmyelinated termination of the auditory-nerve that survives after aminoglycoside damage to the inner ear has not been experimentally determined. Therefore, it was investigated as an independent variable in the model. An unmyelinated terminal length of 10.0 micron was found to most accurately describe the experimental neural strength-duration curves obtained from aminoglycoside-deafened squirrel monkeys. The parameter that had the next most significant effect on the model was fiber diameter which affects all conduction pathways, across the membrane and through the fiber. Finally the results of the model are compared with behavioral data obtained from patients and monkeys implanted with cochlear prostheses. In the companion paper [(1987) Hear. Res. 31, 267-286] predictions of the model are quantitatively compared with single-neuron data from squirrel monkeys.

  4. Stimulation of the human auditory nerve with optical radiation

    Science.gov (United States)

    Fishman, Andrew; Winkler, Piotr; Mierzwinski, Jozef; Beuth, Wojciech; Izzo Matic, Agnella; Siedlecki, Zygmunt; Teudt, Ingo; Maier, Hannes; Richter, Claus-Peter

    2009-02-01

    A novel, spatially selective method to stimulate cranial nerves has been proposed: contact free stimulation with optical radiation. The radiation source is an infrared pulsed laser. The Case Report is the first report ever that shows that optical stimulation of the auditory nerve is possible in the human. The ethical approach to conduct any measurements or tests in humans requires efficacy and safety studies in animals, which have been conducted in gerbils. This report represents the first step in a translational research project to initiate a paradigm shift in neural interfaces. A patient was selected who required surgical removal of a large meningioma angiomatum WHO I by a planned transcochlear approach. Prior to cochlear ablation by drilling and subsequent tumor resection, the cochlear nerve was stimulated with a pulsed infrared laser at low radiation energies. Stimulation with optical radiation evoked compound action potentials from the human auditory nerve. Stimulation of the auditory nerve with infrared laser pulses is possible in the human inner ear. The finding is an important step for translating results from animal experiments to human and furthers the development of a novel interface that uses optical radiation to stimulate neurons. Additional measurements are required to optimize the stimulation parameters.

  5. Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains.

    Science.gov (United States)

    Nourski, Kirill V; Abbas, Paul J; Miller, Charles A; Robinson, Barbara K; Jeng, Fuh-Cherng

    2005-04-01

    This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

  6. Temporary Neurotrophin Treatment Prevents Deafness-Induced Auditory Nerve Degeneration and Preserves Function

    NARCIS (Netherlands)

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B.; Klis, Sjaak F. L.; Grolman, Wilko

    2015-01-01

    After substantial loss of cochlear hair cells, exogenous neurotrophins prevent degeneration of the auditory nerve. Because cochlear implantation, the current therapy for profound sensorineural hearing loss, depends on a functional nerve, application of neurotrophins is being investigated. We address

  7. Power-law dynamics in an auditory-nerve model can account for neural adaptation to sound-level statistics.

    Science.gov (United States)

    Zilany, Muhammad S A; Carney, Laurel H

    2010-08-04

    Neurons in the auditory system respond to recent stimulus-level history by adapting their response functions according to the statistics of the stimulus, partially alleviating the so-called "dynamic-range problem." However, the mechanism and source of this adaptation along the auditory pathway remain unknown. Inclusion of power-law dynamics in a phenomenological model of the inner hair cell (IHC)-auditory nerve (AN) synapse successfully explained neural adaptation to sound-level statistics, including the time course of adaptation of the mean firing rate and changes in the dynamic range observed in AN responses. A direct comparison between model responses to a dynamic stimulus and to an "inversely gated" static background suggested that AN dynamic-range adaptation largely results from the adaptation produced by the response history. These results support the hypothesis that the potential mechanism underlying the dynamic-range adaptation observed at the level of the auditory nerve is located peripheral to the spike generation mechanism and central to the IHC receptor potential.

  8. Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes’ hearing problem:an innovation in multi-channel-array skin-hearing technology

    Institute of Scientific and Technical Information of China (English)

    Jianwen Li; Yan Li; Ming Zhang; Weifang Ma; Xuezong Ma

    2014-01-01

    The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the ifltering principle of hair cells, external voice sig-nals at different frequencies are converted to current signals at corresponding frequencies using electronic multi-channel bandpass ifltering technology. Different positions on the skin can be stimulated by the electrode array, allowing the perception and discrimination of external speech signals to be determined by the skin response to the current signals. Through voice frequen-cy analysis, the frequency range of the band-pass iflter can also be determined. These ifndings demonstrate that the sensory nerves in the skin can help to transfer the voice signal and to dis-tinguish the speech signal, suggesting that the skin sensory nerves are good candidates for the replacement of the auditory nerve in addressing deaf-mutes’ hearing problems. Scientiifc hearing experiments can be more safely performed on the skin. Compared with the artificial cochlea, multi-channel-array skin-hearing aids have lower operation risk in use, are cheaper and are more easily popularized.

  9. Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes' hearing problem: an innovation in multi-channel-array skin-hearing technology.

    Science.gov (United States)

    Li, Jianwen; Li, Yan; Zhang, Ming; Ma, Weifang; Ma, Xuezong

    2014-08-15

    The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different frequencies are converted to current signals at corresponding frequencies using electronic multi-channel bandpass filtering technology. Different positions on the skin can be stimulated by the electrode array, allowing the perception and discrimination of external speech signals to be determined by the skin response to the current signals. Through voice frequency analysis, the frequency range of the band-pass filter can also be determined. These findings demonstrate that the sensory nerves in the skin can help to transfer the voice signal and to distinguish the speech signal, suggesting that the skin sensory nerves are good candidates for the replacement of the auditory nerve in addressing deaf-mutes' hearing problems. Scientific hearing experiments can be more safely performed on the skin. Compared with the artificial cochlea, multi-channel-array skin-hearing aids have lower operation risk in use, are cheaper and are more easily popularized.

  10. Diffusion tensor imaging of the auditory nerve in patients with acquired single-sided deafness

    DEFF Research Database (Denmark)

    Vos, Sjoerd; Haakma, Wieke; Versnel, Huib;

    2015-01-01

    following cochlear hair cell loss, and the amount of degeneration may considerably differ between the two ears, also in patients with bilateral deafness. A measure that reflects the nerve's condition would help to assess the best of both nerves and decide accordingly which ear should be implanted...... DTI metrics from the deaf-sided with the healthy-sided nerves in patients showed no significant differences. There was a small but significant reduction in fractional anisotropy in both auditory nerves in patients compared with normal-hearing controls. These results are the first evidence of possible...... changes in the microstructure of the bilateral auditory nerves as a result of single-sided deafness. Our results also indicate that it is too early to assess the degenerative status of the auditory nerve of a subject-specific basis....

  11. The Effect of Low Omega-3/Omega-6 Ratio on Auditory Nerve Conduction in Rat Pups.

    Directory of Open Access Journals (Sweden)

    Saeid Farahani

    2015-06-01

    Full Text Available The biological effects of omega-3 and omega-6 fatty acids are determined by their mutual interactions. This interaction extremely affects various functions. Lower consumption of omega-3 during gestation leads to various disorders, even in hearing. We aimed to assess the effect of low omega-3/omega-6 ratios on auditory nerve conduction. In this experimental study, the auditory brainstem response test was performed on 24-day-old rat (n=14. The rats were divided into case (low omega-3/omega-6 ratio during gestation and lactation and control groups. Variables such as P1, P3, and P4 absolute latency period, interpeaks (P3-P4, P1-P3, and P1-P4, and P4/P1 amplitude ratio were measured. We found an increased P4 omega-3/omega-6 ratio in the group with a low omega-3/omega-6 ratio (P0.05.  Also, no significant difference was observed between the groups with respect to the P1-P3 interpeak latency (IPL periods (P>0.05; while the P1-P4 and P3-P4 IPLs were significantly increased in the group with a low omega-3/omega-6 ratio (P<0.05. The P4/P1 amplitude ratio significantly decreased in the group with a low omega-3/omega-6 ratio (P<0.05. Results confirmed the negative effects of low omega-3/omega-6 ratio on the auditory system and hearing.

  12. Sensitivity of cochlear nucleus neurons to spatio-temporal changes in auditory nerve activity.

    Science.gov (United States)

    Wang, Grace I; Delgutte, Bertrand

    2012-12-01

    The spatio-temporal pattern of auditory nerve (AN) activity, representing the relative timing of spikes across the tonotopic axis, contains cues to perceptual features of sounds such as pitch, loudness, timbre, and spatial location. These spatio-temporal cues may be extracted by neurons in the cochlear nucleus (CN) that are sensitive to relative timing of inputs from AN fibers innervating different cochlear regions. One possible mechanism for this extraction is "cross-frequency" coincidence detection (CD), in which a central neuron converts the degree of coincidence across the tonotopic axis into a rate code by preferentially firing when its AN inputs discharge in synchrony. We used Huffman stimuli (Carney LH. J Neurophysiol 64: 437-456, 1990), which have a flat power spectrum but differ in their phase spectra, to systematically manipulate relative timing of spikes across tonotopically neighboring AN fibers without changing overall firing rates. We compared responses of CN units to Huffman stimuli with responses of model CD cells operating on spatio-temporal patterns of AN activity derived from measured responses of AN fibers with the principle of cochlear scaling invariance. We used the maximum likelihood method to determine the CD model cell parameters most likely to produce the measured CN unit responses, and thereby could distinguish units behaving like cross-frequency CD cells from those consistent with same-frequency CD (in which all inputs would originate from the same tonotopic location). We find that certain CN unit types, especially those associated with globular bushy cells, have responses consistent with cross-frequency CD cells. A possible functional role of a cross-frequency CD mechanism in these CN units is to increase the dynamic range of binaural neurons that process cues for sound localization.

  13. Assessing the Firing Properties of the Electrically Stimulated Auditory Nerve Using a Convolution Model

    NARCIS (Netherlands)

    Strahl, Stefan B; Ramekers, Dyan; Nagelkerke, Marjolijn M B; Schwarz, Konrad E; Spitzer, Philipp; Klis, Sjaak F L; Grolman, Wilko; Versnel, Huib

    2016-01-01

    The electrically evoked compound action potential (eCAP) is a routinely performed measure of the auditory nerve in cochlear implant users. Using a convolution model of the eCAP, additional information about the neural firing properties can be obtained, which may provide relevant information about th

  14. Assessment and Preservation of Auditory Nerve Integrity in the Deafened Guinea Pig

    NARCIS (Netherlands)

    Ramekers, D.

    2014-01-01

    Profound hearing loss is often caused by cochlear hair cell loss. Cochlear implants (CIs) essentially replace hair cells by encoding sound and conveying the signal by means of pulsatile electrical stimulation to the spiral ganglion cells (SGCs) which form the auditory nerve. SGCs progressively degen

  15. A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement

    Science.gov (United States)

    2013-10-01

    biopolymer scaffold within the internal auditory meatus (IAM) of the guinea pig. (A) The lateral wall of an intact guinea pig temporal bone is shown......Nanofibrous Scaffold for Auditory Nerve Replacement 5b. GRANT NUMBER W81XWH-12-1-0492 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond

  16. Pulsed 808-nm infrared laser stimulation of the auditory nerve in guinea pig cochlea.

    Science.gov (United States)

    Xia, Nan; Wu, Xiao Y; Wang, Xing; Mou, Zong X; Wang, Man Q; Gu, Xin; Zheng, Xiao L; Hou, Wen S

    2014-01-01

    Pulsed near-infrared radiation has been proposed as an alternative stimulus for auditory nerve stimulation and could be potentially used in the design of cochlear implant. Although the infrared with high absorption coefficient of water (i.e., wavelength ranged from 1.8 to 2.2 μm) has been widely investigated, the lymph in the cochlea absorbs most of the infrared energies, and only a small part can arrive at the target auditory nerves. The present study is aimed to test whether the short-wavelength near-infrared irradiation with lower absorption coefficients can penetrate the lymph fluid to stimulate the auditory nerves. An 808-nm near-infrared laser was chosen to stimulate the auditory nerve in the guinea pig cochlea. The infrared pulse was delivered by an optical fiber that was surgically inserted near the round window membrane and oriented toward the spiral ganglion cells in the basal turn of the cochlea. The 2-Hz infrared pulses were used to stimulate the cochlea before and after the deafness with different pulse durations (100-1,000 μs). Optically evoked compound action potentials (oCAPs) were recorded during the infrared radiation. We successfully recorded oCAPs from both normal hearing animals and deafened animals. The oCAP amplitude increased with the infrared radiation energy. The preliminary experiment suggests that the near-infrared with lower absorption coefficients can effectively pass through the lymph filled in the cochlea and stimulate the auditory nerve. Further studies will optimize the deafness animal model and determine the optimal stimulation parameters.

  17. Auditory nerve representation of a complex communication sound in background noise.

    Science.gov (United States)

    Simmons, A M; Schwartz, J J; Ferragamo, M

    1992-05-01

    A population study of auditory nerve responses in the bullfrog, Rana catesbeiana, analyzed the relative contributions of spectral and temporal coding in representing a complex, species-specific communication signal at different stimulus intensities and in the presence of background noise. At stimulus levels of 70 and 80 dB SPL, levels which approximate that received during communication in the natural environment, average rate profiles plotted over fiber characteristic frequency do not reflect the detailed spectral fine structure of the synthetic call. Rate profiles do not change significantly in the presence of background noise. In ambient (no noise) and low noise conditions, both amphibian papilla and basilar papilla fibers phase lock strongly to the waveform periodicity (fundamental frequency) of the synthetic advertisement call. The higher harmonic spectral fine structure of the synthetic call is not accurately reflected in the timing of fiber firing, because firing is "captured" by the fundamental frequency. Only a small number of fibers synchronize preferentially to any harmonic in the call other than the first, and none synchronize to any higher than the third, even when fiber characteristic frequency is close to one of these higher harmonics. Background noise affects fiber temporal responses in two ways: It can reduce synchronization to the fundamental frequency, until fiber responses are masked; or it can shift synchronization from the fundamental to the second or third harmonic of the call. This second effect results in a preservation of temporal coding at high noise levels. These data suggest that bullfrog eighth nerve fibers extract the waveform periodicity of multiple-harmonic stimuli primarily by a temporal code.

  18. Auditory nerve inputs to cochlear nucleus neurons studied with cross-correlation.

    Science.gov (United States)

    Young, E D; Sachs, M B

    2008-06-12

    The strength of synapses between auditory nerve (AN) fibers and ventral cochlear nucleus (VCN) neurons is an important factor in determining the nature of neural integration in VCN neurons of different response types. Synaptic strength was analyzed using cross-correlation of spike trains recorded simultaneously from an AN fiber and a VCN neuron in anesthetized cats. VCN neurons were classified as chopper, primarylike, and onset using previously defined criteria, although onset neurons usually were not analyzed because of their low discharge rates. The correlograms showed an excitatory peak (EP), consistent with monosynaptic excitation, in AN-VCN pairs with similar best frequencies (49% 24/49 of pairs with best frequencies within +/-5%). Chopper and primarylike neurons showed similar EPs, except that the primarylike neurons had shorter latencies and shorter-duration EPs. Large EPs consistent with end bulb terminals on spherical bushy cells were not observed, probably because of the low probability of recording from one. The small EPs observed in primarylike neurons, presumably spherical bushy cells, could be derived from small terminals that accompany end bulbs on these cells. EPs on chopper or primarylike-with-notch neurons were consistent with the smaller synaptic terminals on multipolar and globular bushy cells. Unexpectedly, EPs were observed only at sound levels within about 20 dB of threshold, showing that VCN responses to steady tones shift from a 1:1 relationship between AN and VCN spikes at low sound levels to a more autonomous mode of firing at high levels. In the high level mode, the pattern of output spikes seems to be determined by the properties of the postsynaptic spike generator rather than the input spike patterns. The EP amplitudes did not change significantly when the presynaptic spike was preceded by either a short or long interspike interval, suggesting that synaptic depression and facilitation have little effect under the conditions studied

  19. Assessing the Firing Properties of the Electrically Stimulated Auditory Nerve Using a Convolution Model.

    Science.gov (United States)

    Strahl, Stefan B; Ramekers, Dyan; Nagelkerke, Marjolijn M B; Schwarz, Konrad E; Spitzer, Philipp; Klis, Sjaak F L; Grolman, Wilko; Versnel, Huib

    2016-01-01

    The electrically evoked compound action potential (eCAP) is a routinely performed measure of the auditory nerve in cochlear implant users. Using a convolution model of the eCAP, additional information about the neural firing properties can be obtained, which may provide relevant information about the health of the auditory nerve. In this study, guinea pigs with various degrees of nerve degeneration were used to directly relate firing properties to nerve histology. The same convolution model was applied on human eCAPs to examine similarities and ultimately to examine its clinical applicability. For most eCAPs, the estimated nerve firing probability was bimodal and could be parameterised by two Gaussian distributions with an average latency difference of 0.4 ms. The ratio of the scaling factors of the late and early component increased with neural degeneration in the guinea pig. This ratio decreased with stimulation intensity in humans. The latency of the early component decreased with neural degeneration in the guinea pig. Indirectly, this was observed in humans as well, assuming that the cochlear base exhibits more neural degeneration than the apex. Differences between guinea pigs and humans were observed, among other parameters, in the width of the early component: very robust in guinea pig, and dependent on stimulation intensity and cochlear region in humans. We conclude that the deconvolution of the eCAP is a valuable addition to existing analyses, in particular as it reveals two separate firing components in the auditory nerve.

  20. Mass Potentials Recorded at the Round Window Enable the Detection of Low Spontaneous Rate Fibers in Gerbil Auditory Nerve

    Science.gov (United States)

    Batrel, Charlène; Huet, Antoine; Hasselmann, Florian; Wang, Jing; Desmadryl, Gilles; Nouvian, Régis

    2017-01-01

    Auditory nerve fibers (ANFs) transmit acoustic information from the sensory hair cells to the cochlear nuclei. In experimental and clinical audiology, probing the whole ANF population remains a difficult task, as the ANFs differ greatly in their threshold and onset response to sound. Thus, low spontaneous rate (SR) fibers, which have rather higher thresholds, delay and larger jitter in their first spike latency are not detectable in the far-field compound action potential of the auditory nerve. Here, we developed a new protocol of acoustic stimulation together with electrophysiological signal processing to track the steady state activity of ANFs. Mass potentials at the round window were recorded in response to repetitive 300-ms bursts of 1/3 octave band noise centered on a frequency probe. Analysis was assessed during the last 200-ms of the response to capture the steady-state response of ANFs. To eliminate the microphonic component reflecting the sensory cells activity, repetitive pairs of sounds of opposite polarities were used. The spectral analysis was calculated on the average of two consecutive responses, and the neural gain was calculated by dividing point-by-point the spectrum to sound over unstimulated condition. In response to low-sound-level stimulation, neural gain predominated in the low-frequency cochlear regions, while a second component of responses centered on higher cochlear frequency regions appeared beyond 30 dB SPL. At 60 dB SPL, neural gain showed a bimodal shape, with a notch near 5.6 kHz. In addition to correlate with the functional mapping of ANFs along the tonotopic axis, the deletion of low-SR fibers leads to a reduction in the high-frequency response, where the low-SR fibers are preferentially located. Thus, mass potentials at the round window may provide a useful tool to probe the SR-based distribution of ANFs in humans and in other species in which direct single-unit recordings are difficult to achieve or not feasible. PMID:28085968

  1. Fast negative feedback enables mammalian auditory nerve fibers to encode a wide dynamic range of sound intensities.

    Directory of Open Access Journals (Sweden)

    Mark Ospeck

    Full Text Available Mammalian auditory nerve fibers (ANF are remarkable for being able to encode a 40 dB, or hundred fold, range of sound pressure levels into their firing rate. Most of the fibers are very sensitive and raise their quiescent spike rate by a small amount for a faint sound at auditory threshold. Then as the sound intensity is increased, they slowly increase their spike rate, with some fibers going up as high as ∼300 Hz. In this way mammals are able to combine sensitivity and wide dynamic range. They are also able to discern sounds embedded within background noise. ANF receive efferent feedback, which suggests that the fibers are readjusted according to the background noise in order to maximize the information content of their auditory spike trains. Inner hair cells activate currents in the unmyelinated distal dendrites of ANF where sound intensity is rate-coded into action potentials. We model this spike generator compartment as an attenuator that employs fast negative feedback. Input current induces rapid and proportional leak currents. This way ANF are able to have a linear frequency to input current (f-I curve that has a wide dynamic range. The ANF spike generator remains very sensitive to threshold currents, but efferent feedback is able to lower its gain in response to noise.

  2. Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes’ hearing problem: an innovation in multi-channel-array skin-hearing technology

    OpenAIRE

    Li, Jianwen; Li, Yan; Ming ZHANG; Ma, Weifang; Ma, Xuezong

    2014-01-01

    The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different...

  3. An analog VLSI implementation of the inner hair cell and auditory nerve using a dual AGC model.

    Science.gov (United States)

    Freedman, David S; Cohen, Howard I; Deligeorges, Socrates; Karl, Christian; Hubbard, Allyn E

    2014-04-01

    An analog inner hair cell and auditory nerve circuit using a dual AGC model has been implemented using 0.35 micron mixed-signal technology. A fully-differential current-mode architecture is used and the ability to correct channel mismatch is evaluated with matched layouts as well as with digital current tuning. The Meddis test paradigm is used to examine the analog implementation's auditory processing capabilities and investigate the circuit's ability to correct DC mismatch. The correction techniques used demonstrate the analog inner hair cell and auditory nerve circuit's potential use in low-power, multiple-sensor analog biomimetic systems with highly reproducible signal processing blocks on a single massively parallel integrated circuit.

  4. Organization of the auditory brainstem in a lizard, Gekko gecko. I. Auditory nerve, cochlear nuclei, and superior olivary nuclei

    DEFF Research Database (Denmark)

    Tang, Y. Z.; Christensen-Dalsgaard, J.; Carr, C. E.

    2012-01-01

    We used tract tracing to reveal the connections of the auditory brainstem in the Tokay gecko (Gekko gecko). The auditory nerve has two divisions, a rostroventrally directed projection of mid- to high best-frequency fibers to the nucleus angularis (NA) and a more dorsal and caudal projection of lo...... of auditory connections in lizards and archosaurs but also different processing of low- and high-frequency information in the brainstem. J. Comp. Neurol. 520:17841799, 2012. (C) 2011 Wiley Periodicals, Inc...

  5. Dynamic range adaptation to sound level statistics in the auditory nerve.

    Science.gov (United States)

    Wen, Bo; Wang, Grace I; Dean, Isabel; Delgutte, Bertrand

    2009-11-04

    The auditory system operates over a vast range of sound pressure levels (100-120 dB) with nearly constant discrimination ability across most of the range, well exceeding the dynamic range of most auditory neurons (20-40 dB). Dean et al. (2005) have reported that the dynamic range of midbrain auditory neurons adapts to the distribution of sound levels in a continuous, dynamic stimulus by shifting toward the most frequently occurring level. Here, we show that dynamic range adaptation, distinct from classic firing rate adaptation, also occurs in primary auditory neurons in anesthetized cats for tone and noise stimuli. Specifically, the range of sound levels over which firing rates of auditory nerve (AN) fibers grows rapidly with level shifts nearly linearly with the most probable levels in a dynamic sound stimulus. This dynamic range adaptation was observed for fibers with all characteristic frequencies and spontaneous discharge rates. As in the midbrain, dynamic range adaptation improved the precision of level coding by the AN fiber population for the prevailing sound levels in the stimulus. However, dynamic range adaptation in the AN was weaker than in the midbrain and not sufficient (0.25 dB/dB, on average, for broadband noise) to prevent a significant degradation of the precision of level coding by the AN population above 60 dB SPL. These findings suggest that adaptive processing of sound levels first occurs in the auditory periphery and is enhanced along the auditory pathway.

  6. Effects of rates of spontaneous synaptic vesicle secretions in inner hair cells on information transmission in an auditory nerve fiber model.

    Science.gov (United States)

    Kumsa, Parichat; Mino, Hiroyuki

    2012-01-01

    In this article, we investigate how the rates of spontaneous synaptic vesicle secretions affect information transmission of the spike trains in response to the inner hair cell (IHC) synaptic currents in an auditory nerve fiber (ANF) model through computer simulations. The IHC synaptic currents were modeled by a filtered inhomogeneous Poisson process modulated with sinusoidal functions, while the stochastic ion channel model was incorporated into each node of Ranvier in the ANF model with spiral ganglion. The information rates were estimated from the entropies of the inter-spike intervals of the spike trains to evaluate information transmission in the ANF model. The results show that the information rates increased, reached a maximum, and then decreased as the rate of spontaneous secretion increased, implying a resonance phenomenon dependent on the rate of spontaneous IHC synaptic secretions. In conclusion, this phenomenon similar to the regular stochastic resonance may be observed due to that spontaneous IHC synaptic secretions may act as an origin of fluctuation or noise, and these findings may play a key role in the design of better auditory prostheses.

  7. Evaluation of peripheral compression and auditory nerve fiber intensity coding using auditory steady-state responses

    DEFF Research Database (Denmark)

    Encina Llamas, Gerard; M. Harte, James; Epp, Bastian

    2015-01-01

    The compressive nonlinearity of the auditory system is assumed to be an epiphenomenon of a healthy cochlea and, particularly, of outer-hair cell function. Another ability of the healthy auditory system is to enable communication in acoustical environments with high-level background noises....... Evaluation of these properties provides information about the health state of the system. It has been shown that a loss of outer hair cells leads to a reduction in peripheral compression. It has also recently been shown in animal studies that noise over-exposure, producing temporary threshold shifts, can...

  8. Basic response characteristics of auditory nerve fibers in the grassfrog (Rana temporaria)

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Jørgensen, M B; Kanneworff, M

    1998-01-01

    -excitatory suppression (PS) of their spontaneous activity. The duration of PS increased with sound level, also in fibers showing a decrease in firing rate at high intensities. Most fibers showing one-tone suppression did not show PS at their best suppression frequencies. Strong suppression was observed also in very...... important. Udgivelsesdato: 1998-May...

  9. 人工耳蜗植入前电刺激听神经复合动作电位检测方法的建立和初步应用%The Establishment and Application of Electrically Evoked Auditory Nerve Compound Action Potential Test Method before Cochlear Implantation

    Institute of Scientific and Technical Information of China (English)

    王斌; 曹克利; 魏朝刚; 王轶; 路远

    2012-01-01

    cochlear malformation. After the success of anesthesia, all the patients' tympani bands were generally opened and the multi-channel test electrodes were placed into the tympani bands. The electrodes were connected to the Cochlear speech processor and electrical stimulation generator via the computer. By the Custom Sound EP 2.0 software, the stimulation parameters were adjusted and optimized to perform neural response telemetry (NRT) test. The stimulation intensity decreased or increased by 5 CL gradually until to the threshold. The ECAP waveforms and thresholds were automatically recorded when giving electrical stimulation pulses. After cochlear implantation, the NRT was regularly performed to record ECAP waveforms and thresholds. One month later, the T and C values of mapping were tested after switch-on. The correlation between the ECAP thresholds of the two electrodes and the C values of switch-on were statistically analyzed. Results The presences of ECAP by test electrodes and commercial electrodes were both 90% and the average thresholds were (160.50 ± 15.12) CL and (160.00±11.27) CL respectively, showing no significant difference (P>0.05). The thresholds were related to the C values after witch-on (177.40±10.61) (R2=0.844,r=0.919). Conclusion Through this study, an ECAP test method before cochlear implantation has been successfully developed. The ECAP can provide reliable and effective information about the auditory nerve responses in patients with inner ear and /or auditory pathway abnormalities and no residual hearing. This is useful in evaluating the development of auditory system and predicting the postoperative rehabilitation outcome of the patients.

  10. Development of a voltage-dependent current noise algorithm for conductance-based stochastic modelling of auditory nerve fibres.

    Science.gov (United States)

    Badenhorst, Werner; Hanekom, Tania; Hanekom, Johan J

    2016-12-01

    This study presents the development of an alternative noise current term and novel voltage-dependent current noise algorithm for conductance-based stochastic auditory nerve fibre (ANF) models. ANFs are known to have significant variance in threshold stimulus which affects temporal characteristics such as latency. This variance is primarily caused by the stochastic behaviour or microscopic fluctuations of the node of Ranvier's voltage-dependent sodium channels of which the intensity is a function of membrane voltage. Though easy to implement and low in computational cost, existing current noise models have two deficiencies: it is independent of membrane voltage, and it is unable to inherently determine the noise intensity required to produce in vivo measured discharge probability functions. The proposed algorithm overcomes these deficiencies while maintaining its low computational cost and ease of implementation compared to other conductance and Markovian-based stochastic models. The algorithm is applied to a Hodgkin-Huxley-based compartmental cat ANF model and validated via comparison of the threshold probability and latency distributions to measured cat ANF data. Simulation results show the algorithm's adherence to in vivo stochastic fibre characteristics such as an exponential relationship between the membrane noise and transmembrane voltage, a negative linear relationship between the log of the relative spread of the discharge probability and the log of the fibre diameter and a decrease in latency with an increase in stimulus intensity.

  11. Periodicity extraction in the anuran auditory nerve. II: Phase and temporal fine structure.

    Science.gov (United States)

    Simmons, A M; Reese, G; Ferragamo, M

    1993-06-01

    Discharge patterns of single eighth nerve fibers in the bullfrog, Rana catesbeiana, were analyzed in response to signals consisting of multiple harmonics of a common, low-amplitude fundamental frequency. The signals were chosen to reflect the frequency and amplitude spectrum of the bullfrog's species-specific advertisement call. The phase spectrum of the signals was manipulated to produce envelopes that varied in their shapes from impulselike (sharp) to noiselike (flattened). Peripheral responses to these signals were analyzed by computing the autocorrelation functions of the spike trains and their power spectra, as well as by constructing period histograms over the time intervals of the low-frequency harmonics. In response to a phase aligned signal with an impulsive envelope, most fibers, regardless of their characteristic frequencies or place of origin within the inner ear, synchronize to the fundamental frequency of the signal. The temporal patterns of fiber discharge to these stimuli are not typically captured by that stimulus harmonic closet to the fiber characteristic frequency, as would be expected from a spectral coding mechanism for periodicity extraction, but instead directly reflect the periodicity of the stimulus envelope. Changing the phase relations between the individual harmonics constituting the signal produces changes in temporal discharge patterns of some fibers by shifting predominant synchronization away from the fundamental frequency to the low-frequency spectral peak in the complex stimuli. The proportion of fibers whose firing is captured by the fundamental frequency decreases as the waveform envelope becomes less impulselike. Fiber characteristic frequency is not highly correlated with the harmonic number to which synchronization is strongest. The higher-harmonic spectral fine structure of the signals is not reflected in fiber temporal response, regardless of the shape of the stimulus envelope, even for those harmonics within the range of

  12. Improved Auditory Nerve Survival with Nanoengineered Supraparticles for Neurotrophin Delivery into the Deafened Cochlea

    Science.gov (United States)

    Tan, Justin; Wang, Yajun; Caruso, Frank; Shepherd, Robert K.

    2016-01-01

    Cochlear implants electrically stimulate spiral ganglion neurons (SGNs) in order to provide speech cues to severe-profoundly deaf patients. In normal hearing cochleae the SGNs depend on endogenous neurotrophins secreted by sensory cells in the organ of Corti for survival. SGNs gradually degenerate following deafness and consequently there is considerable interest in developing clinically relevant strategies to provide exogenous neurotrophins to preserve SGN survival. The present study investigated the safety and efficacy of a drug delivery system for the cochlea using nanoengineered silica supraparticles. In the present study we delivered Brain-derived neurotrophic factor (BDNF) over a period of four weeks and evaluated SGN survival as a measure of efficacy. Supraparticles were bilaterally implanted into the basal turn of cochleae in profoundly deafened guinea pigs. One ear received BDNF-loaded supraparticles and the other ear control (unloaded) supraparticles. After one month of treatment the cochleae were examined histologically. There was significantly greater survival of SGNs in cochleae that received BDNF supraparticles compared to the contralateral control cochleae (repeated measures ANOVA, p = 0.009). SGN survival was observed over a wide extent of the cochlea. The supraparticles were well tolerated within the cochlea with a tissue response that was localised to the site of implantation in the cochlear base. Although mild, the tissue response was significantly greater in cochleae treated with BDNF supraparticles compared to the controls (repeated measures ANOVA, p = 0.003). These data support the clinical potential of this technology particularly as the supraparticles can be loaded with a variety of therapeutic drugs. PMID:27788219

  13. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  14. Fast-spiking GABA circuit dynamics in the auditory cortex predict recovery of sensory processing following peripheral nerve damage.

    Science.gov (United States)

    Resnik, Jennifer; Polley, Daniel B

    2017-03-21

    Cortical neurons remap their receptive fields and rescale sensitivity to spared peripheral inputs following sensory nerve damage. To address how these plasticity processes are coordinated over the course of functional recovery, we tracked receptive field reorganization, spontaneous activity, and response gain from individual principal neurons in the adult mouse auditory cortex over a 50-day period surrounding either moderate or massive auditory nerve damage. We related the day-by-day recovery of sound processing to dynamic changes in the strength of intracortical inhibition from parvalbumin-expressing (PV) inhibitory neurons. Whereas the status of brainstem-evoked potentials did not predict the recovery of sensory responses to surviving nerve fibers, homeostatic adjustments in PV-mediated inhibition during the first days following injury could predict the eventual recovery of cortical sound processing weeks later. These findings underscore the potential importance of self-regulated inhibitory dynamics for the restoration of sensory processing in excitatory neurons following peripheral nerve injuries.

  15. Predicting responses in multiple environments

    NARCIS (Netherlands)

    Malosetti Zunin, Marcos; Bustos-Korts, Daniela; Boer, Martin P.; Eeuwijk, van Fred A.

    2016-01-01

    Prediction of the phenotypes for a set of genotypes across multiple environments is a fundamental task in any plant breeding program. Genomic prediction (GP) can assist selection decisions by combining incomplete phenotypic information over multiple environments (MEs) with dense sets of markers.

  16. Modeling auditory evoked brainstem responses to transient stimuli

    DEFF Research Database (Denmark)

    Rønne, Filip Munch; Dau, Torsten; Harte, James;

    2012-01-01

    A quantitative model is presented that describes the formation of auditory brainstem responses (ABR) to tone pulses, clicks and rising chirps as a function of stimulation level. The model computes the convolution of the instantaneous discharge rates using the “humanized” nonlinear auditory-nerve ...

  17. Predicting responses from Rasch measures.

    Science.gov (United States)

    Linacre, John M

    2010-01-01

    There is a growing family of Rasch models for polytomous observations. Selecting a suitable model for an existing dataset, estimating its parameters and evaluating its fit is now routine. Problems arise when the model parameters are to be estimated from the current data, but used to predict future data. In particular, ambiguities in the nature of the current data, or overfit of the model to the current dataset, may mean that better fit to the current data may lead to worse fit to future data. The predictive power of several Rasch and Rasch-related models are discussed in the context of the Netflix Prize. Rasch-related models are proposed based on Singular Value Decomposition (SVD) and Boltzmann Machines.

  18. Predicting response to epigenetic therapy

    DEFF Research Database (Denmark)

    Treppendahl, Marianne B; Kristensen, Lasse S; Grønbæk, Kirsten

    2014-01-01

    Drugs targeting the epigenome are new promising cancer treatment modalities; however, not all patients receive the same benefit from these drugs. In contrast to conventional chemotherapy, responses may take several months after the initiation of treatment to occur. Accordingly, identification of ...

  19. 小儿蜗后听觉神经损害的听力学特征%The Audiological Characteristics of Children with Retrocochlear Auditory Nerve Impairment

    Institute of Scientific and Technical Information of China (English)

    高胜利; 罗仁忠; 邹宇; 温瑞金; 彭峤琛

    2011-01-01

    目的 探讨包含了听神经病在内的以听性脑干反应(ABR)严重异常、畸变产物耳声发射(DPOAE)正常为特征的蜗后听觉神经功能障碍小儿的听力学特征.方法 选取2002~2008年在广州市妇女儿童医疗中心听力专科检查中ABR严重异常(波Ⅴ阈值≥80 dB nHL)、DPOAE正常、排除中耳传导功能异常的患儿182例(350耳)为研究对象,患儿年龄4天~13岁,平均年龄15.67个月.结果 ①182例蜗后听觉神经损害患儿中,107例(58.79%)新生儿期有高胆红素血症,其中34例(18.68%)伴发核黄疸.在首次就诊的原因中,以"运动障碍"为主诉者最多,占32.42%(59例).因新生儿期听力损害高危因素进行听力评估而发现者占26.37%(48例).在伴随的疾病中,64例(35.16%)确诊伴随有脑性瘫痪.②本组182例蜗后病变患儿中,168例(占92.31%)双耳患病,14例(占7.69%)单耳患病.168例双耳均为蜗后病变的患儿中,最大强度刺激双耳均无Ⅰ波分化病例所占比例最高(94例,占55.95%).③在患蜗后听觉神经功能障碍的350耳中,172耳最大强度声刺激(103 dB nHL)ABR无波分化,69耳仅见波I分化,40耳见波I+Ⅲ+V分化,25耳仅见波V分化,20耳见波I+Ⅲ分化,15耳见波Ⅲ+V分化,5耳见波I+V分化,4耳见波Ⅲ分化.结论 高胆红素血症是包含听神经病在内的小儿蜗后听觉神经损害的最主要致病因素.小儿蜗后病变以双耳对称发病多见,双耳不对称患病的现象亦可出现,但相对少见.在蜗后听觉神经功能损害类型中,最常见的类型为ABR从波 I 开始就严重异常.小儿蜗后病变的听力学特征呈多样化.%Objective To explore the audiological characteristics of children with retrocochlear auditory nerve impairment including auditory neuropathy. Methods From 2002 to 2008, one hundred and eighty-two children(350 ears) with severely abnormal ABR( wave V threshold≥80 dB nHL) but normal DPOAE were enrolled in this study. The cases with

  20. Prediction of treatment response to adalimumab

    DEFF Research Database (Denmark)

    Krintel, Sophine B; Dehlendorff, C; Hetland, M L;

    2016-01-01

    At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment...

  1. Brainstem response audiometry in the determination of low-frequency hearing loss : a study of various methods for frequency-specific ABR-threshold assessment

    NARCIS (Netherlands)

    E.A.G.J. Conijn

    1992-01-01

    textabstractBrainstem Electric Response Audiometry (BERA) is a method to visualize some of the electric activity generated in the auditory nerve and the brainstem during the processing of sound. The amplitude of the Auditory Brainstem Response (ABR) is very small (0.05-0.5 flV). The potentials origi

  2. Personalized Nutrition by Prediction of Glycemic Responses.

    Science.gov (United States)

    Zeevi, David; Korem, Tal; Zmora, Niv; Israeli, David; Rothschild, Daphna; Weinberger, Adina; Ben-Yacov, Orly; Lador, Dar; Avnit-Sagi, Tali; Lotan-Pompan, Maya; Suez, Jotham; Mahdi, Jemal Ali; Matot, Elad; Malka, Gal; Kosower, Noa; Rein, Michal; Zilberman-Schapira, Gili; Dohnalová, Lenka; Pevsner-Fischer, Meirav; Bikovsky, Rony; Halpern, Zamir; Elinav, Eran; Segal, Eran

    2015-11-19

    Elevated postprandial blood glucose levels constitute a global epidemic and a major risk factor for prediabetes and type II diabetes, but existing dietary methods for controlling them have limited efficacy. Here, we continuously monitored week-long glucose levels in an 800-person cohort, measured responses to 46,898 meals, and found high variability in the response to identical meals, suggesting that universal dietary recommendations may have limited utility. We devised a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in this cohort and showed that it accurately predicts personalized postprandial glycemic response to real-life meals. We validated these predictions in an independent 100-person cohort. Finally, a blinded randomized controlled dietary intervention based on this algorithm resulted in significantly lower postprandial responses and consistent alterations to gut microbiota configuration. Together, our results suggest that personalized diets may successfully modify elevated postprandial blood glucose and its metabolic consequences. VIDEO ABSTRACT.

  3. Methods for predicting anti-cancer response

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to methods for predicting response of a cancer in a subject to anti-cancer therapies based upon a determination and analysis of a chromosomal aberration score, such as the number of allelic imbalance or the number of telomeric allelic imbalance in the chromosomes...

  4. Predicting Footbridge Response using Stochastic Load Models

    DEFF Research Database (Denmark)

    Pedersen, Lars; Frier, Christian

    2013-01-01

    Walking parameters such as step frequency, pedestrian mass, dynamic load factor, etc. are basically stochastic, although it is quite common to adapt deterministic models for these parameters. The present paper considers a stochastic approach to modeling the action of pedestrians, but when doing s...... as it pinpoints which decisions to be concerned about when the goal is to predict footbridge response. The studies involve estimating footbridge responses using Monte-Carlo simulations and focus is on estimating vertical structural response to single person loading....

  5. Predicting and measuring fluid responsiveness with echocardiography

    Directory of Open Access Journals (Sweden)

    Ashley Miller

    2016-06-01

    Full Text Available Echocardiography is ideally suited to guide fluid resuscitation in critically ill patients. It can be used to assess fluid responsiveness by looking at the left ventricle, aortic outflow, inferior vena cava and right ventricle. Static measurements and dynamic variables based on heart–lung interactions all combine to predict and measure fluid responsiveness and assess response to intravenous fluid esuscitation. Thorough knowledge of these variables, the physiology behind them and the pitfalls in their use allows the echocardiographer to confidently assess these patients and in combination with clinical judgement manage them appropriately.

  6. Clinical predictive factors of pathologic tumor response

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Chi Hwan; Kim, Won Dong; Lee, Sang Jeon; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of)

    2012-09-15

    The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

  7. Cochlear Responses and Auditory Brainstem Response Functions in Adults with Auditory Neuropathy/ Dys-Synchrony and Individuals with Normal Hearing

    Directory of Open Access Journals (Sweden)

    Zahra Jafari

    2007-06-01

    Full Text Available Background and Aim: Physiologic measures of cochlear and auditory nerve function may be of assis¬tance in distinguishing between hearing disorders due primarily to auditory nerve impairment from those due primarily to cochlear hair cells dysfunction. The goal of present study was to measure of co-chlear responses (otoacoustic emissions and cochlear microphonics and auditory brainstem response in some adults with auditory neuropathy/ dys-synchrony and subjects with normal hearing. Materials and Methods: Patients were 16 adults (32 ears in age range of 14-30 years with auditory neu¬ropathy/ dys-synchrony and 16 individuals in age range of 16-30 years from both sexes. The results of transient otoacoustic emissions, cochlear microphonics and auditory brainstem response measures were compared in both groups and the effects of age, sex, ear and degree of hearing loss were studied. Results: The pure-tone average was 48.1 dB HL in auditory neuropathy/dys-synchrony group and the fre¬quency of low tone loss and flat audiograms were higher among other audiogram's shapes. Transient oto¬acoustic emissions were shown in all auditory neuropathy/dys-synchrony people except two cases and its average was near in both studied groups. The latency and amplitude of the biggest reversed co-chlear microphonics response were higher in auditory neuropathy/dys-synchrony patients than control peo¬ple significantly. The correlation between cochlear microphonics amplitude and degree of hearing loss was not significant, and age had significant effect in some cochlear microphonics measures. Audi-tory brainstem response had no response in auditory neuropathy/dys-synchrony patients even with low stim¬uli rates. Conclusion: In adults with speech understanding worsen than predicted from the degree of hearing loss that suspect to auditory neuropathy/ dys-synchrony, the frequency of low tone loss and flat audiograms are higher. Usually auditory brainstem response is absent in

  8. Prediction of psilocybin response in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Erich Studerus

    Full Text Available Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

  9. Prediction of psilocybin response in healthy volunteers.

    Science.gov (United States)

    Studerus, Erich; Gamma, Alex; Kometer, Michael; Vollenweider, Franz X

    2012-01-01

    Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

  10. Predicting Flutter and Forced Response in Turbomachinery

    Science.gov (United States)

    VanZante, Dale E.; Adamczyk, John J.; Srivastava, Rakesh; Bakhle, Milind A.; Shabbir, Aamir; Chen, Jen-Ping; Janus, J. Mark; To, Wai-Ming; Barter, John

    2005-01-01

    TURBO-AE is a computer code that enables detailed, high-fidelity modeling of aeroelastic and unsteady aerodynamic characteristics for prediction of flutter, forced response, and blade-row interaction effects in turbomachinery. Flow regimes that can be modeled include subsonic, transonic, and supersonic, with attached and/or separated flow fields. The three-dimensional Reynolds-averaged Navier-Stokes equations are solved numerically to obtain extremely accurate descriptions of unsteady flow fields in multistage turbomachinery configurations. Blade vibration is simulated by use of a dynamic-grid-deformation technique to calculate the energy exchange for determining the aerodynamic damping of vibrations of blades. The aerodynamic damping can be used to assess the stability of a blade row. TURBO-AE also calculates the unsteady blade loading attributable to such external sources of excitation as incoming gusts and blade-row interactions. These blade loadings, along with aerodynamic damping, are used to calculate the forced responses of blades to predict their fatigue lives. Phase-lagged boundary conditions based on the direct-store method are used to calculate nonzero interblade phase-angle oscillations; this practice eliminates the need to model multiple blade passages, and, hence, enables large savings in computational resources.

  11. Predicting allopurinol response in patients with gout

    Science.gov (United States)

    Duffull, Stephen B.; Merriman, Tony R.; Dalbeth, Nicola; Barclay, Murray L.; Stamp, Lisa K.

    2015-01-01

    Aims The primary aim of this research was to predict the allopurinol maintenance doses required to achieve the target plasma urate of ≤0.36 mmol l−1. Methods A population analysis was conducted in nonmem using oxypurinol and urate plasma concentrations from 133 gout patients. Maintenance dose predictions to achieve the recommended plasma urate target were generated. Results The urate response was best described by a direct effects model. Renal function, diuretic use and body size were found to be significant covariates. Dose requirements increased approximately 2‐fold over a 3‐fold range of total body weight and were 1.25–2 fold higher in those taking diuretics. Renal function had only a modest impact on dose requirements. Conclusions Contrary to current guidelines, the model predicted that allopurinol dose requirements were determined primarily by differences in body size and diuretic use. A revised guide to the likely allopurinol doses to achieve the target plasma urate concentration is proposed. PMID:26451524

  12. Mood Predicts Response to Placebo CPAP

    Directory of Open Access Journals (Sweden)

    Carl J. Stepnowsky

    2012-01-01

    Full Text Available Study Objectives. Continuous positive airway pressure (CPAP therapy is efficacious for treating obstructive sleep apnea (OSA, but recent studies with placebo CPAP (CPAP administered at subtherapeutic pressure have revealed nonspecific (or placebo responses to CPAP treatment. This study examined baseline psychological factors associated with beneficial effects from placebo CPAP treatment. Participants. Twenty-five participants were studied with polysomnography at baseline and after treatment with placebo CPAP. Design. Participants were randomized to either CPAP treatment or placebo CPAP. Baseline mood was assessed with the Profile of Mood States (POMS. Total mood disturbance (POMS-Total was obtained by summing the six POMS subscale scores, with Vigor weighted negatively. The dependent variable was changed in apnea-hypopnea index (ΔAHI, calculated by subtracting pre- from post-CPAP AHI. Negative values implied improvement. Hierarchical regression analysis was performed, with pre-CPAP AHI added as a covariate to control for baseline OSA severity. Results. Baseline emotional distress predicted the drop in AHI in response to placebo CPAP. Highly distressed patients showed greater placebo response, with a 34% drop (i.e., improvement in AHI. Conclusion. These findings underscore the importance of placebo-controlled studies of CPAP treatment. Whereas such trials are routinely included in drug trials, this paper argues for their importance even in mechanical-oriented sleep interventions.

  13. Auditory cortex basal activity modulates cochlear responses in chinchillas.

    Directory of Open Access Journals (Sweden)

    Alex León

    Full Text Available BACKGROUND: The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. METHODOLOGY/PRINCIPAL FINDINGS: Cochlear microphonics (CM, auditory-nerve compound action potentials (CAP and auditory cortex evoked potentials (ACEP were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments and a permanent reduction in five chinchillas (lesion experiments. We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. CONCLUSIONS/SIGNIFICANCE: These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the

  14. Response Predicting LTCC Firing Shrinkage: A Response Surface Analysis Study

    Energy Technology Data Exchange (ETDEWEB)

    Girardi, Michael; Barner, Gregg; Lopez, Cristie; Duncan, Brent; Zawicki, Larry

    2009-02-25

    The Low Temperature Cofired Ceramic (LTCC) technology is used in a variety of applications including military/space electronics, wireless communication, MEMS, medical and automotive electronics. The use of LTCC is growing due to the low cost of investment, short development time, good electrical and mechanical properties, high reliability, and flexibility in design integration (3 dimensional (3D) microstructures with cavities are possible)). The dimensional accuracy of the resulting x/y shrinkage of LTCC substrates is responsible for component assembly problems with the tolerance effect that increases in relation to the substrate size. Response Surface Analysis was used to predict product shrinkage based on specific process inputs (metal loading, layer count, lamination pressure, and tape thickness) with the ultimate goal to optimize manufacturing outputs (NC files, stencils, and screens) in achieving the final product design the first time. Three (3) regression models were developed for the DuPont 951 tape system with DuPont 5734 gold metallization based on green tape thickness.

  15. A model of synaptic vesicle-pool depletion and replenishment can account for the interspike interval distributions and nonrenewal properties of spontaneous spike trains of auditory-nerve fibers.

    Science.gov (United States)

    Peterson, Adam J; Irvine, Dexter R F; Heil, Peter

    2014-11-05

    In mammalian auditory systems, the spiking characteristics of each primary afferent (type I auditory-nerve fiber; ANF) are mainly determined by a single ribbon synapse in a single receptor cell (inner hair cell; IHC). ANF spike trains therefore provide a window into the operation of these synapses and cells. It was demonstrated previously (Heil et al., 2007) that the distribution of interspike intervals (ISIs) of cat ANFs during spontaneous activity can be modeled as resulting from refractoriness operating on a non-Poisson stochastic point process of excitation (transmitter release events from the IHC). Here, we investigate nonrenewal properties of these cat-ANF spontaneous spike trains, manifest as negative serial ISI correlations and reduced spike-count variability over short timescales. A previously discussed excitatory process, the constrained failure of events from a homogeneous Poisson point process, can account for these properties, but does not offer a parsimonious explanation for certain trends in the data. We then investigate a three-parameter model of vesicle-pool depletion and replenishment and find that it accounts for all experimental observations, including the ISI distributions, with only the release probability varying between spike trains. The maximum number of units (single vesicles or groups of simultaneously released vesicles) in the readily releasable pool and their replenishment time constant can be assumed to be constant (∼4 and 13.5 ms, respectively). We suggest that the organization of the IHC ribbon synapses not only enables sustained release of neurotransmitter but also imposes temporal regularity on the release process, particularly when operating at high rates.

  16. Target Predictability, Sustained Attention, and Response Inhibition

    Science.gov (United States)

    Carter, Leonie; Russell, Paul N.; Helton, William S.

    2013-01-01

    We examined whether the sustained attention to response task is a better measure of response inhibition or sustained attention. Participants performed a number detection task for 37.3 min using either a Sustained Attention to Response Task (SART; high Go low No-Go) or a more traditionally formatted vigilance task (TFT; high No-Go low Go) response…

  17. Extreme wave and wind response predictions

    DEFF Research Database (Denmark)

    Jensen, Jørgen Juncher; Olsen, Anders S.; Mansour, Alaa E.

    2011-01-01

    The aim of the paper is to advocate effective stochastic procedures, based on the First Order Reliability Method (FORM) and Monte Carlo simulations (MCS), for extreme value predictions related to wave and wind-induced loads.Due to the efficient optimization procedures implemented in standard FORM...

  18. Slot Machine Response Frequency Predicts Pathological Gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

    2013-01-01

    Slot machines are among the most addictive forms of gambling, and pathological gambling slot machine players represent the largest group of treatment seekers, accounting for 35% to 93% of the population. Pathological gambling sufferers have significantly higher response frequency (games / time......) on slot machines compared with non-problem gamblers, which may suggest increased reinforcement of the gambling behavior in pathological gambling. However, to date it is unknown whether or not the increased response frequency in pathological gambling is associated with symptom severity of the disorder....... This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...

  19. Prediction of sheep responses by near infrared reflectance spectroscopy.

    Science.gov (United States)

    Eckman, D D; Shenk, J S; Wangsness, P J; Westerhaus, M O

    1983-09-01

    Prediction of animal response from near infrared reflectance spectra of feeds was compared with predictions from chemical analyses. Sixty samples of pure and mixed forage-based diets were obtained from sheep intake and digestion trials. Sheep responses measured were digestible energy, dry matter intake, and calculated intake of digestible energy. Diets were analyzed chemically for protein, neutral detergent fiber, and in vitro dry matter disappearance. Coefficients of multiple determination and standard errors for fitting the sheep responses to these 60 diverse diets by regression equations developed from chemical analyses (.62 to .70) or spectra (.63 to .72) were similar. The 60 diets were divided into two sets of 30; one set was used to develop calibration equations for each sheep response, and the second set was used to test the equations. Calibration and errors of prediction were similar. When wavelengths chosen for each of the laboratory measurements were used to fit the sheep responses, standard errors were higher than when responses of sheep were predicted directly from spectra. The scanning instrument has the capability of predicting laboratory analyses and shows potential for predicting animal response as accurately as animal response can be predicted from laboratory analyses.

  20. Mass Law Predicts Hyperbolic Hypoxic Ventilatory Response

    Science.gov (United States)

    Severinghaus, John W.

    The hyperbolic hypoxic ventilatory response vs PaO2, HVRp, is interpreted as relecting a mass hyperbolic relationship of cytochrome PcO2 to cytochrome potential Ec, offset 32 torr by the constant diffusion gradient between arterial blood and cytochrome in CB at its constant metabolic rate dot VO_2 . Ec is taken to be a linear function of redox reduction and CB ventilatory drive. As Ec rises in hypoxia, the absolute potentials of each step in the citric acid cycle rises equally while the potential drop across each step remains constant because flux rate remains constant. A hypothetic HVRs ( dot VE vs SaO2) response curve computed from these assumptions is strikingly non linear. A hypothetic HVRp calculated from an assumed linear HVRs cannot be fit to the observed hyperbolic increase of ventilation in response to isocapnic hypoxia at PO2 less than 40 torr. The incompatibility of these results suggest that in future studies HVRs will not be found to be linear, especially below 80% SaO2 and HVRp will fail to be accurately hyperbolic.

  1. Model for Predicting End User Web Page Response Time

    CERN Document Server

    Nagarajan, Sathya Narayanan

    2012-01-01

    Perceived responsiveness of a web page is one of the most important and least understood metrics of web page design, and is critical for attracting and maintaining a large audience. Web pages can be designed to meet performance SLAs early in the product lifecycle if there is a way to predict the apparent responsiveness of a particular page layout. Response time of a web page is largely influenced by page layout and various network characteristics. Since the network characteristics vary widely from country to country, accurately modeling and predicting the perceived responsiveness of a web page from the end user's perspective has traditionally proven very difficult. We propose a model for predicting end user web page response time based on web page, network, browser download and browser rendering characteristics. We start by understanding the key parameters that affect perceived response time. We then model each of these parameters individually using experimental tests and statistical techniques. Finally, we d...

  2. Dopamine neurons share common response function for reward prediction error.

    Science.gov (United States)

    Eshel, Neir; Tian, Ju; Bukwich, Michael; Uchida, Naoshige

    2016-03-01

    Dopamine neurons are thought to signal reward prediction error, or the difference between actual and predicted reward. How dopamine neurons jointly encode this information, however, remains unclear. One possibility is that different neurons specialize in different aspects of prediction error; another is that each neuron calculates prediction error in the same way. We recorded from optogenetically identified dopamine neurons in the lateral ventral tegmental area (VTA) while mice performed classical conditioning tasks. Our tasks allowed us to determine the full prediction error functions of dopamine neurons and compare them to each other. We found marked homogeneity among individual dopamine neurons: their responses to both unexpected and expected rewards followed the same function, just scaled up or down. As a result, we were able to describe both individual and population responses using just two parameters. Such uniformity ensures robust information coding, allowing each dopamine neuron to contribute fully to the prediction error signal.

  3. Model Predictive Control based on Finite Impulse Response Models

    DEFF Research Database (Denmark)

    Prasath, Guru; Jørgensen, John Bagterp

    2008-01-01

    We develop a regularized l2 finite impulse response (FIR) predictive controller with input and input-rate constraints. Feedback is based on a simple constant output disturbance filter. The performance of the predictive controller in the face of plant-model mismatch is investigated by simulations...

  4. Probabilistic prediction of barrier-island response to hurricanes

    Science.gov (United States)

    Plant, Nathaniel G.; Stockdon, Hilary F.

    2012-01-01

    Prediction of barrier-island response to hurricane attack is important for assessing the vulnerability of communities, infrastructure, habitat, and recreational assets to the impacts of storm surge, waves, and erosion. We have demonstrated that a conceptual model intended to make qualitative predictions of the type of beach response to storms (e.g., beach erosion, dune erosion, dune overwash, inundation) can be reformulated in a Bayesian network to make quantitative predictions of the morphologic response. In an application of this approach at Santa Rosa Island, FL, predicted dune-crest elevation changes in response to Hurricane Ivan explained about 20% to 30% of the observed variance. An extended Bayesian network based on the original conceptual model, which included dune elevations, storm surge, and swash, but with the addition of beach and dune widths as input variables, showed improved skill compared to the original model, explaining 70% of dune elevation change variance and about 60% of dune and shoreline position change variance. This probabilistic approach accurately represented prediction uncertainty (measured with the log likelihood ratio), and it outperformed the baseline prediction (i.e., the prior distribution based on the observations). Finally, sensitivity studies demonstrated that degrading the resolution of the Bayesian network or removing data from the calibration process reduced the skill of the predictions by 30% to 40%. The reduction in skill did not change conclusions regarding the relative importance of the input variables, and the extended model's skill always outperformed the original model.

  5. Model for Predicting End User Web Page Response Time

    OpenAIRE

    Nagarajan, Sathya Narayanan; Ravikumar, Srijith

    2012-01-01

    Perceived responsiveness of a web page is one of the most important and least understood metrics of web page design, and is critical for attracting and maintaining a large audience. Web pages can be designed to meet performance SLAs early in the product lifecycle if there is a way to predict the apparent responsiveness of a particular page layout. Response time of a web page is largely influenced by page layout and various network characteristics. Since the network characteristics vary widely...

  6. Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials

    Science.gov (United States)

    Tétreault, Pascal; Mansour, Ali; Vachon-Presseau, Etienne; Schnitzer, Thomas J.; Apkarian, A. Vania

    2016-01-01

    Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds, and its biological underpinnings are questioned. Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging (fMRI) brain connectivity. This also led to discovering a brain region predicting active drug response and demonstrating the adverse effect of active drug interfering with placebo analgesia. Chronic knee osteoarthritis (OA) pain patients (n = 56) underwent pretreatment brain scans in two clinical trials. Study 1 (n = 17) was a 2-wk single-blinded placebo pill trial. Study 2 (n = 39) was a 3-mo double-blinded randomized trial comparing placebo pill to duloxetine. Study 3, which was conducted in additional knee OA pain patients (n = 42), was observational. fMRI-derived brain connectivity maps in study 1 were contrasted between placebo responders and nonresponders and compared to healthy controls (n = 20). Study 2 validated the primary biomarker and identified a brain region predicting drug response. In both studies, approximately half of the participants exhibited analgesia with placebo treatment. In study 1, right midfrontal gyrus connectivity best identified placebo responders. In study 2, the same measure identified placebo responders (95% correct) and predicted the magnitude of placebo’s effectiveness. By subtracting away linearly modeled placebo analgesia from duloxetine response, we uncovered in 6/19 participants a tendency of duloxetine enhancing predicted placebo response, while in another 6/19, we uncovered a tendency for duloxetine to diminish it. Moreover, the approach led to discovering that right parahippocampus gyrus connectivity predicts drug analgesia after correcting for modeled placebo-related analgesia. Our evidence is consistent with clinical placebo response having biological underpinnings and shows that the method can also reveal that active

  7. Outcome Prediction in Mathematical Models of Immune Response to Infection.

    Directory of Open Access Journals (Sweden)

    Manuel Mai

    Full Text Available Clinicians need to predict patient outcomes with high accuracy as early as possible after disease inception. In this manuscript, we show that patient-to-patient variability sets a fundamental limit on outcome prediction accuracy for a general class of mathematical models for the immune response to infection. However, accuracy can be increased at the expense of delayed prognosis. We investigate several systems of ordinary differential equations (ODEs that model the host immune response to a pathogen load. Advantages of systems of ODEs for investigating the immune response to infection include the ability to collect data on large numbers of 'virtual patients', each with a given set of model parameters, and obtain many time points during the course of the infection. We implement patient-to-patient variability v in the ODE models by randomly selecting the model parameters from distributions with coefficients of variation v that are centered on physiological values. We use logistic regression with one-versus-all classification to predict the discrete steady-state outcomes of the system. We find that the prediction algorithm achieves near 100% accuracy for v = 0, and the accuracy decreases with increasing v for all ODE models studied. The fact that multiple steady-state outcomes can be obtained for a given initial condition, i.e. the basins of attraction overlap in the space of initial conditions, limits the prediction accuracy for v > 0. Increasing the elapsed time of the variables used to train and test the classifier, increases the prediction accuracy, while adding explicit external noise to the ODE models decreases the prediction accuracy. Our results quantify the competition between early prognosis and high prediction accuracy that is frequently encountered by clinicians.

  8. PREDICTION OF FIGHT OR FLIGHT RESPONSE USING ARTIFICIAL NEURAL NETWORKS

    Directory of Open Access Journals (Sweden)

    Abhijit Suresh

    2014-01-01

    Full Text Available The modern society has posed several threats to the public. Public security is declining with increasing anti-social behaviour. Cases of rape and terrorist attacks have become increasingly common and there is a strong demand for a security system to control such modalities. Anti-social behaviour is a key issue of public concern. Public perceptions, however, have been improving recently. The vital response to physical and emotional danger is called fight or flight response. It is a basic survival mechanism occurring in response to a specific stimulus, such as pain or the threat of danger. Predicting the flight and fight response is an important aspect to identify possible areas susceptible to such events and provide emergency assistance to the victims involved. This study analyses various physiological changes associated with fight or flight response and proposes an approach to predict measures that determines whether an individual is under fear caused due the perceived threat. The proposed approach uses feed forward neural networks with back propagation algorithm. With the physiological changes such as blood pressure, heart rate and respiratory rate as inputs, the optimal configuration of neural network was configured and the proposed system is able to predict the measure of fight or flight response with minimal error. By monitoring and identifying the fear measure it is possible to prevent or reduce the damage to the society by activities such as rape and terrorist attacks.

  9. A Mathematical Model for the Prediction of Fluid Responsiveness

    NARCIS (Netherlands)

    Lansdorp, B.; Putten, van M.J.A.M.; Keijzer, de A.; Pickkers, P.; Oostrom, van J.

    2013-01-01

    Fluid therapy is commonly used to improve cardiac output in hemodynamically instable patients in the intensive care unit. However, to predict whether patients will benefit from this intervention (i. e. are volume responsive), is difficult. Dynamic indices, that rely on heart-lung interactions, have

  10. The Pupillary Orienting Response Predicts Adaptive Behavioral Adjustment after Errors.

    Directory of Open Access Journals (Sweden)

    Peter R Murphy

    Full Text Available Reaction time (RT is commonly observed to slow down after an error. This post-error slowing (PES has been thought to arise from the strategic adoption of a more cautious response mode following deployment of cognitive control. Recently, an alternative account has suggested that PES results from interference due to an error-evoked orienting response. We investigated whether error-related orienting may in fact be a pre-cursor to adaptive post-error behavioral adjustment when the orienting response resolves before subsequent trial onset. We measured pupil dilation, a prototypical measure of autonomic orienting, during performance of a choice RT task with long inter-stimulus intervals, and found that the trial-by-trial magnitude of the error-evoked pupil response positively predicted both PES magnitude and the likelihood that the following response would be correct. These combined findings suggest that the magnitude of the error-related orienting response predicts an adaptive change of response strategy following errors, and thereby promote a reconciliation of the orienting and adaptive control accounts of PES.

  11. Footbridge Response Predictions and Their Sensitivity to Stochastic Load Assumptions

    DEFF Research Database (Denmark)

    Pedersen, Lars; Frier, Christian

    2011-01-01

    Knowledge about footbridges response to actions of walking is important in assessments of vibration serviceability. In a number of design codes for footbridges, the vibration serviceability limit state is assessed using a walking load model in which the walking parameters (step frequency...... of pedestrians for predicting footbridge response, which is meaningful, and a step forward. Modelling walking parameters stochastically, however, requires decisions to be made in terms of their statistical distribution and the parameters describing the statistical distribution. The paper investigates...... the sensitivity of results of computations of bridge response to some of the decisions to be made in this respect. This is a useful approach placing focus on which decisions (and which information) are important for sound estimation of bridge response. The studies involve estimating footbridge responses using...

  12. Predictive functional control of integrating process based on impulse response

    Institute of Scientific and Technical Information of China (English)

    Bin ZHANG; Ping LI; Weidong ZHANG

    2004-01-01

    The predictive model is built according to the characteristics of the impulse response of integrating process. In order to eliminate the permanent offset between the setpoint and the process output in the presence of the load disturbance, a novel error compensation method is proposed. Then predictive functional control of integrating process is designed. The method given generates a simple control structure, which can significantly reduce online computation. Furthermore, the tuning of the controller is fairly straightforward. Simulation results indicate that the designed control system is relatively robust to the parameters variation of the process.

  13. Metabolic response at repeat PET/CT predicts pathological response to neoadjuvant chemotherapy in oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gillies, R.S. [Oxford Cancer and Haematology Centre, Department of Oncology, Oxford (United Kingdom); Oxford Cancer and Haematology Centre, Department of Oesophagogastric Surgery, Oxford (United Kingdom); NIHR Biomedical Research Centre, Oxford (United Kingdom); Middleton, M.R. [Oxford Cancer and Haematology Centre, Department of Oncology, Oxford (United Kingdom); NIHR Biomedical Research Centre, Oxford (United Kingdom); Blesing, C.; Patel, K.; Warner, N. [Oxford Cancer and Haematology Centre, Department of Oncology, Oxford (United Kingdom); Marshall, R.E.K.; Maynard, N.D. [Oxford Cancer and Haematology Centre, Department of Oesophagogastric Surgery, Oxford (United Kingdom); Bradley, K.M. [Oxford Cancer and Haematology Centre, Department of Radiology, Oxford (United Kingdom); Gleeson, F.V. [Oxford Cancer and Haematology Centre, Department of Radiology, Oxford (United Kingdom); NIHR Biomedical Research Centre, Oxford (United Kingdom)

    2012-09-15

    Reports have suggested that a reduction in tumour 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) examination during or after neoadjuvant chemotherapy may predict pathological response in oesophageal cancer. Our aim was to determine whether metabolic response predicts pathological response to a standardised neoadjuvant chemotherapy regimen within a prospective clinical trial. Consecutive patients staged with potentially curable oesophageal cancer who underwent treatment within a non-randomised clinical trial were included. A standardised chemotherapy regimen (two cycles of oxaliplatin and 5-fluorouracil) was used. PET/CT was performed before chemotherapy and repeated 24-28 days after the start of cycle 2. Forty-eight subjects were included: mean age 65 years; 37 male. Using the median percentage reduction in SUV{sub max} (42%) to define metabolic response, pathological response was seen in 71% of metabolic responders (17/24) compared with 33% of non-responders (8/24; P = 0.009, sensitivity 68%, specificity 70%). Pathological response was seen in 81% of subjects with a complete metabolic response (13/16) compared with 38% of those with a less than complete response (12/32; P = 0.0042, sensitivity 52%, specificity 87%). There was no significant histology-based effect. There was a significant association between metabolic response and pathological response; however, accuracy in predicting pathological response was relatively low. (orig.)

  14. Fluid responsiveness is predicted by analysis of extra systoles

    DEFF Research Database (Denmark)

    Vistisen, Simon Tilma

    INTRODUCTION. Fluid responsiveness prediction is an unsettled matter for intensive care patients. Preload variables are not reliable and ventilator settings for the vast majority of patients (if at all ventilated) do not accommodate the criteria for otherwise useful dynamic variables [1] (e.......g. pulse pressure variation). Yet, the idea of a varying preload utilised in dynamic variable monitoring may be useful: The extra systolic post-ectopic beat is associated with increased preload, and I hypothesised that systolic blood pressure (SBP) at the post-ectopic beat could be analysed in relation...... to surrounding sinus beats and that the magnitude of the SBP change (DSBP) could predict fluid responsiveness. OBJECTIVES. To study the hypothesis in post-cardiac surgery patients. METHODS. Patients scheduled for a 500 ml volume expansion were observed. In the time frame, 0-30 min prior to volume expansion, ECG...

  15. Predictive factors associated with hepatitis C antiviraltherapy response

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatitis C virus (HCV) infection may lead to significantliver injury, and viral, environmental, host, immunologicand genetic factors may contribute to the differencesin the disease expression and treatment response.In the early 2000s, dual therapy using a combination of pegylated interferon plus ribavirin (PR) becamethe standard of care for HCV treatment. In this PRera, predictive factors of therapy response related tovirus and host have been identified. In 2010/2011,therapeutic regimens for HCV genotype 1 patients weremodified, and the addition of NS3/4a protease inhibitors(boceprevir or telaprevir) to dual therapy increasedthe effectiveness and chances of sustained virologicresponse (SVR). Nevertheless, the first-generation tripletherapy is associated with many adverse events, some ofwhich are serious and associated with death, particularlyin cirrhotic patients. This led to the need to identifyviral and host predictive factors that might influencethe SVR rate to triple therapy and avoid unnecessaryexposure to these drugs. Over the past four years,hepatitis C treatment has been rapidly changing with thedevelopment of new therapies and other developments.Currently, with the more recent generations of pangenotipicantiviral therapies, there have been highersustained virologic rates, and prognostic factors maynot have the same importance and strength as before.Nonetheless, some variables may still be consistent withthe low rates of non-response with regimens that includesofosbuvir, daclatasvir and ledipasvir. In this manuscript,we review the predictive factors of therapy responseacross the different treatment regimens over the lastdecade including the new antiviral drugs.

  16. Prediction of Response to Multimodality Treatment in Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    RalfMetzger; HuanXi; FutoshiMiyazono; HiroshiHigashi; UteWarnecke-Eberz; StephanE.Baldus; JanBrabender; PaulM.Schneider

    2004-01-01

    Patients with locally advanced esophageal cancer have a dismal prognosis when treated exclusively by surgery. This fact prompted many investigators to apply neoadjuvant treatment strategies in an effort to improve survival. Results from phase Ⅲ randomized trials are encouraging however, they revealed that only patients with major histopathological response will benefit from treatment. Therefore, predictive molecular markers indicating response or non-response to neoadjuvant treatment would be extremely helpful in selecting patients for current and future treatment protocols. In this paper we review the role of the molecular markers ERCC1 (excision repair cross-complementing 1 gene) and c-erbB-2 (synonym:HER2/neu) in predicting response to radiochemotherapy and outcome for patients with locally advanced resectable esophageal cancers (cT2-4, Nx, M0). The results are promising and it appears that we might expect to unequivocally identify with ERCC1 and c-erbB-2 respectively, approximately up to one third of patients who fulfil the criteria for neoadjuvant treatment for locally advanced esophageal cancer but will not benefit from our treatment protocol. Integration of such markers in the clinical setting might prevent a substantial number of patients from expensive, non-effective and potentially harmful therapies, and could lead to a more individualized type of combined multimodality treatment in the near future.

  17. Climate modelling, uncertainty and responses to predictions of change

    Energy Technology Data Exchange (ETDEWEB)

    Henderson-Sellers, A. [Climatic Impacts Centre, Macquarie University, Sydney (Australia)

    1996-12-31

    Article 4.1(F) of the Framework Convention on Climate Change commits all parties to take climate change considerations into account, to the extent feasible, in relevant social, economic and environmental policies and actions and to employ methods such as impact assessments to minimize adverse effects of climate change. This could be achieved by, inter alia, incorporating climate change risk assessment into development planning processes, i.e. relating climatic change to issues of habitability and sustainability. Adaptation is an ubiquitous and beneficial natural and human strategy. Future adaptation (adjustment) to climate is inevitable at the least to decrease the vulnerability to current climatic impacts. An urgent issue is the mismatch between the predictions of global climatic change and the need for information on local to regional change in order to develop adaptation strategies. Mitigation efforts are essential since the more successful mitigation activities are, the less need there will be for adaptation responses. And, mitigation responses can be global (e.g. a uniform percentage reduction in greenhouse gas emissions) while adaptation responses will be local to regional in character and therefore depend upon confident predictions of regional climatic change. The dilemma facing policymakers is that scientists have considerable confidence in likely global climatic changes but virtually zero confidence in regional changes. Mitigation and adaptation strategies relevant to climatic change can most usefully be developed in the context of sound understanding of climate, especially the near-surface continental climate, permitting discussion of societally relevant issues. But, climate models can`t yet deliver this type of regionally and locationally specific prediction and some aspects of current research even seem to indicate increased uncertainty. These topics are explored in this paper using the specific example of the prediction of land-surface climate changes.

  18. Synchrony suppression in complex stimulus responses of a biophysical model of the cochlea.

    Science.gov (United States)

    Shamma, S A; Morrish, K A

    1987-05-01

    A minimal biophysical model of the cochlea is used to investigate the validity of the hypothesis that a single compressive nonlinearity at the hair cell level can explain some of the suppression phenomena in cochlear responses to complex stimuli. The dependencies of the model responses on the amplitudes and frequencies of two-tone stimuli resemble in many respects the behavior of the experimental data, and can be traced to explicit biophysical parameters in the model. Most discrepancies between theory and experiment stem from simplifications in parameters of the minimal model that play no direct role in the hypothesis. The analysis and simulations predict further results which, pending experimental verification, may provide a more direct test of the influence of the compressive nonlinearity on the relative amplitudes of the synchronous response components, and hence of its role in synchrony suppression. For instance, regardless of the overall absolute levels of a two-tone stimulus applied to this type of model, the ratio of the amplitudes at the input and the ratio of the corresponding responses at the output remain approximately constant and equal (the output ratio changes by at most 6 dB in favor of the stronger tone). Other nonlinear responses to multitonal stimuli can also be reproduced, such as "spectral edge enhancement" [Horst et al., Peripheral Auditory Mechanisms (Springer, Berlin, 1985)] and some aspects of three-tone suppression [Javel et al., Mechanisms of Hearing (Monash U.P., Australia, 1983)]. In contrast to the complex behavior of suppression with increasing sound intensity and the drastic influence of the compressive nonlinearity on the absolute response measures on the auditory nerve (e.g., average rate and synchrony profiles), the percepts of complex sounds are relatively stable. This suggests that the invariant relative response measures are more likely used in the encoding and CNS extraction of the spectrum of complex stimuli such as speech.

  19. Response expectancy versus response hope in predicting birth-related emotional distress and pain.

    Science.gov (United States)

    Anton, Raluca; David, Daniel

    2013-01-01

    Response expectancies and response hopes have been shown to be two distinct constructs with important implications for nonvolitional outcomes. More specifically, studies show that response expectancies: (1) are sufficient to cause nonvolitional outcomes, (2) are not mediated by other psychological variables, and (3) are self-confirming while seemingly automatic. A new programmatic research line has differentiated between people's response expectancies and their response hopes regarding nonvolitional outcomes and showed that even if response hope and response expectancy are separate constructs, they are not unrelated. These concepts have not yet been studied in pregnant women. Moreover, determining the causal factors that best explain the variance of emotional distress and pain in pregnancy is of great importance. Thus, the aim of this study was to investigate the interrelations between response expectancy and response hope in pregnant women with respect to (1) emotional distress prior to giving birth and (2) pain during giving birth. Additionally, self-reported labor hours were analyzed as a secondary outcome. Results show that response expectancy for pain directly predicts pain, and that the discrepancy between response hopes and response expectancies is a strong predictor of investigated outcomes. Thus, our results support the idea that preventive psychological interventions for pregnant women should emphasize adjusting response expectancies and response hopes regarding the pain and emotional distress associated with giving birth. We believe that the results have both theoretical and practical implications and the topic deserves further investigation.

  20. MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Cros, J; Hentic, O; Rebours, V; Zappa, M; Gille, N; Theou-Anton, N; Vernerey, D; Maire, F; Lévy, P; Bedossa, P; Paradis, V; Hammel, P; Ruszniewski, P; Couvelard, A

    2016-08-01

    Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

  1. Predictive factors for response to Lamivudine in chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    SILVA Luiz Caetano da

    2000-01-01

    Full Text Available BACKGROUND: Lamivudine has been shown to be an efficient drug for chronic hepatitis B (CHB treatment. AIM: To investigate predictive factors of response, using a quantitative method with high sensitivity. METHODS: We carried out a prospective trial of lamivudine in 35 patients with CHB and evidence for viral replication, regardless to their HBeAg status. Lamivudine was given for 12 months at 300 mg daily and 150 mg thereafter. Response was considered when DNA was undetectable by PCR after 6 months of treatment. Viral replication was monitored by end-point dilution PCR. Mutation associated with resistance to lamivudine was detected by DNA sequencing in non-responder patients. RESULTS: Response was observed in 23/35 patients (65.7% but only in 5/15 (33.3% HBeAg positive patients. Only three pre-treatment variables were associated to low response: HBeAg (p = 0.006, high viral load (DNA-VHB > 3 x 10(6 copies/ml (p = 0.004 and liver HBcAg (p = 0.0028. YMDD mutations were detected in 7/11 non-responder patients. CONCLUSIONS: HBeAg positive patients with high viral load show a high risk for developing drug resistance. On the other hand, HBeAg negative patients show a good response to lamivudine even with high viremia.

  2. Human arm posture prediction in response to isometric endpoint forces.

    Science.gov (United States)

    Davoudabadi Farahani, Saeed; Andersen, Michael Skipper; de Zee, Mark; Rasmussen, John

    2015-11-26

    The ability to predict the musculoskeletal response to external loads has multiple applications for the design of machines with a human interface and for the prediction of outcomes of musculoskeletal interventions. In this study, we applied an inverse-inverse dynamics technique to investigate its ability to predict arm posture in response to isometric hand forces. For each subject, we made a three-dimensional musculoskeletal model using the AnyBody Modelling System (AMS). Then, we had each subject-specific model hold a weight anteriorly to the right shoulder joint at a distance of half of the arm length. We selected the glenohumeral abduction angle (GHAA) as the only free parameter. Subsequently, we used inverse-inverse dynamics to find the optimal GHAA that minimised a performance criterion with physiological constraints. In this study, we investigated the performance of two different objective functions: summation of squared muscle activity (SSMA) and summation of squared normalised joint torques (SSNJT). To validate the simulation results, arm posture responses to different isometric downward hand forces were measured for six healthy male subjects. Five trials were performed for each loading condition. The results showed that, with an increase in hand load, there was a reduced GHAA in all subjects. Another interesting finding was that self-selected postures for lighter tasks varied more than postures for heavier tasks for all subjects. To understand this, we investigated the curvature of the objective function as a function of the load and observed an increased curvature with increased load. This may explain the reduced intra-subject variations observed for increasing loads.

  3. Global genetic variations predict brain response to faces.

    Science.gov (United States)

    Dickie, Erin W; Tahmasebi, Amir; French, Leon; Kovacevic, Natasa; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun; Büchel, Christian; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Gallinat, Juergen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Nichols, Thomas; Lathrop, Mark; Loth, Eva; Pausova, Zdenka; Rietschel, Marcela; Smolka, Michal N; Ströhle, Andreas; Toro, Roberto; Schumann, Gunter; Paus, Tomáš

    2014-08-01

    Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼ 500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40-50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R(2) = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R(2) = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network.

  4. Global genetic variations predict brain response to faces.

    Directory of Open Access Journals (Sweden)

    Erin W Dickie

    2014-08-01

    Full Text Available Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼ 500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML, we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI in a community-based sample of adolescents (n = 1,620. Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40-50% in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R(2 = 0.38, p<0.001. Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001 and the magnitude of brain response (R(2 = 0.32, p<0.001. Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network.

  5. Assays for predicting and monitoring responses to lung cancer immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Cristina Teixid; Niki Karachaliou; Maria Gonzlez-Cao; Daniela Morales-Espinosa; Rafael Rosell

    2015-01-01

    AbstrAct Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 (PD-1) and its ligand (PD-L1), have recently emerged as important targets. hTe interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor effcacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer (NSCLC). Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. hTerefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry (IHC) with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack speciifcity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-1/PD-L1 pathway.

  6. Aggression Questionnaire hostility scale predicts anger in response to mistreatment.

    Science.gov (United States)

    Felsten, G; Hill, V

    1999-01-01

    We tested the hypotheses that the hostility and anger scales of the Buss and Perry (1992) [Buss, A. H. & Perry, M. (1992). The Aggression Questionnaire. Journal of Personality and Social Psychology, 63, 452-459.] Aggression Questionnaire would predict anger in college students in response to mistreatment. We found low and high hostility groups did not differ in anger at baseline or after completing a task without provocation, but the high hostility group reported greater anger than the low group after the onset of provocation, which required all students to redo completed tasks because some students (confederates) were observed cheating. Hostility also influenced anxiety and depression, but only anger was greater as a result of the provocation in the high than in the low hostility group. The anger scale did not predict anger in response to provocation, but anger was higher in the high than the low anger group before the provocation. These findings support the construct validity of the Aggression Questionnaire hostility scale as a measure of suspicion, resentment and sensitivity to mistreatment.

  7. Modeling of Cancer Stem Cell State Transitions Predicts Therapeutic Response.

    Directory of Open Access Journals (Sweden)

    Mary E Sehl

    Full Text Available Cancer stem cells (CSCs possess capacity to both self-renew and generate all cells within a tumor, and are thought to drive tumor recurrence. Targeting the stem cell niche to eradicate CSCs represents an important area of therapeutic development. The complex nature of many interacting elements of the stem cell niche, including both intracellular signals and microenvironmental growth factors and cytokines, creates a challenge in choosing which elements to target, alone or in combination. Stochastic stimulation techniques allow for the careful study of complex systems in biology and medicine and are ideal for the investigation of strategies aimed at CSC eradication. We present a mathematical model of the breast cancer stem cell (BCSC niche to predict population dynamics during carcinogenesis and in response to treatment. Using data from cell line and mouse xenograft experiments, we estimate rates of interconversion between mesenchymal and epithelial states in BCSCs and find that EMT/MET transitions occur frequently. We examine bulk tumor growth dynamics in response to alterations in the rate of symmetric self-renewal of BCSCs and find that small changes in BCSC behavior can give rise to the Gompertzian growth pattern observed in breast tumors. Finally, we examine stochastic reaction kinetic simulations in which elements of the breast cancer stem cell niche are inhibited individually and in combination. We find that slowing self-renewal and disrupting the positive feedback loop between IL-6, Stat3 activation, and NF-κB signaling by simultaneous inhibition of IL-6 and HER2 is the most effective combination to eliminate both mesenchymal and epithelial populations of BCSCs. Predictions from our model and simulations show excellent agreement with experimental data showing the efficacy of combined HER2 and Il-6 blockade in reducing BCSC populations. Our findings will be directly examined in a planned clinical trial of combined HER2 and IL-6 targeted

  8. Prestimulation phase predicts the TMS-evoked response.

    Science.gov (United States)

    Kundu, Bornali; Johnson, Jeffrey S; Postle, Bradley R

    2014-10-15

    Prestimulation oscillatory phase and power in particular frequency bands predict perception of at-threshold visual stimuli and of transcranial magnetic stimulation (TMS)-induced phosphenes. These effects may be due to changes in cortical excitability, such that certain ranges of power and/or phase values result in a state in which a particular brain area is more receptive to input, thereby biasing behavior. However, the effects of trial-by-trial fluctuations in phase and power of ongoing oscillations on the brain's electrical response to TMS itself have thus far not been addressed. The present study adopts a combined TMS and electroencepalography (EEG) approach to determine whether the TMS-evoked response is sensitive to momentary fluctuations in prestimulation phase and/or power in different frequency bands. Specifically, TMS was applied to superior parietal lobule while subjects performed a short-term memory task. Results showed that the prestimulation phase, particularly within the beta (15-25 Hz) band, predicted pulse-by-pulse variations in the global mean field amplitude. No such relationship was observed between prestimulation power and the global mean field amplitude. Furthermore, TMS-evoked power in the beta band fluctuated with prestimulation phase in the beta band in a manner that differed from spontaneous brain activity. These effects were observed in areas at and distal to the stimulation site. Together, these results confirm the idea that fluctuating phase of ongoing neuronal oscillations create "windows of excitability" in the brain, and they give insight into how TMS interacts with ongoing brain activity on a pulse-by-pulse basis.

  9. Prediction of Mass Spectral Response Factors from Predicted Chemometric Data for Druglike Molecules

    Science.gov (United States)

    Cramer, Christopher J.; Johnson, Joshua L.; Kamel, Amin M.

    2017-02-01

    A method is developed for the prediction of mass spectral ion counts of drug-like molecules using in silico calculated chemometric data. Various chemometric data, including polar and molecular surface areas, aqueous solvation free energies, and gas-phase and aqueous proton affinities were computed, and a statistically significant relationship between measured mass spectral ion counts and the combination of aqueous proton affinity and total molecular surface area was identified. In particular, through multilinear regression of ion counts on predicted chemometric data, we find that log10(MS ion counts) = -4.824 + c 1•PA + c 2•SA, where PA is the aqueous proton affinity of the molecule computed at the SMD(aq)/M06-L/MIDI!//M06-L/MIDI! level of electronic structure theory, SA is the total surface area of the molecule in its conjugate base form, and c 1 and c 2 have values of -3.912 × 10-2 mol kcal-1 and 3.682 × 10-3 Å-2. On a 66-molecule training set, this regression exhibits a multiple R value of 0.791 with p values for the intercept, c 1, and c 2 of 1.4 × 10-3, 4.3 × 10-10, and 2.5 × 10-6, respectively. Application of this regression to an 11-molecule test set provides a good correlation of prediction with experiment ( R = 0.905) albeit with a systematic underestimation of about 0.2 log units. This method may prove useful for semiquantitative analysis of drug metabolites for which MS response factors or authentic standards are not readily available.

  10. The markers predicting response to Hepatitis C virus treatment and evaluation of treatment responses

    Directory of Open Access Journals (Sweden)

    Özgür Günal

    2012-09-01

    Full Text Available Objectives: Currently pegylated interferon alpha (peg-IFN and ribavirin treatment is recommended for chronic hepatitis Ctreatment. The aim of treatment is to provide sustained viral response (SVR.Material and methods: A total of 125 patients, who have been treated for chronic hepatitis C diagnosis and are followed upuntil 6 months after treatment, were enrolled into the study. Markers, which have indicated treatment response against hepatitisC virus treatment, treatment responses according to peg-IFNα type used, and experienced side effects in patients havebeen compared.Results: Of patients, 103 were (82.4% female and 22 were (17.6% male and mean of age was 54.74±7.93 years. Markersindicating SVR in our study were calculated as rapid viral response (RVR (p2 (p<0.034. Predictive parameters for EVR in our studywere defined as absence of diabetes in patients, high baseline lymphocyte numbers (2024.74±625.93 and high baseline cholesterollevel (in EVR positive patients 180.47±32.77 mg/dl; in EVR negatives 152.00±24.56. There was no statistical differencebetween peg-IFN type in patients and RVR, EVR and SVR. Also there was no statistical difference in hematological side effects(neutropenia, anemia, and thrombocytopenia in both treatment groups.Conclusions: As the efficacy of treatment against HCV is defined, predictive markers for the treatment response are becomingmore significant. Therefore, it is concluded that these factors should also be considered in patient treatment plans. J MicrobiolInfect Dis 2012; 2(3: 100-108Key words: Treatment of Hepatitis C, Sustained Viral Response, Markers of Treatment

  11. NEURAL NETWORKS PREDICTION FOR SEISMIC RESPONSE OF STRUCTURE UNDER THE LEVENBERG-MARQUARDT ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    徐赵东; 沈亚鹏; 李爱群

    2003-01-01

    Objective To investigate the prediction effect of neural networks for seismic response of structure under the Levenberg-Marquardt(LM) algorithm. Results Based on identification and prediction ability of neural networks for nonlinear systems, and combined with LM algorithm, a multi-layer forward networks is adopted to predict the seismic responses of structure. The networks is trained in batch by the shaking table test data of three-floor reinforced concrete structure firstly, then the seismic responses of structure are predicted under the unused excitation data, and the predict responses are compared with the experiment responses. The error curves between the prediction and the experimental results show the efficiency of the method. Conclusion LM algorithm has very good convergence rate, and the neural networks can predict the seismic response of the structure well.

  12. Outsmarting cancer: the power of hybrid genomic/proteomic biomarkers to predict drug response.

    Science.gov (United States)

    Rexer, Brent N; Arteaga, Carlos L

    2014-01-01

    A recent study by Niepel and colleagues describes a novel approach to predicting response to targeted anti-cancer therapies. The authors used biochemical profiling of signaling activity in basal and ligand-stimulated states for a panel of receptor and intracellular kinases to develop predictive models of drug sensitivity. In some cases, the response to ligand stimulation predicted drug response better than did target abundance or genomic alterations in the targeted pathway. Furthermore, combining biochemical profiles with genomic information was better at predicting drug response. This work suggests that incorporating biochemical signaling profiles with genomic alterations should provide powerful predictors of response to molecularly targeted therapies.

  13. Predicting Metapopulation Responses To Conservation In Human-Dominated Landscapes

    Directory of Open Access Journals (Sweden)

    Zachary S. Ladin

    2016-10-01

    Full Text Available Loss of habitat to urbanization is a primary cause of population declines as human-dominated landscapes expand at increasing rates. Understanding how the relative effects of different conservation strategies is important to slow population declines for species in urban landscapes. We studied the wood thrush Hylocichla mustelina, a declining forest-breeding Neotropical migratory species, and umbrella species for forest-breeding songbirds, within the urbanized mid-Atlantic United States. We integrated 40 years of demographic data with contemporary metapopulation model simulations of breeding wood thrushes to predict population responses to differing conservation scenarios. We compared four conservation scenarios over a 30-year time period (2014–2044 representing A current observed state (Null, B replacing impervious surface with forest (Reforest, C reducing brown-headed cowbird Molothrus ater parasitism pressure (Cowbird removal, and D simultaneous reforesting and cowbird removal. Compared to the Null scenario, the Reforest scenario increased mean annual population trends by 54 % , the Remove cowbirds scenario increased mean annual population trends by 38 %, and the scenario combining reforestation and cowbird removal increased mean annual population trends by 98 %. Mean annual growth rates (λ per site were greater in the Reforest (λ = 0.94 and Remove cowbirds (λ = 0.92 compared to the Null (λ = 0.88 model scenarios. However, only by combining the positive effects of reforestation and cowbird removal did wood thrush populations stop declining (λ = 1.00. Our results suggest that independently replacing impervious surface with forest habitat around forest patches and removing cowbirds may slow current negative population trends. Furthermore, conservation efforts that combine reforestation and cowbird removal may potentially benefit populations of wood thrushes and other similarly forest-breeding songbird species within urbanized fragmented

  14. Intraoperative Neural Response Telemetry and Neural Recovery Function: a Comparative Study between Adults and Children

    Science.gov (United States)

    Carvalho, Bettina; Hamerschmidt, Rogerio; Wiemes, Gislaine

    2014-01-01

    Introduction Neural response telemetry (NRT) is a method of capturing the action potential of the distal portion of the auditory nerve in cochlear implant (CI) users, using the CI itself to elicit and record the answers. In addition, it can also measure the recovery function of the auditory nerve (REC), that is, the refractory properties of the nerve. It is not clear in the literature whether the responses from adults are the same as those from children. Objective To compare the results of NRT and REC between adults and children undergoing CI surgery. Methods Cross-sectional, descriptive, and retrospective study of the results of NRT and REC for patients undergoing IC at our service. The NRT is assessed by the level of amplitude (microvolts) and REC as a function of three parameters: A (saturation level, in microvolts), t0 (absolute refractory period, in seconds), and tau (curve of the model function), measured in three electrodes (apical, medial, and basal). Results Fifty-two patients were evaluated with intraoperative NRT (26 adults and 26 children), and 24 with REC (12 adults and 12 children). No statistically significant difference was found between intraoperative responses of adults and children for NRT or for REC's three parameters, except for parameter A of the basal electrode. Conclusion The results of intraoperative NRT and REC were not different between adults and children, except for parameter A of the basal electrode. PMID:25992145

  15. PREDICTS: Projecting Responses of Ecological Diversity in Changing Terrestrial Systems

    Directory of Open Access Journals (Sweden)

    Georgina Mace

    2012-12-01

    Full Text Available The PREDICTS project (www.predicts.org.uk is a three-year NERC-funded project to model and predict at a global scale how local terrestrial diversity responds to human pressures such as land use, land cover, pollution, invasive species and infrastructure. PREDICTS is a collaboration between Imperial College London, the UNEP World Conservation Monitoring Centre, Microsoft Research Cambridge, UCL and the University of Sussex. In order to meet its aims, the project relies on extensive data describing the diversity and composition of biological communities at a local scale. Such data are collected on a vast scale through the committed efforts of field ecologists. If you have appropriate data that you would be willing to share with us, please get in touch (enquiries@predicts.org.uk. All contributions will be acknowledged appropriately and all data contributors will be included as co-authors on an open-access paper describing the database.

  16. Method discussion for quick response grey prediction of stronger aftershocks of an earthquake sequence

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    In this paper, we take occurrence process of early strong aftershocks of a main-after shock type′s earthquake sequence as a complex grey system, and introduce predicting method for its stronger aftershocks by grey predicting theory. Through inspection prediction for 1998 Zhangbei MS=6.2 earthquake sequence, it shows that the grey predicting method maybe has active significance for the investigation of quick response prediction problems of stronger aftershocks of an earthquake sequence.

  17. Older Persons' Reasoning about Responsibility for Health: Variations and Predictions

    Science.gov (United States)

    Kjellstrom, Sofia; Ross, Sara Nora

    2011-01-01

    With many Western societies structured for adults to live longer and take responsibility for their health, it is valuable to investigate how older persons reason about this demand. Using mixed methods, this pilot studied how older persons reason about responsibility for health and their responsibility as a patient. Interviews with a small Swedish…

  18. Life history theory predicts fish assemblage response to hydrologic regimes.

    Science.gov (United States)

    Mims, Meryl C; Olden, Julian D

    2012-01-01

    The hydrologic regime is regarded as the primary driver of freshwater ecosystems, structuring the physical habitat template, providing connectivity, framing biotic interactions, and ultimately selecting for specific life histories of aquatic organisms. In the present study, we tested ecological theory predicting directional relationships between major dimensions of the flow regime and life history composition of fish assemblages in perennial free-flowing rivers throughout the continental United States. Using long-term discharge records and fish trait and survey data for 109 stream locations, we found that 11 out of 18 relationships (61%) tested between the three life history strategies (opportunistic, periodic, and equilibrium) and six hydrologic metrics (two each describing flow variability, predictability, and seasonality) were statistically significant (P history strategies, with 82% of all significant relationships observed supporting predictions from life history theory. Specifically, we found that (1) opportunistic strategists were positively related to measures of flow variability and negatively related to predictability and seasonality, (2) periodic strategists were positively related to high flow seasonality and negatively related to variability, and (3) the equilibrium strategists were negatively related to flow variability and positively related to predictability. Our study provides important empirical evidence illustrating the value of using life history theory to understand both the patterns and processes by which fish assemblage structure is shaped by adaptation to natural regimes of variability, predictability, and seasonality of critical flow events over broad biogeographic scales.

  19. Prediction of First-Order Vessel Responses with Applications to Decision Support Systems

    DEFF Research Database (Denmark)

    Nielsen, Ulrik D.; Iseki, Toshio

    2015-01-01

    The paper presents a practical and simple approach for making vessel response predictions. Features of the procedure include a) predictions which are scaled so to better agree with corresponding true, future values to be measured at the time the predictions apply at; and b) predictions that are a......The paper presents a practical and simple approach for making vessel response predictions. Features of the procedure include a) predictions which are scaled so to better agree with corresponding true, future values to be measured at the time the predictions apply at; and b) predictions...... that are assigned an uncertainty measure to reflect a level of confidence. The approach is tested with full-scale data and the obtained results/predictions agree well with measured values. Potentially, the procedure is therefore very useful in future developments of general decision support systems....

  20. The reduced cochlear output and the failure to adapt the central auditory response causes tinnitus in noise exposed rats.

    Directory of Open Access Journals (Sweden)

    Lukas Rüttiger

    Full Text Available Tinnitus is proposed to be caused by decreased central input from the cochlea, followed by increased spontaneous and evoked subcortical activity that is interpreted as compensation for increased responsiveness of central auditory circuits. We compared equally noise exposed rats separated into groups with and without tinnitus for differences in brain responsiveness relative to the degree of deafferentation in the periphery. We analyzed (1 the number of CtBP2/RIBEYE-positive particles in ribbon synapses of the inner hair cell (IHC as a measure for deafferentation; (2 the fine structure of the amplitudes of auditory brainstem responses (ABR reflecting differences in sound responses following decreased auditory nerve activity and (3 the expression of the activity-regulated gene Arc in the auditory cortex (AC to identify long-lasting central activity following sensory deprivation. Following moderate trauma, 30% of animals exhibited tinnitus, similar to the tinnitus prevalence among hearing impaired humans. Although both tinnitus and no-tinnitus animals exhibited a reduced ABR wave I amplitude (generated by primary auditory nerve fibers, IHCs ribbon loss and high-frequency hearing impairment was more severe in tinnitus animals, associated with significantly reduced amplitudes of the more centrally generated wave IV and V and less intense staining of Arc mRNA and protein in the AC. The observed severe IHCs ribbon loss, the minimal restoration of ABR wave size, and reduced cortical Arc expression suggest that tinnitus is linked to a failure to adapt central circuits to reduced cochlear input.

  1. Prediction and set-dependent scaling of early postural responses in cerebellar patients.

    Science.gov (United States)

    Timmann, D; Horak, F B

    1997-02-01

    We reported previously that patients with cerebellar deficits were unable to scale the magnitude of their early automatic postural responses to the predicted amplitudes of surface translations based on central set from prior experience. The present study investigated whether this deficit in set-dependent amplitude scaling was based predominantly on the cerebellar patient's disability (i) to predict perturbation amplitudes on the basis of prior experience, (ii) to scale the gain or magnitude of upcoming postural responses or (iii) to habituate postural responses. The increase in size of the early postural response when a larger than actual platform amplitude was expected and decrease when a smaller one was expected was defined as a measure of set-dependent amplitude prediction. The suppression of the postural response when the same platform velocity was repeated was used as a measure of habituation. The correlation between the size of early postural responses and platform amplitudes when presented serially, but not randomly, tested the ability to scale the gain of postural responses based on prior experience. Results show that although cerebellar patients could predict perturbation amplitudes based on prior experience, they could not use this prediction to modify precisely the gain of responses. The ability to habituate the magnitude of postural responses was not affected by cerebellar lesions. Thus, the cerebellum might not be critical for predicting upcoming events or for habituating to repeated postural stimuli, although it is important for accurate tuning of response gain based on prediction.

  2. Ovarian response prediction in GnRH antagonist treatment for IVF using anti-Mullerian hormone

    NARCIS (Netherlands)

    Hamdine, O.; Eijkemans, M.J.; Lentjes, E.W.; Torrance, H.L.; Macklon, N.S.; Fauser, B.C.; Broekmans, F.J.

    2015-01-01

    STUDY QUESTION: What is the clinical value of anti-Mullerian hormone (AMH) for the prediction of high or low ovarian response in controlled ovarian stimulation for IVF using GnRH antagonist treatment? SUMMARY ANSWER: AMH as a single test has substantial accuracy for ovarian response prediction in Gn

  3. Predicting fluid responsiveness with transthoracic echocardiography is not yet evidence based

    DEFF Research Database (Denmark)

    Wetterslev, M; Haase, N; Johansen, R R;

    2013-01-01

    an integrated tool in the intensive care unit, this systematic review examined studies evaluating the predictive value of TTE for fluid responsiveness. In October 2012, we searched Pubmed, EMBASE and Web of Science for studies evaluating the predictive value of TTE-derived variables for fluid responsiveness...

  4. Analysis of LFP phase predicts sensory response of barrel cortex.

    Science.gov (United States)

    Haslinger, R; Ulbert, I; Moore, C I; Brown, E N; Devor, A

    2006-09-01

    Several previous studies have shown the existence of Up and Down states and have linked their magnitude (e.g., depolarization level) to the size of sensory-evoked responses. Here, we studied how the temporal dynamics of such states influence the sensory-evoked response to vibrissa deflection. Under alpha-chloralose anesthesia, barrel cortex exhibits strong quasi-periodic approximately 1-Hz local field potential (LFP) oscillations generated by the synchronized fluctuation of large populations of neurons between depolarized (Up) and hyperpolarized (Down) states. Using a linear depth electrode array, we recorded the LFP and multiunit activity (MUA) simultaneously across multiple layers of the barrel column and used the LFP to approximate the subthreshold Up-Down fluctuations. Our central finding is that the MUA response is a strong function of the LFP oscillation's phase. When only ongoing LFP magnitude was considered, the response was largest in the Down state, in agreement with previous studies. However, consideration of the LFP phase revealed that the MUA response varied smoothly as a function of LFP phase in a manner that was not monotonically dependent on LFP magnitude. The LFP phase is therefore a better predictor of the MUA response than the LFP magnitude is. Our results suggest that, in the presence of ongoing oscillations, there can be a continuum of response properties and that each phase may, at times, need to be considered a distinct cortical state.

  5. Fuzzy predictive filtering in nonlinear economic model predictive control for demand response

    DEFF Research Database (Denmark)

    Santos, Rui Mirra; Zong, Yi; Sousa, Joao M. C.;

    2016-01-01

    The performance of a model predictive controller (MPC) is highly correlated with the model's accuracy. This paper introduces an economic model predictive control (EMPC) scheme based on a nonlinear model, which uses a branch-and-bound tree search for solving the inherent non-convex optimization...... problem. Moreover, to reduce the computation time and improve the controller's performance, a fuzzy predictive filter is introduced. With the purpose of testing the developed EMPC, a simulation controlling the temperature levels of an intelligent office building (PowerFlexHouse), with and without fuzzy...

  6. Mechanistic Modeling Framework for Predicting Extreme Battery Response

    Energy Technology Data Exchange (ETDEWEB)

    Geller, Anthony S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-11-01

    The objectives of this project are to address the root cause implications of thermal runaway of Li-ion batteries by delivering a software architecture solution that can lead to the development of predictive mechanisms that are based on identification of species.

  7. Sadness prediction and response: effects of age and agreeableness.

    Science.gov (United States)

    Pearman, Ann; Andreoletti, Carrie; Isaacowitz, Derek M

    2010-04-01

    Research has suggested that both age and personality play a role in emotional experience and regulation, but these variables have not been considered together to determine the relative contribution of each. This study simultaneously examined age and agreeableness differences in the experience of sad stimuli. Participants were 46 younger adults (age, M = 22.04 years, SD = 5.41 years) and 48 older adults (age, M = 74.23, SD = 7.82 years). Participants were asked to predict how sad stimuli (i.e., sad photos) would make them feel and were then measured on their actual reaction to the stimuli (reactivity) as well as on their emotional recovery. Agreeableness, but not age, was related to predicted levels of sadness, such that the more agreeable, the higher the predicted sadness (beta = 0.37). In contrast to expectations, prediction accuracy was not related to age or agreeableness. For emotional reactivity, agreeableness (beta = 0.16), but not age, was related to reactivity to sad stimuli (i.e., more agreeable, higher reactivity). Finally, age (beta = 0.14) was significantly related to emotional recovery such that the older adults reported lower levels of sadness at posttest than did the younger adults. Similarly, people who were more agreeable also reported better emotional recovery (beta = 0.15). These relationships were not affected by depression or pretest sadness ratings. Overall, these findings suggest distinct roles for age and agreeableness in predicting different components of the emotion regulation process. An individual with advanced age, high levels of agreeableness, or both may be well-positioned for resilience throughout the emotion regulation process.

  8. Reduced-Order Models for Acoustic Response Prediction

    Science.gov (United States)

    2011-07-01

    allowed to vibrate, decaying freely. Temporal frequencies and amplitudes are estimated using a variant of a method proposed by Agneni and Balis Crema [44...less than 0.06" may require the coupled ROM for accurate predictions. The phenomena can be explained as follows: The acoustic modes of the coupled...free vibration identification via the Hilbert transform. J. of Sound and Vibration, 1997, 208(3), 475-489. 44. Agneni, A. and Balis Crema, L

  9. Using unknown knowns to predict coastal response to future climate

    Science.gov (United States)

    Plant, N. G.; Lentz, E. E.; Gutierrez, B.; Thieler, E. R.; Passeri, D. L.

    2015-12-01

    The coastal zone, including its bathymetry, topography, ecosystem, and communities, depends on and responds to a wide array of natural and engineered processes associated with climate variability. Climate affects the frequency of coastal storms, which are only resolved probabilistically for future conditions, as well as setting the pace for persistent processes (e.g., waves driving daily alongshore transport; beach nourishment). It is not clear whether persistent processes or extreme events contribute most to the integrated evolution of the coast. Yet, observations of coastal change record the integration of persistent and extreme processes. When these observations span a large spatial domain and/or temporal range they may reflect a wide range of forcing and boundary conditions that include different levels of sea-level rise, storminess, sediment input, engineering activities, and elevation distributions. We have been using a statistical approach to characterize the interrelationships between oceanographic, ecological, and geomorphic processes—including the role played by human activities via coastal protection, beach nourishment, and other forms of coastal management. The statistical approach, Bayesian networks, incorporates existing information to establish underlying prior expectations for the distributions and inter-correlations of variables most relevant to coastal geomorphic evolution. This underlying information can then be used to make predictions. We demonstrate several examples of the utility of this approach using data as constraints and then propagating the constraints and uncertainty to make predictions of unobserved variables that include changes in shorelines, dunes, and overwash deposits. We draw on data from the Gulf and Atlantic Coasts of the United States, resolving time scales of years to a century. The examples include both short-term storm impacts and long-term evolution associated with sea-level rise. We show that the Bayesian network can

  10. Global genetic variations predict brain response to faces

    DEFF Research Database (Denmark)

    Dickie, Erin W; Tahmasebi, Amir; French, Leon;

    2014-01-01

    Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼ 500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximu...

  11. MTR-18 Predictive Biomarkers Of Bevacizumab Response In Recurrent Glioblastoma Patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn;

    2015-01-01

    with the proneural GBM subtype have a survival benefit when treated with BEV in combination with standard treatment. However, no validated biomarkers able to predict BEV response have been identified and the biology reflecting a clinical BEV response is poorly understood. The primary objective of this study...... was to evaluate the predictive and prognostic value of GBM subtypes in recurrent GBM patients treated with BEV therapy. The secondary objective was to identify biomarkers able to predict response to BEV therapy in recurrent GBM patients. METHODS: A total of 90 recurrent GBM patients treated with BEV combination...... and multifocal disease. RESULTS: Molecular subtypes were not associated with response or survival. However, two independent predictive biomarkers (gene1 down-regulated and gene2 up-regulated in responders, respectively) of BEV response and survival were identified. Results will be presented....

  12. Trend modelling of wave parameters and application in onboard prediction of ship responses

    DEFF Research Database (Denmark)

    Montazeri, Najmeh; Nielsen, Ulrik Dam; Jensen, J. Juncher

    2015-01-01

    This paper presents a trend analysis for prediction of sea state parameters onboard shipsduring voyages. Given those parameters, a JONSWAP model and also the transfer functions, prediction of wave induced ship responses are thus made. The procedure is tested with full-scale data of an in-service ......This paper presents a trend analysis for prediction of sea state parameters onboard shipsduring voyages. Given those parameters, a JONSWAP model and also the transfer functions, prediction of wave induced ship responses are thus made. The procedure is tested with full-scale data of an in...

  13. Predicting nonlinear properties of metamaterials from the linear response.

    Science.gov (United States)

    O'Brien, Kevin; Suchowski, Haim; Rho, Junsuk; Salandrino, Alessandro; Kante, Boubacar; Yin, Xiaobo; Zhang, Xiang

    2015-04-01

    The discovery of optical second harmonic generation in 1961 started modern nonlinear optics. Soon after, R. C. Miller found empirically that the nonlinear susceptibility could be predicted from the linear susceptibilities. This important relation, known as Miller's Rule, allows a rapid determination of nonlinear susceptibilities from linear properties. In recent years, metamaterials, artificial materials that exhibit intriguing linear optical properties not found in natural materials, have shown novel nonlinear properties such as phase-mismatch-free nonlinear generation, new quasi-phase matching capabilities and large nonlinear susceptibilities. However, the understanding of nonlinear metamaterials is still in its infancy, with no general conclusion on the relationship between linear and nonlinear properties. The key question is then whether one can determine the nonlinear behaviour of these artificial materials from their exotic linear behaviour. Here, we show that the nonlinear oscillator model does not apply in general to nonlinear metamaterials. We show, instead, that it is possible to predict the relative nonlinear susceptibility of large classes of metamaterials using a more comprehensive nonlinear scattering theory, which allows efficient design of metamaterials with strong nonlinearity for important applications such as coherent Raman sensing, entangled photon generation and frequency conversion.

  14. Predictive Response Value of Pre- and Postchemoradiotherapy Variables in Rectal Cancer: An Analysis of Histological Data.

    Science.gov (United States)

    Santos, Marisa D; Silva, Cristina; Rocha, Anabela; Nogueira, Carlos; Matos, Eduarda; Lopes, Carlos

    2016-01-01

    Background. Neoadjuvant chemoradiotherapy (nCRT) followed by curative surgery in locally advanced rectal cancer (LARC) improves pelvic disease control. Survival improvement is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. Potential predictive factors for Mandard response are analyzed. Materials and Methods. 167 patients with LARC were treated with nCRT and curative surgery. Tumor biopsies and surgical specimens were reviewed and analyzed regarding mitotic count, necrosis, desmoplastic reaction, and inflammatory infiltration grade. Surgical specimens were classified according to Mandard TRG. The patients were divided as "good responders" (Mandard TRG1-2) and "bad responders" (Mandard TRG3-5). According to results from our previous data, good responders have better prognosis than bad responders. We examined predictive factors for Mandard response and performed statistical analysis. Results. In univariate analysis, distance from anal verge and ten other postoperative variables related with nCRT tumor response had predictive value for Mandard response. In multivariable analysis only mitotic count, necrosis, and differentiation grade in surgical specimen had predictive value. Conclusions. There is a lack of clinical and pathological preoperative variables able to predict Mandard response. Only postoperative pathological parameters related with nCRT response have predictive value.

  15. Conceptualizing, Understanding, and Predicting Responsible Decisions and Quality Input

    Science.gov (United States)

    Wall, N.; PytlikZillig, L. M.

    2012-12-01

    In areas such as climate change, where uncertainty is high, it is arguably less difficult to tell when efforts have resulted in changes in knowledge, than when those efforts have resulted in responsible decisions. What is a responsible decision? More broadly, when it comes to citizen input, what is "high quality" input? And most importantly, how are responsible decisions and quality input enhanced? The aim of this paper is to contribute to the understanding of the different dimensions of "responsible" or "quality" public input and citizen decisions by comparing and contrasting the different predictors of those different dimensions. We first present different possibilities for defining, operationalizing and assessing responsible or high quality decisions. For example, responsible decisions or quality input might be defined as using specific content (e.g., using climate change information in decisions appropriately), as using specific processes (e.g., investing time and effort in learning about and discussing the issues prior to making decisions), or on the basis of some judgment of the decision or input itself (e.g., judgments of the rationale provided for the decisions, or number of issues considered when giving input). Second, we present results from our work engaging people with science policy topics, and the different ways that we have tried to define these two constructs. In the area of climate change specifically, we describe the development of a short survey that assesses exposure to climate information, knowledge of and attitudes toward climate change, and use of climate information in one's decisions. Specifically, the short survey was developed based on a review of common surveys of climate change related knowledge, attitudes, and behaviors, and extensive piloting and cognitive interviews. Next, we analyze more than 200 responses to that survey (data collection is currently ongoing and will be complete after the AGU deadline), and report the predictors of

  16. 5-HTTLPR differentially predicts brain network responses to emotional faces

    DEFF Research Database (Denmark)

    Fisher, Patrick M; Grady, Cheryl L; Madsen, Martin K

    2015-01-01

    resonance imaging in 76 healthy adults. We observed robust increased response to emotional faces in the amygdala, hippocampus, caudate, fusiform gyrus, superior temporal sulcus and lateral prefrontal and occipito-parietal cortices. We observed dissociation between 5-HTTLPR groups such that LA LA individuals...... of the face-processing network. These findings provide additional insight into neurobiological mechanisms through which 5-HTTLPR genotype may affect personality and related risk for neuropsychiatric illness....

  17. Implicit Learning Abilities Predict Treatment Response in Autism Spectrum Disorders

    Science.gov (United States)

    2015-09-01

    30/15 Simons Foundation 1.8 CM Ext Advancing a Standardized Research Protocol to Study Treatment Effects in Individuals with Autism Spectrum...participants, collecting data from all of the research subjects and is responsible for performing analyses. Funding Support: RFA 336363 Lord (PI) 7... Autism Spectrum Disorder Role: Co-Investigator Name: BJ Casey Project Role: Co-Investigator Research Identifier: BJCASEY (era commons) Nearest

  18. VO2 prediction and cardiorespiratory responses during underwater treadmill exercise.

    Science.gov (United States)

    Greene, Nicholas P; Greene, Elizabeth S; Carbuhn, Aaron F; Green, John S; Crouse, Stephen F

    2011-06-01

    We compared cardiorespiratory responses to exercise on an underwater treadmill (UTM) and land treadmill (LTM) and derived an equation to estimate oxygen consumption (VO2) during UTM exercise. Fifty-five men and women completed one LTM and five UTM exercise sessions on separate days. The UTM sessions consisted of chest-deep immersion, with 0, 25, 50, 75, and 100% water-jet resistance. All session treadmill velocities increased every 3 min from 53.6 to 187.8 m x min(-1). Cardiorespiratory responses were similar between LTM and UTM when jet resistance for UTM was 50%. Using multiple regression analysis, weight-relative VO2 could be estimated as: VO2 (mLO2 c kg(-1) x min(-1)) = 0.19248 x height (cm) + 0.17422 x jet resistance (% max) + 0.14092 x velocity (m x min(-1)) -0.12794 x weight (kg)-27.82849, R2 = .82. Our data indicate that similar LTM and UTM cardiorespiratory responses are achievable, and we provide a reasonable estimate of UTM VO2.

  19. Anger responses to psychosocial stress predict heart rate and cortisol stress responses in men but not women.

    Science.gov (United States)

    Lupis, Sarah B; Lerman, Michelle; Wolf, Jutta M

    2014-11-01

    While previous research has suggested that anger and fear responses to stress are linked to distinct sympathetic nervous system (SNS) stress responses, little is known about how these emotions predict hypothalamus-pituitary-adrenal (HPA) axis reactivity. Further, earlier research primarily relied on retrospective self-report of emotion. The current study aimed at addressing both issues in male and female individuals by assessing the role of anger and fear in predicting heart rate and cortisol stress responses using both self-report and facial coding analysis to assess emotion responses. We exposed 32 healthy students (18 female; 19.6±1.7 yr) to an acute psychosocial stress paradigm (TSST) and measured heart rate and salivary cortisol levels throughout the protocol. Anger and fear before and after stress exposure was assessed by self-report, and video recordings of the TSST were assessed by a certified facial coder to determine emotion expression (FACS). Self-reported emotions and emotion expressions did not correlate (all p>.23). Increases in self-reported fear predicted blunted cortisol responses in men (β=0.41, p=.04). Also for men, longer durations of anger expression predicted exaggerated cortisol responses (β=0.67 p=.004), and more anger incidences predicted exaggerated cortisol and heart rate responses (β=0.51, p=.033; β=0.46, p=.066, resp.). Anger and fear did not predict SNS or HPA activity for females (all p>.23). The current differential self-report and facial coding findings support the use of multiple modes of emotion assessment. Particularly, FACS but not self-report revealed a robust anger-stress association that could have important downstream health effects for men. For women, future research may clarify the role of other emotions, such as self-conscious expressions of shame, for physiological stress responses. A better understanding of the emotion-stress link may contribute to behavioral interventions targeting health-promoting ways of

  20. A Coupled Probabilistic Wake Vortex and Aircraft Response Prediction Model

    Science.gov (United States)

    Gloudemans, Thijs; Van Lochem, Sander; Ras, Eelco; Malissa, Joel; Ahmad, Nashat N.; Lewis, Timothy A.

    2016-01-01

    Wake vortex spacing standards along with weather and runway occupancy time, restrict terminal area throughput and impose major constraints on the overall capacity and efficiency of the National Airspace System (NAS). For more than two decades, the National Aeronautics and Space Administration (NASA) has been conducting research on characterizing wake vortex behavior in order to develop fast-time wake transport and decay prediction models. It is expected that the models can be used in the systems level design of advanced air traffic management (ATM) concepts that safely increase the capacity of the NAS. It is also envisioned that at a later stage of maturity, these models could potentially be used operationally, in groundbased spacing and scheduling systems as well as on the flight deck.

  1. Touch and personality: extraversion predicts somatosensory brain response.

    Science.gov (United States)

    Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael

    2012-08-01

    The Five-Factor-Model describes human personality in five core dimensions (extraversion, neuroticism, agreeableness, conscientiousness, and openness). These factors are supposed to have different neural substrates. For example, it has been suggested that behavioral differences between introverts and extraverts can be explained by the fact that introverts exhibit an inherent drive to compensate for overactive cortical activity in reticulo-thalamo-cortical pathways. The current study examined if responses in somatosensory cortices due to tactile stimulation are affected by personality traits. Based on previous studies and theoretical models we hypothesized a relationship of extraversion with somatosensory responses in primary somatosensory cortex (SI). In order to test this hypothesis we applied nonpainful tactile stimulation on the fingers of both hands of 23 healthy young participants (mean 25 years, standard deviation ± 2.8 years). Personality traits were assessed according to the Five-Factor-Model (NEO-FFI). Neuromagnetic source imaging revealed that the cortical activity (dipole strengths) for sources in SI were closely associated with the personality trait extraversion. Thus, the less extraverted the participants were, the higher was the cortical activity in SI. This relationship was in particular valid for the right hemisphere. We conclude that personality seems to depend on primary cortex activity. Furthermore, our results provide further evidence for an inter-hemispheric asymmetry of the social brain.

  2. Improving models to predict phenological responses to global change

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, Andrew D. [Harvard College, Cambridge, MA (United States)

    2015-11-25

    The term phenology describes both the seasonal rhythms of plants and animals, and the study of these rhythms. Plant phenological processes, including, for example, when leaves emerge in the spring and change color in the autumn, are highly responsive to variation in weather (e.g. a warm vs. cold spring) as well as longer-term changes in climate (e.g. warming trends and changes in the timing and amount of rainfall). We conducted a study to investigate the phenological response of northern peatland communities to global change. Field work was conducted at the SPRUCE experiment in northern Minnesota, where we installed 10 digital cameras. Imagery from the cameras is being used to track shifts in plant phenology driven by elevated carbon dioxide and elevated temperature in the different SPRUCE experimental treatments. Camera imagery and derived products (“greenness”) is being posted in near-real time on a publicly available web page (http://phenocam.sr.unh.edu/webcam/gallery/). The images will provide a permanent visual record of the progression of the experiment over the next 10 years. Integrated with other measurements collected as part of the SPRUCE program, this study is providing insight into the degree to which phenology may mediate future shifts in carbon uptake and storage by peatland ecosystems. In the future, these data will be used to develop improved models of vegetation phenology, which will be tested against ground observations collected by a local collaborator.

  3. Individual Differences in Gelotophobia Predict Responses to Joy and Contempt

    Directory of Open Access Journals (Sweden)

    Jennifer Hofmann

    2015-04-01

    Full Text Available In a paradigm facilitating smile misattribution, facial responses and ratings to contempt and joy were investigated in individuals with or without gelotophobia (fear of being laughed at. Participants from two independent samples (N1 = 83, N2 = 50 rated the intensity of eight emotions in 16 photos depicting joy, contempt, and different smiles. Facial responses were coded by the Facial Action Coding System in the second study. Compared with non-fearful individuals, gelotophobes rated joy smiles as less joyful and more contemptuous. Moreover, gelotophobes showed less facial joy and more contempt markers. The contempt ratings were comparable between the two groups. Looking at the photos of smiles lifted the positive mood of non-gelotophobes, whereas gelotophobes did not experience an increase. We hypothesize that the interpretation bias of “joyful faces hiding evil minds” (i.e., being also contemptuous and exhibiting less joy facially may complicate social interactions for gelotophobes and serve as a maintaining factor of gelotophobia.

  4. Camera response prediction for various capture settings using the spectral sensitivity and crosstalk model.

    Science.gov (United States)

    Qiu, Jueqin; Xu, Haisong

    2016-09-01

    In this paper, a camera response formation model is proposed to accurately predict the responses of images captured under various exposure settings. Differing from earlier works that estimated the camera relative spectral sensitivity, our model constructs the physical spectral sensitivity curves and device-dependent parameters that convert the absolute spectral radiances of target surfaces to the camera readout responses. With this model, the camera responses to miscellaneous combinations of surfaces and illuminants could be accurately predicted. Thus, creating an "imaging simulator" by using the colorimetric and photometric research based on the cameras would be of great convenience.

  5. Gene Expression Profiles Can Predict Panitumumab Monotherapy Responsiveness in Human Tumor Xenograft Models

    Directory of Open Access Journals (Sweden)

    Michael J. Boedigheimer

    2013-02-01

    Conclusion A model was constructed from microarray data that prospectively predict responsiveness to panitumumab in xenograft models. This approach may help identify patients, independent of disease origin, likely to benefit from panitumumab.

  6. A noise level prediction method based on electro-mechanical frequency response function for capacitors.

    Science.gov (United States)

    Zhu, Lingyu; Ji, Shengchang; Shen, Qi; Liu, Yuan; Li, Jinyu; Liu, Hao

    2013-01-01

    The capacitors in high-voltage direct-current (HVDC) converter stations radiate a lot of audible noise which can reach higher than 100 dB. The existing noise level prediction methods are not satisfying enough. In this paper, a new noise level prediction method is proposed based on a frequency response function considering both electrical and mechanical characteristics of capacitors. The electro-mechanical frequency response function (EMFRF) is defined as the frequency domain quotient of the vibration response and the squared capacitor voltage, and it is obtained from impulse current experiment. Under given excitations, the vibration response of the capacitor tank is the product of EMFRF and the square of the given capacitor voltage in frequency domain, and the radiated audible noise is calculated by structure acoustic coupling formulas. The noise level under the same excitations is also measured in laboratory, and the results are compared with the prediction. The comparison proves that the noise prediction method is effective.

  7. A combined clinical and biomarker approach to predict diuretic response in acute heart failure

    NARCIS (Netherlands)

    Ter Maaten, Jozine M; Valente, Mattia A E; Metra, Marco; Bruno, Noemi; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; van Veldhuisen, Dirk J; Hillege, Hans L; Damman, Kevin; Voors, Adriaan A

    2015-01-01

    BACKGROUND: Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic resp

  8. Predicting the Response of Electricity Load to Climate Change

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, Patrick [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Colman, Jesse [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kalendra, Eric [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2015-07-28

    Our purpose is to develop a methodology to quantify the impact of climate change on electric loads in the United States. We perform simple linear regression, assisted by geospatial smoothing, on paired temperature and load time-series to estimate the heating- and coolinginduced sensitivity to temperature across 300 transmission zones and 16 seasonal and diurnal time periods. The estimated load sensitivities can be coupled with climate scenarios to quantify the potential impact of climate change on load, with a primary application being long-term electricity scenarios. The method allows regional and seasonal differences in climate and load response to be reflected in the electricity scenarios. While the immediate product of this analysis was designed to mesh with the spatial and temporal resolution of a specific electricity model to enable climate change scenarios and analysis with that model, we also propose that the process could be applied for other models and purposes.

  9. Prediction of response to interferon therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Søndergaard, Helle Bach; Koch-Henriksen, N;

    2014-01-01

    OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the genes encoding interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been associated with disease activity in multiple sclerosis (MS) patients treated with interferon (IFN)-β. We analysed whether SNPs in the IRF5, IRF8 and GPC5...... genes are associated with clinical disease activity in MS patients beginning de novo treatment with IFN-β. METHODS: The SNPs rs2004640, rs3807306 and rs4728142 in IRF5, rs13333054 and rs17445836 in IRF8 and rs10492503 in GPC5 were genotyped in 575 patients with relapsing-remitting MS followed...... years of treatment (hazard ratio 2.04, 95% confidence interval 1.47-2.85).The gene variants in IRF5, IRF8 and GPC5 were not associated with risk of relapse or disease progression. CONCLUSIONS: Pretreatment relapse rate and clinical disease activity during the first 2 years of treatment may be associated...

  10. Poor Response to Periodontal Treatment May Predict Future Cardiovascular Disease.

    Science.gov (United States)

    Holmlund, A; Lampa, E; Lind, L

    2017-03-01

    Periodontal disease has been associated with cardiovascular disease (CVD), but whether the response to the treatment of periodontal disease affects this association has not been investigated in any large prospective study. Periodontal data obtained at baseline and 1 y after treatment were available in 5,297 individuals with remaining teeth who were treated at a specialized clinic for periodontal disease. Poor response to treatment was defined as having >10% sites with probing pocket depth >4 mm deep and bleeding on probing at ≥20% of the sites 1 y after active treatment. Fatal/nonfatal incidence rate of CVD (composite end point of myocardial infarction, stroke, and heart failure) was obtained from the Swedish cause-of-death and hospital discharge registers. Poisson regression analysis was performed to analyze future risk of CVD. During a median follow-up of 16.8 y (89,719 person-years at risk), those individuals who did not respond well to treatment (13.8% of the sample) had an increased incidence of CVD ( n = 870) when compared with responders (23.6 vs. 15.3%, P 4 mm, and number of teeth, the incidence rate ratio for CVD among poor responders was 1.28 (95% CI, 1.07 to 1.53; P = 0.007) as opposed to good responders. The incidence rate ratio among poor responders increased to 1.39 (95% CI, 1.13 to 1.73; P = 0.002) for those with the most remaining teeth. Individuals who did not respond well to periodontal treatment had an increased risk for future CVD, indicating that successful periodontal treatment might influence progression of subclinical CVD.

  11. Serotonin modulates the effects of Pavlovian aversive predictions on response vigor.

    Science.gov (United States)

    Crockett, Molly J; Clark, Luke; Apergis-Schoute, Annemieke M; Morein-Zamir, Sharon; Robbins, Trevor W

    2012-09-01

    Updated theoretical accounts of the role of serotonin (5-HT) in motivation propose that 5-HT operates at the intersection of aversion and inhibition, promoting withdrawal in the face of aversive predictions. However, the specific cognitive mechanisms through which 5-HT modulates withdrawal behavior remain poorly understood. Behavioral inhibition in response to punishments reflects at least two concurrent processes: instrumental aversive predictions linking stimuli, responses, and punishments, and Pavlovian aversive predictions linking stimuli and punishments irrespective of response. In the current study, we examined to what extent 5-HT modulates the impact of instrumental vs Pavlovian aversive predictions on behavioral inhibition. We used acute tryptophan depletion to lower central 5-HT levels in healthy volunteers, and observed behavior in a novel task designed to measure the influence of Pavlovian and instrumental aversive predictions on choice (response bias) and response vigor (response latencies). After placebo treatment, participants were biased against responding on the button that led to punishment, and they were slower to respond in a punished context, relative to a non-punished context. Specifically, participants slowed their responses in the presence of stimuli predictive of punishments. Tryptophan depletion removed the bias against responding on the punished button, and abolished slowing in the presence of punished stimuli, irrespective of response. We suggest that this set of results can be explained by a role for 5-HT in Pavlovian aversive predictions. These findings suggest additional specificity for the influence of 5-HT on aversively motivated behavioral inhibition and extend recent models of the role of 5-HT in aversive predictions.

  12. The database of the PREDICTS (Projecting Responses of Ecological Diversity in Changing Terrestrial Systems) project

    DEFF Research Database (Denmark)

    Hudson, Lawrence N; Newbold, Tim; Contu, Sara

    2017-01-01

    The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity ...

  13. Modeling transducer impulse responses for predicting calibrated pressure pulses with the ultrasound simulation program Field II

    DEFF Research Database (Denmark)

    Bæk, David; Jensen, Jørgen Arendt; Willatzen, Morten

    2010-01-01

    FIELD II is a simulation software capable of predicting the field pressure in front of transducers having any complicated geometry. A calibrated prediction with this program is, however, dependent on an exact voltage-to-surface acceleration impulse response of the transducer. Such impulse respons...

  14. Estimating the predictive quality of dose-response after model selection.

    Science.gov (United States)

    Hu, Chuanpu; Dong, Yingwen

    2007-07-20

    Prediction of dose-response is important in dose selection in drug development. As the true dose-response shape is generally unknown, model selection is frequently used, and predictions based on the final selected model. Correctly assessing the quality of the predictions requires accounting for the uncertainties caused by the model selection process, which has been difficult. Recently, a new approach called data perturbation has emerged. It allows important predictive characteristics be computed while taking model selection into consideration. We study, through simulation, the performance of data perturbation in estimating standard error of parameter estimates and prediction errors. Data perturbation was found to give excellent prediction error estimates, although at times large Monte Carlo sizes were needed to obtain good standard error estimates. Overall, it is a useful tool to characterize uncertainties in dose-response predictions, with the potential of allowing more accurate dose selection in drug development. We also look at the influence of model selection on estimation bias. This leads to insights into candidate model choices that enable good dose-response prediction.

  15. One-tone suppression in the frog auditory nerve

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Jørgensen, M B

    1996-01-01

    frequencies ranged from 700 to 1200 Hz. Spontaneous activities for the fibers showing one-tone suppression ranged from 3 to 75 spikes/s. Spontaneous activities above 40 spikes/s and the phenomenon of one-tone suppression itself has not been reported previously for frogs. The population of fibers showing one...

  16. Habitat specialization predicts genetic response to fragmentation in tropical birds.

    Science.gov (United States)

    Khimoun, Aurélie; Eraud, Cyril; Ollivier, Anthony; Arnoux, Emilie; Rocheteau, Vincent; Bely, Marine; Lefol, Emilie; Delpuech, Martin; Carpentier, Marie-Laure; Leblond, Gilles; Levesque, Anthony; Charbonnel, Anaïs; Faivre, Bruno; Garnier, Stéphane

    2016-08-01

    Habitat fragmentation is one of the most severe threats to biodiversity as it may lead to changes in population genetic structure, with ultimate modifications of species evolutionary potential and local extinctions. Nonetheless, fragmentation does not equally affect all species and identifying which ecological traits are related to species sensitivity to habitat fragmentation could help prioritization of conservation efforts. Despite the theoretical link between species ecology and extinction proneness, comparative studies explicitly testing the hypothesis that particular ecological traits underlies species-specific population structure are rare. Here, we used a comparative approach on eight bird species, co-occurring across the same fragmented landscape. For each species, we quantified relative levels of forest specialization and genetic differentiation among populations. To test the link between forest specialization and susceptibility to forest fragmentation, we assessed species responses to fragmentation by comparing levels of genetic differentiation between continuous and fragmented forest landscapes. Our results revealed a significant and substantial population structure at a very small spatial scale for mobile organisms such as birds. More importantly, we found that specialist species are more affected by forest fragmentation than generalist ones. Finally, our results suggest that even a simple habitat specialization index can be a satisfying predictor of genetic and demographic consequences of habitat fragmentation, providing a reliable practical and quantitative tool for conservation biology.

  17. Prediction of transcriptional regulatory elements for plant hormone responses based on microarray data

    Directory of Open Access Journals (Sweden)

    Yamaguchi-Shinozaki Kazuko

    2011-02-01

    Full Text Available Abstract Background Phytohormones organize plant development and environmental adaptation through cell-to-cell signal transduction, and their action involves transcriptional activation. Recent international efforts to establish and maintain public databases of Arabidopsis microarray data have enabled the utilization of this data in the analysis of various phytohormone responses, providing genome-wide identification of promoters targeted by phytohormones. Results We utilized such microarray data for prediction of cis-regulatory elements with an octamer-based approach. Our test prediction of a drought-responsive RD29A promoter with the aid of microarray data for response to drought, ABA and overexpression of DREB1A, a key regulator of cold and drought response, provided reasonable results that fit with the experimentally identified regulatory elements. With this succession, we expanded the prediction to various phytohormone responses, including those for abscisic acid, auxin, cytokinin, ethylene, brassinosteroid, jasmonic acid, and salicylic acid, as well as for hydrogen peroxide, drought and DREB1A overexpression. Totally 622 promoters that are activated by phytohormones were subjected to the prediction. In addition, we have assigned putative functions to 53 octamers of the Regulatory Element Group (REG that have been extracted as position-dependent cis-regulatory elements with the aid of their feature of preferential appearance in the promoter region. Conclusions Our prediction of Arabidopsis cis-regulatory elements for phytohormone responses provides guidance for experimental analysis of promoters to reveal the basis of the transcriptional network of phytohormone responses.

  18. Macrobenthic species response surfaces along estuarine gradients: prediction by logistic regression

    NARCIS (Netherlands)

    Ysebaert, T.; Meire, P.; Herman, P.M.J.; Verbeek, H.

    2002-01-01

    This study aims at contributing to the development of statistical models to predict macrobenthic species response to environmental conditions in estuarine ecosystems. Ecological response surfaces are derived for 10 estuarine macrobenthic species. Logistic regression is applied on a large data set, p

  19. Exposure-response functions for (or versus?) the prediction of annoyance in specific situations

    NARCIS (Netherlands)

    Janssen, S.A.; Vos, H.

    2012-01-01

    Based on data from many surveys, exposure-response functions have been derived to describe the average expected annoyance response at a certain noise level. These have been used to define acceptable levels of environmental noise for separate noise sources. However, the prediction of the annoyance re

  20. Regional brain activity and strenuous exercise: predicting affective responses using EEG asymmetry.

    Science.gov (United States)

    Hall, Eric E; Ekkekakis, Panteleimon; Petruzzello, Steven J

    2007-05-01

    Previous research using the model proposed by Davidson has shown that resting frontal electroencephalographic (EEG) asymmetry can predict affective responses to aerobic exercise at moderate intensities. Specifically, greater relative left frontal activity has been shown to predict positive affect (i.e., energy) following exercise. The purpose of this study was to determine if resting frontal EEG asymmetry would predict affective responses following strenuous exercise. Thirty participants (13 women, 17 men) completed a maximal graded exercise test on a treadmill. EEG was recorded prior to exercise. Affect was measured by the Activation Deactivation Adjective Check List prior to the graded exercise test, immediately following, 10 and 20-min following exercise. Greater relative left frontal activity predicted tiredness and calmness during recovery from exercise, but not tension or energy. Tiredness and calmness following exercise covaried, suggesting that tiredness following exercise might not have been linked with displeasure. These findings offer further support for the link between EEG asymmetry and affective responses to exercise.

  1. Predictive Factors of Clinical Response of Infliximab Therapy in Active Nonradiographic Axial Spondyloarthritis Patients

    Science.gov (United States)

    Lin, Zhiming; Liao, Zetao; Huang, Jianlin; Ai, Maixing; Pan, Yunfeng; Wu, Henglian; Lu, Jun; Cao, Shuangyan; Li, Li; Wei, Qiujing; Tang, Deshen; Wei, Yanlin; Li, Tianwang; Wu, Yuqiong; Xu, Manlong; Li, Qiuxia; Jin, Ou; Yu, Buyun; Gu, Jieruo

    2015-01-01

    Objectives. To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. Methods. Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. Results. Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P = 0.005), CRP (AUC = 0.75; P = 0.017), and ASDAS (AUC = 0.778, P = 0.007) significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P = 0.040) significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald χ2 = 6.87, P = 0.009, and wald χ2 = 5.171, P = 0.023). Conclusions. Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients. PMID:26273654

  2. Stathmin Protein Level, a Potential Predictive Marker for Taxane Treatment Response in Endometrial Cancer

    OpenAIRE

    Werner, Henrica M.J.; Jone Trovik; Halle, Mari K.; Elisabeth Wik; Akslen, Lars A; Even Birkeland; Therese Bredholt; Tangen, Ingvild L.; Camilla Krakstad; Salvesen, Helga B.

    2014-01-01

    Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin prote...

  3. Does an understanding of ecosystems responses to rainfall pulses improve predictions of responses of drylands to climate change?

    Science.gov (United States)

    Drylands will experience more intense and frequent droughts and floods. Ten-year field experiments manipulating the amount and variability of precipitation suggest that we cannot predict responses of drylands to climate change based on pulse experimentation. Long-term drought experiments showed no e...

  4. The neuronal response to electrical constant-amplitude pulse train stimulation: additive Gaussian noise.

    Science.gov (United States)

    Matsuoka, A J; Abbas, P J; Rubinstein, J T; Miller, C A

    2000-11-01

    Experimental results from humans and animals show that electrically evoked compound action potential (EAP) responses to constant-amplitude pulse train stimulation can demonstrate an alternating pattern, due to the combined effects of highly synchronized responses to electrical stimulation and refractory effects (Wilson et al., 1994). One way to improve signal representation is to reduce the level of across-fiber synchrony and hence, the level of the amplitude alternation. To accomplish this goal, we have examined EAP responses in the presence of Gaussian noise added to the pulse train stimulus. Addition of Gaussian noise at a level approximately -30 dB relative to EAP threshold to the pulse trains decreased the amount of alternation, indicating that stochastic resonance may be induced in the auditory nerve. The use of some type of conditioning stimulus such as Gaussian noise may provide a more 'normal' neural response pattern.

  5. Gut microbiota signatures predict host and microbiota responses to dietary interventions in obese individuals.

    Directory of Open Access Journals (Sweden)

    Katri Korpela

    Full Text Available BACKGROUND: Interactions between the diet and intestinal microbiota play a role in health and disease, including obesity and related metabolic complications. There is great interest to use dietary means to manipulate the microbiota to promote health. Currently, the impact of dietary change on the microbiota and the host metabolism is poorly predictable and highly individual. We propose that the responsiveness of the gut microbiota may depend on its composition, and associate with metabolic changes in the host. METHODOLOGY: Our study involved three independent cohorts of obese adults (n = 78 from Belgium, Finland, and Britain, participating in different dietary interventions aiming to improve metabolic health. We used a phylogenetic microarray for comprehensive fecal microbiota analysis at baseline and after the intervention. Blood cholesterol, insulin and inflammation markers were analyzed as indicators of host response. The data were divided into four training set - test set pairs; each intervention acted both as a part of a training set and as an independent test set. We used linear models to predict the responsiveness of the microbiota and the host, and logistic regression to predict responder vs. non-responder status, or increase vs. decrease of the health parameters. PRINCIPAL FINDINGS: Our models, based on the abundance of several, mainly Firmicute species at baseline, predicted the responsiveness of the microbiota (AUC  =  0.77-1; predicted vs. observed correlation  =  0.67-0.88. Many of the predictive taxa showed a non-linear relationship with the responsiveness. The microbiota response associated with the change in serum cholesterol levels with an AUC of 0.96, highlighting the involvement of the intestinal microbiota in metabolic health. CONCLUSION: This proof-of-principle study introduces the first potential microbial biomarkers for dietary responsiveness in obese individuals with impaired metabolic health, and reveals the

  6. Driver Vision Based Perception-Response Time Prediction and Assistance Model on Mountain Highway Curve

    Science.gov (United States)

    Li, Yi; Chen, Yuren

    2016-01-01

    To make driving assistance system more humanized, this study focused on the prediction and assistance of drivers’ perception-response time on mountain highway curves. Field tests were conducted to collect real-time driving data and driver vision information. A driver-vision lane model quantified curve elements in drivers’ vision. A multinomial log-linear model was established to predict perception-response time with traffic/road environment information, driver-vision lane model, and mechanical status (last second). A corresponding assistance model showed a positive impact on drivers’ perception-response times on mountain highway curves. Model results revealed that the driver-vision lane model and visual elements did have important influence on drivers’ perception-response time. Compared with roadside passive road safety infrastructure, proper visual geometry design, timely visual guidance, and visual information integrality of a curve are significant factors for drivers’ perception-response time. PMID:28042851

  7. Driver Vision Based Perception-Response Time Prediction and Assistance Model on Mountain Highway Curve

    Directory of Open Access Journals (Sweden)

    Yi Li

    2016-12-01

    Full Text Available To make driving assistance system more humanized, this study focused on the prediction and assistance of drivers’ perception-response time on mountain highway curves. Field tests were conducted to collect real-time driving data and driver vision information. A driver-vision lane model quantified curve elements in drivers’ vision. A multinomial log-linear model was established to predict perception-response time with traffic/road environment information, driver-vision lane model, and mechanical status (last second. A corresponding assistance model showed a positive impact on drivers’ perception-response times on mountain highway curves. Model results revealed that the driver-vision lane model and visual elements did have important influence on drivers’ perception-response time. Compared with roadside passive road safety infrastructure, proper visual geometry design, timely visual guidance, and visual information integrality of a curve are significant factors for drivers’ perception-response time.

  8. Driver Vision Based Perception-Response Time Prediction and Assistance Model on Mountain Highway Curve.

    Science.gov (United States)

    Li, Yi; Chen, Yuren

    2016-12-30

    To make driving assistance system more humanized, this study focused on the prediction and assistance of drivers' perception-response time on mountain highway curves. Field tests were conducted to collect real-time driving data and driver vision information. A driver-vision lane model quantified curve elements in drivers' vision. A multinomial log-linear model was established to predict perception-response time with traffic/road environment information, driver-vision lane model, and mechanical status (last second). A corresponding assistance model showed a positive impact on drivers' perception-response times on mountain highway curves. Model results revealed that the driver-vision lane model and visual elements did have important influence on drivers' perception-response time. Compared with roadside passive road safety infrastructure, proper visual geometry design, timely visual guidance, and visual information integrality of a curve are significant factors for drivers' perception-response time.

  9. Controllability modulates the neural response to predictable but not unpredictable threat in humans.

    Science.gov (United States)

    Wood, Kimberly H; Wheelock, Muriah D; Shumen, Joshua R; Bowen, Kenton H; Ver Hoef, Lawrence W; Knight, David C

    2015-10-01

    Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress.

  10. Predictive value of Pre-treatment Amygdala volume for Electroconvulsive Therapy Response in Severely Depressed Patients

    Directory of Open Access Journals (Sweden)

    Freek eTen Doesschate

    2014-11-01

    Full Text Available Background Electroconvulsive therapy (ECT is an effective treatment for patients with severe depression. Knowledge on factors predicting therapeutic response may help to identify patients who will benefit most from the intervention. Based on the neuroplasticity hypothesis, volumes of the amygdala and hippocampus are possible candidates for predicting treatment outcome. Therefore, this prospective cohort study examines the predictive value of amygdala and hippocampal volumes for the effectiveness of ECT.Methods Prior to ECT, 53 severely unipolar depressed patients (mean age 57±14 years; 40% [n=21] male received structural magnetic resonance imaging at 1.5 Tesla. Normalized amygdala and hippocampal volumes were calculated based on automatic segmentation by FreeSurfer. Regression analyses were used to test if the normalized volumes could predict the response to a course of ECT, based on the Montgomery-Åsberg Depression Rating Scale (MADRS scores. ResultsA larger amygdala volume independently and significantly predicted a lower post-ECT MADRS score (β = -0.347, P=0.013. The left amygdala volume had greater predictive value for treatment outcome relative to the right amygdala volume. Hippocampal volume had no independent predictive value.Conclusion A larger pretreatment amygdala volume predicted more effective ECT, independent of other known predictors. Almost all patients continued their medication during the study, which might have influenced the course of treatment in ways that were not taken into account.

  11. Predicting survey responses: how and why semantics shape survey statistics on organizational behaviour.

    Science.gov (United States)

    Arnulf, Jan Ketil; Larsen, Kai Rune; Martinsen, Øyvind Lund; Bong, Chih How

    2014-01-01

    Some disciplines in the social sciences rely heavily on collecting survey responses to detect empirical relationships among variables. We explored whether these relationships were a priori predictable from the semantic properties of the survey items, using language processing algorithms which are now available as new research methods. Language processing algorithms were used to calculate the semantic similarity among all items in state-of-the-art surveys from Organisational Behaviour research. These surveys covered areas such as transformational leadership, work motivation and work outcomes. This information was used to explain and predict the response patterns from real subjects. Semantic algorithms explained 60-86% of the variance in the response patterns and allowed remarkably precise prediction of survey responses from humans, except in a personality test. Even the relationships between independent and their purported dependent variables were accurately predicted. This raises concern about the empirical nature of data collected through some surveys if results are already given a priori through the way subjects are being asked. Survey response patterns seem heavily determined by semantics. Language algorithms may suggest these prior to administering a survey. This study suggests that semantic algorithms are becoming new tools for the social sciences, opening perspectives on survey responses that prevalent psychometric theory cannot explain.

  12. Predicting survey responses: how and why semantics shape survey statistics on organizational behaviour.

    Directory of Open Access Journals (Sweden)

    Jan Ketil Arnulf

    Full Text Available Some disciplines in the social sciences rely heavily on collecting survey responses to detect empirical relationships among variables. We explored whether these relationships were a priori predictable from the semantic properties of the survey items, using language processing algorithms which are now available as new research methods. Language processing algorithms were used to calculate the semantic similarity among all items in state-of-the-art surveys from Organisational Behaviour research. These surveys covered areas such as transformational leadership, work motivation and work outcomes. This information was used to explain and predict the response patterns from real subjects. Semantic algorithms explained 60-86% of the variance in the response patterns and allowed remarkably precise prediction of survey responses from humans, except in a personality test. Even the relationships between independent and their purported dependent variables were accurately predicted. This raises concern about the empirical nature of data collected through some surveys if results are already given a priori through the way subjects are being asked. Survey response patterns seem heavily determined by semantics. Language algorithms may suggest these prior to administering a survey. This study suggests that semantic algorithms are becoming new tools for the social sciences, opening perspectives on survey responses that prevalent psychometric theory cannot explain.

  13. Prediction of Hemodynamic Response to Epinephrine via Model-Based System Identification.

    Science.gov (United States)

    Bighamian, Ramin; Soleymani, Sadaf; Reisner, Andrew T; Seri, Istvan; Hahn, Jin-Oh

    2016-01-01

    In this study, we present a system identification approach to the mathematical modeling of hemodynamic responses to vasopressor-inotrope agents. We developed a hybrid model called the latency-dose-response-cardiovascular (LDC) model that incorporated 1) a low-order lumped latency model to reproduce the delay associated with the transport of vasopressor-inotrope agent and the onset of physiological effect, 2) phenomenological dose-response models to dictate the steady-state inotropic, chronotropic, and vasoactive responses as a function of vasopressor-inotrope dose, and 3) a physiological cardiovascular model to translate the agent's actions into the ultimate response of blood pressure. We assessed the validity of the LDC model to fit vasopressor-inotrope dose-response data using data collected from five piglet subjects during variable epinephrine infusion rates. The results suggested that the LDC model was viable in modeling the subjects' dynamic responses: After tuning the model to each subject, the r (2) values for measured versus model-predicted mean arterial pressure were consistently higher than 0.73. The results also suggested that intersubject variability in the dose-response models, rather than the latency models, had significantly more impact on the model's predictive capability: Fixing the latency model to population-averaged parameter values resulted in r(2) values higher than 0.57 between measured versus model-predicted mean arterial pressure, while fixing the dose-response model to population-averaged parameter values yielded nonphysiological predictions of mean arterial pressure. We conclude that the dose-response relationship must be individualized, whereas a population-averaged latency-model may be acceptable with minimal loss of model fidelity.

  14. Use of molecular markers for predicting therapy response in cancer patients.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Predictive markers are factors that are associated with upfront response or resistance to a particular therapy. Predictive markers are important in oncology as tumors of the same tissue of origin vary widely in their response to most available systemic therapies. Currently recommended oncological predictive markers include both estrogen and progesterone receptors for identifying patients with breast cancers likely to benefit from hormone therapy, HER-2 for the identification of breast cancer patients likely to benefit from trastuzumab, specific K-RAS mutations for the identification of patients with advanced colorectal cancer unlikely to benefit from either cetuximab or panitumumab and specific EGFR mutations for selecting patients with advanced non-small-cell lung cancer for treatment with tyrosine kinase inhibitors such as gefitinib and erlotinib. The availability of predictive markers should increase drug efficacy and decrease toxicity, thus leading to a more personalized approach to cancer treatment.

  15. Predictions of Unbalanced Response of Turbo Compressor Equipped with Active Magnetic Bearings through System Identification

    Energy Technology Data Exchange (ETDEWEB)

    Baek, SeongKi; NOh, Myounggyu; Park, Young Woo [Chungnam National Univ., Daejeon (Korea, Republic of); Lee, Kiwook; Lee, Nam Soo; Jeog, Jinhee [LG Electronics, Gumi (Korea, Republic of)

    2016-01-15

    Since vibrations in rotating machinery is a direct cause of performance degradation and failures, it is very important to predict the level of vibrations as well as have a method to lower the vibrations to an acceptable level. However, the changes in balancing during installation and the vibrational modes of the support structure are difficult to predict. This paper presents a method for predicting the unbalanced response of a turbo-compressor supported by active magnetic bearings (AMBs). Transfer functions of the rotor are obtained through system identification using AMBs. These transfer functions contain not only the dynamics of the rotor but also the vibrational modes of the support structure. Using these transfer functions, the unbalanced response is calculated and compared with the run-up data obtained from a compressor prototype. The predictions revealed the effects of the support structure, validating the efficacy of the method.

  16. Hazards Response of Energetic Materials - Initiation Mechanisms, Experimental Characterization, and Development of Predictive Capability

    Energy Technology Data Exchange (ETDEWEB)

    Maienschein, J; Nichols III, A; Reaugh, J; McClelland, M; Hsu, P C

    2005-04-15

    We present our approach to develop a predictive capability for hazards -- thermal and non-shock impact -- response of energetic material systems based on: (A) identification of relevant processes; (B) characterization of the relevant properties; (C) application of property data to predictive models; and (D) application of the models into predictive simulation. This paper focuses on the first two elements above, while a companion paper by Nichols et al focuses on the final two elements. We outline the underlying mechanisms of hazards response and their interactions, and present our experimental work to characterize the necessary material parameters, including thermal ignition, thermal and mechanical properties, fracture/fragmentation behavior, deflagration rates, and the effect of material damage. We also describe our validation test, the Scaled Thermal Explosion Experiment. Finally, we integrate the entire collection of data into a qualitative understanding that is useful until such time as the predictive models become available.

  17. Predicting Climate Change using Response Theory: Global Averages and Spatial Patterns

    CERN Document Server

    Lucarini, Valerio; Ragone, Francesco

    2015-01-01

    The provision of accurate methods for predicting the climate response to anthropogenic and natural forcings is a key contemporary scientific challenge. Using a simplified and efficient open-source general circulation model of the atmosphere featuring O($10^5$) degrees of freedom, we show how it is possible to approach such a problem using nonequilibrium statistical mechanics. Response theory allows one to practically compute the time-dependent measure supported on the pullback attractor of the climate system, whose dynamics is non-autonomous as a result of time-dependent forcings. We propose a simple yet efficient method for predicting - at any lead time and in an ensemble sense - the change in climate properties resulting from increase in the concentration of CO$_2$ using test perturbation model runs. We assess strengths and limitations of the response theory in predicting the changes in the globally averaged values of surface temperature and of the yearly total precipitation, as well as their spatial patter...

  18. Personalized in vitro cancer models to predict therapeutic response: Challenges and a framework for improvement.

    Science.gov (United States)

    Morgan, Molly M; Johnson, Brian P; Livingston, Megan K; Schuler, Linda A; Alarid, Elaine T; Sung, Kyung E; Beebe, David J

    2016-09-01

    Personalized cancer therapy focuses on characterizing the relevant phenotypes of the patient, as well as the patient's tumor, to predict the most effective cancer therapy. Historically, these methods have not proven predictive in regards to predicting therapeutic response. Emerging culture platforms are designed to better recapitulate the in vivo environment, thus, there is renewed interest in integrating patient samples into in vitro cancer models to assess therapeutic response. Successful examples of translating in vitro response to clinical relevance are limited due to issues with patient sample acquisition, variability and culture. We will review traditional and emerging in vitro models for personalized medicine, focusing on the technologies, microenvironmental components, and readouts utilized. We will then offer our perspective on how to apply a framework derived from toxicology and ecology towards designing improved personalized in vitro models of cancer. The framework serves as a tool for identifying optimal readouts and culture conditions, thus maximizing the information gained from each patient sample.

  19. Predictive Modeling of the Constitutive Response of Precipitation Hardened Ni-Rich NiTi

    Science.gov (United States)

    Cox, A.; Franco, B.; Wang, S.; Baxevanis, T.; Karaman, I.; Lagoudas, D. C.

    2017-03-01

    The effective thermomechanical response of precipitation hardened near-equiatomic Ni-rich NiTi alloys is predicted on the basis of composition and heat treatment using a microscale-informed model. The model takes into account the structural effects of the precipitates (precipitate volume fraction, elastic properties, elastic mismatch between the precipitates and the matrix, and coherency stresses due to the lattice mismatch between the precipitates and the matrix) on the reversible martensitic transformation under load as well as the chemical effects resulting from the Ni-depletion of the matrix during precipitate growth. The post-aging thermomechanical response is predicted based on finite element simulations on representative microstructures, using the response of the solutionized material and time-temperature-martensitic transformation temperature maps. The predictions are compared with experiments for materials of different initial compositions and heat treatments and reasonably good agreement is demonstrated for relatively low precipitate volume fractions.

  20. The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

    OpenAIRE

    Hudson, Lawrence N; Newbold, Tim; Contu, Sara; Hill, Samantha L L; Lysenko, Igor; De Palma, Adriana; Phillips, Helen R P; Alhusseini, Tamera I.; Bedford, Felicity E.; Bennett, Dominic J.; Booth, Hollie; Burton, Victoria J.; Chng, Charlotte W. T.; Choimes, Argyrios; Correia, David L.P.

    2017-01-01

    The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make free...

  1. The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

    OpenAIRE

    Hudson, Lawrence N; Newbold, Tim; Contu, Sara; Hill, Samantha L L; Lysenko, Igor; De Palma, Adriana; Phillips, Helen R P; Alhusseini, Tamera I.; Bedford, Felicity E.; Bennett, Dominic J.; Booth, Hollie; Burton, Victoria J.; Chng, Charlotte W. T.; Choimes, Argyrios; Correia, David L.P.

    2016-01-01

    The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make free...

  2. MULTISTAGE ADAPTIVE HIGHER-ORDER NONLINEAR FINITE IMPULSE RESPONSE FILTERS FOR CHAOTIC TIME SERIES PREDICTIONS

    Institute of Scientific and Technical Information of China (English)

    ZHANG JIA-SHU; XIAO XIAN-CI

    2001-01-01

    A multistage adaptive higher-order nonlinear finite impulse response (MAHONFIR) filter is proposed to predict chaotic time series. Using this approach, we may readily derive the decoupled parallel algorithm for the adaptation of the coefficients of the MAHONFIR filter, to guarantee a more rapid convergence of the adaptive weights to their optimal values. Numerical simulation results show that the MAHONFIR filters proposed here illustrate a very good performance for making an adaptive prediction of chaotic time series.

  3. The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

    OpenAIRE

    Hudson, Lawrence N; Newbold, Tim; Contu, Sara; Hill, Samantha L.L.; Lysenko, Igor; De Palma, Adriana; Phillips, Helen R. P.; Alhusseini, Tamera I.; Bedford, Felicity E.; Bennett, Dominic J.; Booth, Hollie; Burton, Victoria J.; Chng , Charlotte W. T.; Choimes, Argyrios; Correia, David L.P.

    2017-01-01

    The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make free...

  4. The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

    OpenAIRE

    Hudson, Lawrence N; Newbold, Tim; Contu, Sara; Hill, Samantha L.L.; Lysenko, Igor; De Palma, Adriana; Phillips, Helen R. P.; Alhusseini, Tamera I.; Bedford, Felicity E.; Bennett, Dominic J.; Booth, Hollie; Burton, Victoria J.; Chng , Charlotte W. T.; Choimes, Argyrios; Correia, David L.P.

    2016-01-01

    Abstract The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and ...

  5. Clinical utility of C-reactive protein to predict treatment response during cystic fibrosis pulmonary exacerbations

    Science.gov (United States)

    Sharma, Ashutosh; Kirkpatrick, Gordon; Chen, Virginia; Skolnik, Kate; Hollander, Zsuzsanna; Wilcox, Pearce; Quon, Bradley S.

    2017-01-01

    Rationale C-reactive protein (CRP) is a systemic marker of inflammation that correlates with disease status in cystic fibrosis (CF). The clinical utility of CRP measurement to guide pulmonary exacerbation (PEx) treatment decisions remains uncertain. Objectives To determine whether monitoring CRP during PEx treatment can be used to predict treatment response. We hypothesized that early changes in CRP can be used to predict treatment response. Methods We reviewed all PEx events requiring hospitalization for intravenous (IV) antibiotics over 2 years at our institution. 83 PEx events met our eligibility criteria. CRP levels from admission to day 5 were evaluated to predict treatment non-response, using a modified version of a prior published composite definition. CRP was also evaluated to predict time until next exacerbation (TUNE). Measurements and main results 53% of 83 PEx events were classified as treatment non-response. Paradoxically, 24% of PEx events were characterized by a ≥ 50% increase in CRP levels within the first five days of treatment. Absolute change in CRP from admission to day 5 was not associated with treatment non-response (p = 0.58). Adjusted for FEV1% predicted, admission log10 CRP was associated with treatment non-response (OR: 2.39; 95% CI: 1.14 to 5.91; p = 0.03) and shorter TUNE (HR: 1.60; 95% CI: 1.13 to 2.27; p = 0.008). The area under the receiver operating characteristics (ROC) curve of admission CRP to predict treatment non-response was 0.72 (95% CI 0.61–0.83; p 75 mg/L with a specificity of 90% for treatment non-response. Conclusions Admission CRP predicts treatment non-response and time until next exacerbation. A very elevated admission CRP (>75mg/L) is highly specific for treatment non-response and might be used to target high-risk patients for future interventional studies aimed at improving exacerbation outcomes. PMID:28178305

  6. Predicting Anticancer Drug Responses Using a Dual-Layer Integrated Cell Line-Drug Network Model.

    Directory of Open Access Journals (Sweden)

    Naiqian Zhang

    Full Text Available The ability to predict the response of a cancer patient to a therapeutic agent is a major goal in modern oncology that should ultimately lead to personalized treatment. Existing approaches to predicting drug sensitivity rely primarily on profiling of cancer cell line panels that have been treated with different drugs and selecting genomic or functional genomic features to regress or classify the drug response. Here, we propose a dual-layer integrated cell line-drug network model, which uses both cell line similarity network (CSN data and drug similarity network (DSN data to predict the drug response of a given cell line using a weighted model. Using the Cancer Cell Line Encyclopedia (CCLE and Cancer Genome Project (CGP studies as benchmark datasets, our single-layer model with CSN or DSN and only a single parameter achieved a prediction performance comparable to the previously generated elastic net model. When using the dual-layer model integrating both CSN and DSN, our predicted response reached a 0.6 Pearson correlation coefficient with observed responses for most drugs, which is significantly better than the previous results using the elastic net model. We have also applied the dual-layer cell line-drug integrated network model to fill in the missing drug response values in the CGP dataset. Even though the dual-layer integrated cell line-drug network model does not specifically model mutation information, it correctly predicted that BRAF mutant cell lines would be more sensitive than BRAF wild-type cell lines to three MEK1/2 inhibitors tested.

  7. Neutrophil biomarkers predict response to therapy with tumor necrosis factor inhibitors in rheumatoid arthritis.

    Science.gov (United States)

    Wright, Helen L; Cox, Trevor; Moots, Robert J; Edwards, Steven W

    2017-03-01

    Neutrophils are implicated in the pathology of rheumatoid arthritis (RA), but the mechanisms regulating their activation are largely unknown. RA is a heterogeneous disease, and whereas many patients show clinical improvement during TNF inhibitor (TNFi) therapy, a significant proportion fails to respond. In vitro activation of neutrophils with agents, including TNF, results in rapid and selective changes in gene expression, but how neutrophils contribute to TNF signaling in RA and whether TNFi sensitivity involves differential neutrophil responses are unknown. With the use of RNA sequencing (RNA-Seq), we analyzed blood neutrophils from 20 RA patients, pre-TNFi therapy, to identify biomarkers of response, measured by a decrease in disease activity score based on 28 joint count (DAS28), 12 wk post-therapy. Biomarkers were validated by quantitative PCR (qPCR) of blood neutrophils from 2 further independent cohorts of RA patients: 16 pre-TNFi and 16 predisease-modifying anti-rheumatic drugs (DMARDs). Twenty-three neutrophil transcripts predicted a 12-wk response to TNFi: 10 (IFN-regulated) genes predicting a European League against Rheumatism (EULAR) good response and 13 different genes [neutrophil granule protein (NGP) genes] predicting a nonresponse. Statistical analysis indicated a predictive sensitivity and specificity of each gene in the panel of >80%, with some 100% specific. A combination of 3 genes [cytidine monophosphate kinase 2 (CMPK2), IFN-induced protein with tetratricopeptide repeats 1B (IFIT1B), and RNASE3] had the greatest predictive power [area under the curve (AUC) 0.94]. No correlation was found for a response to DMARDs. We conclude that this panel of genes is selective for predicting a response to TNFi and is not a surrogate marker for disease improvement. We also show that in RA, there is great plasticity in neutrophil phenotype, with circulating cells expressing genes normally only expressed in more immature cells.

  8. Predictive value of brain perfusion SPECT for ketamine response in hyperalgesic fibromyalgia

    Energy Technology Data Exchange (ETDEWEB)

    Guedj, Eric; Cammilleri, Serge; Colavolpe, Cecile; Taieb, David; Laforte, Catherine de; Mundler, Olivier [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Assistance Publique des Hopitaux de Marseille, Marseille Cedex 5 (France); Niboyet, Jean [Clinique La Phoceanne, Unite d' Etude et de Traitement de la Douleur, Marseille (France)

    2007-08-15

    Ketamine has been used successfully in various proportions of fibromyalgia (FM) patients. However, the response to this specific treatment remains largely unpredictable. We evaluated brain SPECT perfusion before treatment with ketamine, using voxel-based analysis. The objective was to determine the predictive value of brain SPECT for ketamine response. Seventeen women with FM (48 {+-} 11 years; ACR criteria) were enrolled in the study. Brain SPECT was performed before any change was made in therapy in the pain care unit. We considered that a patient was a good responder to ketamine if the VAS score for pain decreased by at least 50% after treatment. A voxel-by-voxel group analysis was performed using SPM2, in comparison to a group of ten healthy women matched for age. The VAS score for pain was 81.8 {+-} 4.2 before ketamine and 31.8 {+-} 27.1 after ketamine. Eleven patients were considered ''good responders'' to ketamine. Responder and non-responder subgroups were similar in terms of pain intensity before ketamine. In comparison to responding patients and healthy subjects, non-responding patients exhibited a significant reduction in bilateral perfusion of the medial frontal gyrus. This cluster of hypoperfusion was highly predictive of non-response to ketamine (positive predictive value 100%, negative predictive value 91%). Brain perfusion SPECT may predict response to ketamine in hyperalgesic FM patients. (orig.)

  9. On the best learning algorithm for web services response time prediction

    DEFF Research Database (Denmark)

    Madsen, Henrik; Albu, Razvan-Daniel; Popentiu-Vladicescu, Florin

    2013-01-01

    an application is. A Web service is better imagined as an application "segment," or better as a program enabler. Performance is an important quality aspect of Web services because of their distributed nature. Predicting the response of web services during their operation is very important.......In this article we will examine the effect of different learning algorithms, while training the MLP (Multilayer Perceptron) with the intention of predicting web services response time. Web services do not necessitate a user interface. This may seem contradictory to most people's concept of what...

  10. Pareto Optimization Identifies Diverse Set of Phosphorylation Signatures Predicting Response to Treatment with Dasatinib.

    Science.gov (United States)

    Klammer, Martin; Dybowski, J Nikolaj; Hoffmann, Daniel; Schaab, Christoph

    2015-01-01

    Multivariate biomarkers that can predict the effectiveness of targeted therapy in individual patients are highly desired. Previous biomarker discovery studies have largely focused on the identification of single biomarker signatures, aimed at maximizing prediction accuracy. Here, we present a different approach that identifies multiple biomarkers by simultaneously optimizing their predictive power, number of features, and proximity to the drug target in a protein-protein interaction network. To this end, we incorporated NSGA-II, a fast and elitist multi-objective optimization algorithm that is based on the principle of Pareto optimality, into the biomarker discovery workflow. The method was applied to quantitative phosphoproteome data of 19 non-small cell lung cancer (NSCLC) cell lines from a previous biomarker study. The algorithm successfully identified a total of 77 candidate biomarker signatures predicting response to treatment with dasatinib. Through filtering and similarity clustering, this set was trimmed to four final biomarker signatures, which then were validated on an independent set of breast cancer cell lines. All four candidates reached the same good prediction accuracy (83%) as the originally published biomarker. Although the newly discovered signatures were diverse in their composition and in their size, the central protein of the originally published signature - integrin β4 (ITGB4) - was also present in all four Pareto signatures, confirming its pivotal role in predicting dasatinib response in NSCLC cell lines. In summary, the method presented here allows for a robust and simultaneous identification of multiple multivariate biomarkers that are optimized for prediction performance, size, and relevance.

  11. Early improvement with pregabalin predicts endpoint response in patients with generalized anxiety disorder: an integrated and predictive data analysis.

    Science.gov (United States)

    Montgomery, Stuart A; Lyndon, Gavin; Almas, Mary; Whalen, Ed; Prieto, Rita

    2017-01-01

    Generalized anxiety disorder (GAD), a common mental disorder, has several treatment options including pregabalin. Not all patients respond to treatment; quickly determining which patients will respond is an important treatment goal. Patient-level data were pooled from nine phase II and III randomized, double-blind, short-term, placebo-controlled trials of pregabalin for the treatment of GAD. Efficacy outcomes included the change from baseline in the Hamilton Anxiety Scale (HAM-A) total score and psychic and somatic subscales. Predictive modelling assessed baseline characteristics and early clinical responses to determine those predictive of clinical improvement at endpoint. A total of 2155 patients were included in the analysis (1447 pregabalin, 708 placebo). Pregabalin significantly improved the HAM-A total score compared with the placebo at endpoint, treatment difference (95% confidence interval), -2.61 (-3.21 to -2.01), Ppredictive of an endpoint greater than or equal to 50% improvement in the HAM-A total score. Pregabalin is an effective treatment option for patients with GAD. Patients with early response to pregabalin are more likely to respond significantly at endpoint.

  12. Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.

    Directory of Open Access Journals (Sweden)

    Tao Huang

    Full Text Available More and more people are concerned by the risk of unexpected side effects observed in the later steps of the development of new drugs, either in late clinical development or after marketing approval. In order to reduce the risk of the side effects, it is important to look out for the possible xenobiotic responses at an early stage. We attempt such an effort through a prediction by assuming that similarities in microarray profiles indicate shared mechanisms of action and/or toxicological responses among the chemicals being compared. A large time course microarray database derived from livers of compound-treated rats with thirty-four distinct pharmacological and toxicological responses were studied. The mRMR (Minimum-Redundancy-Maximum-Relevance method and IFS (Incremental Feature Selection were used to select a compact feature set (141 features for the reduction of feature dimension and improvement of prediction performance. With these 141 features, the Leave-one-out cross-validation prediction accuracy of first order response using NNA (Nearest Neighbor Algorithm was 63.9%. Our method can be used for pharmacological and xenobiotic responses prediction of new compounds and accelerate drug development.

  13. Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn;

    2016-01-01

    Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers for bevac......Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers...... for bevacizumab response in recurrent glioblastoma patients. Methods: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized Nano...

  14. DISIS: prediction of drug response through an iterative sure independence screening.

    Directory of Open Access Journals (Sweden)

    Yun Fang

    Full Text Available Prediction of drug response based on genomic alterations is an important task in the research of personalized medicine. Current elastic net model utilized a sure independence screening to select relevant genomic features with drug response, but it may neglect the combination effect of some marginally weak features. In this work, we applied an iterative sure independence screening scheme to select drug response relevant features from the Cancer Cell Line Encyclopedia (CCLE dataset. For each drug in CCLE, we selected up to 40 features including gene expressions, mutation and copy number alterations of cancer-related genes, and some of them are significantly strong features but showing weak marginal correlation with drug response vector. Lasso regression based on the selected features showed that our prediction accuracies are higher than those by elastic net regression for most drugs.

  15. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.

    Science.gov (United States)

    Gao, Hui; Korn, Joshua M; Ferretti, Stéphane; Monahan, John E; Wang, Youzhen; Singh, Mallika; Zhang, Chao; Schnell, Christian; Yang, Guizhi; Zhang, Yun; Balbin, O Alejandro; Barbe, Stéphanie; Cai, Hongbo; Casey, Fergal; Chatterjee, Susmita; Chiang, Derek Y; Chuai, Shannon; Cogan, Shawn M; Collins, Scott D; Dammassa, Ernesta; Ebel, Nicolas; Embry, Millicent; Green, John; Kauffmann, Audrey; Kowal, Colleen; Leary, Rebecca J; Lehar, Joseph; Liang, Ying; Loo, Alice; Lorenzana, Edward; Robert McDonald, E; McLaughlin, Margaret E; Merkin, Jason; Meyer, Ronald; Naylor, Tara L; Patawaran, Montesa; Reddy, Anupama; Röelli, Claudia; Ruddy, David A; Salangsang, Fernando; Santacroce, Francesca; Singh, Angad P; Tang, Yan; Tinetto, Walter; Tobler, Sonja; Velazquez, Roberto; Venkatesan, Kavitha; Von Arx, Fabian; Wang, Hui Qin; Wang, Zongyao; Wiesmann, Marion; Wyss, Daniel; Xu, Fiona; Bitter, Hans; Atadja, Peter; Lees, Emma; Hofmann, Francesco; Li, En; Keen, Nicholas; Cozens, Robert; Jensen, Michael Rugaard; Pryer, Nancy K; Williams, Juliet A; Sellers, William R

    2015-11-01

    Profiling candidate therapeutics with limited cancer models during preclinical development hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous patient responses for patient-selection strategies. We established ∼1,000 patient-derived tumor xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, we performed in vivo compound screens using a 1 × 1 × 1 experimental design (PDX clinical trial or PCT) to assess the population responses to 62 treatments across six indications. We demonstrate both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. In addition, our results suggest that PCTs may represent a more accurate approach than cell line models for assessing the clinical potential of some therapeutic modalities. We therefore propose that this experimental paradigm could potentially improve preclinical evaluation of treatment modalities and enhance our ability to predict clinical trial responses.

  16. The Potential of an in Vitro Digestion Method for Predicting Glycemic Response of Foods and Meals

    Directory of Open Access Journals (Sweden)

    Konstantina Argyri

    2016-04-01

    Full Text Available Increased interest in glycemic response derives from its linkage with chronic diseases, including obesity and type 2 diabetes. Our objective was to develop an in vitro method that predicts glycemic response. We proposed a simulated gastrointestinal digestion protocol that uses the concentration of dialyzable glucose (glucose in the soluble low molecular weight fraction of digests as an index for the prediction of glycemic response. For protocol evaluation, dialyzable glucose from 30 foods or meals digested in vitro were compared with published values for their glycemic index (GI (nine foods, glycemic load (GL (16 foods and glycemic response (14 meals. The correlations were significant when comparing dialyzable glucose with GL (Spearman’s rho = 0.953, p < 0.001, GI (Spearman’s rho = 0.800, p = 0.010 and glycemic response (Spearman’s rho = 0.736, p = 0.003. These results demonstrate that despite limitations associated with in vitro approaches, the proposed protocol may be a useful tool for predicting glycemic response of foods or meals.

  17. Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Bajpai, Jyoti; Bakhshi, Sameer [Dr. B. R. A. Institute Rotary Cancer Hospital, Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi (India); Gamnagatti, Shivanand [All India Institute of Medical Sciences, Department of Radiodiagnosis, New Delhi (India); Kumar, Rakesh; Malhotra, Arun [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Sreenivas, Vishnubhatla [All India Institute of Medical Sciences, Department of Biostatistics, New Delhi (India); Sharma, Mehar Chand; Safaya, Rajni [All India Institute of Medical Sciences, Department of Pathology, New Delhi (India); Khan, Shah Alam; Rastogi, Shishir [All India Institute of Medical Sciences, Department of Orthopedics, New Delhi (India)

    2011-04-15

    Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. Thirty-one treatment-naive osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response {>=}90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma. (orig.)

  18. Dynamic preload indicators fail to predict fluid responsiveness in open-chest conditions

    NARCIS (Netherlands)

    de Waal, Eric E. C.; Rex, Steffen; Kruitwagen, Cas L. J. J.; Kalkman, Cor J.; Buhre, Wolfgang F.

    2009-01-01

    Objective: Dynamic preload indicators like pulse pressure variation (PPV) and stroke volume variation (SVV) are increasingly being used for optimizing cardiac preload since they have been demonstrated to predict fluid responsiveness in a variety of perioperative settings. However, in open-chest cond

  19. Predicting People's Environmental Behaviour: Theory of Planned Behaviour and Model of Responsible Environmental Behaviour

    Science.gov (United States)

    Chao, Yu-Long

    2012-01-01

    Using different measures of self-reported and other-reported environmental behaviour (EB), two important theoretical models explaining EB--Hines, Hungerford and Tomera's model of responsible environmental behaviour (REB) and Ajzen's theory of planned behaviour (TPB)--were compared regarding the fit between model and data, predictive ability,…

  20. Pre- and post-radiotherapy MRI results as a predictive model for response in laryngeal carcinoma

    NARCIS (Netherlands)

    Ljumanovic, Redina; Langendijk, Johannes A.; Hoekstra, Otto S.; Knol, Dirk L.; Leemans, C. Rene; Castelijns, Jonas A.

    2008-01-01

    The purpose was to determine if pre-radiotherapy (RT) and/or post-radiotherapy magnetic resonance (MR) imaging can predict response in patients with laryngeal carcinoma treated with RT. Pre- and post-RT MR examinations of 80 patients were retrospectively reviewed and associated with regard to local

  1. TP53 mutations predict decitabine-induced complete responses in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Chang, Chun-Kang; Zhao, You-Shan; Xu, Feng; Guo, Juan; Zhang, Zheng; He, Qi; Wu, Dong; Wu, Ling-Yun; Su, Ji-Ying; Song, Lu-Xi; Xiao, Chao; Li, Xiao

    2017-02-01

    To identify the molecular signatures that predict responses to decitabine (DAC), we examined baseline gene mutations (28 target genes) in 109 myelodysplastic syndrome (MDS) patients at diagnosis. We determined that TP53 mutations predicted complete response (CR), as 10 of 15 patients (66·7%) who possessed TP53 mutations achieved a CR. Univariate and multivariate analyses showed that TP53 mutations are the only molecular signatures predictive of a CR to DAC in MDS. Among the ten patients with TP53 mutations who achieved a CR, nine presented with complex karyotypes due to abnormalities involving chromosome 5 and/or chromosome 7, and eight possessed monosomies. Although TP53 mutations were associated with a higher frequency of CRs, they were not associated with improved survival. Poor outcomes were attributed to early relapses and transformation to acute myeloid leukaemia after CR. Post-DAC therapy patient gene mutation profiles showed that most CR patients exhibited fewer gene mutations after achieving a CR. It seems that suppression of these gene mutations was facilitated by DAC, resulting in a CR. In summary, TP53 mutations might predict decitabine-induced complete responses in patients with MDS. DAC-induced responses may result from partial suppression of malignant clones containing mutated TP53 genes.

  2. Tetrahydrobiopterin responsiveness in phenylketonuria : prediction with the 48-hour loading test and genotype

    NARCIS (Netherlands)

    Anjema, Karen; van Rijn, Margreet; Hofstede, Floris C; Bosch, Annet M; Hollak, Carla E M; Rubio-Gozalbo, Estela; de Vries, Maaike C; Janssen, Mirian C H; Boelen, Carolien C A; Burgerhof, Johannes G M; Blau, Nenad; Fokkema, Margaretha; van Spronsen, Francjan J

    2013-01-01

    Background: How to efficiently diagnose tetrahydrobiopterin (BH4) responsiveness in patients with phenylketonuria remains unclear. This study investigated the positive predictive value (PPV) of the 48-hour BH4 loading test and the additional value of genotype. Methods: Data of the 48-hour BH4 loadin

  3. Predicting Social Responsibility and Belonging in Urban After-School Physical Activity Programs with Underserved Children

    Science.gov (United States)

    Martin, Jeffrey J.; Byrd, Brigid; Garn, Alex; McCaughtry, Nate; Kulik, Noel; Centeio, Erin

    2016-01-01

    The purpose of this cross sectional study was to predict feelings of belonging and social responsibility based on the motivational climate perceptions and contingent self-worth of children participating in urban after-school physical activity programs. Three-hundred and four elementary school students from a major Midwestern city participated.…

  4. A noise level prediction method based on electro-mechanical frequency response function for capacitors.

    Directory of Open Access Journals (Sweden)

    Lingyu Zhu

    Full Text Available The capacitors in high-voltage direct-current (HVDC converter stations radiate a lot of audible noise which can reach higher than 100 dB. The existing noise level prediction methods are not satisfying enough. In this paper, a new noise level prediction method is proposed based on a frequency response function considering both electrical and mechanical characteristics of capacitors. The electro-mechanical frequency response function (EMFRF is defined as the frequency domain quotient of the vibration response and the squared capacitor voltage, and it is obtained from impulse current experiment. Under given excitations, the vibration response of the capacitor tank is the product of EMFRF and the square of the given capacitor voltage in frequency domain, and the radiated audible noise is calculated by structure acoustic coupling formulas. The noise level under the same excitations is also measured in laboratory, and the results are compared with the prediction. The comparison proves that the noise prediction method is effective.

  5. Starvation stress during larval development reveals predictive adaptive response in adult worker honey bees (Apis mellifera)

    Science.gov (United States)

    A variety of organisms exhibit developmental plasticity that results in differences in adult morphology, physiology or behavior. This variation in the phenotype, called “Predictive Adaptive Response (PAR),” gives a selective advantage in an adult's environment if the adult experiences environments s...

  6. Noninvasively derived stroke volume variation by finger volume clamping can reliably predict fluid responsiveness

    NARCIS (Netherlands)

    Vos, Jaap Jan; Poterman, Marieke; Struys, Michel; Scheeren, Thomas; Kalmar, A.F.

    2013-01-01

    Background and Goal of Study:  Dynamic preload variables derived from the arterial pressure waveform have been shown to accurately predict fluid responsiveness in mechanically ventilated patients. One of these variables, stroke volume variation (SVV), can also be obtained noninvasively by the finger

  7. Predicting Non-response to Ranibizumab in Patients with Neovascular Age-related Macular Degeneration

    NARCIS (Netherlands)

    Asten, F. van; Rovers, M.M.; Lechanteur, Y.T.E.; Smailhodzic, D.; Muether, P.S.; Chen, J.; Hollander, A.I. den; Fauser, S.; Hoyng, C.B.; Wilt, G.J. van der; Klevering, B.J.

    2014-01-01

    Abstract Purpose: To validate known and determine new predictors of non-response to ranibizumab in patients with neovascular age-related macular degeneration (AMD) and to incorporate these factors into a prediction rule. METHODS: This multicenter, observational cohort study included 391 patients tre

  8. Predictive Power of the Baseline QRS Complex Duration for Clinical Response to Cardiac Resynchronisation Therapy

    Directory of Open Access Journals (Sweden)

    Ali Kazemisaeid

    2011-02-01

    Full Text Available Background: Determination of predictors of response to cardiac resynchronisation therapy (CRT in patients with moderate to severe heart failure accompanied by a ventricular dyssynchrony can play a major role in improving candidate selection for CRT.Objectives: We evaluated whether the baseline QRS duration could be used to discriminate responders from non-responders to CRT.Methods: Eighty three consecutive patients with moderate to severe heart failure and with successful implantation of a CRT device at our centre were included in the study. QRS durations were measured on 12-lead surface electrocardiogram before and 6 months after implantation of the CRT device, using the widest QRS complex in leads II, V1 and V6. Clinical response to CRT was defined as an improvement of ≥1 grade in NYHA class.Results: Optimal cut-off value to discriminate baseline QRS duration for predicting clinical response to CRT was identified at 152 ms, yielding a sensitivity of 73.3%, a specificity of 56.5% as well as positive and negative predictive values of 81.5% and 44.8%, respectively. The discriminatory pow- er of the baseline QRS duration for response to CRT assessed by the ROC curve was 0.6402 (95% CI: 0.4976 – 0.7829. Baseline QRS duration ≥ 152 ms could effectively predict clinical response to CRT after adjusting for covariates (OR = 3.743, p = 0.017.Conclusion: Baseline QRS duration can effectively predict clinical response to CRT and optimal cut-off value to discriminate baseline QRS duration for response to CRT is 152 ms.

  9. Evaluation of Response Prediction Procedures using Full Scale Measurements for a Container Ship

    DEFF Research Database (Denmark)

    Andersen, Ingrid Marie Vincent; Jensen, Jørgen Juncher; Nielsen, Ulrik Dam

    2013-01-01

    on superposition of sinus-oidal components. The conditional processes do not need offline training and will be applied to measured time series in order to evaluate the accuracy of response predictions within the next 1-30 seconds. The number of measured points and the time distances between them are varied......This paper deals with the analysis of recent full-scale strain measurements in the hull of a large container carrier covering several months of operation. The focus is on the real-time prediction accuracy of responses 5-15 seconds ahead of the measurements. Such results are less applicable...... to determine the best solutions. A procedure based on 11 measured points spaced 1 sec, covering the last 10 sec of the instantaneous measured signal seems generally able to give fair predictions up to 5-10 sec ahead of the current time. The full-scale data is provided through the EU FP7 project Tools for Ultra...

  10. Using Appraisal Theory to Predict Emotional and Coping Responses to Hurtful Messages

    Directory of Open Access Journals (Sweden)

    Amy M. Bippus

    2012-12-01

    Full Text Available Based on appraisal theory (Lazarus 1991; 1999, this study examined the degree to which primary and secondary cognitive appraisals of hurtful messages predict the amountof hurt individuals feel, and the coping behaviors they enact. This study presents a significant step forward in its operationalization of both primary and secondary appraisal variables by treating hurt as an outcome, rather than an antecedent, of the appraisal process, and considers an extensive range of coping responses. We surveyed participants (N = 217 about hurtful messages they received within an array of relationship types. The results revealed that fours types of appraisals predicted the amount of hurt recipients experienced. All coping behaviors except positive reappraisal were significantly predicted by the primary appraisals (categories of risk and secondary appraisals (perceived intentionality and frequency of hurtful messages. The findings explicate appraisal theory’s potential in explaining individuals’ responses to hurtful communication.

  11. The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer

    Directory of Open Access Journals (Sweden)

    Gómez-Río Manuel

    2010-12-01

    Full Text Available Abstract Background We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT to predict the histopathologic response in locally advanced rectal cancer (LARC treated with preoperative chemoradiation (CRT. Methods The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders. Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR was investigated. Results Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%; This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. Conclusions We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accurately.

  12. Predictive value of brain perfusion SPECT for rTMS response in pharmacoresistant depression

    Energy Technology Data Exchange (ETDEWEB)

    Richieri, Raphaelle; Lancon, Christophe [Sainte-Marguerite University Hospital, Department of Psychiatry, Marseille (France); La Timone University, EA 3279 - Self-perceived Health Assessment Research Unit, School of Medicine, Marseille (France); Boyer, Laurent [La Timone University, EA 3279 - Self-perceived Health Assessment Research Unit, School of Medicine, Marseille (France); La Timone University Hospital, Assistance Publique - Hopitaux de Marseille, Department of Public Health, Marseille (France); Farisse, Jean [Sainte-Marguerite University Hospital, Department of Psychiatry, Marseille (France); Colavolpe, Cecile; Mundler, Olivier [La Timone University Hospital, Assistance Publique - Hopitaux de Marseille, Service Central de Biophysique et Medecine Nucleaire, Marseille (France); Universite de la Mediterranee, Centre Europeen de Recherche en Imagerie Medicale (CERIMED), Marseille (France); Guedj, Eric [La Timone University Hospital, Assistance Publique - Hopitaux de Marseille, Service Central de Biophysique et Medecine Nucleaire, Marseille (France); Universite de la Mediterranee, Centre Europeen de Recherche en Imagerie Medicale (CERIMED), Marseille (France); Hopital de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Marseille Cedex 5 (France)

    2011-09-15

    The aim of this study was to determine the predictive value of whole-brain voxel-based regional cerebral blood flow (rCBF) for repetitive transcranial magnetic stimulation (rTMS) response in patients with pharmacoresistant depression. Thirty-three right-handed patients who met DSM-IV criteria for major depressive disorder (unipolar or bipolar depression) were included before rTMS. rTMS response was defined as at least 50% reduction in the baseline Beck Depression Inventory scores. The predictive value of {sup 99m}Tc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) for rTMS response was studied before treatment by comparing rTMS responders to non-responders at voxel level using Statistical Parametric Mapping (SPM) (p < 0.001, uncorrected). Of the patients, 18 (54.5%) were responders to rTMS and 15 were non-responders (45.5%). There were no statistically significant differences in demographic and clinical characteristics (p > 0.10). In comparison to responders, non-responders showed significant hypoperfusions (p < 0.001, uncorrected) in the left medial and bilateral superior frontal cortices (BA10), the left uncus/parahippocampal cortex (BA20/BA35) and the right thalamus. The area under the curve for the combination of SPECT clusters to predict rTMS response was 0.89 (p < 0.001). Sensitivity, specificity, positive predictive value and negative predictive value for the combination of clusters were: 94, 73, 81 and 92%, respectively. This study shows that, in pharmacoresistant depression, pretreatment rCBF of specific brain regions is a strong predictor for response to rTMS in patients with homogeneous demographic/clinical features. (orig.)

  13. Prediction of pore-water pressure response to rainfall using support vector regression

    Science.gov (United States)

    Babangida, Nuraddeen Muhammad; Mustafa, Muhammad Raza Ul; Yusuf, Khamaruzaman Wan; Isa, Mohamed Hasnain

    2016-05-01

    Nonlinear complex behavior of pore-water pressure responses to rainfall was modelled using support vector regression (SVR). Pore-water pressure can rise to disturbing levels that may result in slope failure during or after rainfall. Traditionally, monitoring slope pore-water pressure responses to rainfall is tedious and expensive, in that the slope must be instrumented with necessary monitors. Data on rainfall and corresponding responses of pore-water pressure were collected from such a monitoring program at a slope site in Malaysia and used to develop SVR models to predict pore-water pressure fluctuations. Three models, based on their different input configurations, were developed. SVR optimum meta-parameters were obtained using k-fold cross validation and a grid search. Model type 3 was adjudged the best among the models and was used to predict three other points on the slope. For each point, lag intervals of 30 min, 1 h and 2 h were used to make the predictions. The SVR model predictions were compared with predictions made by an artificial neural network model; overall, the SVR model showed slightly better results. Uncertainty quantification analysis was also performed for further model assessment. The uncertainty components were found to be low and tolerable, with d-factor of 0.14 and 74 % of observed data falling within the 95 % confidence bound. The study demonstrated that the SVR model is effective in providing an accurate and quick means of obtaining pore-water pressure response, which may be vital in systems where response information is urgently needed.

  14. Prediction of pore-water pressure response to rainfall using support vector regression

    Science.gov (United States)

    Babangida, Nuraddeen Muhammad; Mustafa, Muhammad Raza Ul; Yusuf, Khamaruzaman Wan; Isa, Mohamed Hasnain

    2016-11-01

    Nonlinear complex behavior of pore-water pressure responses to rainfall was modelled using support vector regression (SVR). Pore-water pressure can rise to disturbing levels that may result in slope failure during or after rainfall. Traditionally, monitoring slope pore-water pressure responses to rainfall is tedious and expensive, in that the slope must be instrumented with necessary monitors. Data on rainfall and corresponding responses of pore-water pressure were collected from such a monitoring program at a slope site in Malaysia and used to develop SVR models to predict pore-water pressure fluctuations. Three models, based on their different input configurations, were developed. SVR optimum meta-parameters were obtained using k-fold cross validation and a grid search. Model type 3 was adjudged the best among the models and was used to predict three other points on the slope. For each point, lag intervals of 30 min, 1 h and 2 h were used to make the predictions. The SVR model predictions were compared with predictions made by an artificial neural network model; overall, the SVR model showed slightly better results. Uncertainty quantification analysis was also performed for further model assessment. The uncertainty components were found to be low and tolerable, with d-factor of 0.14 and 74 % of observed data falling within the 95 % confidence bound. The study demonstrated that the SVR model is effective in providing an accurate and quick means of obtaining pore-water pressure response, which may be vital in systems where response information is urgently needed.

  15. Predicting plant responses to mycorrhizae: integrating evolutionary history and plant traits.

    Science.gov (United States)

    Reinhart, Kurt O; Wilson, Gail W T; Rinella, Matthew J

    2012-07-01

    We assessed whether (1) arbuscular mycorrhizal colonization of roots (RC) and/or plant responses to arbuscular mycorrhizae (MR) vary with plant phylogeny and (2) MR and RC can be more accurately predicted with a phylogenetic predictor relative to a null model and models with plant trait and taxonomic predictors. In a previous study, MR and RC of 95 grassland species were measured. We constructed a phylogeny for these species and found it explained variation in MR and RC. Next, we used multiple regressions to identify the models that most accurately predicted plant MR. Models including either phylogenetic or phenotypic and taxonomic information similarly improved our ability to predict MR relative to a null model. Our study illustrates the complex evolutionary associations among species and constraints of using phylogenetic information, relative to plant traits, to predict how a plant species will interact with AMF.

  16. Using biomarkers to predict treatment response in major depressive disorder: evidence from past and present studies.

    Science.gov (United States)

    Thase, Michael E

    2014-12-01

    Major depressive disorder (MDD) is a heterogeneous condition with a variable response to a wide range of treatments. Despite intensive efforts, no biomarker has been identified to date that can reliably predict response or non-response to any form of treatment, nor has one been identified that can be used to identify those at high risk of developing treatment-resistant depression (ie, non-response to a sequence of treatments delivered for adequate duration and intensity). This manuscript reviews some past areas of research that have proved informative, such as studies using indexes of hypercortisolism or sleep disturbance, and more recent research findings using measures of inflammation and different indicators of regional cortical activation to predict treatment response. It is concluded that, although no method has yet been demonstrated to be sufficiently accurate to be applied in clinical practice, progress has been made. It thus seems likely that--at some point in the not-too-distant future--it will be possible to prospectively identify, at least for some MDD patients, the likelihood of response or non-response to cognitive therapy or various antidepressant medications.

  17. Therapygenetics: 5-HTTLPR genotype predicts the response to exposure therapy for agoraphobia.

    Science.gov (United States)

    Knuts, Inge; Esquivel, Gabriel; Kenis, Gunter; Overbeek, Thea; Leibold, Nicole; Goossens, Lies; Schruers, Koen

    2014-08-01

    This study was intended to assess the extent to which the low-expression allele of the serotonin transporter gene promoter predicts better response to exposure-based behavior therapy in patients with panic disorder with agoraphobia (PDA). Ninety-nine patients with PDA underwent a 1-week in vivo exposure-based behavior therapy program and provided saliva samples to extract genomic DNA and classify individuals according to four allelic forms (SA, SG, LA, LG) of the 5-HTT-linked polymorphic region (5-HTTLPR). We determined whether the 5-HTTLPR genotype predicted change in avoidance behavior in PDA following treatment. After controlling for pre-treatment avoidance behavior, the 5-HTTLPR low-expression genotypes showed a more favorable response to exposure therapy two weeks following treatment, compared to the other patients. This study suggests a genetic contribution to treatment outcome following behavior therapy and implicates the serotonergic system in response to exposure-based treatments in PDA.

  18. RBFNN Model for Predicting Nonlinear Response of Uniformly Loaded Paddle Cantilever

    Directory of Open Access Journals (Sweden)

    Abdullah H. Abdullah

    2009-01-01

    Full Text Available The Radial basis Function neural network (RBFNN model has been developed for the prediction of nonlinear response for paddle Cantilever with built-in edges and different sizes, thickness and uniform loads. Learning data was performed by using a nonlinear finite element program, incremental stages of the nonlinear finite element analysis were generated by using 25 schemes of built paddle Cantilevers with different thickness and uniform distributed loads. The neural network model has 5 input nodes representing the uniform distributed load and paddle size, length, width and thickness, eight nodes at hidden layer and one output node representing the max. deflection response (1500×1 represent the deflection response of load. Regression analysis between finite element results and values predicted by the neural network model shows the least error.

  19. Synthesising empirical results to improve predictions of post-wildfire runoff and erosion response

    Science.gov (United States)

    Shakesby, Richard A.; Moody, John A.; Martin, Deborah A.; Robichaud, Peter R.

    2016-01-01

    Advances in research into wildfire impacts on runoff and erosion have demonstrated increasing complexity of controlling factors and responses, which, combined with changing fire frequency, present challenges for modellers. We convened a conference attended by experts and practitioners in post-wildfire impacts, meteorology and related research, including modelling, to focus on priority research issues. The aim was to improve our understanding of controls and responses and the predictive capabilities of models. This conference led to the eight selected papers in this special issue. They address aspects of the distinctiveness in the controls and responses among wildfire regions, spatiotemporal rainfall variability, infiltration, runoff connectivity, debris flow formation and modelling applications. Here we summarise key findings from these papers and evaluate their contribution to improving understanding and prediction of post-wildfire runoff and erosion under changes in climate, human intervention and population pressure on wildfire-prone areas.

  20. Doppler ultrasound scoring to predict chemotherapeutic response in advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Singh Tej B

    2007-08-01

    Full Text Available Abstract Background Doppler ultrasonography (US is increasingly being utilized as an imaging modality in breast cancer. It is used to study the vascular characteristics of the tumor. Neoadjuvant chemotherapy is the standard modality of treatment in locally advanced breast cancer. Histological examination remains the gold standard to assess the chemotherapy response. However, based on the color Doppler findings, a new scoring system that could predict histological response following chemotherapy is proposed. Methods Fifty cases of locally advanced infiltrating duct carcinoma of the breast were studied. The mean age of the patients was 44.5 years. All patients underwent clinical, Doppler and histopathological assessment followed by three cycles of CAF (Cyclophosphamide, Adriamycin and 5-Fluorouracil chemotherapy, repeat clinical and Doppler examination and surgery. The resected specimens were examined histopathologically and histological response was correlated with Doppler findings. The Doppler characteristics of the tumor were graded as 1–4 for 50% and complete disappearance of flow signals respectively. A cumulative score was calculated and compared with histopathological response. Results were analyzed using Chi square test, sensitivity, specificity, positive and negative predictive values. Results The maximum Doppler score according to the proposed scoring system was twelve and minimum three. Higher scores corresponded with a more favorable histopathological response. Twenty four patients had complete response to chemotherapy. Sixteen of these 24 patients (66.7% had a cumulative Doppler score more than nine. The sensitivity of cumulative score >5 was 91.7% and specificity was 38.5%. The area under the ROC curve of the cumulative score >9 was 0.72. Conclusion Doppler scoring can be accurately used to objectively predict the response to chemotherapy in patients with locally advanced breast cancer and it correlates well with histopathological

  1. Doppler ultrasound scoring to predict chemotherapeutic response in advanced breast cancer

    Science.gov (United States)

    Kumar, Anand; Singh, Seema; Pradhan, Satyajit; Shukla, Ram C; Ansari, Mumtaz A; Singh, Tej B; Shyam, Rohit; Gupta, Saroj

    2007-01-01

    Background Doppler ultrasonography (US) is increasingly being utilized as an imaging modality in breast cancer. It is used to study the vascular characteristics of the tumor. Neoadjuvant chemotherapy is the standard modality of treatment in locally advanced breast cancer. Histological examination remains the gold standard to assess the chemotherapy response. However, based on the color Doppler findings, a new scoring system that could predict histological response following chemotherapy is proposed. Methods Fifty cases of locally advanced infiltrating duct carcinoma of the breast were studied. The mean age of the patients was 44.5 years. All patients underwent clinical, Doppler and histopathological assessment followed by three cycles of CAF (Cyclophosphamide, Adriamycin and 5-Fluorouracil) chemotherapy, repeat clinical and Doppler examination and surgery. The resected specimens were examined histopathologically and histological response was correlated with Doppler findings. The Doppler characteristics of the tumor were graded as 1–4 for 50% and complete disappearance of flow signals respectively. A cumulative score was calculated and compared with histopathological response. Results were analyzed using Chi square test, sensitivity, specificity, positive and negative predictive values. Results The maximum Doppler score according to the proposed scoring system was twelve and minimum three. Higher scores corresponded with a more favorable histopathological response. Twenty four patients had complete response to chemotherapy. Sixteen of these 24 patients (66.7%) had a cumulative Doppler score more than nine. The sensitivity of cumulative score >5 was 91.7% and specificity was 38.5%. The area under the ROC curve of the cumulative score >9 was 0.72. Conclusion Doppler scoring can be accurately used to objectively predict the response to chemotherapy in patients with locally advanced breast cancer and it correlates well with histopathological response. PMID:17725837

  2. Spatially pooled contrast responses predict neural and perceptual similarity of naturalistic image categories.

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    Iris I A Groen

    Full Text Available The visual world is complex and continuously changing. Yet, our brain transforms patterns of light falling on our retina into a coherent percept within a few hundred milliseconds. Possibly, low-level neural responses already carry substantial information to facilitate rapid characterization of the visual input. Here, we computationally estimated low-level contrast responses to computer-generated naturalistic images, and tested whether spatial pooling of these responses could predict image similarity at the neural and behavioral level. Using EEG, we show that statistics derived from pooled responses explain a large amount of variance between single-image evoked potentials (ERPs in individual subjects. Dissimilarity analysis on multi-electrode ERPs demonstrated that large differences between images in pooled response statistics are predictive of more dissimilar patterns of evoked activity, whereas images with little difference in statistics give rise to highly similar evoked activity patterns. In a separate behavioral experiment, images with large differences in statistics were judged as different categories, whereas images with little differences were confused. These findings suggest that statistics derived from low-level contrast responses can be extracted in early visual processing and can be relevant for rapid judgment of visual similarity. We compared our results with two other, well- known contrast statistics: Fourier power spectra and higher-order properties of contrast distributions (skewness and kurtosis. Interestingly, whereas these statistics allow for accurate image categorization, they do not predict ERP response patterns or behavioral categorization confusions. These converging computational, neural and behavioral results suggest that statistics of pooled contrast responses contain information that corresponds with perceived visual similarity in a rapid, low-level categorization task.

  3. Prediction of cortical responses to simultaneous electrical stimulation of the retina

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    Halupka, Kerry J.; Shivdasani, Mohit N.; Cloherty, Shaun L.; Grayden, David B.; Wong, Yan T.; Burkitt, Anthony N.; Meffin, Hamish

    2017-02-01

    Objective. Simultaneous electrical stimulation of multiple electrodes has shown promise in diversifying the responses that can be elicited by retinal prostheses compared to interleaved single electrode stimulation. However, the effects of interactions between electrodes are not well understood and clinical trials with simultaneous stimulation have produced inconsistent results. We investigated the effects of multiple electrode stimulation of the retina by developing a model of cortical responses to retinal stimulation. Approach. Electrical stimuli consisting of temporally sparse, biphasic current pulses, with amplitudes sampled from a bi-dimensional Gaussian distribution, were simultaneously delivered to the retina across a 42-channel electrode array implanted in the suprachoroidal space of anesthetized cats. Visual cortex activity was recorded using penetrating microelectrode arrays. These data were used to identify a linear-nonlinear model of cortical responses to retinal stimulation. The ability of the model to generalize was tested by predicting responses to non-white patterned stimuli. Main results. The model accurately predicted two cortical activity measures: multi-unit neural responses and evoked potential responses to white noise stimuli. The model also provides information about electrical receptive fields, including the relative effects of each stimulating electrode on every recording site. Significance. We have demonstrated a simple model that accurately describes cortical responses to simultaneous stimulation of a suprachoroidal retinal prosthesis. Overall, our results demonstrate that cortical responses to simultaneous multi-electrode stimulation of the retina are repeatable and predictable, and that interactions between electrodes during simultaneous stimulation are predominantly linear. The model shows promise for determining optimal stimulation paradigms for exploiting interactions between electrodes to shape neural activity, thereby improving

  4. EndoPredict predicts for the response to neoadjuvant chemotherapy in ER-positive, HER2-negative breast cancer.

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    Bertucci, François; Finetti, Pascal; Viens, Patrice; Birnbaum, Daniel

    2014-12-01

    The EndoPredict (EP) signature is a prognostic 11-gene expression signature specifically developed in ER+/HER2- node-negative/positive breast cancer. It is associated with relapse-free survival in patients treated with adjuvant hormone therapy, suggesting that EP low-risk patients could be treated with adjuvant hormone therapy alone whereas high-risk patients would deserve addition of adjuvant chemotherapy. Thus, it is important to determine whether EP high-risk patients are or are not more sensitive to chemotherapy than low-risk patients. Here, we have assessed the EP predictive value for pathological complete response to neoadjuvant chemotherapy in ER+/HER2- breast cancer. We gathered gene expression and histoclinical data of 553 pre-treatment ER+/HER2- breast carcinomas treated with anthracycline-based neoadjuvant chemotherapy. We searched for correlation between the pathological complete response (pCR) and the EP score-based classification. The overall pCR rate was 12%. Fifty-one percent of samples were classified as low-risk according to the EP score and 49% as high-risk. EP classification was associated with a pCR rate of 7% in the low-risk group and 17% in the high-risk group (p < 0.001). In multivariate analysis, the EP score remained significantly associated with pCR. Many genes upregulated in the high-risk tumours were involved in cell proliferation, whereas many genes upregulated in the low-risk tumours were involved in ER-signalling and stroma. Despite higher chemosensitivity, the high-risk group was associated with worse disease-free survival. In conclusion, EP high-risk ER+/HER2- breast cancers are more likely to respond to anthracycline-based chemotherapy.

  5. Pulse pressure variation and prediction of fluid responsiveness in patients ventilated with low tidal volumes

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    Clarice Daniele Alves de Oliveira-Costa

    2012-07-01

    Full Text Available OBJECTIVE: To determine the utility of pulse pressure variation (ΔRESP PP in predicting fluid responsiveness in patients ventilated with low tidal volumes (V T and to investigate whether a lower ΔRESP PP cut-off value should be used when patients are ventilated with low tidal volumes. METHOD: This cross-sectional observational study included 37 critically ill patients with acute circulatory failure who required fluid challenge. The patients were sedated and mechanically ventilated with a V T of 6-7 ml/kg ideal body weight, which was monitored with a pulmonary artery catheter and an arterial line. The mechanical ventilation and hemodynamic parameters, including ΔRESP PP, were measured before and after fluid challenge with 1,000 ml crystalloids or 500 ml colloids. Fluid responsiveness was defined as an increase in the cardiac index of at least 15%. ClinicalTrial.gov: NCT01569308. RESULTS: A total of 17 patients were classified as responders. Analysis of the area under the ROC curve (AUC showed that the optimal cut-off point for ΔRESP PP to predict fluid responsiveness was 10% (AUC = 0.74. Adjustment of the ΔRESP PP to account for driving pressure did not improve the accuracy (AUC = 0.76. A ΔRESP PP>10% was a better predictor of fluid responsiveness than central venous pressure (AUC = 0.57 or pulmonary wedge pressure (AUC = 051. Of the 37 patients, 25 were in septic shock. The AUC for ΔRESP PP>10% to predict responsiveness in patients with septic shock was 0.484 (sensitivity, 78%; specificity, 93%. CONCLUSION: The parameter D RESP PP has limited value in predicting fluid responsiveness in patients who are ventilated with low tidal volumes, but a ΔRESP PP>10% is a significant improvement over static parameters. A ΔRESP PP > 10% may be particularly useful for identifying responders in patients with septic shock.

  6. PET-Based Treatment Response Evaluation in Rectal Cancer: Prediction and Validation

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    Janssen, Marco H.M., E-mail: marco.janssen@maastro.nl [Department of Radiation Oncology (MAASTRO), GROW Research Institute, University Medical Centre Maastricht, Maastricht (Netherlands); Oellers, Michel C.; Stiphout, Ruud G.P.M. van [Department of Radiation Oncology (MAASTRO), GROW Research Institute, University Medical Centre Maastricht, Maastricht (Netherlands); Riedl, Robert G. [Department of Pathology, University Medical Centre Maastricht, Maastricht (Netherlands); Bogaard, Jorgen van den; Buijsen, Jeroen; Lambin, Philippe; Lammering, Guido [Department of Radiation Oncology (MAASTRO), GROW Research Institute, University Medical Centre Maastricht, Maastricht (Netherlands)

    2012-02-01

    Purpose: To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders. The predictive strength of the model was validated in a second patient group, treated and imaged identical to the patients on which the predictive model was based. Methods and Materials: Fifty-one rectal cancer patients were prospectively included in this study. All patients underwent fluorodeoxyglucose (FDG) PET-computed tomography (CT) imaging both before the start of chemoradiotherapy (CRT) and after 2 weeks of treatment. Preoperative treatment with CRT was followed by a total mesorectal excision. From the resected specimen, the tumor regression grade (TRG) was scored according to the Mandard criteria. From one patient group (n = 30), the metabolic treatment response was correlated with the pathological treatment response, resulting in a receiver operating characteristic (ROC) curve based cutoff value for the reduction of maximum standardized uptake value (SUV{sub max}) within the tumor to differentiate pathological responders (TRG 1-2) from nonresponders (TRG 3-5). The applicability of the selected cutoff value for new patients was validated in a second patient group (n = 21). Results: When correlating the metabolic and pathological treatment response for the first patient group using ROC curve analysis (area under the curve = 0.98), a cutoff value of 48% SUV{sub max} reduction was selected to differentiate pathological responders from nonresponders (specificity of 100%, sensitivity of 64%). Applying this cutoff value to the second patient group resulted in a specificity and sensitivity of, respectively, 93% and 83%, with only one of the pathological nonresponders being false positively predicted as pathological responding. Conclusions: For rectal cancer, an accurate PET-based prediction of the pathological treatment response is feasible already after 2 weeks of CRT. The presented predictive model could be used to

  7. Lateralization for speech predicts therapeutic response to cognitive behavioral therapy for depression.

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    Kishon, Ronit; Abraham, Karen; Alschuler, Daniel M; Keilp, John G; Stewart, Jonathan W; McGrath, Patrick J; Bruder, Gerard E

    2015-08-30

    A prior study (Bruder, G.E., Stewart, J.W., Mercier, M.A., Agosti, V., Leite, P., Donovan, S., Quitkin, F.M., 1997. Outcome of cognitive-behavioral therapy for depression: relation of hemispheric dominance for verbal processing. Journal of Abnormal Psychology 106, 138-144.) found left hemisphere advantage for verbal dichotic listening was predictive of clinical response to cognitive behavioral therapy (CBT) for depression. This study aimed to confirm this finding and to examine the value of neuropsychological tests, which have shown promise for predicting antidepressant response. Twenty depressed patients who subsequently completed 14 weeks of CBT and 74 healthy adults were tested on a Dichotic Fused Words Test (DFWT). Patients were also tested on the National Adult Reading Test to estimate IQ, and word fluency, choice RT, and Stroop neuropsychological tests. Left hemisphere advantage on the DFWT was more than twice as large in CBT responders as in non-responders, and was associated with improvement in depression following treatment. There was no difference between responders and non-responders on neuropsychological tests. The results support the hypothesis that the ability of individuals with strong left hemisphere dominance to recruit frontal and temporal cortical regions involved in verbal dichotic listening predicts CBT response. The large effect size, sensitivity and specificity of DFWT predictions suggest the potential value of this brief and inexpensive test as an indicator of whether a patient will benefit from CBT for depression.

  8. Cortical Response Similarities Predict which Audiovisual Clips Individuals Viewed, but Are Unrelated to Clip Preference.

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    David A Bridwell

    Full Text Available Cortical responses to complex natural stimuli can be isolated by examining the relationship between neural measures obtained while multiple individuals view the same stimuli. These inter-subject correlation's (ISC's emerge from similarities in individual's cortical response to the shared audiovisual inputs, which may be related to their emergent cognitive and perceptual experience. Within the present study, our goal is to examine the utility of using ISC's for predicting which audiovisual clips individuals viewed, and to examine the relationship between neural responses to natural stimuli and subjective reports. The ability to predict which clips individuals viewed depends on the relationship of the EEG response across subjects and the nature in which this information is aggregated. We conceived of three approaches for aggregating responses, i.e. three assignment algorithms, which we evaluated in Experiment 1A. The aggregate correlations algorithm generated the highest assignment accuracy (70.83% chance = 33.33% and was selected as the assignment algorithm for the larger sample of individuals and clips within Experiment 1B. The overall assignment accuracy was 33.46% within Experiment 1B (chance = 06.25%, with accuracies ranging from 52.9% (Silver Linings Playbook to 11.75% (Seinfeld within individual clips. ISC's were significantly greater than zero for 15 out of 16 clips, and fluctuations within the delta frequency band (i.e. 0-4 Hz primarily contributed to response similarities across subjects. Interestingly, there was insufficient evidence to indicate that individuals with greater similarities in clip preference demonstrate greater similarities in cortical responses, suggesting a lack of association between ISC and clip preference. Overall these results demonstrate the utility of using ISC's for prediction, and further characterize the relationship between ISC magnitudes and subjective reports.

  9. Cortical Response Similarities Predict which Audiovisual Clips Individuals Viewed, but Are Unrelated to Clip Preference.

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    Bridwell, David A; Roth, Cullen; Gupta, Cota Navin; Calhoun, Vince D

    2015-01-01

    Cortical responses to complex natural stimuli can be isolated by examining the relationship between neural measures obtained while multiple individuals view the same stimuli. These inter-subject correlation's (ISC's) emerge from similarities in individual's cortical response to the shared audiovisual inputs, which may be related to their emergent cognitive and perceptual experience. Within the present study, our goal is to examine the utility of using ISC's for predicting which audiovisual clips individuals viewed, and to examine the relationship between neural responses to natural stimuli and subjective reports. The ability to predict which clips individuals viewed depends on the relationship of the EEG response across subjects and the nature in which this information is aggregated. We conceived of three approaches for aggregating responses, i.e. three assignment algorithms, which we evaluated in Experiment 1A. The aggregate correlations algorithm generated the highest assignment accuracy (70.83% chance = 33.33%) and was selected as the assignment algorithm for the larger sample of individuals and clips within Experiment 1B. The overall assignment accuracy was 33.46% within Experiment 1B (chance = 06.25%), with accuracies ranging from 52.9% (Silver Linings Playbook) to 11.75% (Seinfeld) within individual clips. ISC's were significantly greater than zero for 15 out of 16 clips, and fluctuations within the delta frequency band (i.e. 0-4 Hz) primarily contributed to response similarities across subjects. Interestingly, there was insufficient evidence to indicate that individuals with greater similarities in clip preference demonstrate greater similarities in cortical responses, suggesting a lack of association between ISC and clip preference. Overall these results demonstrate the utility of using ISC's for prediction, and further characterize the relationship between ISC magnitudes and subjective reports.

  10. Use of Germline Polymorphisms in Predicting Concurrent Chemoradiotherapy Response in Esophageal Cancer

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    Chen, Pei-Chun [Department of Statistics and Informatics Science, Providence University, Taiwan (China); Chen, Yen-Ching [Institute of Epidemiology Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Research Center for Gene, Environment, and Human Health, College of Public Health, National Taiwan University, Taiwan (China); Department of Public Health, Institute of Epidemiology, National Taiwan University, Taiwan (China); Lai, Liang-Chuan [Graduate Institute of Physiology, National Taiwan University, Taiwan (China); Tsai, Mong-Hsun [Institute of Biotechnology, National Taiwan University, Taiwan (China); Chen, Shin-Kuang [National Clinical Trial and Research Center, National Taiwan University Hospital, Taiwan (China); Yang, Pei-Wen; Lee, Yung-Chie [Department of Surgery, National Taiwan University Hospital, Taiwan (China); Hsiao, Chuhsing K. [Research Center for Gene, Environment, and Human Health, College of Public Health, National Taiwan University, Taiwan (China); Department of Public Health, Institute of Epidemiology, National Taiwan University, Taiwan (China); Bioinformatics and Biostatistics Core, Research Center for Medical Excellence, National Taiwan University, Taiwan (China); Lee, Jang-Ming, E-mail: jangming@ntuh.gov.tw [Department of Surgery, National Taiwan University Hospital, Taiwan (China); Chuang, Eric Y., E-mail: chuangey@ntu.edu.tw [National Clinical Trial and Research Center, National Taiwan University Hospital, Taiwan (China); Bioinformatics and Biostatistics Core, Research Center for Medical Excellence, National Taiwan University, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taiwan (China)

    2012-04-01

    Purpose: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged {>=}70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

  11. Early Prediction and Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy Using Quantitative DCE-MRI

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    Alina Tudorica

    2016-02-01

    Full Text Available The purpose is to compare quantitative dynamic contrast-enhanced (DCE magnetic resonance imaging (MRI metrics with imaging tumor size for early prediction of breast cancer response to neoadjuvant chemotherapy (NACT and evaluation of residual cancer burden (RCB. Twenty-eight patients with 29 primary breast tumors underwent DCE-MRI exams before, after one cycle of, at midpoint of, and after NACT. MRI tumor size in the longest diameter (LD was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors guidelines. Pharmacokinetic analyses of DCE-MRI data were performed with the standard Tofts and Shutter-Speed models (TM and SSM. After one NACT cycle the percent changes of DCE-MRI parameters Ktrans (contrast agent plasma/interstitium transfer rate constant, ve (extravascular and extracellular volume fraction, kep (intravasation rate constant, and SSM-unique τi (mean intracellular water lifetime are good to excellent early predictors of pathologic complete response (pCR vs. non-pCR, with univariate logistic regression C statistics value in the range of 0.804 to 0.967. ve values after one cycle and at NACT midpoint are also good predictors of response, with C ranging 0.845 to 0.897. However, RECIST LD changes are poor predictors with C = 0.609 and 0.673, respectively. Post-NACT Ktrans, τi, and RECIST LD show statistically significant (P < .05 correlations with RCB. The performances of TM and SSM analyses for early prediction of response and RCB evaluation are comparable. In conclusion, quantitative DCE-MRI parameters are superior to imaging tumor size for early prediction of therapy response. Both TM and SSM analyses are effective for therapy response evaluation. However, the τi parameter derived only with SSM analysis allows the unique opportunity to potentially quantify therapy-induced changes in tumor energetic metabolism.

  12. Predicting the Perceptual Consequences of Hidden Hearing Loss

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    Andrew J. Oxenham

    2016-12-01

    Full Text Available Recent physiological studies in several rodent species have revealed that permanent damage can occur to the auditory system after exposure to a noise that produces only a temporary shift in absolute thresholds. The damage has been found to occur in the synapses between the cochlea’s inner hair cells and the auditory nerve, effectively severing part of the connection between the ear and the brain. This synaptopathy has been termed hidden hearing loss because its effects are not thought to be revealed in standard clinical, behavioral, or physiological measures of absolute threshold. It is currently unknown whether humans suffer from similar deficits after noise exposure. Even if synaptopathy occurs in humans, it remains unclear what the perceptual consequences might be or how they should best be measured. Here, we apply a simple theoretical model, taken from signal detection theory, to provide some predictions for what perceptual effects could be expected for a given loss of synapses. Predictions are made for a number of basic perceptual tasks, including tone detection in quiet and in noise, frequency discrimination, level discrimination, and binaural lateralization. The model’s predictions are in line with the empirical observations that a 50% loss of synapses leads to changes in threshold that are too small to be reliably measured. Overall, the model provides a simple initial quantitative framework for understanding and predicting the perceptual effects of synaptopathy in humans.

  13. Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia.

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    Tully, Laura M; Lincoln, Sarah Hope; Hooker, Christine I

    2014-01-01

    LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia.

  14. Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia

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    Laura M. Tully, PhD

    2014-01-01

    Full Text Available LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9 during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia.

  15. A new ovarian response prediction index (ORPI: implications for individualised controlled ovarian stimulation

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    Oliveira Joao Batista A

    2012-11-01

    Full Text Available Abstract Background The objective was to present a new ovarian response prediction index (ORPI, which was based on anti-Müllerian hormone (AMH levels, antral follicle count (AFC and age, and to verify whether it could be a reliable predictor of the ovarian stimulation response. Methods A total of 101 patients enrolled in the ICSI programme were included. The ORPI values were calculated by multiplying the AMH level (ng/ml by the number of antral follicles (2–9 mm, and the result was divided by the age (years of the patient (ORPI=(AMH x AFC/Patient age. Results The regression analysis demonstrated significant (PP=0.006 and collecting greater than or equal to 4 oocytes (OR: 49.25; PPP Conclusions The ORPI exhibited an excellent ability to predict a low ovarian response and a good ability to predict a collection of greater than or equal to 4 MII oocytes, an excessive ovarian response and the occurrence of pregnancy in infertile women. The ORPI might be used to improve the cost-benefit ratio of ovarian stimulation regimens by guiding the selection of medications and by modulating the doses and regimens according to the actual needs of the patients.

  16. Predicted responses for a particulate detection system in a continuous stack monitor.

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    Tries, Mark A; Holloman, Ryan L; Bobe, Leo M

    2002-10-01

    Predicted counting rate responses were developed for a particulate detection system that is used for continuous monitoring for the presence of radioactive particulates in the effluent air from a research reactor. The particulate detection system consists of a moving filter paper assembly, a plastic scintillation detector, and a rate meter output, and is part of a comprehensive stack monitoring system. A predicted response was derived for the case of a steady-state activity distribution across the surface of the moving filter paper that is in proximity to the detector and was determined to be 1.59 x 10(7) cpm per unit airborne concentration of 138Cs (expressed in units of Bq cm(-3)), where 138Cs was used as an indicator for a hypothetical fission product release. The corresponding response model provided by the manufacturer was found to underestimate airborne activity concentrations by about an order of magnitude. A predicted response also was derived for the case of a rapid change in airborne activity concentration, which was formulated based on the kinetics of the rate meter circuit and was used to establish alarm settings and detection limits for the particulate detection system.

  17. From Vivaldi to Beatles and back: predicting lateralized brain responses to music.

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    Alluri, Vinoo; Toiviainen, Petri; Lund, Torben E; Wallentin, Mikkel; Vuust, Peter; Nandi, Asoke K; Ristaniemi, Tapani; Brattico, Elvira

    2013-12-01

    We aimed at predicting the temporal evolution of brain activity in naturalistic music listening conditions using a combination of neuroimaging and acoustic feature extraction. Participants were scanned using functional Magnetic Resonance Imaging (fMRI) while listening to two musical medleys, including pieces from various genres with and without lyrics. Regression models were built to predict voxel-wise brain activations which were then tested in a cross-validation setting in order to evaluate the robustness of the hence created models across stimuli. To further assess the generalizability of the models we extended the cross-validation procedure by including another dataset, which comprised continuous fMRI responses of musically trained participants to an Argentinean tango. Individual models for the two musical medleys revealed that activations in several areas in the brain belonging to the auditory, limbic, and motor regions could be predicted. Notably, activations in the medial orbitofrontal region and the anterior cingulate cortex, relevant for self-referential appraisal and aesthetic judgments, could be predicted successfully. Cross-validation across musical stimuli and participant pools helped identify a region of the right superior temporal gyrus, encompassing the planum polare and the Heschl's gyrus, as the core structure that processed complex acoustic features of musical pieces from various genres, with or without lyrics. Models based on purely instrumental music were able to predict activation in the bilateral auditory cortices, parietal, somatosensory, and left hemispheric primary and supplementary motor areas. The presence of lyrics on the other hand weakened the prediction of activations in the left superior temporal gyrus. Our results suggest spontaneous emotion-related processing during naturalistic listening to music and provide supportive evidence for the hemispheric specialization for categorical sounds with realistic stimuli. We herewith introduce

  18. Pareto Optimization Identifies Diverse Set of Phosphorylation Signatures Predicting Response to Treatment with Dasatinib.

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    Martin Klammer

    Full Text Available Multivariate biomarkers that can predict the effectiveness of targeted therapy in individual patients are highly desired. Previous biomarker discovery studies have largely focused on the identification of single biomarker signatures, aimed at maximizing prediction accuracy. Here, we present a different approach that identifies multiple biomarkers by simultaneously optimizing their predictive power, number of features, and proximity to the drug target in a protein-protein interaction network. To this end, we incorporated NSGA-II, a fast and elitist multi-objective optimization algorithm that is based on the principle of Pareto optimality, into the biomarker discovery workflow. The method was applied to quantitative phosphoproteome data of 19 non-small cell lung cancer (NSCLC cell lines from a previous biomarker study. The algorithm successfully identified a total of 77 candidate biomarker signatures predicting response to treatment with dasatinib. Through filtering and similarity clustering, this set was trimmed to four final biomarker signatures, which then were validated on an independent set of breast cancer cell lines. All four candidates reached the same good prediction accuracy (83% as the originally published biomarker. Although the newly discovered signatures were diverse in their composition and in their size, the central protein of the originally published signature - integrin β4 (ITGB4 - was also present in all four Pareto signatures, confirming its pivotal role in predicting dasatinib response in NSCLC cell lines. In summary, the method presented here allows for a robust and simultaneous identification of multiple multivariate biomarkers that are optimized for prediction performance, size, and relevance.

  19. Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens.

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    Deborah Chasman

    2016-07-01

    Full Text Available Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.

  20. Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates.

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    Cicin-Sain, Luka; Smyk-Pearson, Susan; Smyk-Paerson, Sue; Currier, Noreen; Byrd, Laura; Koudelka, Caroline; Robinson, Tammie; Swarbrick, Gwendolyn; Tackitt, Shane; Legasse, Alfred; Fischer, Miranda; Nikolich-Zugich, Dragana; Park, Byung; Hobbs, Theodore; Doane, Cynthia J; Mori, Motomi; Axthelm, Michael K; Axthelm, Michael T; Lewinsohn, Deborah A; Nikolich-Zugich, Janko

    2010-06-15

    Aging is usually accompanied by diminished immune protection upon infection or vaccination. Although aging results in well-characterized changes in the T cell compartment of long-lived, outbred, and pathogen-exposed organisms, their relevance for primary Ag responses remain unclear. Therefore, it remains unclear whether and to what extent the loss of naive T cells, their partial replacement by oligoclonal memory populations, and the consequent constriction of TCR repertoire limit the Ag responses in aging primates. We show in this study that aging rhesus monkeys (Macaca mulatta) exhibit poor CD8 T cell and B cell responses in the blood and poor CD8 responses in the lungs upon vaccination with the modified vaccinia strain Ankara. The function of APCs appeared to be maintained in aging monkeys, suggesting that the poor response was likely intrinsic to lymphocytes. We found that the loss of naive CD4 and CD8 T cells, and the appearance of persisting T cell clonal expansions predicted poor CD8 responses in individual monkeys. There was strong correlation between early CD8 responses in the transitory CD28+ CD62L- CD8+ T cell compartment and the peak Ab titers upon boost in individual animals, as well as a correlation of both parameters of immune response to the frequency of naive CD8+ T cells in old but not in adult monkeys. Therefore, our results argue that T cell repertoire constriction and naive cell loss have prognostic value for global immune function in aging primates.

  1. Integrating Transcriptomic and Proteomic Data Using Predictive Regulatory Network Models of Host Response to Pathogens.

    Science.gov (United States)

    Chasman, Deborah; Walters, Kevin B; Lopes, Tiago J S; Eisfeld, Amie J; Kawaoka, Yoshihiro; Roy, Sushmita

    2016-07-01

    Mammalian host response to pathogenic infections is controlled by a complex regulatory network connecting regulatory proteins such as transcription factors and signaling proteins to target genes. An important challenge in infectious disease research is to understand molecular similarities and differences in mammalian host response to diverse sets of pathogens. Recently, systems biology studies have produced rich collections of omic profiles measuring host response to infectious agents such as influenza viruses at multiple levels. To gain a comprehensive understanding of the regulatory network driving host response to multiple infectious agents, we integrated host transcriptomes and proteomes using a network-based approach. Our approach combines expression-based regulatory network inference, structured-sparsity based regression, and network information flow to infer putative physical regulatory programs for expression modules. We applied our approach to identify regulatory networks, modules and subnetworks that drive host response to multiple influenza infections. The inferred regulatory network and modules are significantly enriched for known pathways of immune response and implicate apoptosis, splicing, and interferon signaling processes in the differential response of viral infections of different pathogenicities. We used the learned network to prioritize regulators and study virus and time-point specific networks. RNAi-based knockdown of predicted regulators had significant impact on viral replication and include several previously unknown regulators. Taken together, our integrated analysis identified novel module level patterns that capture strain and pathogenicity-specific patterns of expression and helped identify important regulators of host response to influenza infection.

  2. Pupillary response predicts multiple object tracking load, error rate, and conscientiousness, but not inattentional blindness.

    Science.gov (United States)

    Wright, Timothy J; Boot, Walter R; Morgan, Chelsea S

    2013-09-01

    Research on inattentional blindness (IB) has uncovered few individual difference measures that predict failures to detect an unexpected event. Notably, no clear relationship exists between primary task performance and IB. This is perplexing as better task performance is typically associated with increased effort and should result in fewer spare resources to process the unexpected event. We utilized a psychophysiological measure of effort (pupillary response) to explore whether differences in effort devoted to the primary task (multiple object tracking) are related to IB. Pupillary response was sensitive to tracking load and differences in primary task error rates. Furthermore, pupillary response was a better predictor of conscientiousness than primary task errors; errors were uncorrelated with conscientiousness. Despite being sensitive to task load, individual differences in performance and conscientiousness, pupillary response did not distinguish between those who noticed the unexpected event and those who did not. Results provide converging evidence that effort and primary task engagement may be unrelated to IB.

  3. Skin conductance response to the pain of others predicts later costly helping.

    Directory of Open Access Journals (Sweden)

    Grit Hein

    Full Text Available People show autonomic responses when they empathize with the suffering of another person. However, little is known about how these autonomic changes are related to prosocial behavior. We measured skin conductance responses (SCRs and affect ratings in participants while either receiving painful stimulation themselves, or observing pain being inflicted on another person. In a later session, they could prevent the infliction of pain in the other by choosing to endure pain themselves. Our results show that the strength of empathy-related vicarious skin conductance responses predicts later costly helping. Moreover, the higher the match between SCR magnitudes during the observation of pain in others and SCR magnitude during self pain, the more likely a person is to engage in costly helping. We conclude that prosocial motivation is fostered by the strength of the vicarious autonomic response as well as its match with first-hand autonomic experience.

  4. Predicting the Response to Intravenous Immunoglobulins in an Animal Model of Chronic Neuritis

    Science.gov (United States)

    Pfaff, Johannes; Mathys, Christian; Mausberg, Anne K.; Bendszus, Martin; Pham, Mirko; Hartung, Hans-Peter; Kieseier, Bernd C.

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disabling autoimmune disorder of the peripheral nervous system (PNS). Intravenous immunoglobulins (IVIg) are effective in CIDP, but the treatment response varies greatly between individual patients. Understanding this interindividual variability and predicting the response to IVIg constitute major clinical challenges in CIDP. We previously established intercellular adhesion molecule (ICAM)-1 deficient non-obese diabetic (NOD) mice as a novel animal model of CIDP. Here, we demonstrate that similar to human CIDP patients, ICAM-1 deficient NOD mice respond to IVIg treatment by clinical and histological measures. Nerve magnetic resonance imaging and histology demonstrated that IVIg ameliorates abnormalities preferentially in distal parts of the sciatic nerve branches. The IVIg treatment response also featured great heterogeneity allowing us to identify IVIg responders and non-responders. An increased production of interleukin (IL)-17 positively predicted IVIg treatment responses. In human sural nerve biopsy sections, high numbers of IL-17 producing cells were associated with younger age and shorter disease duration. Thus, our novel animal model can be utilized to identify prognostic markers of treatment responses in chronic inflammatory neuropathies and we identify IL-17 production as one potential such prognostic marker. PMID:27711247

  5. Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Henrica M J Werner

    Full Text Available Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.

  6. Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer.

    Science.gov (United States)

    Werner, Henrica M J; Trovik, Jone; Halle, Mari K; Wik, Elisabeth; Akslen, Lars A; Birkeland, Even; Bredholt, Therese; Tangen, Ingvild L; Krakstad, Camilla; Salvesen, Helga B

    2014-01-01

    Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.

  7. A decline of LAMP- 2 predicts ursodeoxycholic acid response in primary biliary cirrhosis.

    Science.gov (United States)

    Wang, Lu; Guo, Guan-ya; Wang, Jing-bo; Zhou, Xin-min; Yang, Qiong; Han, Zhe-yi; Li, Qiang; Zhang, Jing-wen; Cai, Yun; Ren, Xiao-li; Zhou, Xia; Chen, Rui-Rui; Shi, Yong-quan; Han, Ying; Fan, Dai-ming

    2015-04-20

    Biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis (PBC) is variable. We have previously reported that augmented expression of lysosome-associated membrane protein 2 (LAMP-2) was correlated with the severity of PBC. This study aimed to determine whether serum LAMP-2 could serve as a predictor of biochemical response to UDCA. The efficiency of serum LAMP-2 to predict biochemical response was assessed after 1 year of UDCA treatment in PBC patients by a retrospective analysis. We found that the basal serum LAMP-2 level was increased in PBC, especially in patients with stage III-IV (p = 0.010) or TBIL > 1 mg/dL (p = 0.014). Baseline serum LAMP-2 was higher in non-responders than that in responders, but the difference was statistically insignificant. However, after UDCA treatment, serum LAMP-2 level decreased prominently in the first 3 months, which was more obvious in responders. Further studies showed that the 35% decline of LAMP-2 after treatment for 3 months could be stated as an indicator of UDCA response with the sensitivity of 62.9% and specificity of 75.0% by Paris criteria. Meanwhile the specificity and sensitivity were identified as 63.5% and 64.1% by Barcelona criteria. Together, a decline in LAMP-2 might help to predict the response to UDCA.

  8. Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted?

    Directory of Open Access Journals (Sweden)

    Aurea Lima

    2015-06-01

    Full Text Available Background: Methotrexate (MTX is widely used for rheumatoid arthritis (RA treatment. Single nucleotide polymorphisms (SNPs could be used as predictors of patients’ therapeutic outcome variability. Therefore, this study aims to evaluate the influence of SNPs in genes encoding for MTX membrane transport proteins in order to predict clinical response to MTX. Methods: Clinicopathological data from 233 RA patients treated with MTX were collected, clinical response defined, and patients genotyped for 23 SNPs. Genotype and haplotype analyses were performed using multivariate methods and a genetic risk index (GRI for non-response was created. Results: Increased risk for non-response was associated to SLC22A11 rs11231809 T carriers; ABCC1 rs246240 G carriers; ABCC1 rs3784864 G carriers; CGG haplotype for ABCC1 rs35592, rs2074087 and rs3784864; and CGG haplotype for ABCC1 rs35592, rs246240 and rs3784864. GRI demonstrated that patients with Index 3 were 16-fold more likely to be non-responders than those with Index 1. Conclusions: This study revealed that SLC22A11 and ABCC1 may be important to identify those patients who will not benefit from MTX treatment, highlighting the relevance in translating these results to clinical practice. However, further validation by independent studies is needed to develop the field of personalized medicine to predict clinical response to MTX treatment.

  9. Prediction analysis of dose equivalent responses of neutron dosemeters used at a MOX fuel facility.

    Science.gov (United States)

    Tsujimura, N; Yoshida, T; Takada, C

    2011-07-01

    To predict how accurately neutron dosemeters can measure the neutron dose equivalent (rate) in MOX fuel fabrication facility work environments, the dose equivalent responses of neutron dosemeters were calculated by the spectral folding method. The dosemeters selected included two types of personal dosemeter, namely a thermoluminescent albedo neutron dosemeter and an electronic neutron dosemeter, three moderator-based neutron survey meters, and one special instrument called an H(p)(10) monitor. The calculations revealed the energy dependences of the responses expected within the entire range of neutron spectral variations observed in neutron fields at workplaces.

  10. Predicting failure response of spot welded joints using recent extensions to the Gurson model

    DEFF Research Database (Denmark)

    Nielsen, Kim Lau

    2010-01-01

    The plug failure modes of resistance spot welded shear-lab and cross-tension test specimens are studied, using recent extensions to the Gurson model. A comparison of the predicted mechanical response is presented when using either: (i) the Gurson-Tvergaard-Needleman model (GTN-model), (ii......) the shear-modified GTN-model by Nahshon and Hutchinson that also describes damage development at low triaxiality (NH-model) or (iii) the Gologanu-Leblond-Devaux model (GLD-model) accounting for non-spherical void growth. The failure responses predicted by the various models are discussed in relation...... to their approximate description of the nucleation, growth and coalescence of microvoids. Using the void shape factor of the GLD-model, a simple approach for approximating void nucleation by either particle fracture or particle-matrix decohesion is applied and a study of the subsequent void shape evolution...

  11. Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues.

    Science.gov (United States)

    Rapuano, Kristina M; Zieselman, Amanda L; Kelley, William M; Sargent, James D; Heatherton, Todd F; Gilbert-Diamond, Diane

    2017-01-03

    Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body mass and adiposity, a dominant model was most predictive of NAcc size and responsivity to food cues. These findings suggest that children genetically at risk for obesity are predisposed to represent reward signals more strongly, which, in turn, may contribute to unhealthy eating behaviors later in life.

  12. Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues

    Science.gov (United States)

    Rapuano, Kristina M.; Zieselman, Amanda L.; Kelley, William M.; Sargent, James D.; Heatherton, Todd F.

    2017-01-01

    Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9–12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body mass and adiposity, a dominant model was most predictive of NAcc size and responsivity to food cues. These findings suggest that children genetically at risk for obesity are predisposed to represent reward signals more strongly, which, in turn, may contribute to unhealthy eating behaviors later in life. PMID:27994159

  13. Fractional Diffusion Based Modelling and Prediction of Human Brain Response to External Stimuli

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2015-01-01

    Full Text Available Human brain response is the result of the overall ability of the brain in analyzing different internal and external stimuli and thus making the proper decisions. During the last decades scientists have discovered more about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research, there were fewer efforts which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling and prediction of the human EEG signal, as an alert state of overall human brain activity monitoring, upon receiving external stimuli, based on fractional diffusion equations. The results of this modeling show very good agreement with the real human EEG signal and thus this model can be used for many types of applications such as prediction of seizure onset in patient with epilepsy.

  14. Pulse pressure variation to predict fluid responsiveness in spontaneously breathing patients: tidal vs. forced inspiratory breathing.

    Science.gov (United States)

    Hong, D M; Lee, J M; Seo, J H; Min, J J; Jeon, Y; Bahk, J H

    2014-07-01

    We evaluated whether pulse pressure variation can predict fluid responsiveness in spontaneously breathing patients. Fifty-nine elective thoracic surgical patients were studied before induction of general anaesthesia. After volume expansion with hydroxyethyl starch 6 ml.kg(-1) , patients were defined as responders by a ≥ 15% increase in the cardiac index. Haemodynamic variables were measured before and after volume expansion and pulse pressure variations were calculated during tidal breathing and during forced inspiratory breathing. Median (IQR [range]) pulse pressure variation during forced inspiratory breathing was significantly higher in responders (n = 29) than in non-responders (n = 30) before volume expansion (18.2 (IQR 14.7-18.2 [9.3-31.3])% vs. 10.1 (IQR 8.3-12.6 [4.8-21.1])%, respectively, p breathing could predict fluid responsiveness (area under the curve 0.910, p breathing can be used to guide fluid management in spontaneously breathing patients.

  15. Analysis of Long Wave Infrared (LWIR) Soil Data to Predict Reflectance Response

    Science.gov (United States)

    2009-08-01

    Chemistry 382:1987–1992. Lyon, R. J. P. 1964. Evaluation of infrared spectrophotometry for compositional analy- sis of lunar and planetary soils; Part 2...ER D C/ G SL T R -0 9 -2 5 Analysis of Long Wave Infrared (LWIR) Soil Data to Predict Reflectance Response Janet E. Simms, Ernest S...Approved for public release; distribution is unlimited. ERDC/GSL TR-09-25 August 2009 Analysis of Long Wave Infrared (LWIR) Soil Data to

  16. A rest-activity biomarker to predict response to SSRIs in major depressive disorder.

    Science.gov (United States)

    McCall, W Vaughn

    2015-05-01

    Most adults with Major Depressive Disorder (MDD) will not experience a remission with the first antidepressant trial. No practical biomarkers presently exist to predict responsiveness to antidepressants. Herein we report pilot data for a rest-activity biomarker of antidepressant response. Fifty-eight medication-free adults with MDD underwent a week-long collection of actigraphic data before beginning a 9 week open label trial of fluoxetine, coupled with blinded randomized assignment to eszopiclone/placebo. Depression severity was repeatedly measured with the Hamilton Rating Scale for Depression (HRSD). Baseline actigraphic data was analyzed with functional data analysis to create smoothed 24-h curves of activity. The time of the lowest point of activity (the bathyphase) was calculated for each patient, as well the mean difference between bedtime and the bathyphase (BBD). At the end of treatment, patients were characterized as treatment responders (50% reduction in HRSD) or non-responders, and receiver operating curves were calculated to find the optimal cut point of the BBD for prediction of treatment response. The best cut point for BBD was at 260.2 min, resulting in an effect size of 1.45, and with a positive predictive value of 0.75 and a negative predictive value of 0.88. We conclude that actigraphically-determined measures of rest-activity patterns show promise as potential biomarker predictors of antidepressant response. However, this conclusion is based upon a small number of patients who received only one choice of antidepressant, for a single trial. Replication with a larger sample is needed.

  17. Genetic and physiological bases for phenological responses to current and predicted climates

    OpenAIRE

    Wilczek, A. M.; Burghardt, L. T.; Cobb, A. R.; Cooper, M D; Welch, S. M.; Schmitt, J

    2010-01-01

    We are now reaching the stage at which specific genetic factors with known physiological effects can be tied directly and quantitatively to variation in phenology. With such a mechanistic understanding, scientists can better predict phenological responses to novel seasonal climates. Using the widespread model species Arabidopsis thaliana, we explore how variation in different genetic pathways can be linked to phenology and life-history variation across geographical regions and seasons. We sho...

  18. Diffusion-weighted magnetic resonance imaging to predict response of hepatocellular carcinoma to chemoembolization

    Institute of Scientific and Technical Information of China (English)

    Johnathan; C; Chung; Neel; K; Naik; Robert; J; Lewandowski; Mary; F; Mulcahy; Laura; M; Kulik; Kent; T; Sato; Robert; K; Ryu; Riad; Salem; Andrew; C; Larson; Reed; A; Omary

    2010-01-01

    AIM: To investigate whether intra-procedural diffusion- weighted magnetic resonance imaging can predict response of hepatocellular carcinoma (HCC) during trans- catheter arterial chemoembolization (TACE). METHODS: Sixteen patients (15 male), aged 59 ±11 years (range: 42-81 years) underwent a total of 21 separate treatments for unresectable HCC in a hybrid magnetic resonance/interventional radiology suite. Ana- tomical imaging and diffusion-weighted imaging (b = 0, 500 s/mm2) were performed on a 1.5-T unit. ...

  19. A Semi-Supervised Approach for Refining Transcriptional Signatures of Drug Response and Repositioning Predictions.

    Directory of Open Access Journals (Sweden)

    Francesco Iorio

    Full Text Available We present a novel strategy to identify drug-repositioning opportunities. The starting point of our method is the generation of a signature summarising the consensual transcriptional response of multiple human cell lines to a compound of interest (namely the seed compound. This signature can be derived from data in existing databases, such as the connectivity-map, and it is used at first instance to query a network interlinking all the connectivity-map compounds, based on the similarity of their transcriptional responses. This provides a drug neighbourhood, composed of compounds predicted to share some effects with the seed one. The original signature is then refined by systematically reducing its overlap with the transcriptional responses induced by drugs in this neighbourhood that are known to share a secondary effect with the seed compound. Finally, the drug network is queried again with the resulting refined signatures and the whole process is carried on for a number of iterations. Drugs in the final refined neighbourhood are then predicted to exert the principal mode of action of the seed compound. We illustrate our approach using paclitaxel (a microtubule stabilising agent as seed compound. Our method predicts that glipizide and splitomicin perturb microtubule function in human cells: a result that could not be obtained through standard signature matching methods. In agreement, we find that glipizide and splitomicin reduce interphase microtubule growth rates and transiently increase the percentage of mitotic cells-consistent with our prediction. Finally, we validated the refined signatures of paclitaxel response by mining a large drug screening dataset, showing that human cancer cell lines whose basal transcriptional profile is anti-correlated to them are significantly more sensitive to paclitaxel and docetaxel.

  20. Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia

    OpenAIRE

    Laura M. Tully, PhD; Sarah Hope Lincoln, MA; Christine I. Hooker, PhD

    2014-01-01

    LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investiga...

  1. Simple regional strain pattern analysis to predict response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Risum, Niels; Jons, Christian; Olsen, Niels T;

    2012-01-01

    A classical strain pattern of early contraction in one wall and prestretching of the opposing wall followed by late contraction has previously been associated with left bundle branch block (LBBB) activation and short-term response to cardiac resynchronization therapy (CRT). Aims of this study were...... to establish the long-term predictive value of an LBBB-related strain pattern and to identify changes in contraction patterns during short-term and long-term CRT....

  2. Standard error of inverse prediction for dose-response relationship: approximate and exact statistical inference.

    Science.gov (United States)

    Demidenko, Eugene; Williams, Benjamin B; Flood, Ann Barry; Swartz, Harold M

    2013-05-30

    This paper develops a new metric, the standard error of inverse prediction (SEIP), for a dose-response relationship (calibration curve) when dose is estimated from response via inverse regression. SEIP can be viewed as a generalization of the coefficient of variation to regression problem when x is predicted using y-value. We employ nonstandard statistical methods to treat the inverse prediction, which has an infinite mean and variance due to the presence of a normally distributed variable in the denominator. We develop confidence intervals and hypothesis testing for SEIP on the basis of the normal approximation and using the exact statistical inference based on the noncentral t-distribution. We derive the power functions for both approaches and test them via statistical simulations. The theoretical SEIP, as the ratio of the regression standard error to the slope, is viewed as reciprocal of the signal-to-noise ratio, a popular measure of signal processing. The SEIP, as a figure of merit for inverse prediction, can be used for comparison of calibration curves with different dependent variables and slopes. We illustrate our theory with electron paramagnetic resonance tooth dosimetry for a rapid estimation of the radiation dose received in the event of nuclear terrorism.

  3. Rapid brain responses independently predict gain maximization and loss minimization during economic decision making.

    Science.gov (United States)

    San Martín, René; Appelbaum, Lawrence G; Pearson, John M; Huettel, Scott A; Woldorff, Marty G

    2013-04-17

    Success in many decision-making scenarios depends on the ability to maximize gains and minimize losses. Even if an agent knows which cues lead to gains and which lead to losses, that agent could still make choices yielding suboptimal rewards. Here, by analyzing event-related potentials (ERPs) recorded in humans during a probabilistic gambling task, we show that individuals' behavioral tendencies to maximize gains and to minimize losses are associated with their ERP responses to the receipt of those gains and losses, respectively. We focused our analyses on ERP signals that predict behavioral adjustment: the frontocentral feedback-related negativity (FRN) and two P300 (P3) subcomponents, the frontocentral P3a and the parietal P3b. We found that, across participants, gain maximization was predicted by differences in amplitude of the P3b for suboptimal versus optimal gains (i.e., P3b amplitude difference between the least good and the best gains). Conversely, loss minimization was predicted by differences in the P3b amplitude to suboptimal versus optimal losses (i.e., difference between the worst and the least bad losses). Finally, we observed that the P3a and P3b, but not the FRN, predicted behavioral adjustment on subsequent trials, suggesting a specific adaptive mechanism by which prior experience may alter ensuing behavior. These findings indicate that individual differences in gain maximization and loss minimization are linked to individual differences in rapid neural responses to monetary outcomes.

  4. Measurement and Prediction of the Thermomechanical Response of Shape Memory Alloy Hybrid Composite Beams

    Science.gov (United States)

    Davis, Brian; Turner, Travis L.; Seelecke, Stefan

    2005-01-01

    Previous work at NASA Langley Research Center (LaRC) involved fabrication and testing of composite beams with embedded, pre-strained shape memory alloy (SMA) ribbons within the beam structures. That study also provided comparison of experimental results with numerical predictions from a research code making use of a new thermoelastic model for shape memory alloy hybrid composite (SMAHC) structures. The previous work showed qualitative validation of the numerical model. However, deficiencies in the experimental-numerical correlation were noted and hypotheses for the discrepancies were given for further investigation. The goal of this work is to refine the experimental measurement and numerical modeling approaches in order to better understand the discrepancies, improve the correlation between prediction and measurement, and provide rigorous quantitative validation of the numerical analysis/design tool. The experimental investigation is refined by a more thorough test procedure and incorporation of higher fidelity measurements such as infrared thermography and projection moire interferometry. The numerical results are produced by a recently commercialized version of the constitutive model as implemented in ABAQUS and are refined by incorporation of additional measured parameters such as geometric imperfection. Thermal buckling, post-buckling, and random responses to thermal and inertial (base acceleration) loads are studied. The results demonstrate the effectiveness of SMAHC structures in controlling static and dynamic responses by adaptive stiffening. Excellent agreement is achieved between the predicted and measured results of the static and dynamic thermomechanical response, thereby providing quantitative validation of the numerical tool.

  5. Predicting methylphenidate response in attention deficit hyperactivity disorder: a preliminary study.

    Science.gov (United States)

    Johnston, Blair A; Coghill, David; Matthews, Keith; Steele, J Douglas

    2015-01-01

    Methylphenidate (MPH) is established as the main pharmacological treatment for patients with attention deficit hyperactivity disorder (ADHD). Whilst MPH is generally a highly effective treatment, not all patients respond, and some experience adverse reactions. Currently, there is no reliable method to predict how patients will respond, other than by exposure to a trial of medication. In this preliminary study, we sought to investigate whether an accurate predictor of clinical response to methylphenidate could be developed for individual patients, using sociodemographic, clinical and neuropsychological measures. Of the 43 boys with ADHD included in this proof-of-concept study, 30 were classed as responders and 13 as non-responders to MPH, with no significant differences in age nor verbal intelligence quotient (IQ) between the groups. Here we report the application of a multivariate analysis approach to the prediction of clinical response to MPH, which achieved an accuracy of 77% (p = 0.005). The most important variables to the classifier were performance on a 'go/no go' task and comorbid conduct disorder. This preliminary study suggested that further investigation is merited. Achieving a highly significant accuracy of 77% for the prediction of MPH response is an encouraging step towards finding a reliable and clinically useful method that could minimise the number of children needlessly being exposed to MPH.

  6. Ovarian response prediction in GnRH antagonist treatment for IVF using anti-Müllerian hormone

    NARCIS (Netherlands)

    Hamdine, O.; Eijkemans, M. J C; Lentjes, E. W G; Torrance, H. L.; Macklon, N. S.; Fauser, B. C J M; Broekmans, F. J.

    2015-01-01

    STUDY QUESTION What is the clinical value of anti-Müllerian hormone (AMH) for the prediction of high or low ovarian response in controlled ovarian stimulation for IVF using GnRH antagonist treatment? SUMMARY ANSWER AMH as a single test has substantial accuracy for ovarian response prediction in GnRH

  7. The eye is listening: Music-induced arousal and individual differences predict pupillary responses

    Directory of Open Access Journals (Sweden)

    Bruno eGingras

    2015-11-01

    Full Text Available Pupillary responses are a well-known indicator of emotional arousal but have not yet been systematically investigated in response to music. Here, we measured pupillary dilations evoked by short musical excerpts normalized for intensity and selected for their stylistic uniformity. Thirty participants (15 females provided subjective ratings of music-induced felt arousal, tension, pleasantness and familiarity for 80 classical music excerpts. The pupillary responses evoked by these excerpts were measured in another thirty participants (15 females. We probed the role of listener-specific characteristics such as mood, stress reactivity, self-reported role of music in life, liking for the selected excerpts, as well as of subjective responses to music, in pupillary responses. Linear mixed model analyses showed that a greater role of music in life was associated with larger dilations, and that larger dilations were also predicted for excerpts rated as more arousing or tense. However, an interaction between arousal and liking for the excerpts suggested that pupillary responses were modulated less strongly by arousal when the excerpts were particularly liked. An analogous interaction was observed between tension and liking. Additionally, males exhibited larger dilations than females. Overall, these findings suggest a complex interplay between bottom-up and top-down influences on pupillary responses to music.

  8. Alexithymia predicts arousal-based processing deficits and discordance between emotion response systems during emotional imagery.

    Science.gov (United States)

    Peasley-Miklus, Catherine E; Panayiotou, Georgia; Vrana, Scott R

    2016-03-01

    Alexithymia is believed to involve deficits in emotion processing and imagery ability. Previous findings suggest that it is especially related to deficits in processing the arousal dimension of emotion, and that discordance may exist between self-report and physiological responses to emotional stimuli in alexithymia. The current study used a well-established emotional imagery paradigm to examine emotion processing deficits and discordance in participants (N = 86) selected based on their extreme scores on the Toronto Alexithymia Scale-20. Physiological (skin conductance, heart rate, and corrugator and zygomaticus electromyographic responses) and self-report (valence, arousal ratings) responses were monitored during imagery of anger, fear, joy, and neutral scenes and emotionally neutral high arousal (action) scenes. Results from regression analyses indicated that alexithymia was largely unrelated to responses on valence-based measures (facial electromyography, valence ratings), but that it was related to arousal-based measures. Specifically, alexithymia was related to higher heart rate during neutral and lower heart rate during fear imagery. Alexithymia did not predict differential responses to action versus neutral imagery, suggesting specificity of deficits to emotional contexts. Evidence for discordance between physiological responses and self-report in alexithymia was obtained from within-person analyses using multilevel modeling. Results are consistent with the idea that alexithymic deficits are specific to processing emotional arousal, and suggest difficulties with parasympathetic control and emotion regulation. Alexithymia is also associated with discordance between self-reported emotional experience and physiological response to emotion, consistent with prior evidence.

  9. Rapid Detection of Neutrophil Oxidative Burst Capacity is Predictive of Whole Blood Cytokine Responses.

    Directory of Open Access Journals (Sweden)

    Philip J Vernon

    Full Text Available Maladaptive immune responses, particularly cytokine and chemokine-driven, are a significant contributor to the deleterious inflammation present in many types of injury and infection. Widely available applications to rapidly assess individual inflammatory capacity could permit identification of patients at risk for exacerbated immune responses and guide therapy. Here we evaluate neutrophil oxidative burst (NOX capacity measured by plate reader to immuno-type Rhesus Macaques as an acute strategy to rapidly detect inflammatory capacity and predict maladaptive immune responses as assayed by cytokine array.Whole blood was collected from anesthetized Rhesus Macaques (n = 25 and analyzed for plasma cytokine secretion (23-plex Luminex assay and NOX capacity. For cytokine secretion, paired samples were either unstimulated or ex-vivo lipopolysaccharide (LPS-stimulated (100μg/mL/24h. NOX capacity was measured in dihydrorhodamine-123 loaded samples following phorbol 12-myristate 13-acetate (PMA/ionomycin treatment. Pearson's test was utilized to correlate NOX capacity with cytokine secretion, p<0.05 considered significant.LPS stimulation induced secretion of the inflammatory molecules G-CSF, IL-1β, IL-1RA, IL-6, IL-10, IL-12/23(p40, IL-18, MIP-1α, MIP-1β, and TNFα. Although values were variable, several cytokines correlated with NOX capacity, p-values≤0.0001. Specifically, IL-1β (r = 0.66, IL-6 (r = 0.74, the Th1-polarizing cytokine IL-12/23(p40 (r = 0.78, and TNFα (r = 0.76 were strongly associated with NOX.NOX capacity correlated with Th1-polarizing cytokine secretion, indicating its ability to rapidly predict inflammatory responses. These data suggest that NOX capacity may quickly identify patients at risk for maladaptive immune responses and who may benefit from immuno-modulatory therapies. Future studies will assess the in-vivo predictive value of NOX in animal models of immune-mediated pathologies.

  10. Allergen-specific IL-5 responses in early childhood predict asthma at age eight.

    Directory of Open Access Journals (Sweden)

    Christina Weber-Chrysochoou

    Full Text Available BACKGROUND: The pattern of development of allergen-specific T cell cytokine responses in early childhood and their relation to later disease is poorly understood. Here we describe longitudinal changes in allergen-stimulated T cell cytokine responses and their relation to asthma and allergic disease during the first 8 years of life. METHODS: Subjects with a family history of asthma, who were enrolled antenatally in the Childhood Asthma Prevention Study (public trials registration number ACTRN12605000042640, had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of T cell cytokine responses to HDM extract performed at ages 18 months (n = 281, 3 years (n = 349, 5 years (n = 370 and 8 years (n = 275. We measured interleukin (IL- 13 at 3, 5 and 8 years, and IL-5, IL-10, and interferon-γ (IFN-γ, at 18 months, 3, 5 and 8 years by ELISA. A cohort analysis was undertaken. Independent effects of cytokine responses at each age on the risk of asthma and allergic outcomes at age 8 years were estimated by multivariable logistic regression. RESULTS: HDM-specific IL-5 responses increased with age. HDM-specific IL-13 and IL-10 responses peaked at age 5 years. HDM-specific IL-5 responses at 3 years, 5 years and 8 years were significantly associated with the presence of asthma and atopy at 8 years. IL-13 responses at 3 years, 5 years and 8 years were significantly associated with atopy at 8 years, but this association was not independent of the effect of IL-5. Other HDM-specific cytokine responses were not independently related to asthma or eczema at 8 years. CONCLUSION: HDM-specific IL-5 responses at age 3 years or later are the best measure of T cell function for predicting asthma at age 8 years.

  11. Mode-locking neurodynamics predict human auditory brainstem responses to musical intervals.

    Science.gov (United States)

    Lerud, Karl D; Almonte, Felix V; Kim, Ji Chul; Large, Edward W

    2014-02-01

    The auditory nervous system is highly nonlinear. Some nonlinear responses arise through active processes in the cochlea, while others may arise in neural populations of the cochlear nucleus, inferior colliculus and higher auditory areas. In humans, auditory brainstem recordings reveal nonlinear population responses to combinations of pure tones, and to musical intervals composed of complex tones. Yet the biophysical origin of central auditory nonlinearities, their signal processing properties, and their relationship to auditory perception remain largely unknown. Both stimulus components and nonlinear resonances are well represented in auditory brainstem nuclei due to neural phase-locking. Recently mode-locking, a generalization of phase-locking that implies an intrinsically nonlinear processing of sound, has been observed in mammalian auditory brainstem nuclei. Here we show that a canonical model of mode-locked neural oscillation predicts the complex nonlinear population responses to musical intervals that have been observed in the human brainstem. The model makes predictions about auditory signal processing and perception that are different from traditional delay-based models, and may provide insight into the nature of auditory population responses. We anticipate that the application of dynamical systems analysis will provide the starting point for generic models of auditory population dynamics, and lead to a deeper understanding of nonlinear auditory signal processing possibly arising in excitatory-inhibitory networks of the central auditory nervous system. This approach has the potential to link neural dynamics with the perception of pitch, music, and speech, and lead to dynamical models of auditory system development.

  12. Model-based Comparative Prediction of Transcription-Factor Binding Motifs in Anabolic Responses in Bone

    Institute of Scientific and Technical Information of China (English)

    Andy; B.; Chen; Kazunori; Hamamura; Guohua; Wang; Weirong; Xing; Subburaman; Mohan; Hiroki; Yokota; Yunlong; Liu

    2007-01-01

    Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs (TFBMs) through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins (BMPs) are two known treatments to strengthen bone. We addressed a question: Is there any TFBM that stimulates both "anabolic responses of mechanical loading" and "BMP-mediated osteogenic signaling"? Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated recep- tor (PPAR). The post-modeling in vitro analysis using mouse osteoblast cells sup- ported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.

  13. Unsupervised feature learning improves prediction of human brain activity in response to natural images.

    Directory of Open Access Journals (Sweden)

    Umut Güçlü

    2014-08-01

    Full Text Available Encoding and decoding in functional magnetic resonance imaging has recently emerged as an area of research to noninvasively characterize the relationship between stimulus features and human brain activity. To overcome the challenge of formalizing what stimulus features should modulate single voxel responses, we introduce a general approach for making directly testable predictions of single voxel responses to statistically adapted representations of ecologically valid stimuli. These representations are learned from unlabeled data without supervision. Our approach is validated using a parsimonious computational model of (i how early visual cortical representations are adapted to statistical regularities in natural images and (ii how populations of these representations are pooled by single voxels. This computational model is used to predict single voxel responses to natural images and identify natural images from stimulus-evoked multiple voxel responses. We show that statistically adapted low-level sparse and invariant representations of natural images better span the space of early visual cortical representations and can be more effectively exploited in stimulus identification than hand-designed Gabor wavelets. Our results demonstrate the potential of our approach to better probe unknown cortical representations.

  14. Integrated Experimental and Modeling Studies to Predict the Impact Response of Explosives and Propellants

    Energy Technology Data Exchange (ETDEWEB)

    Maienschein, J L; Nichols III, A L; Reaugh, J E; McClelland, M E; Hsu, P C

    2005-05-25

    Understanding and predicting the impact response of explosives and propellants remains a challenging area in the energetic materials field. Efforts are underway at LLNL (and other laboratories) to apply modern diagnostic tools and computational analysis to move beyond the current level of imprecise approximations towards a predictive approach more closely based on fundamental understanding of the relevant mechanisms. In this paper we will discuss a set of underlying mechanisms that govern the impact response of explosives and propellants: (a) mechanical insult (impact) leading to material damage and/or direct ignition; (b) ignition leading to flame spreading; (c) combustion being driven by flame spreading, perhaps in damaged materials; (d) combustion causing further material damage; (e) combustion leading to pressure build-up or relief; (f) pressure changes driving the rates of combustion and flame spread; (g) pressure buildup leading to structural response and damage, which causes many of the physical hazards. We will briefly discuss our approach to modeling up these mechanistic steps using ALE 3D, the LLNL hydrodynamic code with fully coupled chemistry, heat flow, mass transfer, and slow mechanical motion as well as hydrodynamic processes. We will identify the necessary material properties needed for our models, and will discuss our experimental efforts to characterize these properties and the overall mechanistic steps, in order to develop and parameterize the models in ALE 3D and to develop a qualitative understanding of impact response.

  15. Forward and Inverse Modelling Approaches for Prediction of Light Stimulus from Electrophysiological Response in Plants

    CERN Document Server

    Chatterjee, Shre Kumar; Das, Saptarshi; Manzella, Veronica; Vitaletti, Andrea; Masi, Elisa; Santopolo, Luisa; Mancuso, Stefano; Maharatna, Koushik

    2014-01-01

    In this paper, system identification approach has been adopted to develop a novel dynamical model for describing the relationship between light as an environmental stimulus and the electrical response as the measured output for a bay leaf (Laurus nobilis) plant. More specifically, the target is to predict the characteristics of the input light stimulus (in terms of on-off timing, duration and intensity) from the measured electrical response - leading to an inverse problem. We explored two major classes of system estimators to develop dynamical models - linear and nonlinear - and their several variants for establishing a forward and also an inverse relationship between the light stimulus and plant electrical response. The best class of models are given by the Nonlinear Hammerstein-Wiener (NLHW) estimator showing good data fitting results over other linear and nonlinear estimators in a statistical sense. Consequently, a few set of models using different functional variants of NLHW has been developed and their a...

  16. Acceleration response spectrum for prediction of structural vibration due to individual bouncing

    Science.gov (United States)

    Chen, Jun; Wang, Lei; Racic, Vitomir; Lou, Jiayue

    2016-08-01

    This study is designed to develop an acceleration response spectrum that can be used in vibration serviceability assessment of civil engineering structures, such as floors and grandstands those are dynamically excited by individual bouncing. The spectrum is derived from numerical simulations and statistical analysis of acceleration responses of a single degree of freedom system with variable natural frequency and damping under a large number of experimentally measured individual bouncing loads. Its mathematical representation is fit for fast yet reliable application in design practice and is comprised of three equations that describe three distinct frequency regions observed in the actual data: the first resonant plateau (2-3.5 Hz), the second resonant plateau (4-7 Hz) and a descension region (7-15 Hz). Finally, this paper verifies the proposed response spectrum approach to predict structural vibration by direct comparison against numerical simulations and experimental results.

  17. A computer program for predicting nonlinear uniaxial material responses using viscoplastic models

    Science.gov (United States)

    Chang, T. Y.; Thompson, R. L.

    1984-01-01

    A computer program was developed for predicting nonlinear uniaxial material responses using viscoplastic constitutive models. Four specific models, i.e., those due to Miller, Walker, Krieg-Swearengen-Rhode, and Robinson, are included. Any other unified model is easily implemented into the program in the form of subroutines. Analysis features include stress-strain cycling, creep response, stress relaxation, thermomechanical fatigue loop, or any combination of these responses. An outline is given on the theoretical background of uniaxial constitutive models, analysis procedure, and numerical integration methods for solving the nonlinear constitutive equations. In addition, a discussion on the computer program implementation is also given. Finally, seven numerical examples are included to demonstrate the versatility of the computer program developed.

  18. Predicting Climate Change Using Response Theory: Global Averages and Spatial Patterns

    Science.gov (United States)

    Lucarini, Valerio; Ragone, Francesco; Lunkeit, Frank

    2016-04-01

    The provision of accurate methods for predicting the climate response to anthropogenic and natural forcings is a key contemporary scientific challenge. Using a simplified and efficient open-source general circulation model of the atmosphere featuring O(10^5 ) degrees of freedom, we show how it is possible to approach such a problem using nonequilibrium statistical mechanics. Response theory allows one to practically compute the time-dependent measure supported on the pullback attractor of the climate system, whose dynamics is non-autonomous as a result of time-dependent forcings. We propose a simple yet efficient method for predicting—at any lead time and in an ensemble sense—the change in climate properties resulting from increase in the concentration of CO_2 using test perturbation model runs. We assess strengths and limitations of the response theory in predicting the changes in the globally averaged values of surface temperature and of the yearly total precipitation, as well as in their spatial patterns. The quality of the predictions obtained for the surface temperature fields is rather good, while in the case of precipitation a good skill is observed only for the global average. We also show how it is possible to define accurately concepts like the inertia of the climate system or to predict when climate change is detectable given a scenario of forcing. Our analysis can be extended for dealing with more complex portfolios of forcings and can be adapted to treat, in principle, any climate observable. Our conclusion is that climate change is indeed a problem that can be effectively seen through a statistical mechanical lens, and that there is great potential for optimizing the current coordinated modelling exercises run for the preparation of the subsequent reports of the Intergovernmental Panel for Climate Change.

  19. Predicting Climate Change Using Response Theory: Global Averages and Spatial Patterns

    Science.gov (United States)

    Lucarini, Valerio; Ragone, Francesco; Lunkeit, Frank

    2017-02-01

    The provision of accurate methods for predicting the climate response to anthropogenic and natural forcings is a key contemporary scientific challenge. Using a simplified and efficient open-source general circulation model of the atmosphere featuring O(10^5) degrees of freedom, we show how it is possible to approach such a problem using nonequilibrium statistical mechanics. Response theory allows one to practically compute the time-dependent measure supported on the pullback attractor of the climate system, whose dynamics is non-autonomous as a result of time-dependent forcings. We propose a simple yet efficient method for predicting—at any lead time and in an ensemble sense—the change in climate properties resulting from increase in the concentration of CO_2 using test perturbation model runs. We assess strengths and limitations of the response theory in predicting the changes in the globally averaged values of surface temperature and of the yearly total precipitation, as well as in their spatial patterns. The quality of the predictions obtained for the surface temperature fields is rather good, while in the case of precipitation a good skill is observed only for the global average. We also show how it is possible to define accurately concepts like the inertia of the climate system or to predict when climate change is detectable given a scenario of forcing. Our analysis can be extended for dealing with more complex portfolios of forcings and can be adapted to treat, in principle, any climate observable. Our conclusion is that climate change is indeed a problem that can be effectively seen through a statistical mechanical lens, and that there is great potential for optimizing the current coordinated modelling exercises run for the preparation of the subsequent reports of the Intergovernmental Panel for Climate Change.

  20. Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks.

    Directory of Open Access Journals (Sweden)

    Petros-Pavlos Ypsilantis

    Full Text Available Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.

  1. Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks.

    Science.gov (United States)

    Ypsilantis, Petros-Pavlos; Siddique, Musib; Sohn, Hyon-Mok; Davies, Andrew; Cook, Gary; Goh, Vicky; Montana, Giovanni

    2015-01-01

    Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.

  2. Mood color choice helps to predict response to hypnotherapy in patients with irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Tarrier Nicholas

    2010-12-01

    Full Text Available Abstract Background Approximately two thirds of patients with irritable bowel syndrome (IBS respond well to hypnotherapy. However, it is time consuming as well as expensive to provide and therefore a way of predicting outcome would be extremely useful. The use of imagery and color form an integral part of the hypnotherapeutic process and we have hypothesised that investigating color and how it relates to mood might help to predict response to treatment. In order to undertake this study we have previously developed and validated a method of presenting colors to individuals for research purposes called the Manchester Color Wheel (MCW. Using this instrument we have been able to classify colors into positive, neutral and negative shades and this study aimed to assess their predictive role in hypnotherapy. Methods 156 consecutive IBS patients (aged 14-74, mean 42.0 years, 127 (81% females, 29 (19% males were studied. Before treatment, each patient was asked to relate their mood to a color on the MCW as well as completing the IBS Symptom Severity Score, the Hospital Anxiety and Depression (HAD Scale, the Non-colonic Symptom Scale, the Quality of Life Scale and the Tellegen Absorption Scale (TAS which is a measure of hypnotisability. Following hypnotherapy all these measures were repeated with the exception of the TAS. Results For patients with a positive mood color the odds of responding to hypnotherapy were nine times higher than that of those choosing either a neutral or negative color or no color at all (odds ratio: 8.889; p = 0.042. Furthermore, a high TAS score and the presence of HAD anxiety also had good predictive value (odds ratio: 4.024; p = 0.092, 3.917; p Conclusion A positive mood color, especially when combined with HAD anxiety and a high TAS score, predict a good response to hypnotherapy.

  3. Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kao, W.-Y. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Chiou, Y.-Y., E-mail: yychiou@vghtpe.gov.tw [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hung, H.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Su, C.-W., E-mail: cwsu2@vghtpe.gov.tw [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Chou, Y.-H. [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, J.-C. [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan (China); Huo, T.-I. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Huang, Y.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, W.-C. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China)

    2012-05-15

    Aims: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Materials and methods: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of {>=}100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. Results: After a median follow-up of 26.7 {+-} 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and {>=}100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of {>=}100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count {<=}10{sup 5}/mm{sup 3} (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. Conclusions: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

  4. Can personality traits and gender predict the response to morphine? An experimental cold pain study.

    Science.gov (United States)

    Pud, Dorit; Yarnitsky, David; Sprecher, Elliot; Rogowski, Zeev; Adler, Rivka; Eisenberg, Elon

    2006-02-01

    The aim of the present study was to examine the possible role of personality traits, in accordance with Cloninger's theory, and gender, in the variability of responsiveness to opioids. Specifically, it was intended to test whether or not the three personality dimensions - harm avoidance (HA), reward dependence (RD) and novelty seeking (NS) - as suggested by Cloninger, can predict inter-personal differences in responsiveness to morphine after exposure to experimental cold pain. Thirty-four healthy volunteers (15 females, 19 males) were given the cold pressor test (CPT). Pain threshold, tolerance, and magnitude (VAS) were measured before and after (six measures, 30 min apart) the administration of either 0.5 mg/kg oral morphine sulphate (n=21) or 0.33 mg/kg oral active placebo (diphenhydramine) (n=13) in a randomized, double blind design. Assessment of the three personality traits, according to Cloninger's Tridimensional Personality Questionnaire, was performed before the CPT. A high HA score (but not RD, NS, or baseline values of the three pain parameters) predicted a significantly larger pain relief following the administration of morphine sulphate (but not of the placebo). Women exhibited a larger response in response to both treatments, as indicated by a significantly increased threshold and tolerance following morphine sulphate as well as significantly increased tolerance and decreased magnitude following placebo administration. The present study confirms the existence of individual differences in response to analgesic treatment. It suggests that high HA personality trait is associated with better responsiveness to morphine treatment, and that females respond better than men to both morphine and placebo.

  5. Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy.

    Science.gov (United States)

    Schoeler, Natasha E; Leu, Costin; White, Jon; Plagnol, Vincent; Ellard, Sian; Matarin, Mar; Yellen, Gary; Thiele, Elizabeth A; Mackay, Mark; McMahon, Jacinta M; Scheffer, Ingrid E; Sander, Josemir W; Cross, J Helen; Sisodiya, Sanjay M

    2015-12-01

    In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: ≥ 50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF)>0.01, using PLINK. Response to KDT in individuals with variants with MAFBAD sequencing data and diet response data. Six SNPs in KCNJ11 and two in BAD had MAF>0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAFBAD do not predict response to KDT for epilepsy. We can exclude, with 80% power, association from variants with a MAF of >0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes.

  6. A germline predictive signature of response to platinum chemotherapy in esophageal cancer.

    Science.gov (United States)

    Rumiato, Enrica; Boldrin, Elisa; Malacrida, Sandro; Battaglia, Giorgio; Bocus, Paolo; Castoro, Carlo; Cagol, Matteo; Chiarion-Sileni, Vanna; Ruol, Alberto; Amadori, Alberto; Saggioro, Daniela

    2016-05-01

    Platinum-based neoadjuvant therapy is the standard treatment for esophageal cancer (EC). At present, no reliable response markers exist, and patient therapeutic outcome is variable and very often unpredictable. The aim of this study was to understand the contribution of host constitutive DNA polymorphisms in discriminating between responder and nonresponder patients. DNA collected from 120 EC patients treated with platinum-based neoadjuvant chemotherapy was analyzed using drug metabolism enzymes and transporters (DMET) array platform that interrogates polymorphisms in 225 genes of drug metabolism and disposition. Four gene variants of DNA repair machinery, 2 in ERCC1 (rs11615; rs3212986), and 2 in XPD (rs1799793; rs13181) were also studied. Association analysis was performed with pTest software and corrected by permutation test. Predictive models of response were created using the receiver-operating characteristics curve approach and adjusted by the bootstrap procedure. Sixteen single nucleotide polymorphisms (SNPs) of the DMET array resulted significantly associated with either good or poor response; no association was found for the 4 variants mapping in DNA repair genes. The predictive power of 5 DMET SNPs mapping in ABCC2, ABCC3, CYP2A6, PPARG, and SLC7A8 genes was greater than that of clinical factors alone (area under the curve [AUC] = 0.74 vs 0.62). Interestingly, their combination with the clinical variables significantly increased the predictivity of the model (AUC = 0.78 vs 0.62, P = 0.0016). In conclusion, we identified a genetic signature of response to platinum-based neoadjuvant chemotherapy in EC patients. Our results also disclose the potential benefit of combining genetic and clinical variables for personalized EC management.

  7. Female anthropometric variability and their effects on predicted thermoregulatory responses to work in the heat

    Science.gov (United States)

    Yokota, Miyo; Berglund, Larry G.; Bathalon, Gaston P.

    2012-03-01

    The use of thermoregulatory models for assessing physiological responses of workers in thermally stressful situations has been increasing because of the risks and costs related to human studies. In a previous study (Yokota et al. Eur J Appl Physiol 104:297-302, 2008), the effects of anthropometric variability on predicted physiological responses to heat stress in U.S. Army male soldiers were evaluated. Five somatotypes were identified in U.S. Army male multivariate anthropometric distribution. The simulated heat responses, using a thermoregulatory model, were different between somatotypes. The present study further extends this line of research to female soldiers. Anthropometric somatotypes were identified using multivariate analysis [height, weight, percent body fat (%BF)] and the predicted physiological responses to simulated exercise and heat stress using a thermoregulatory model were evaluated. The simulated conditions included walking at ~3 mph (4.8 km/h) for 300 min and wearing battle dress uniform and body armor in a 30°C, 25% relative humidity (RH) environment without solar radiation. Five major somatotypes (tall-fat, tall-lean, average, short-lean, and short-fat), identified through multivariate analysis of anthropometric distributions, showed different tolerance levels to simulated heat stress: lean women were predicted to maintain their core temperatures (Tc) lower than short-fat or tall-fat women. The measured Tc of female subjects obtained from two heat studies (data1: 30°C, 32% RH, protective garments, ~225 w·m-2 walk for 90 min; data2: 32°C, 75% RH, hot weather battle dress uniform, ~378 ± 32 w·m-2 for 30 min walk/30 min rest cycles for 120 min) were utilized for validation. Validation results agreed with the findings in this study: fat subjects tended to have higher core temperatures than medium individuals (data2) and lean subjects maintained lower core temperatures than medium subjects (data1).

  8. Assessing conservation relevance of organism-environment relations using predicted changes in response variables

    Science.gov (United States)

    Gutzwiller, Kevin J.; Barrow, Wylie C.; White, Joseph D.; Johnson-Randall, Lori; Cade, Brian S.; Zygo, Lisa M.

    2010-01-01

    1. Organism–environment models are used widely in conservation. The degree to which they are useful for informing conservation decisions – the conservation relevance of these relations – is important because lack of relevance may lead to misapplication of scarce conservation resources or failure to resolve important conservation dilemmas. Even when models perform well based on model fit and predictive ability, conservation relevance of associations may not be clear without also knowing the magnitude and variability of predicted changes in response variables. 2. We introduce a method for evaluating the conservation relevance of organism–environment relations that employs confidence intervals for predicted changes in response variables. The confidence intervals are compared to a preselected magnitude of change that marks a threshold (trigger) for conservation action. To demonstrate the approach, we used a case study from the Chihuahuan Desert involving relations between avian richness and broad-scale patterns of shrubland. We considered relations for three winters and two spatial extents (1- and 2-km-radius areas) and compared predicted changes in richness to three thresholds (10%, 20% and 30% change). For each threshold, we examined 48 relations. 3. The method identified seven, four and zero conservation-relevant changes in mean richness for the 10%, 20% and 30% thresholds respectively. These changes were associated with major (20%) changes in shrubland cover, mean patch size, the coefficient of variation for patch size, or edge density but not with major changes in shrubland patch density. The relative rarity of conservation-relevant changes indicated that, overall, the relations had little practical value for informing conservation decisions about avian richness. 4. The approach we illustrate is appropriate for various response and predictor variables measured at any temporal or spatial scale. The method is broadly applicable across ecological

  9. Network-based approaches for drug response prediction and targeted therapy development in cancer.

    Science.gov (United States)

    Dorel, Mathurin; Barillot, Emmanuel; Zinovyev, Andrei; Kuperstein, Inna

    2015-08-21

    Signaling pathways implicated in cancer create a complex network with numerous regulatory loops and redundant pathways. This complexity explains frequent failure of one-drug-one-target paradigm of treatment, resulting in drug resistance in patients. To overcome the robustness of cell signaling network, cancer treatment should be extended to a combination therapy approach. Integrating and analyzing patient high-throughput data together with the information about biological signaling machinery may help deciphering molecular patterns specific to each patient and finding the best combinations of candidates for therapeutic targeting. We review state of the art in the field of targeted cancer medicine from the computational systems biology perspective. We summarize major signaling network resources and describe their characteristics with respect to applicability for drug response prediction and intervention targets suggestion. Thus discuss methods for prediction of drug sensitivity and intervention combinations using signaling networks together with high-throughput data. Gradual integration of these approaches into clinical routine will improve prediction of response to standard treatments and adjustment of intervention schemes.

  10. Prediction and Validation of Promoters Involved in the Abscisic Acid Response in Physcomitrella patens

    Institute of Scientific and Technical Information of China (English)

    Gerrit Timmerhaus; Sebastian T.Hanke; Karl Buchta; Stefan A. Rensing

    2011-01-01

    Detection of cis-regulatory elements, such as transcription factor binding sites (TFBS), through utilization of ortholog conservation is possible only if genomic data from closely related organisms are available. An alternative ap-proach is the detection of TFBS based on their overrepresentation in promoters of co-regulated genes. However, this ap-proach usually suffers from a high rate of false-positive prediction. Here, we have conducted a case study using promoters of genes known to be strongly induced by the phytohormone abscisic acid (ABA)in the model plant Physcornitrella patens,a moss. Putative TFBS were detected using three de novo motif detection tools in a strict consensus approach. The resulting motifs were validated using data from microarray expression profiling and were able to predict ABA-induced genes with high specificity (90.48%)at mediocre sensitivity (33.33%). In addition, 27 genes predicted to contain ABA-responsive TFBS were validated using real-time PCR. Here, a total of 37% of the genes could be shown to be induced upon ABA treatment,while 70% were found to be regulated by ABA. We conclude that the consensus approach for motif detection using co-regulation information can be used to identify genes that are regulated under a given stimulus. In terms of evolution, we find that the ABA response has apparently been conserved since the first land plants on the level of families involved in transcriptional regulation.

  11. Predictive computational modeling of the mucosal immune responses during Helicobacter pylori infection.

    Directory of Open Access Journals (Sweden)

    Adria Carbo

    Full Text Available T helper (Th cells play a major role in the immune response and pathology at the gastric mucosa during Helicobacter pylori infection. There is a limited mechanistic understanding regarding the contributions of CD4+ T cell subsets to gastritis development during H. pylori colonization. We used two computational approaches: ordinary differential equation (ODE-based and agent-based modeling (ABM to study the mechanisms underlying cellular immune responses to H. pylori and how CD4+ T cell subsets influenced initiation, progression and outcome of disease. To calibrate the model, in vivo experimentation was performed by infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell subsets in the stomach and gastric lymph nodes (GLN on days 0, 7, 14, 30 and 60 post-infection. Our computational model reproduced the dynamics of effector and regulatory pathways in the gastric lamina propria (LP in silico. Simulation results show the induction of a Th17 response and a dominant Th1 response, together with a regulatory response characterized by high levels of mucosal Treg cells. We also investigated the potential role of peroxisome proliferator-activated receptor γ (PPARγ activation on the modulation of host responses to H. pylori by using loss-of-function approaches. Specifically, in silico results showed a predominance of Th1 and Th17 cells in the stomach of the cell-specific PPARγ knockout system when compared to the wild-type simulation. Spatio-temporal, object-oriented ABM approaches suggested similar dynamics in induction of host responses showing analogous T cell distributions to ODE modeling and facilitated tracking lesion formation. In addition, sensitivity analysis predicted a crucial contribution of Th1 and Th17 effector responses as mediators of histopathological changes in the gastric mucosa during chronic stages of infection, which were experimentally validated in mice. These integrated immunoinformatics approaches

  12. TFF3 is a valuable predictive biomarker of endocrine response in metastatic breast cancer.

    Science.gov (United States)

    May, Felicity E B; Westley, Bruce R

    2015-06-01

    The stratification of breast cancer patients for endocrine therapies by oestrogen or progesterone receptor expression is effective but imperfect. The present study aims were to validate microarray studies that demonstrate TFF3 regulation by oestrogen and its association with oestrogen receptors in breast cancer, to evaluate TFF3 as a biomarker of endocrine response, and to investigate TFF3 function. Microarray data were validated by quantitative RT-PCR and northern and western transfer analyses. TFF3 was induced by oestrogen, and its induction was inhibited by antioestrogens, tamoxifen, 4-hydroxytamoxifen and fulvestrant in oestrogen-responsive breast cancer cells. The expression of TFF3 mRNA was associated with oestrogen receptor mRNA in breast tumours (Pearson's coefficient=0.762, P=0.000). Monoclonal antibodies raised against the TFF3 protein detected TFF3 by immunohistochemistry in oesophageal submucosal glands, intestinal goblet and neuroendocrine cells, Barrett's metaplasia and intestinal metaplasia. TFF3 protein expression was associated with oestrogen receptor, progesterone receptor and TFF1 expression in malignant breast cells. TFF3 is a specific and sensitive predictive biomarker of response to endocrine therapy, degree of response and duration of response in unstratified metastatic breast cancer patients (P=0.000, P=0.002 and P=0.002 respectively). Multivariate binary logistic regression analysis demonstrated that TFF3 is an independent biomarker of endocrine response and degree of response, and this was confirmed in a validation cohort. TFF3 stimulated migration and invasion of breast cancer cells. In conclusion, TFF3 expression is associated with response to endocrine therapy, and outperforms oestrogen receptor, progesterone receptor and TFF1 as an independent biomarker, possibly because it mediates the malign effects of oestrogen on invasion and metastasis.

  13. Thymidylate Synthase as a Predictive Biomarker for Pemetrexed Response in NSCLC

    Directory of Open Access Journals (Sweden)

    Ali A. Bukhari

    2013-01-01

    Full Text Available In recent years, major strides in cancer research have made it possible to select personalized chemotherapy recommendations based on an individual patient’s tumor biology. The prognostic and/or predictive ability of biomarkers seeks to tailor the use of targeted chemotherapy and can result in improved clinical outcomes with reduced toxicity. A proliferation of new technology and pharmacotherapeutics in the setting of current FDA Clinical Laboratory Improvement Amendment (CLIA standards has resulted in a recent surge in direct-to-physician biomarker tests. However, in the absence of clinical validation, there is the concern that the biomarkers may be utilized prematurely, resulting in improper chemotherapy selection and patient harm. Thymidylate synthase (TS has been marketed as a predictive biomarker for the use of pemetrexed in NSCLC. We will examine the evidence behind the use of TS as a predictive biomarker to predict response to pemetrexed in NSCLC. At this time, the evidence does not currently support using TS assays to guide chemotherapy selection outside of a clinical research protocol.

  14. Response surface and artificial neural network prediction model and optimization for surface roughness in machining

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Sahoo

    2015-04-01

    Full Text Available The present paper deals with the development of prediction model using response surface methodology and artificial neural network and optimizes the process parameter using 3D surface plot. The experiment has been conducted using coated carbide insert in machining AISI 1040 steel under dry environment. The coefficient of determination value for RSM model is found to be high (R2 = 0.99 close to unity. It indicates the goodness of fit for the model and high significance of the model. The percentage of error for RSM model is found to be only from -2.63 to 2.47. The maximum error between ANN model and experimental lies between -1.27 and 0.02 %, which is significantly less than the RSM model. Hence, both the proposed RSM and ANN prediction model sufficiently predict the surface roughness, accurately. However, ANN prediction model seems to be better compared with RSM model. From the 3D surface plots, the optimal parametric combination for the lowest surface roughness is d1-f1-v3 i.e. depth of cut of 0.1 mm, feed of 0.04 mm/rev and cutting speed of 260 m/min respectively.

  15. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis

    Science.gov (United States)

    Sieberts, Solveig K.; Zhu, Fan; García-García, Javier; Stahl, Eli; Pratap, Abhishek; Pandey, Gaurav; Pappas, Dimitrios; Aguilar, Daniel; Anton, Bernat; Bonet, Jaume; Eksi, Ridvan; Fornés, Oriol; Guney, Emre; Li, Hongdong; Marín, Manuel Alejandro; Panwar, Bharat; Planas-Iglesias, Joan; Poglayen, Daniel; Cui, Jing; Falcao, Andre O.; Suver, Christine; Hoff, Bruce; Balagurusamy, Venkat S. K.; Dillenberger, Donna; Neto, Elias Chaibub; Norman, Thea; Aittokallio, Tero; Ammad-ud-din, Muhammad; Azencott, Chloe-Agathe; Bellón, Víctor; Boeva, Valentina; Bunte, Kerstin; Chheda, Himanshu; Cheng, Lu; Corander, Jukka; Dumontier, Michel; Goldenberg, Anna; Gopalacharyulu, Peddinti; Hajiloo, Mohsen; Hidru, Daniel; Jaiswal, Alok; Kaski, Samuel; Khalfaoui, Beyrem; Khan, Suleiman Ali; Kramer, Eric R.; Marttinen, Pekka; Mezlini, Aziz M.; Molparia, Bhuvan; Pirinen, Matti; Saarela, Janna; Samwald, Matthias; Stoven, Véronique; Tang, Hao; Tang, Jing; Torkamani, Ali; Vert, Jean-Phillipe; Wang, Bo; Wang, Tao; Wennerberg, Krister; Wineinger, Nathan E.; Xiao, Guanghua; Xie, Yang; Yeung, Rae; Zhan, Xiaowei; Zhao, Cheng; Calaza, Manuel; Elmarakeby, Haitham; Heath, Lenwood S.; Long, Quan; Moore, Jonathan D.; Opiyo, Stephen Obol; Savage, Richard S.; Zhu, Jun; Greenberg, Jeff; Kremer, Joel; Michaud, Kaleb; Barton, Anne; Coenen, Marieke; Mariette, Xavier; Miceli, Corinne; Shadick, Nancy; Weinblatt, Michael; de Vries, Niek; Tak, Paul P.; Gerlag, Danielle; Huizinga, Tom W. J.; Kurreeman, Fina; Allaart, Cornelia F.; Louis Bridges Jr., S.; Criswell, Lindsey; Moreland, Larry; Klareskog, Lars; Saevarsdottir, Saedis; Padyukov, Leonid; Gregersen, Peter K.; Friend, Stephen; Plenge, Robert; Stolovitzky, Gustavo; Oliva, Baldo; Guan, Yuanfang; Mangravite, Lara M.

    2016-01-01

    Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h2=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data. PMID:27549343

  16. Snoring Sounds Predict Obstruction Sites and Surgical Response in Patients with Obstructive Sleep Apnea Hypopnea Syndrome

    Science.gov (United States)

    Lee, Li-Ang; Lo, Yu-Lun; Yu, Jen-Fang; Lee, Gui-She; Ni, Yung-Lun; Chen, Ning-Hung; Fang, Tuan-Jen; Huang, Chung-Guei; Cheng, Wen-Nuan; Li, Hsueh-Yu

    2016-01-01

    Snoring sounds generated by different vibrators of the upper airway may be useful indicators of obstruction sites in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). This study aimed to investigate associations between snoring sounds, obstruction sites, and surgical responses (≥50% reduction in the apnea-hypopnea index [AHI] and DISE), and relocation pharyngoplasty. All patients received follow-up polysomnography after 6 months. Fifteen (42%) patients with at least two complete obstruction sites defined by DISE were significantly, positively associated with maximal snoring sound intensity (40–300 Hz; odds ratio [OR], 1.25, 95% confidence interval [CI] 1.05–1.49) and body mass index (OR, 1.48, 95% CI 1.02–2.15) after logistic regression analysis. Tonsil obstruction was significantly, inversely correlated with mean snoring sound intensity (301–850 Hz; OR, 0.84, 95% CI 0.74–0.96). Moreover, baseline tonsil obstruction detected by either DISE or mean snoring sound intensity (301–850 Hz), and AHI could significantly predict the surgical response. Our findings suggest that snoring sound detection may be helpful in determining obstruction sites and predict surgical responses. PMID:27471038

  17. Dissociation predicts treatment response in eye-movement desensitization and reprocessing for posttraumatic stress disorder.

    Science.gov (United States)

    Bae, Hwallip; Kim, Daeho; Park, Yong Chon

    2016-01-01

    Using clinical data from a specialized trauma clinic, this study investigated pretreatment clinical factors predicting response to eye-movement desensitization and reprocessing (EMDR) among adult patients diagnosed with posttraumatic stress disorder (PTSD). Participants were evaluated using the Clinician-Administered PTSD Scale (CAPS), the Symptom Checklist-90-Revised, the Beck Depression Inventory, and the Dissociative Experiences Scale before treatment and were reassessed using the CAPS after treatment and at 6-month follow-up. A total of 69 patients underwent an average of 4 sessions of EMDR, and 60 (87%) completed the posttreatment evaluation, including 8 participants who terminated treatment prematurely. Intent-to-treat analysis revealed that 39 (65%) of the 60 patients were classified as responders and 21 (35%) as nonresponders when response was defined as more than a 30% decrease in total CAPS score. The nonresponders had higher levels of dissociation (depersonalization and derealization) and numbing symptoms, but other PTSD symptoms, such as avoidance, hyperarousal, and intrusion, were not significantly different. The number of psychiatric comorbidities was also associated with treatment nonresponse. The final logistic regression model yielded 2 significant variables: dissociation (p < .001) and more than 2 comorbidities compared to none (p < .05). These results indicate that complex symptom patterns in PTSD may predict treatment response and support the inclusion of the dissociative subtype of PTSD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

  18. The effects of incidentally learned temporal and spatial predictability on response times and visual fixations during target detection and discrimination.

    Science.gov (United States)

    Beck, Melissa R; Hong, S Lee; van Lamsweerde, Amanda E; Ericson, Justin M

    2014-01-01

    Responses are quicker to predictable stimuli than if the time and place of appearance is uncertain. Studies that manipulate target predictability often involve overt cues to speed up response times. However, less is known about whether individuals will exhibit faster response times when target predictability is embedded within the inter-trial relationships. The current research examined the combined effects of spatial and temporal target predictability on reaction time (RT) and allocation of overt attention in a sustained attention task. Participants responded as quickly as possible to stimuli while their RT and eye movements were measured. Target temporal and spatial predictability were manipulated by altering the number of: 1) different time intervals between a response and the next target; and 2) possible spatial locations of the target. The effects of target predictability on target detection (Experiment 1) and target discrimination (Experiment 2) were tested. For both experiments, shorter RTs as target predictability increased across both space and time were found. In addition, the influences of spatial and temporal target predictability on RT and the overt allocation of attention were task dependent; suggesting that effective orienting of attention relies on both spatial and temporal predictability. These results indicate that stimulus predictability can be increased without overt cues and detected purely through inter-trial relationships over the course of repeated stimulus presentations.

  19. The effects of incidentally learned temporal and spatial predictability on response times and visual fixations during target detection and discrimination.

    Directory of Open Access Journals (Sweden)

    Melissa R Beck

    Full Text Available Responses are quicker to predictable stimuli than if the time and place of appearance is uncertain. Studies that manipulate target predictability often involve overt cues to speed up response times. However, less is known about whether individuals will exhibit faster response times when target predictability is embedded within the inter-trial relationships. The current research examined the combined effects of spatial and temporal target predictability on reaction time (RT and allocation of overt attention in a sustained attention task. Participants responded as quickly as possible to stimuli while their RT and eye movements were measured. Target temporal and spatial predictability were manipulated by altering the number of: 1 different time intervals between a response and the next target; and 2 possible spatial locations of the target. The effects of target predictability on target detection (Experiment 1 and target discrimination (Experiment 2 were tested. For both experiments, shorter RTs as target predictability increased across both space and time were found. In addition, the influences of spatial and temporal target predictability on RT and the overt allocation of attention were task dependent; suggesting that effective orienting of attention relies on both spatial and temporal predictability. These results indicate that stimulus predictability can be increased without overt cues and detected purely through inter-trial relationships over the course of repeated stimulus presentations.

  20. Mediofrontal event-related potentials in response to positive, negative and unsigned prediction errors.

    Science.gov (United States)

    Sambrook, Thomas D; Goslin, Jeremy

    2014-08-01

    Reinforcement learning models make use of reward prediction errors (RPEs), the difference between an expected and obtained reward. There is evidence that the brain computes RPEs, but an outstanding question is whether positive RPEs ("better than expected") and negative RPEs ("worse than expected") are represented in a single integrated system. An electrophysiological component, feedback related negativity, has been claimed to encode an RPE but its relative sensitivity to the utility of positive and negative RPEs remains unclear. This study explored the question by varying the utility of positive and negative RPEs in a design that controlled for other closely related properties of feedback and could distinguish utility from salience. It revealed a mediofrontal sensitivity to utility, for positive RPEs at 275-310ms and for negative RPEs at 310-390ms. These effects were preceded and succeeded by a response consistent with an unsigned prediction error, or "salience" coding.

  1. Beyond the effective mass approximation: predictive theory of the nonlinear optical response of conduction electrons

    CERN Document Server

    Yu, Shukai; Talbayev, Diyar

    2016-01-01

    We present an experimental and computational study of the nonlinear optical response of conduction electrons to intense terahertz (THz) electric field. Our observations (saturable absorption and an amplitude-dependent group refractive index) can be understood on the qualitative level as the breakdown of the effective mass approximation. However, a predictive theoretical description of the nonlinearity has been missing. We propose a model based on the semiclassical electron dynamics, a realistic band structure, and the free electron Drude parameters to accurately calculate the experimental observables in InSb. Our results open a path to predictive modeling of the conduction-electron optical nonlinearity in semiconductors, metamaterials, as well as high-field effects in THz plasmonics.

  2. Characterizing climate predictability and model response variability from multiple initial condition and multi-model ensembles

    CERN Document Server

    Kumar, Devashish

    2016-01-01

    Climate models are thought to solve boundary value problems unlike numerical weather prediction, which is an initial value problem. However, climate internal variability (CIV) is thought to be relatively important at near-term (0-30 year) prediction horizons, especially at higher resolutions. The recent availability of significant numbers of multi-model (MME) and multi-initial condition (MICE) ensembles allows for the first time a direct sensitivity analysis of CIV versus model response variability (MRV). Understanding the relative agreement and variability of MME and MICE ensembles for multiple regions, resolutions, and projection horizons is critical for focusing model improvements, diagnostics, and prognosis, as well as impacts, adaptation, and vulnerability studies. Here we find that CIV (MICE agreement) is lower (higher) than MRV (MME agreement) across all spatial resolutions and projection time horizons for both temperature and precipitation. However, CIV dominates MRV over higher latitudes generally an...

  3. Optimum surface roughness prediction for titanium alloy by adopting response surface methodology

    Science.gov (United States)

    Yang, Aimin; Han, Yang; Pan, Yuhang; Xing, Hongwei; Li, Jinze

    Titanium alloy has been widely applied in industrial engineering products due to its advantages of great corrosion resistance and high specific strength. This paper investigated the processing parameters for finish turning of titanium alloy TC11. Firstly, a three-factor central composite design of experiment, considering the cutting speed, feed rate and depth of cut, are conducted in titanium alloy TC11 and the corresponding surface roughness are obtained. Then a mathematic model is constructed by the response surface methodology to fit the relationship between the process parameters and the surface roughness. The prediction accuracy was verified by the one-way ANOVA. Finally, the contour line of the surface roughness under different combination of process parameters are obtained and used for the optimum surface roughness prediction. Verification experimental results demonstrated that material removal rate (MRR) at the obtained optimum can be significantly improved without sacrificing the surface roughness.

  4. Early perturbation in mitochondria redox homeostasis in response to environmental stress predicts cell fate in diatoms.

    Science.gov (United States)

    van Creveld, Shiri Graff; Rosenwasser, Shilo; Schatz, Daniella; Koren, Ilan; Vardi, Assaf

    2015-02-01

    Diatoms are ubiquitous marine photosynthetic eukaryotes that are responsible for about 20% of global photosynthesis. Nevertheless, little is known about the redox-based mechanisms that mediate diatom sensing and acclimation to environmental stress. Here we used a redox-sensitive green fluorescent protein sensor targeted to various subcellular organelles in the marine diatom Phaeodactylum tricornutum, to map the spatial and temporal oxidation patterns in response to environmental stresses. Specific organelle oxidation patterns were found in response to various stress conditions such as oxidative stress, nutrient limitation and exposure to diatom-derived infochemicals. We found a strong correlation between the mitochondrial glutathione (GSH) redox potential (EGSH) and subsequent induction of cell death in response to the diatom-derived unsaturated aldehyde 2E,4E/Z-decadienal (DD), and a volatile halocarbon (BrCN) that mediate trophic-level interactions in marine diatoms. Induction of cell death in response to DD was mediated by oxidation of mitochondrial EGSH and was reversible by application of GSH only within a narrow time frame. We found that cell fate can be accurately predicted by a distinct life-death threshold of mitochondrial EGSH (-335 mV). We propose that compartmentalized redox-based signaling can integrate the input of diverse environmental cues and will determine cell fate decisions as part of algal acclimation to stress conditions.

  5. High-resolution MRI predicts steroid injection response in carpal tunnel syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, Takatoshi; Oki, Hodaka; Kinoshita, Shunsuke; Yamashita, Yoshiko; Takahashi, Hiroyuki; Hayashida, Yoshiko; Korogi, Yukunori [University of Occupational and Environmental Health School of Medicine, Department of Radiology, Kitakyushu (Japan); Oshige, Takahisa; Sakai, Akinori [University of Occupational and Environmental Health School of Medicine, Department of Orthopaedic Surgery, Kitakyushu (Japan); Matsuyama, Atsushi; Hisaoka, Masanori [University of Occupational and Environmental Health School of Medicine, Department of Pathology and Oncology, Kitakyushu (Japan)

    2014-03-15

    To correlate median nerve T2 signal and shape at the carpal tunnel with steroid injection (SI) response in carpal tunnel syndrome (CTS) patients. One hundred and sixty-three CTS wrists of 92 consecutive patients who were scheduled to undergo SI were prospectively evaluated with 3-T magnetic resonance imaging (MRI) and a nerve conduction study. All patients underwent axial high-resolution T2-weighted MRI (in-plane resolution of 0.25 x 0.25 mm). The CTS wrists were classified into three groups according to the nerve T2 signal and the flattening ratio at the hook of hamate level: group 1, high and oval; group 2, high and flat; group 3, low and flat. Clinical response to SI was evaluated at 6 months after injection. One hundred and thirteen of the 163 wrists (69.3 %) responded well to SI. The percentage of improvement was 81.7 % (49/60) in group 1, 69.9 % (51/73) in group 2, and 43.3 % (13/30) in group 3 (P < 0.01). On stepwise logistic regression analysis high-resolution MRI was the only significant independent factor for SI response in CTS patients (P < 0.01). High-resolution MRI correlates well with SI response in CTS patients and seems useful for predicting SI response. (orig.)

  6. Pressure integration technique for predicting wind-induced response in high-rise buildings

    Directory of Open Access Journals (Sweden)

    Aly Mousaad Aly

    2013-12-01

    Full Text Available This paper presents a procedure for response prediction in high-rise buildings under wind loads. The procedure is illustrated in an application example of a tall building exposed to both cross-wind and along-wind loads. The responses of the building in the lateral directions combined with torsion are estimated simultaneously. Results show good agreement with recent design standards; however, the proposed procedure has the advantages of accounting for complex mode shapes, non-uniform mass distribution, and interference effects from the surrounding. In addition, the technique allows for the contribution of higher modes. For accurate estimation of the acceleration response, it is important to consider not only the first two lateral vibrational modes, but also higher modes. Ignoring the contribution of higher modes may lead to underestimation of the acceleration response; on the other hand, it could result in overestimation of the displacement response. Furthermore, the procedure presented in this study can help decision makers, involved in a tall building design/retrofit to choose among innovative solutions like aerodynamic mitigation, structural member size adjustment, damping enhancement, and/or materials change, with an objective to improve the resiliency and the serviceability under extreme wind actions.

  7. Predicting spike occurrence and neuronal responsiveness from LFPs in primary somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Riccardo Storchi

    Full Text Available Local Field Potentials (LFPs integrate multiple neuronal events like synaptic inputs and intracellular potentials. LFP spatiotemporal features are particularly relevant in view of their applications both in research (e.g. for understanding brain rhythms, inter-areal neural communication and neuronal coding and in the clinics (e.g. for improving invasive Brain-Machine Interface devices. However the relation between LFPs and spikes is complex and not fully understood. As spikes represent the fundamental currency of neuronal communication this gap in knowledge strongly limits our comprehension of neuronal phenomena underlying LFPs. We investigated the LFP-spike relation during tactile stimulation in primary somatosensory (S-I cortex in the rat. First we quantified how reliably LFPs and spikes code for a stimulus occurrence. Then we used the information obtained from our analyses to design a predictive model for spike occurrence based on LFP inputs. The model was endowed with a flexible meta-structure whose exact form, both in parameters and structure, was estimated by using a multi-objective optimization strategy. Our method provided a set of nonlinear simple equations that maximized the match between models and true neurons in terms of spike timings and Peri Stimulus Time Histograms. We found that both LFPs and spikes can code for stimulus occurrence with millisecond precision, showing, however, high variability. Spike patterns were predicted significantly above chance for 75% of the neurons analysed. Crucially, the level of prediction accuracy depended on the reliability in coding for the stimulus occurrence. The best predictions were obtained when both spikes and LFPs were highly responsive to the stimuli. Spike reliability is known to depend on neuron intrinsic properties (i.e. on channel noise and on spontaneous local network fluctuations. Our results suggest that the latter, measured through the LFP response variability, play a dominant role.

  8. Can a Clinical Test of Reaction Time Predict a Functional Head-Protective Response?

    Science.gov (United States)

    ECKNER, JAMES T.; LIPPS, DAVID B.; KIM, HOGENE; RICHARDSON, JAMES K.; ASHTON-MILLER, JAMES A.

    2015-01-01

    Purpose Reaction time is commonly prolonged after a sport-related concussion. Besides being a marker for injury, a rapid reaction time is necessary for protective maneuvers that can reduce the frequency and severity of additional head impacts. The purpose of this study was to determine whether a clinical test of simple visuomotor reaction time predicted the time taken to raise the hands to protect the head from a rapidly approaching ball. Methods Twenty-six healthy adult participants recruited from campus and community recreation and exercise facilities completed two experimental protocols during a single session: a manual visuomotor simple reaction time test (RTclin) and a sport-related head-protective response (RTsprt). RTclin measured the time required to catch a thin vertically oriented device on its release by the tester and was calculated from the distance the device fell before being arrested. RTsprt measured the time required to raise the hands from waist level to block a foam tennis ball fired toward the subject’s face from an air cannon and was determined using an optoelectronic camera system. A correlation coefficient was calculated between RTclin and RTsprt, with linear regression used to assess for effect modification by other covariates. Results A strong positive correlation was found between RTclin and RTsprt (r = 0.725, P < 0.001) independent of age, gender, height, or weight. Conclusions RTclin is predictive of a functional sport-related head-protective response. To our knowledge, this is the first demonstration of a clinical test predicting the ability to protect the head in a simulated sport environment. This correlation with a functional head-protective response is a relevant consideration for the potential use of RTclin as part of a multifaceted concussion assessment program. PMID:20689458

  9. Systemic Inflammatory Response and Serum Lipopolysaccharide Levels Predict Multiple Organ Failure and Death in Alcoholic Hepatitis

    Science.gov (United States)

    Michelena, Javier; Altamirano, José; Abraldes, Juan G.; Affò, Silvia; Morales-Ibanez, Oriol; Sancho-Bru, Pau; Dominguez, Marlene; García-Pagán, Juan Carlos; Fernández, Javier; Arroyo, Vicente; Ginès, Pere; Louvet, Alexandre; Mathurin, Philippe; Mehal, Wajahat Z.; Caballería, Juan; Bataller, Ramón

    2015-01-01

    Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P <0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P=0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone. Conclusion In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids. PMID:25761863

  10. Predicting potential responses to future climate in an alpine ungulate: interspecific interactions exceed climate effects.

    Science.gov (United States)

    Mason, Tom H E; Stephens, Philip A; Apollonio, Marco; Willis, Stephen G

    2014-12-01

    The altitudinal shifts of many montane populations are lagging behind climate change. Understanding habitual, daily behavioural rhythms, and their climatic and environmental influences, could shed light on the constraints on long-term upslope range-shifts. In addition, behavioural rhythms can be affected by interspecific interactions, which can ameliorate or exacerbate climate-driven effects on ecology. Here, we investigate the relative influences of ambient temperature and an interaction with domestic sheep (Ovis aries) on the altitude use and activity budgets of a mountain ungulate, the Alpine chamois (Rupicapra rupicapra). Chamois moved upslope when it was hotter but this effect was modest compared to that of the presence of sheep, to which they reacted by moving 89-103 m upslope, into an entirely novel altitudinal range. Across the European Alps, a range-shift of this magnitude corresponds to a 46% decrease in the availability of suitable foraging habitat. This highlights the importance of understanding how factors such as competition and disturbance shape a given species' realised niche when predicting potential future responses to change. Furthermore, it exposes the potential for manipulations of species interactions to ameliorate the impacts of climate change, in this case by the careful management of livestock. Such manipulations could be particularly appropriate for species where competition or disturbance already strongly restricts their available niche. Our results also reveal the potential role of behavioural flexibility in responses to climate change. Chamois reduced their activity when it was warmer, which could explain their modest altitudinal migrations. Considering this behavioural flexibility, our model predicts a small 15-30 m upslope shift by 2100 in response to climate change, less than 4% of the altitudinal shift that would be predicted using a traditional species distribution model-type approach (SDM), which assumes that species' behaviour

  11. Precise prediction model and simplified scoring system for sustained combined response to interferon-α

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To establish a predictive algorithm which may serve for selecting optimal candidates for interferon-α(IFN-α) treatment.METHODS:A total of 474 IFN-α treated hepatitis B virus e antigen(HBeAg)-positive patients were enrolled in the present study.The patients' baseline characteristics,such as age,gender,blood tests,activity grading(G) of intrahepatic inflammation,score(S) of liver fibrosis,hepatitis B virus(HBV) DNA and genotype were evaluated;therapy duration and response of each patient at the 24th wk af...

  12. Comparison between genomic predictions using daughter yield deviation and conventional estimated breeding value as response variables

    DEFF Research Database (Denmark)

    Guo, Gang; Lund, Mogens Sandø; Zhang, Y;

    2010-01-01

    This study compared genomic predictions using conventional estimated breeding values (EBV) and daughter yield deviations (DYD) as response variables based on simulated data. Eight scenarios were simulated in regard to heritability (0.05 and 0.30), number of daughters per sire (30, 100, and unequal......), the EBV and DYD approaches provided similar genomic estimated breeding value (GEBV) reliabilities, except for scenarios with unequal numbers of daughters and half of sires without genotype, for which the EBV approach was superior to the DYD approach (by 1.2 and 2.4%). Using a Bayesian mixture prior model...

  13. Ultrasound Doppler but not temporal summation of pain predicts DAS28 response in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, Anton W; Rifbjerg-Madsen, Signe; Christensen, Robin;

    2016-01-01

    them could predict the treatment response in RA. METHODS: Patients were recruited from Departments of Rheumatology in the Copenhagen area and from private clinics. RA patients, who were scheduled to initiate therapy with either a conventional synthetic DMARD (csDMARD; including DMARD-naïve patients......) or a biologic DMARD (bDMARD) agent (including bDMARD switch), were included and examined before the start of treatment and after 4 months. During the 4 months, patients received routine care from their treating rheumatologist. RESULTS: Multiple regression analysis was conducted, with change in DAS28...

  14. Measurement and Prediction of the Thermomechanical Response of Shape Memory Alloy Hybrid Composite Beams

    Science.gov (United States)

    Davis, Brian; Turner, Travis L.; Seelecke, Stefan

    2008-01-01

    An experimental and numerical investigation into the static and dynamic responses of shape memory alloy hybrid composite (SMAHC) beams is performed to provide quantitative validation of a recently commercialized numerical analysis/design tool for SMAHC structures. The SMAHC beam specimens consist of a composite matrix with embedded pre-strained SMA actuators, which act against the mechanical boundaries of the structure when thermally activated to adaptively stiffen the structure. Numerical results are produced from the numerical model as implemented into the commercial finite element code ABAQUS. A rigorous experimental investigation is undertaken to acquire high fidelity measurements including infrared thermography and projection moire interferometry for full-field temperature and displacement measurements, respectively. High fidelity numerical results are also obtained from the numerical model and include measured parameters, such as geometric imperfection and thermal load. Excellent agreement is achieved between the predicted and measured results of the static and dynamic thermomechanical response, thereby providing quantitative validation of the numerical tool.

  15. Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, M.; Jeppesen, Ulla

    2007-01-01

    The response of tumor cells to platinum-based chemotherapy involves DNA repair mechanisms. Excision repair cross-complementation group 1 (ercc1) is one of the leading genes involved in DNA repair, and several studies have linked ercc1 to platinum resistance in cell lines and in human cancers....... A common single nucleotide polymorphism (SNP) of ercc1 at codon 118 has been proposed to impair ercc1 translation and reduce ERCC1 protein expression and consequently influence the response to platinum-based chemotherapy. The primary aim of the present study was to evaluate ERCC1 expression and ercc1 codon...... 118 polymorphism in epithelial ovarian cancer (EOC) and their possible predictive value in patients treated with platinum-based chemotherapy. Formalin-fixed, paraffin-embedded tissue sections from 159 patients with advanced EOC were used for immunohistochemistry. Ercc1 codon 118 SNP genotyping...

  16. Surrogate modelling and optimization using shape-preserving response prediction: A review

    Science.gov (United States)

    Leifsson, Leifur; Koziel, Slawomir

    2016-03-01

    Computer simulation models are ubiquitous in modern engineering design. In many cases, they are the only way to evaluate a given design with sufficient fidelity. Unfortunately, an added computational expense is associated with higher fidelity models. Moreover, the systems being considered are often highly nonlinear and may feature a large number of designable parameters. Therefore, it may be impractical to solve the design problem with conventional optimization algorithms. A promising approach to alleviate these difficulties is surrogate-based optimization (SBO). Among proven SBO techniques, the methods utilizing surrogates constructed from corrected physics-based low-fidelity models are, in many cases, the most efficient. This article reviews a particular technique of this type, namely, shape-preserving response prediction (SPRP), which works on the level of the model responses to correct the underlying low-fidelity models. The formulation and limitations of SPRP are discussed. Applications to several engineering design problems are provided.

  17. Sexual selection predicts advancement of avian spring migration in response to climate change

    DEFF Research Database (Denmark)

    Spottiswoode, Claire N; Tøttrup, Anders P; Coppack, Timothy

    2006-01-01

    Global warming has led to earlier spring arrival of migratory birds, but the extent of this advancement varies greatly among species, and it remains uncertain to what degree these changes are phenotypically plastic responses or microevolutionary adaptations to changing environmental conditions. We...... with stronger female choice. We test this hypothesis comparatively by investigating the degree of long-term change in spring passage at two ringing stations in northern Europe in relation to a synthetic estimate of the strength of female choice, composed of degree of extra-pair paternity, relative testes size...... in the timing of first-arriving individuals, suggesting that selection has not only acted on protandrous males. These results suggest that sexual selection may have an impact on the responses of organisms to climate change, and knowledge of a species' mating system might help to inform attempts at predicting...

  18. Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus

    DEFF Research Database (Denmark)

    Pena, Michelle J; Heinzel, Andreas; Rossing, Peter;

    2016-01-01

    validated in patients with type 1 diabetes and macroalbuminuria (n = 50) treated with losartan 100 mg/day. Molecular process analysis was performed to link metabolites to molecular mechanisms contributing to ARB response. RESULTS: In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1...... to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria. METHODS: Liquid chromatography-tandem mass spectrometry metabolomics was performed on serum samples. Data from patients with type 2 diabetes and microalbuminuria (n = 49) treated with irbesartan 300 mg/day were used for discovery....... LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally...

  19. Earthquake Risk - SEISMIC_SHAKING_PREDICTED_RESPONSE_RP35_IN: Predicted Responses of Geologic Materials to Seismically Induced Ground Shaking (Indiana Geological Survey, 1:500,000, Polygon Shapefile)

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — SEISMIC_SHAKING_PREDICTED_RESPONSE_RP35_IN is a polygon shapefile that shows the distribution and classification of National Earthquake Hazards Reduction Program...

  20. Improving Prediction Skill of Imperfect Turbulent Models Through Statistical Response and Information Theory

    Science.gov (United States)

    Majda, Andrew J.; Qi, Di

    2016-02-01

    Turbulent dynamical systems with a large phase space and a high degree of instabilities are ubiquitous in climate science and engineering applications. Statistical uncertainty quantification (UQ) to the response to the change in forcing or uncertain initial data in such complex turbulent systems requires the use of imperfect models due to the lack of both physical understanding and the overwhelming computational demands of Monte Carlo simulation with a large-dimensional phase space. Thus, the systematic development of reduced low-order imperfect statistical models for UQ in turbulent dynamical systems is a grand challenge. This paper applies a recent mathematical strategy for calibrating imperfect models in a training phase and accurately predicting the response by combining information theory and linear statistical response theory in a systematic fashion. A systematic hierarchy of simple statistical imperfect closure schemes for UQ for these problems is designed and tested which are built through new local and global statistical energy conservation principles combined with statistical equilibrium fidelity. The forty mode Lorenz 96 (L-96) model which mimics forced baroclinic turbulence is utilized as a test bed for the calibration and predicting phases for the hierarchy of computationally cheap imperfect closure models both in the full phase space and in a reduced three-dimensional subspace containing the most energetic modes. In all of phase spaces, the nonlinear response of the true model is captured accurately for the mean and variance by the systematic closure model, while alternative methods based on the fluctuation-dissipation theorem alone are much less accurate. For reduced-order model for UQ in the three-dimensional subspace for L-96, the systematic low-order imperfect closure models coupled with the training strategy provide the highest predictive skill over other existing methods for general forced response yet have simple design principles based on a

  1. TNF-α Promoter Polymorphisms Predict the Response to Etanercept More Powerfully than that to Infliximab/Adalimumab in Spondyloarthritis.

    Science.gov (United States)

    Liu, Jing; Dong, Zheng; Zhu, Qi; He, Dongyi; Ma, Yanyun; Du, Aiping; He, Fan; Zhao, Dongbao; Xu, Xia; Zhang, Hui; Jin, Li; Wang, Jiucun

    2016-08-31

    While previous studies have researched in association analyses between TNFα promoter polymorphisms and responses to TNF blockers in spondyloarthritis patients, their results were conflicting. Therefore, we aimed to determine whether TNFα promoter polymorphisms could predict response to TNF blockers and find the source of heterogeneity. Data were extracted and analyzed from published articles and combined with our unpublished data. We found that the greatest potential sources of heterogeneity in the results were gender ratio, disease type, continents, and TNF blockers. Then Stratification analysis showed that the TNFα -308 G allele and the -238 G allele predicted a good response to TNF blockers (OR = 2.64 [1.48-4.73]; 2.52 [1.46-4.37]). However, G alleles of TNFα -308 and -238 could predict the response to etanercept (OR = 4.02 [2.24-7.23]; 5.17 [2.29-11.67]) much more powerfully than the response to infiliximab/adalimumab (OR = 1.68 [1.02-2.78]; 1.28 [0.57-2.86]). TNFα -857 could not predict the response in either subgroup. Cumulative meta-analysis performed in ankylosing spondylitis patients presented the odds ratio decreased with stricter response criteria. In conclusion, TNFα -308 A/G and -238 A/G are more powerful to predict the response to Etanercept and it is dependent on the criteria of response.

  2. The Neurodynamics of Affect in the Laboratory Predicts Persistence of Real-World Emotional Responses.

    Science.gov (United States)

    Heller, Aaron S; Fox, Andrew S; Wing, Erik K; McQuisition, Kaitlyn M; Vack, Nathan J; Davidson, Richard J

    2015-07-22

    Failure to sustain positive affect over time is a hallmark of depression and other psychopathologies, but the mechanisms supporting the ability to sustain positive emotional responses are poorly understood. Here, we investigated the neural correlates associated with the persistence of positive affect in the real world by conducting two experiments in humans: an fMRI task of reward responses and an experience-sampling task measuring emotional responses to a reward obtained in the field. The magnitude of DLPFC engagement to rewards administered in the laboratory predicted reactivity of real-world positive emotion following a reward administered in the field. Sustained ventral striatum engagement in the laboratory positively predicted the duration of real-world positive emotional responses. These results suggest that common pathways are associated with the unfolding of neural processes over seconds and with the dynamics of emotions experienced over minutes. Examining such dynamics may facilitate a better understanding of the brain-behavior associations underlying emotion. Significance statement: How real-world emotion, experienced over seconds, minutes, and hours, is instantiated in the brain over the course of milliseconds and seconds is unknown. We combined a novel, real-world experience-sampling task with fMRI to examine how individual differences in real-world emotion, experienced over minutes and hours, is subserved by affective neurodynamics of brain activity over the course of seconds. When winning money in the real world, individuals sustaining positive emotion the longest were those with the most prolonged ventral striatal activity. These results suggest that common pathways are associated with the unfolding of neural processes over seconds and with the dynamics of emotions experienced over minutes. Examining such dynamics may facilitate a better understanding of the brain-behavior associations underlying emotion.

  3. Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Aghaei, Faranak; Tan, Maxine; Liu, Hong; Zheng, Bin, E-mail: Bin.Zheng-1@ou.edu [School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma 73019 (United States); Hollingsworth, Alan B. [Mercy Women’s Center, Mercy Health Center, Oklahoma City, Oklahoma 73120 (United States); Qian, Wei [Department of Electrical and Computer Engineering, University of Texas, El Paso, Texas 79968 (United States)

    2015-11-15

    Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.

  4. Predicting blood flow responses to rhythmic handgrip exercise from one second isometric contractions.

    Science.gov (United States)

    Cook, M; Smart, N A; Van der Touw, T

    2016-11-08

    The aim of this work was to predict blood flow responses to rhythmic handgrip exercise from one second isometric contractions. Seven healthy men were studied. Each subject performed a single 1 s handgrip contraction at 10 %, 20 % and 40 % of the maximum handgrip strength. We then repeatedly summed hyperaemic responses from single contractions to predict hyperaemic response to a prolonged bout of rhythmic exercise. There was similarity between steady state brachial blood flow velocity (BBV) extrapolated from single handgrip contractions and during 2 min of rhythmic exercise for 20 % (10.0+/-3.8 cm/s vs. 10.2+/-2.6 cm/s, r=0.93, p=0.003) and 40 % of maximum contractions (14.2+/-5.5 cm/s vs. 15.6+/-3.4 cm/s, r=0.88, p=0.009), but not for 10 % (7.5+/-4.1 cm/s vs. 5.7+/-3.3 cm/s, r=0.94, p=0.018). BBV progressively rose substantially higher during rhythmic contractions than peak BBV observed during single contractions at matched intensity. Respective peak BBV during single contractions and steady state BBV rhythmic contractions were 4.4+/-2.1 and 5.7+/-3.3 cm.s(-1) at 10 % forearm strength (p=0.14), 5.6+/-2.4 and 10.2+/-2.8 cm.s(-1) at 20 % (p=0.002), and 7.0+/-2.5 and 15.6+/-3.6 cm.s(-1) at 40 % (p=0.003). In conclusion, there is similarity between the summated blood flow velocity calculated from a single 1 s muscle contraction and the steady state blood flow velocity response of rhythmic exercise.

  5. [Predict response to decitabine in patients with myelodysplastic syndrome and related neoplasms].

    Science.gov (United States)

    Zhao, Y S; Guo, J; Xu, F; Wu, D; Wu, L Y; Song, L L; Xiao, C; Li, X; Chang, C K

    2017-02-14

    Objective: To identify clinical and molecular signatures for predicting response to decitabine (DAC) in patients with myelodysplastic syndrome (MDS) and related neoplasms. Methods: The clinical characteristics of 109 patients with MDS and related neoplasms who were treated with DAC were analyzed retrospectively and the next target sequencing was performed to define recurrently mutated genes in these disease samples, to examine the association of the clinical and molecular signatures with response to DAC treatment. Results: Of 109 MDS and related neoplasms patients, there were 70 males and 39 females, the median age was 61 years old (ranges: 17-85 years old) . According to the international prognostic scoring system (IPSS) , 46 cases were included in the relatively low risk group (low risk and intermediate-1 risk) , 63 in the relative high risk group (intermediate-2 and high risk) . There were 21 cases with complex karyotype, 17 chromosome 7 abnormality and 17 monosomal karyotype. The median courses of DAC treatment was 4 (2-11) . A total of 74 patients achieved response (67.9%) and 30 (27.5%) achieved complete response (CR) . Univariate analysis found that CR was higher in patients with high risk of IPSS, complex karyotypes, monosomal karyotypes, chromosome 7 abnormality, and platelet doubling after one cycle of DAC treatment. Patients with TP53 gene mutation were more likely to receive CR, 10 of 15 patients with TP53 mutations achieved CR. (66.7%) , which was significantly higher than that of the patients without TP53 gene mutation (21.3%) (P=0.001) . Multivariate analysis showed that TP53 gene mutation, platelet doubling after one cycle of DAC treatment and the complex karyotype were independent prognostic factors for CR. Of them, TP53 gene mutation is the strongest predictor (OR=4.39, 95%CI, 1.20-16.06, P=0.026) . Conclusion: TP53 mutation, platelet doubling after one cycle of DAC treatment and complex karyotypes could predict CR to DAC.

  6. When power shapes interpersonal behavior: Low relationship power predicts men's aggressive responses to low situational power.

    Science.gov (United States)

    Overall, Nickola C; Hammond, Matthew D; McNulty, James K; Finkel, Eli J

    2016-08-01

    When does power in intimate relationships shape important interpersonal behaviors, such as psychological aggression? Five studies tested whether possessing low relationship power was associated with aggressive responses, but (a) only within power-relevant relationship interactions when situational power was low, and (b) only by men because masculinity (but not femininity) involves the possession and demonstration of power. In Studies 1 and 2, men lower in relationship power exhibited greater aggressive communication during couples' observed conflict discussions, but only when they experienced low situational power because they were unable to influence their partner. In Study 3, men lower in relationship power reported greater daily aggressive responses toward their partner, but only on days when they experienced low situational power because they were either (a) unable to influence their partner or (b) dependent on their partner for support. In Study 4, men who possessed lower relationship power exhibited greater aggressive responses during couples' support-relevant discussions, but only when they had low situational power because they needed high levels of support. Study 5 provided evidence for the theoretical mechanism underlying men's aggressive responses to low relationship power. Men who possessed lower relationship power felt less manly on days they faced low situational power because their partner was unwilling to change to resolve relationship problems, which in turn predicted greater aggressive behavior toward their partner. These results demonstrate that fully understanding when and why power is associated with interpersonal behavior requires differentiating between relationship and situational power. (PsycINFO Database Record

  7. Predicting the responsiveness of soil biodiversity to deforestation: a cross-biome study.

    Science.gov (United States)

    Crowther, Thomas W; Maynard, Daniel S; Leff, Jonathan W; Oldfield, Emily E; McCulley, Rebecca L; Fierer, Noah; Bradford, Mark A

    2014-09-01

    The consequences of deforestation for aboveground biodiversity have been a scientific and political concern for decades. In contrast, despite being a dominant component of biodiversity that is essential to the functioning of ecosystems, the responses of belowground biodiversity to forest removal have received less attention. Single-site studies suggest that soil microbes can be highly responsive to forest removal, but responses are highly variable, with negligible effects in some regions. Using high throughput sequencing, we characterize the effects of deforestation on microbial communities across multiple biomes and explore what determines the vulnerability of microbial communities to this vegetative change. We reveal consistent directional trends in the microbial community response, yet the magnitude of this vegetation effect varied between sites, and was explained strongly by soil texture. In sandy sites, the difference in vegetation type caused shifts in a suite of edaphic characteristics, driving substantial differences in microbial community composition. In contrast, fine-textured soil buffered microbes against these effects and there were minimal differences between communities in forest and grassland soil. These microbial community changes were associated with distinct changes in the microbial catabolic profile, placing community changes in an ecosystem functioning context. The universal nature of these patterns allows us to predict where deforestation will have the strongest effects on soil biodiversity, and how these effects could be mitigated.

  8. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.

    Directory of Open Access Journals (Sweden)

    Howard Y Chang

    2004-02-01

    Full Text Available Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are unclear. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. The genes comprising this fibroblast common serum response are coordinately regulated in many human tumors, allowing us to identify tumors with gene expression signatures suggestive of active wounds. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. The molecular features that define this wound-like phenotype are evident at an early clinical stage, persist during treatment, and predict increased risk of metastasis and death in breast, lung, and gastric carcinomas. Thus, the transcriptional signature of the response of fibroblasts to serum provides a possible link between cancer progression and wound healing, as well as a powerful predictor of the clinical course in several common carcinomas.

  9. Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy

    Institute of Scientific and Technical Information of China (English)

    Sawako Taji; Masuji Morita; Masafumi Taniwaki; Kenichi Nomura; Yosuke Matsumoto; Hideaki Sakabe; Naohisa Yoshida; Shoji Mitsufuji; Kazuhiro Nishida; Shigeo Horiike; Shigeo Nakamura

    2005-01-01

    AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosaassociated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy.METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy,the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissuefluorescence in situ hybridization (FISH), using chromosomespecific α-satellite DNA probes for chromosomes 3,7,12,and 18 and YAC clones for t(11;18)(q21;q21).RESULTS: Seven of the 13 patients had complete regression(CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients.CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.

  10. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy.

    Science.gov (United States)

    Beck, Laurence H; Fervenza, Fernando C; Beck, David M; Bonegio, Ramon G B; Malik, Fahim A; Erickson, Stephen B; Cosio, Fernando G; Cattran, Daniel C; Salant, David J

    2011-08-01

    Autoantibodies to the M-type phospholipase A(2) receptor (PLA(2)R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA(2)R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria. We measured the amount of anti-PLA(2)R using Western blot immunoassay in serial serum samples from a total of 35 patients treated with rituximab for membranous nephropathy in two distinct cohorts. Pretreatment samples from 25 of 35 (71%) patients contained anti-PLA(2)R, and these autoantibodies declined or disappeared in 17 (68%) of these patients within 12 months after rituximab. Those who demonstrated this immunologic response fared better clinically: 59% and 88% attained complete or partial remission by 12 and 24 months, respectively, compared with 0% and 33% among those with persistent anti-PLA(2)R levels. Changes in antibody levels preceded changes in proteinuria. One subject who relapsed during follow-up had a concomitant return of anti-PLA(2)R. In summary, measuring anti-PLA(2)R levels by immunoassay may be a method to follow and predict response to treatment with rituximab in membranous nephropathy.

  11. In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease.

    Science.gov (United States)

    Atreya, Raja; Neumann, Helmut; Neufert, Clemens; Waldner, Maximilian J; Billmeier, Ulrike; Zopf, Yurdagül; Willma, Marcus; App, Christine; Münster, Tino; Kessler, Hermann; Maas, Stefanie; Gebhardt, Bernd; Heimke-Brinck, Ralph; Reuter, Eva; Dörje, Frank; Rau, Tilman T; Uter, Wolfgang; Wang, Thomas D; Kiesslich, Ralf; Vieth, Michael; Hannappel, Ewald; Neurath, Markus F

    2014-03-01

    As antibodies to tumor necrosis factor (TNF) suppress immune responses in Crohn's disease by binding to membrane-bound TNF (mTNF), we created a fluorescent antibody for molecular mTNF imaging in this disease. Topical antibody administration in 25 patients with Crohn's disease led to detection of intestinal mTNF(+) immune cells during confocal laser endomicroscopy. Patients with high numbers of mTNF(+) cells showed significantly higher short-term response rates (92%) at week 12 upon subsequent anti-TNF therapy as compared to patients with low amounts of mTNF(+) cells (15%). This clinical response in the former patients was sustained over a follow-up period of 1 year and was associated with mucosal healing observed in follow-up endoscopy. These data indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatment and can be used for personalized medicine in Crohn's disease and autoimmune or inflammatory disorders.

  12. Neutrophil-to-Lymphocyte Ratio for Predicting Loss of Response to Infliximab in Ulcerative Colitis

    Science.gov (United States)

    Nishida, Yu; Yamagami, Hirokazu; Yukawa, Tomomi; Otani, Koji; Nagami, Yasuaki; Tanaka, Fumio; Taira, Koichi; Kamata, Noriko; Tanigawa, Tetsuya; Shiba, Masatsugu; Watanabe, Kenji; Watanabe, Toshio; Tominaga, Kazunari; Fujiwara, Yasuhiro

    2017-01-01

    Objectives Neutrophil-to-lymphocyte ratio (NLR) has been used to determine the outcome in malignancies and coronary heart disease. Some reports considered the value of NLR as a predictor of response to infliximab in patients with Crohn’s disease or rheumatoid arthritis; however, no similar studies have been reported for ulcerative colitis (UC). This study aimed to evaluate the clinical significance of the baseline NLR in patients with UC treated by infliximab. Materials and Methods Patients with moderate-to-severe active UC who received the first infliximab infusion in our hospital between 2010 and 2015, who showed clinical response during the induction period, were retrospectively evaluated for long-term outcomes and risk factors for loss of response (LOR) during infliximab maintenance therapy. Baseline inflammatory markers including NLR were measured within one week before the initiation of infliximab. Results Fifty-nine patients with moderate-to-severe active UC started treatment with infliximab and 37 patients (62.7%) experienced clinical response after induction therapy. Fourteen of 37 patients on maintenance therapy lost the response during follow-up. Baseline NLR of patients with LOR was significantly higher than in patients with sustained response. The NLR cut-off value of 4.488 was predictive of LOR, using receiver operating characteristic analysis (sensitivity: 78.6%, specificity: 78.3%). A univariate analysis revealed a significant relationship between relapse-free survival and the NLR (P = 0.018). Multivariate analysis indicated the NLR as an independent prognostic factor for LOR (hazard ratio = 3.86, 95% confidence interval: 1.20–12.4, P = 0.023). Conclusions Baseline NLR is a useful prognostic marker in patients with moderate-to-severe active UC treated with infliximab, and may contribute to appropriate use of infliximab. PMID:28076386

  13. Prediction

    CERN Document Server

    Sornette, Didier

    2010-01-01

    This chapter first presents a rather personal view of some different aspects of predictability, going in crescendo from simple linear systems to high-dimensional nonlinear systems with stochastic forcing, which exhibit emergent properties such as phase transitions and regime shifts. Then, a detailed correspondence between the phenomenology of earthquakes, financial crashes and epileptic seizures is offered. The presented statistical evidence provides the substance of a general phase diagram for understanding the many facets of the spatio-temporal organization of these systems. A key insight is to organize the evidence and mechanisms in terms of two summarizing measures: (i) amplitude of disorder or heterogeneity in the system and (ii) level of coupling or interaction strength among the system's components. On the basis of the recently identified remarkable correspondence between earthquakes and seizures, we present detailed information on a class of stochastic point processes that has been found to be particu...

  14. A Framework for Prediction of Response to HCV Therapy Using Different Data Mining Techniques

    Directory of Open Access Journals (Sweden)

    Enas M. F. El Houby

    2014-01-01

    Full Text Available Hepatitis C which is a widely spread disease all over the world is a fatal liver disease caused by Hepatitis C Virus (HCV. The only approved therapy is interferon plus ribavirin. The number of responders to this treatment is low, while its cost is high and side effects are undesirable. Treatment response prediction will help in reducing the patients who suffer from the side effects and high costs without achieving recovery. The aim of this research is to develop a framework which can select the best model to predict HCV patients’ response to the treatment of HCV from clinical information. The framework contains three phases which are preprocessing phase to prepare the data for applying Data Mining (DM techniques, DM phase to apply different DM techniques, and evaluation phase to evaluate and compare the performance of the built models and select the best model as the recommended one. Different DM techniques had been applied which are associative classification, artificial neural network, and decision tree to evaluate the framework. The experimental results showed the effectiveness of the framework in selecting the best model which is the model built by associative classification using histology activity index, fibrosis stage, and alanine amino transferase.

  15. EEG biomarkers in major depressive disorder: discriminative power and prediction of treatment response.

    Science.gov (United States)

    Olbrich, Sebastian; Arns, Martijn

    2013-10-01

    Major depressive disorder (MDD) has high population prevalence and is associated with substantial impact on quality of life, not least due to an unsatisfactory time span of sometimes several weeks from initiation of treatment to clinical response. Therefore extensive research focused on the identification of cost-effective and widely available electroencephalogram (EEG)-based biomarkers that not only allow distinguishing between patients and healthy controls but also have predictive value for treatment response for a variety of treatments. In this comprehensive overview on EEG research on MDD, biomarkers that are either assessed at baseline or during the early course of treatment and are helpful in discriminating patients from healthy controls and assist in predicting treatment outcome are reviewed, covering recent decades up to now. Reviewed markers include quantitative EEG (QEEG) measures, connectivity measures, EEG vigilance-based measures, sleep-EEG-related measures and event-related potentials (ERPs). Further, the value and limitations of these different markers are discussed. Finally, the need for integrated models of brain function and the necessity for standardized procedures in EEG biomarker research are highlighted to enhance future research in this field.

  16. EGFR expression level predicts response and overall survival in gastric cancer PDTX model treated with cetuximab

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective:hTe aim of this study was to determine whether the EGFR statuscould significantly predict some benefit in overall survival and response to cetuximab in advanced GC xenografts.Methods: Two hundred xenografts derived from 20 GC patients were established. Then they were divided into cetuximab treated group and control group randomly.Results:Among the cetuximab treated group, 4 GC cases were identified responded to cetuximab.hTose cetuximab treated PDX models had longer OS than non-treated. High EGFR mRNA expression and immunohistochemistry score are more prone to response to cetuximab. EGFR amplification, mRNA and protein overexpression were associated with the OS in cetuximab treated PDX models. Moreover, in the PDX models derived from EGFR ampliifcation, mRNA or protein overexpression cases, the OS is signiifcantly different between the cetuximab treated and control group, while the OS in not statistically different in other cases.Conclusion:EGFR status predicts sensitivity to therapy and survival in GC treated with cetuximab, especially the mRNA and protein expression level.

  17. The cortisol response to anticipated intergroup interactions predicts self-reported prejudice.

    Directory of Open Access Journals (Sweden)

    Erik Bijleveld

    Full Text Available OBJECTIVES: While prejudice has often been shown to be rooted in experiences of threat, the biological underpinnings of this threat-prejudice association have received less research attention. The present experiment aims to test whether activations of the hypothalamus-pituitary-adrenal (HPA axis, due to anticipated interactions with out-group members, predict self-reported prejudice. Moreover, we explore potential moderators of this relationship (i.e., interpersonal similarity; subtle vs. blatant prejudice. METHODOLOGY/PRINCIPAL FINDINGS: Participants anticipated an interaction with an out-group member who was similar or dissimilar to the self. To index HPA activation, cortisol responses to this event were measured. Then, subtle and blatant prejudices were measured via questionnaires. Findings indicated that only when people anticipated an interaction with an out-group member who was dissimilar to the self, their cortisol response to this event significantly predicted subtle (r = .50 and blatant (r = .53 prejudice. CONCLUSIONS: These findings indicate that prejudicial attitudes are linked to HPA-axis activity. Furthermore, when intergroup interactions are interpreted to be about individuals (and not so much about groups, experienced threat (or its biological substrate is less likely to relate to prejudice. This conclusion is discussed in terms of recent insights from social neuroscience.

  18. Final Scientific Technical Report: INTEGRATED PREDICTIVE DEMAND RESPONSE CONTROLLER FOR COMMERCIAL BUILDINGS

    Energy Technology Data Exchange (ETDEWEB)

    Wenzel, Mike

    2013-10-14

    This project provides algorithms to perform demand response using the thermal mass of a building. Using the thermal mass of the building is an attractive method for performing demand response because there is no need for capital expenditure. The algorithms rely on the thermal capacitance inherent in the building?s construction materials. A near-optimal ?day ahead? predictive approach is developed that is meant to keep the building?s electrical demand constant during the high cost periods. This type of approach is appropriate for both time-of-use and critical peak pricing utility rate structures. The approach uses the past days data in order to determine the best temperature setpoints for the building during the high price periods on the next day. A second ?model predictive approach? (MPC) uses a thermal model of the building to determine the best temperature for the next sample period. The approach uses constant feedback from the building and is capable of appropriately handling real time pricing. Both approaches are capable of using weather forecasts to improve performance.

  19. ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Miao Yun

    Full Text Available Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC method in two independent cohorts of nasopharygeal carcinoma (NPC cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS (P<0.05. Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response could significantly stratify risk (low, intermediate and high for DSS in NPC patients (P<0.001. These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

  20. Prediction of the mechanical response of the femur with uncertain elastic properties.

    Science.gov (United States)

    Wille, Hagen; Rank, Ernst; Yosibash, Zohar

    2012-04-30

    A mandatory requirement for any reliable prediction of the mechanical response of bones, based on quantitative computer tomography, is an accurate relationship between material properties (usually Young's modulus E) and bone density ρ. Many such E-ρ relationships are available based on different experiments on femur specimens with a large spread due to uncertainties. The first goal of this study is to pool and analyze the relevant available experimental data and develop a stochasticE-ρ relationship. This analysis highlights that there is no experimental data available to cover the entire density range of the human femur and that some "popular" E-ρ relationships are based on data that contains extreme scatter, while others are based on a very limited amount of information. The second goal is to use the newly developed stochastic E-ρ relationship in high-order finite element analyses (FEAs) for the computation of strains and displacements in two human proximal femurs, mimicking in vitro experiments. When compared with the experimental observations, the FEA predictions using the median of the stochastic E-ρ relationship follow the underlying distribution of the stochastic E-ρ relationship. Thus, most deviations of the FEA predictions from experimental observations can possibly be explained by uncertain elastic properties of the femur.

  1. Adolescent neighborhood quality predicts adult dACC response to social exclusion.

    Science.gov (United States)

    Gonzalez, Marlen Z; Beckes, Lane; Chango, Joanna; Allen, Joseph P; Coan, James A

    2015-07-01

    Neuroimaging studies using the social-exclusion paradigm Cyberball indicate increased dorsal anterior cingulate cortex (dACC) and right insula activity as a function of exclusion. However, comparatively less work has been done on how social status factors may moderate this finding. This study used the Cyberball paradigm with 85 (45 females) socio-economically diverse participants from a larger longitudinal sample. We tested whether neighborhood quality during adolescence would predict subsequent neural responding to social exclusion in young adulthood. Given previous behavioral studies indicating greater social vigilance and negative evaluation as a function of lower status, we expected that lower adolescent neighborhood quality would predict greater dACC activity during exclusion at young adulthood. Our findings indicate that young adults who lived in low-quality neighborhoods in adolescence showed greater dACC activity to social exclusion than those who lived in higher quality neighborhoods. Lower neighborhood quality also predicted greater prefrontal activation in the superior frontal gyrus, dorsal medial prefrontal cortex and the middle frontal gyrus, possibly indicating greater regulatory effort. Finally, this effect was not driven by subsequent ratings of distress during exclusion. In sum, adolescent neighborhood quality appears to potentiate neural responses to social exclusion in young adulthood, effects that are independent of felt distress.

  2. Response-predictive gene expression profiling of glioma progenitor cells in vitro.

    Directory of Open Access Journals (Sweden)

    Sylvia Moeckel

    Full Text Available BACKGROUND: High-grade gliomas are amongst the most deadly human tumors. Treatment results are disappointing. Still, in several trials around 20% of patients respond to therapy. To date, diagnostic strategies to identify patients that will profit from a specific therapy do not exist. METHODS: In this study, we used serum-free short-term treated in vitro cell cultures to predict treatment response in vitro. This approach allowed us (a to enrich specimens for brain tumor initiating cells and (b to confront cells with a therapeutic agent before expression profiling. RESULTS: As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed to predict therapy-induced impairment of proliferation in vitro. CONCLUSION: For the tyrosine kinase inhibitor Sunitinib used in this dataset, the approach revealed additional predictive information in comparison to the evaluation of classical signaling analysis.

  3. Non-invasive prediction of blood lactate response to constant power outputs from incremental exercise tests.

    Science.gov (United States)

    Sullivan, C S; Casaburi, R; Storer, T W; Wasserman, K

    1995-01-01

    We determined the ability of gas exchange analyses during incremental exercise tests (IXT) to predict blood lactate levels associated with a range of constant power output cycle ergometer tests. Twenty-seven healthy young men performed duplicate IXT and four 15-min constant power output tests at intensities ranging from moderate to very severe, before and after a training program. End-exercise blood lactate levels were approximated from superficial venous samples obtained 60 s after each constant power output test. From IXT, the power outputs corresponding to peak oxygen uptake (Wmax) and lactic acidosis threshold (WLAT), were determined. We examined the ability of four measures of exercise intensity to predict blood lactate levels for power outputs above the LAT: (1) power output (W), (2) power difference (W-WLAT), (3) power fraction (W/Wmax) and (4) power difference to delta ratio [(W-WLAT)/(Wmax-WLAT)]. Correlation coefficients were r = 0.38, 0.69, 0.75, and 0.81, respectively. The best linear regression prediction equation was: lactate (mmol.l-1) = 12.2[(W-WLAT)/(Wmax-WLAT)] + 0.7 mmol.l-1. This relationship was not significantly affected by training, despite increased values of LAT and peak oxygen uptake. Normalizing exercise intensity to the range of power outputs between WLAT and Wmax provided an estimate of blood lactate response to constant power outputs with a standard error of the estimate of 1.66 mmol.l-1.

  4. Exploring the Inflammatory Metabolomic Profile to Predict Response to TNF-α Inhibitors in Rheumatoid Arthritis.

    Science.gov (United States)

    Cuppen, Bart V J; Fu, Junzeng; van Wietmarschen, Herman A; Harms, Amy C; Koval, Slavik; Marijnissen, Anne C A; Peeters, Judith J W; Bijlsma, Johannes W J; Tekstra, Janneke; van Laar, Jacob M; Hankemeier, Thomas; Lafeber, Floris P J G; van der Greef, Jan

    2016-01-01

    In clinical practice, approximately one-third of patients with rheumatoid arthritis (RA) respond insufficiently to TNF-α inhibitors (TNFis). The aim of the study was to explore the use of a metabolomics to identify predictors for the outcome of TNFi therapy, and study the metabolomic fingerprint in active RA irrespective of patients' response. In the metabolomic profiling, lipids, oxylipins, and amines were measured in serum samples of RA patients from the observational BiOCURA cohort, before start of biological treatment. Multivariable logistic regression models were established to identify predictors for good- and non-response in patients receiving TNFi (n = 124). The added value of metabolites over prediction using clinical parameters only was determined by comparing the area under receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, positive- and negative predictive value and by the net reclassification index (NRI). The models were further validated by 10-fold cross validation and tested on the complete TNFi treatment cohort including moderate responders. Additionally, metabolites were identified that cross-sectionally associated with the RA disease activity score based on a 28-joint count (DAS28), erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Out of 139 metabolites, the best-performing predictors were sn1-LPC(18:3-ω3/ω6), sn1-LPC(15:0), ethanolamine, and lysine. The model that combined the selected metabolites with clinical parameters showed a significant larger AUC-ROC than that of the model containing only clinical parameters (p = 0.01). The combined model was able to discriminate good- and non-responders with good accuracy and to reclassify non-responders with an improvement of 30% (total NRI = 0.23) and showed a prediction error of 0.27. For the complete TNFi cohort, the NRI was 0.22. In addition, 88 metabolites were associated with DAS28, ESR or CRP (p<0.05). Our study established an accurate prediction model

  5. Global DNA methylation is altered by neoadjuvant chemoradiotherapy in rectal cancer and may predict response to treatment - A pilot study.

    LENUS (Irish Health Repository)

    Tsang, J S

    2014-07-28

    In rectal cancer, not all tumours display a response to neoadjuvant treatment. An accurate predictor of response does not exist to guide patient-specific treatment. DNA methylation is a distinctive molecular pathway in colorectal carcinogenesis. Whether DNA methylation is altered by neoadjuvant treatment and a potential response predictor is unknown. We aimed to determine whether DNA methylation is altered by neoadjuvant chemoradiotherapy (CRT) and to determine its role in predicting response to treatment.

  6. Preoperative neutrophil response as a predictive marker of clinical outcome following open heart surgery and the impact of leukocyte filtration.

    LENUS (Irish Health Repository)

    Soo, Alan W

    2010-11-01

    Open heart surgery is associated with a massive systemic inflammatory response. Neutrophils, are the main mediator of this response. We hypothesised that the degree of neutrophil activation and inflammatory response to open heart surgery varies individually and correlates with clinical outcome. The aim of this study was to determine if individual clinical outcome can be predicted preoperatively through assessment of in-vitro stimulated neutrophil responses. Following that, the effects of neutrophil depletion through leukocyte filters are examined.

  7. An electrically actuated imperfect microbeam: Dynamical integrity for interpreting and predicting the device response

    KAUST Repository

    Ruzziconi, Laura

    2013-02-20

    In this study we deal with a microelectromechanical system (MEMS) and develop a dynamical integrity analysis to interpret and predict the experimental response. The device consists of a clamped-clamped polysilicon microbeam, which is electrostatically and electrodynamically actuated. It has non-negligible imperfections, which are a typical consequence of the microfabrication process. A single-mode reduced-order model is derived and extensive numerical simulations are performed in a neighborhood of the first symmetric natural frequency, via frequency response diagrams and behavior chart. The typical softening behavior is observed and the overall scenario is explored, when both the frequency and the electrodynamic voltage are varied. We show that simulations based on direct numerical integration of the equation of motion in time yield satisfactory agreement with the experimental data. Nevertheless, these theoretical predictions are not completely fulfilled in some aspects. In particular, the range of existence of each attractor is smaller in practice than in the simulations. This is because these theoretical curves represent the ideal limit case where disturbances are absent, which never occurs under realistic conditions. A reliable prediction of the actual (and not only theoretical) range of existence of each attractor is essential in applications. To overcome this discrepancy and extend the results to the practical case where disturbances exist, a dynamical integrity analysis is developed. After introducing dynamical integrity concepts, integrity profiles and integrity charts are drawn. They are able to describe if each attractor is robust enough to tolerate the disturbances. Moreover, they detect the parameter range where each branch can be reliably observed in practice and where, instead, becomes vulnerable, i.e. they provide valuable information to operate the device in safe conditions according to the desired outcome and depending on the expected disturbances

  8. Applying dynamic parameters to predict hemodynamic response to volume expansion in spontaneously breathing patients with septic shock.

    Science.gov (United States)

    Lanspa, Michael J; Grissom, Colin K; Hirshberg, Eliotte L; Jones, Jason P; Brown, Samuel M

    2013-02-01

    Volume expansion is a mainstay of therapy in septic shock, although its effect is difficult to predict using conventional measurements. Dynamic parameters, which vary with respiratory changes, appear to predict hemodynamic response to fluid challenge in mechanically ventilated, paralyzed patients. Whether they predict response in patients who are free from mechanical ventilation is unknown. We hypothesized that dynamic parameters would be predictive in patients not receiving mechanical ventilation. This is a prospective, observational, pilot study. Patients with early septic shock and who were not receiving mechanical ventilation received 10-mL/kg volume expansion (VE) at their treating physician's discretion after initial resuscitation in the emergency department. We used transthoracic echocardiography to measure vena cava collapsibility index and aortic velocity variation before VE. We used a pulse contour analysis device to measure stroke volume variation (SVV). Cardiac index was measured immediately before and after VE using transthoracic echocardiography. Hemodynamic response was defined as an increase in cardiac index 15% or greater. Fourteen patients received VE, five of whom demonstrated a hemodynamic response. Vena cava collapsibility index and SVV were predictive (area under the curve = 0.83, 0.92, respectively). Optimal thresholds were calculated: vena cava collapsibility index, 15% or greater (positive predictive value, 62%; negative predictive value, 100%; P = 0.03); SVV, 17% or greater (positive predictive value 100%, negative predictive value 82%, P = 0.03). Aortic velocity variation was not predictive. Vena cava collapsibility index and SVV predict hemodynamic response to fluid challenge patients with septic shock who are not mechanically ventilated. Optimal thresholds differ from those described in mechanically ventilated patients.

  9. Prognostic and Predictive Biomarkers of Endocrine Responsiveness for Estrogen Receptor Positive Breast Cancer.

    Science.gov (United States)

    Ma, Cynthia X; Bose, Ron; Ellis, Matthew J

    2016-01-01

    The estrogen-dependent nature of breast cancer is the fundamental basis for endocrine therapy. The presence of estrogen receptor (ER), the therapeutic target of endocrine therapy, is a prerequisite for this therapeutic approach. However, estrogen-independent growth often exists de novo at diagnosis or develops during the course of endocrine therapy. Therefore ER alone is insufficient in predicting endocrine therapy efficacy. Several RNA-based multigene assays are now available in clinical practice to assess distant recurrence risk, with majority of these assays evaluated in patients treated with 5 years of adjuvant endocrine therapy. While MammaPrint and Oncotype Dx are most predictive of recurrence risk within the first 5 years of diagnosis, Prosigna, Breast Cancer Index (BCI), and EndoPredict Clin have also demonstrated utility in predicting late recurrence. In addition, PAM50, or Prosigna, provides further biological insights by classifying breast cancers into intrinsic molecular subtypes. Additional strategies are under investigation in prospective clinical trials to differentiate endocrine sensitive and resistant tumors and include on-treatment Ki-67 and Preoperative Endocrine Prognostic Index (PEPI) score in the setting of neoadjuvant endocrine therapy. These biomarkers have become important tools in clinical practice for the identification of low risk patients for whom chemotherapy could be avoided. However, there is much work ahead toward the development of a molecular classification that informs the biology and novel therapeutic targets in high-risk disease as chemotherapy has only modest benefit in this population. The recognition of somatic mutations and their relationship to endocrine therapy responsiveness opens important opportunities toward this goal.

  10. [{sup 18}F]FDG-PET predicts complete pathological response of breast cancer to neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Berriolo-Riedinger, Alina; Touzery, Claude; Riedinger, Jean-Marc; Toubeau, Michel; Boichot, Christophe; Cochet, Alexandre [Centre Georges Francois Leclerc, Department of Nuclear Medicine, Dijon (France); Coudert, Bruno; Fumoleau, Pierre [Centre Georges Francois Leclerc, Department of Medical Oncology, Dijon (France); Arnould, Laurent [Centre Georges Francois Leclerc, Department of Pathology, Dijon (France); Brunotte, Francois [Centre Georges Francois Leclerc, Department of Nuclear Medicine, Dijon (France); CNRS UMR 5158, Dijon (France)

    2007-12-15

    To evaluate, in breast cancer patients treated by neoadjuvant chemotherapy, the predictive value of reduction in FDG uptake with regard to complete pathological response (pCR). Forty-seven women with non-metastatic, non-inflammatory, large or locally advanced breast cancer were included. Tumour uptake of FDG was evaluated before and after the first course of neoadjuvant chemotherapy. Four indices were used: maximal and average SUV without or with correction by body surface area and glycaemia (SUV{sub max}, SUV{sub avg}, SUV{sub max-BSA-G} and SUV{sub avg-BSA-G}, respectively). The predictive value of reduction in FDG uptake with respect to pCR was studied by logistic regression analysis. Relationships between baseline [{sup 18}F]FDG uptake and prognostic parameters were assessed. The relative decrease in FDG uptake ({delta}SUV) after the first course of neoadjuvant chemotherapy was significantly greater in the pCR group than in the non-pCR group (p < 0.000066). The four FDG uptake indices were all strongly correlated with each other. A decrease in SUV{sub max-BSA-G} of 85.4% {+-} 21.9% was found in pCR patients, versus 22.6% {+-} 36.6% in non-pCR patients. {delta}SUV{sub max-BSA-G} <-60% predicted the pCR with an accuracy of 87% and {delta}SUVs were found to be only factors predictive of the pCR at multivariate analysis. An elevated baseline SUV was associated with high mitotic activity (p < 0.0016), tumour grading (p < 0.004), high nuclear pleomorphism score (p < 0.03) and negative hormonal receptor status (p < 0.005). In breast cancer patients, after only one course of neoadjuvant chemotherapy the reduction in FDG uptake is an early and powerful predictor of pCR. (orig.)

  11. Predicting the profile of nutrients available for absorption: from nutrient requirement to animal response and environmental impact

    OpenAIRE

    Dijkstra, J.; Kebreab, E; Mills, J.A.N.; Pellikaan, W.F.; López, S.; Bannink, A; France, J.

    2007-01-01

    Current feed evaluation systems for dairy cattle aim to match nutrient requirements with nutrient intake at pre-defined production levels. These systems were not developed to address, and are not suitable to predict, the responses to dietary changes in terms of production level and product composition, excretion of nutrients to the environment, and nutrition related disorders. The change from a requirement to a response system to meet the needs of various stakeholders requires prediction of t...

  12. Implicit learning of predictable sound sequences modulates human brain responses at different levels of the auditory hierarchy

    Directory of Open Access Journals (Sweden)

    Françoise eLecaignard

    2015-09-01

    Full Text Available Deviant stimuli, violating regularities in a sensory environment, elicit the Mismatch Negativity (MMN, largely described in the Event-Related Potential literature. While it is widely accepted that the MMN reflects more than basic change detection, a comprehensive description of mental processes modulating this response is still lacking. Within the framework of predictive coding, deviance processing is part of an inference process where prediction errors (the mismatch between incoming sensations and predictions established through experience are minimized. In this view, the MMN is a measure of prediction error, which yields specific expectations regarding its modulations by various experimental factors. In particular, it predicts that the MMN should decrease as the occurrence of a deviance becomes more predictable. We conducted a passive oddball EEG study and manipulated the predictability of sound sequences by means of different temporal structures. Importantly, our design allows comparing mismatch responses elicited by predictable and unpredictable violations of a simple repetition rule and therefore departs from previous studies that investigate violations of different time-scale regularities. We observed a decrease of the MMN with predictability and interestingly, a similar effect at earlier latencies, within 70 ms after deviance onset. Following these pre-attentive responses, a reduced P3a was measured in the case of predictable deviants. We conclude that early and late deviance responses reflect prediction errors, triggering belief updating within the auditory hierarchy. Beside, in this passive study, such perceptual inference appears to be modulated by higher-level implicit learning of sequence statistical structures. Our findings argue for a hierarchical model of auditory processing where predictive coding enables implicit extraction of environmental regularities.

  13. A Comparison of Sales Response Predictions From Demand Models Applied to Store-Level versus Panel Data

    NARCIS (Netherlands)

    Andrews, Rick L.; Currim, Imran S.; Leeflang, Peter S. H.

    2011-01-01

    In order to generate sales promotion response predictions, marketing analysts estimate demand models using either disaggregated (consumer-level) or aggregated (store-level) scanner data. Comparison of predictions from these demand models is complicated by the fact that models may accommodate differe

  14. Life-history traits predict perennial species response to fire in a desert ecosystem

    Science.gov (United States)

    Shryock, Daniel F.; DeFalco, Lesley A.; Esque, Todd C.

    2014-01-01

    The Mojave Desert of North America has become fire-prone in recent decades due to invasive annual grasses that fuel wildfires following years of high rainfall. Perennial species are poorly adapted to fire in this system, and post-fire shifts in species composition have been substantial but variable across community types. To generalize across a range of conditions, we investigated whether simple life-history traits could predict how species responded to fire. Further, we classified species into plant functional types (PFTs) based on combinations of life-history traits and evaluated whether these groups exhibited a consistent fire-response. Six life-history traits varied significantly between burned and unburned areas in short (up to 4 years) or long-term (up to 52 years) post-fire datasets, including growth form, lifespan, seed size, seed dispersal, height, and leaf longevity. Forbs and grasses consistently increased in abundance after fire, while cacti were reduced and woody species exhibited a variable response. Woody species were classified into three PFTs based on combinations of life-history traits. Species in Group 1 increased in abundance after fire and were characterized by short lifespans, small, wind-dispersed seeds, low height, and deciduous leaves. Species in Group 2 were reduced by fire and distinguished from Group 1 by longer lifespans and evergreen leaves. Group 3 species, which also decreased after fire, were characterized by long lifespans, large non-wind dispersed seeds, and taller heights. Our results show that PFTs based on life-history traits can reliably predict the responses of most species to fire in the Mojave Desert. Dominant, long-lived species of this region possess a combination of traits limiting their ability to recover, presenting a clear example of how a novel disturbance regime may shift selective environmental pressures to favor alternative life-history strategies.

  15. Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

    Science.gov (United States)

    Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2015-12-01

    Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972.

  16. Left ventricular 12 segmental strain imaging predicts response to cardiac resynchronization therapy

    Institute of Scientific and Technical Information of China (English)

    DONG Ying-xue; Jae K.Oh; YANG Yan-zong; Yong-mei Cha

    2013-01-01

    Background The number of non-responders to cardiac resynchronization therapy (CRT) exposes the need for better patient selection criteria for CRT.This study aimed to identify echocardiographic parameters that would predict the response to CRT.Methods Forty-five consecutive patients receiving CRT-D implantation for heart failure (HF) were included in this prospective study.New York Heart Association (NYHA) class,6-minute walk distance,electrograph character,and multi echocardiographic parameters,especially in strain patterns,were measured and compared before and six months after CRT in the responder and non-responder groups.Response to CRT was defined as a decrease in left ventricular endsystolic volume (LVESV) of 15% or more at 6-month follow up.Results Twenty-two (48.9%) patients demonstrated a response to CRT at 6-month follow-up.Significant improvement in NYHA class (P <0.01),left ventricular end-diastolic volume (LVEDV) (P <0.01),and 6-minute walk distance (P <0.01) was shown in this group.Although there was an interventricular mechanical delay determined by the difference between left and right ventricular pre-ejection intervals ((42.87±19.64) ms vs.(29.43±18.19) ms,P=0.02),the standard deviation of time to peak myocardial strain among 12 basal,mid and apical segments (Tε-SD) ((119.97±43.32) ms vs.(86.62±36.86) ms,P=0.01) and the non-ischemic etiology (P=0.03) were significantly higher in responders than non-responders,only the Tε-SD (OR=1.02,95% Cl=1.01-1.04,P=0.02) proved to be a favorable predictor of CRT response after multivariate Logistic regression analysis.Conclusion The left ventricular 12 segmental strain imaging is a promising echocardiographic parameter for predicting CRT response.

  17. Stroke volume variation compared with pulse pressure variation and cardiac index changes for prediction of fluid responsiveness in mechanically ventilated patients

    Directory of Open Access Journals (Sweden)

    Randa Aly Soliman

    2015-04-01

    Conclusions: Baseline stroke volume variation ⩾8.15% predicted fluid responsiveness in mechanically ventilated patients with acute circulatory failure. The study also confirmed the ability of pulse pressure variation to predict fluid responsiveness.

  18. Xenobiotic metabolizing enzyme gene polymorphisms predict response to lung volume reduction surgery

    Directory of Open Access Journals (Sweden)

    DeMeo Dawn L

    2007-08-01

    Full Text Available Abstract Background In the National Emphysema Treatment Trial (NETT, marked variability in response to lung volume reduction surgery (LVRS was observed. We sought to identify genetic differences which may explain some of this variability. Methods In 203 subjects from the NETT Genetics Ancillary Study, four outcome measures were used to define response to LVRS at six months: modified BODE index, post-bronchodilator FEV1, maximum work achieved on a cardiopulmonary exercise test, and University of California, San Diego shortness of breath questionnaire. Sixty-four single nucleotide polymorphisms (SNPs were genotyped in five genes previously shown to be associated with chronic obstructive pulmonary disease susceptibility, exercise capacity, or emphysema distribution. Results A SNP upstream from glutathione S-transferase pi (GSTP1; p = 0.003 and a coding SNP in microsomal epoxide hydrolase (EPHX1; p = 0.02 were each associated with change in BODE score. These effects appeared to be strongest in patients in the non-upper lobe predominant, low exercise subgroup. A promoter SNP in EPHX1 was associated with change in BODE score (p = 0.008, with the strongest effects in patients with upper lobe predominant emphysema and low exercise capacity. One additional SNP in GSTP1 and three additional SNPs in EPHX1 were associated (p Conclusion Genetic variants in GSTP1 and EPHX1, two genes encoding xenobiotic metabolizing enzymes, were predictive of response to LVRS. These polymorphisms may identify patients most likely to benefit from LVRS.

  19. Early Prediction of Long-Term Response to Cabergoline in Patients with Macroprolactinomas

    Directory of Open Access Journals (Sweden)

    Youngki Lee

    2014-09-01

    Full Text Available BackgroundCabergoline is typically effective for treating prolactinomas; however, some patients display cabergoline resistance, and the early characteristics of these patients remain unclear. We analyzed early indicators predicting long-term response to cabergoline.MethodsWe retrospectively reviewed the cases of 44 patients with macroprolactinomas who received cabergoline as first-line treatment; the patients were followed for a median of 16 months. The influence of various clinical parameters on outcomes was evaluated.ResultsForty patients (90.9% were treated medically and displayed tumor volume reduction (TVR of 74.7%, a prolactin normalization (NP rate of 81.8%, and a complete response (CR; TVR >50% with NP, without surgery rate of 70.5%. Most patients (93.1% with TVR ≥25% and NP at 3 months eventually achieved CR, whereas only 50% of patients with TVR ≥25% without NP and no patients with TVR 25% at 3 months without NP, particularly those with huge prolactinomas, because a delayed response may be achieved. As surgery can reduce the cabergoline dose necessary for successful disease control, it should be considered for cabergoline-resistant patients.

  20. Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

    Science.gov (United States)

    Marsden, Karen E; Ma, Wei Ji; Deci, Edward L; Ryan, Richard M; Chiu, Pearl H

    2015-06-01

    The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as the free-choice time spent on a task when this was not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural responses in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy, and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest that human performance is guided by a "tonic" and "phasic" relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic).

  1. Shy birds play it safe: personality in captivity predicts risk responsiveness during reproduction in the wild.

    Science.gov (United States)

    Cole, Ella F; Quinn, John L

    2014-05-01

    Despite a growing body of evidence linking personality to life-history variation and fitness, the behavioural mechanisms underlying these relationships remain poorly understood. One mechanism thought to play a key role is how individuals respond to risk. Relatively reactive and proactive (or shy and bold) personality types are expected to differ in how they manage the inherent trade-off between productivity and survival, with bold individuals being more risk-prone with lower survival probability, and shy individuals adopting a more risk-averse strategy. In the great tit (Parus major), the shy-bold personality axis has been well characterized in captivity and linked to fitness. Here, we tested whether 'exploration behaviour', a captive assay of the shy-bold axis, can predict risk responsiveness during reproduction in wild great tits. Relatively slow-exploring (shy) females took longer than fast-exploring (bold) birds to resume incubation after a novel object, representing an unknown threat, was attached to their nest-box, with some shy individuals not returning within the 40 min trial period. Risk responsiveness was consistent within individuals over days. These findings provide rare, field-based experimental evidence that shy individuals prioritize survival over reproductive investment, supporting the hypothesis that personality reflects life-history variation through links with risk responsiveness.

  2. Predicting therapeutic response to secondary treatment with bupropion: dichotic listening tests of functional brain asymmetry.

    Science.gov (United States)

    Bruder, Gerard E; Stewart, Jonathan W; Schaller, Jennifer D; McGrath, Patrick J

    2007-10-31

    Studies using neuroimaging, electrophysiologic and cognitive measures have raised hopes for developing predictors of therapeutic response to antidepressants. Pretreatment measures of functional brain asymmetry have been found to be related to response to the selective serotonin reuptake inhibitor fluoxetine. This report examines the extent to which dichotic listening tests also predict clinical response to an antidepressant with a different mechanism of action, i.e., bupropion. Dichotic listening data were obtained for 17 unmedicated depressed patients who were subsequently treated with bupropion. Right-handed outpatients were tested on dichotic fused-words and complex-tones tests. Seven patients who responded to bupropion and 10 nonresponders did not differ in gender, age or education. Bupropion responders had significantly larger left-hemisphere advantage for perceiving words when compared to nonresponders, but there was no difference in their right-hemisphere advantage for tones. All patients having a left-hemisphere advantage above the normal mean responded to bupropion, whereas only 9% of patients below the normal mean responded to treatment. These findings should encourage further study of the clinical value of dichotic listening and other measures of functional brain asymmetry for identifying depressed patients who most benefit from treatment with different classes of antidepressants.

  3. Posterior superior temporal sulcus responses predict perceived pleasantness of skin stroking

    Directory of Open Access Journals (Sweden)

    Monika Davidovic

    2016-09-01

    Full Text Available Love and affection is expressed through a range of physically intimate gestures, including caresses. Recent studies suggest that posterior temporal lobe areas typically associated with visual processing of social cues also respond to interpersonal touch. Here, we asked whether these areas are selective to caress-like skin stroking. We collected functional magnetic resonance imaging (fMRI data from 23 healthy participants and compared brain responses to skin stroking and vibration. We did not find any significant differences between stroking and vibration in the posterior temporal lobe; however, right posterior superior temporal sulcus (pSTS responses predicted healthy participant's perceived pleasantness of skin stroking, but not vibration. These findings link right pSTS responses to individual variability in perceived pleasantness of caress-like tactile stimuli. We speculate that the right pSTS may play a role in the translation of tactile stimuli into positively valenced, socially relevant interpersonal touch and that this system may be affected in disorders associated with impaired attachment.

  4. Quantitation of HBsAg predicts response to entecavir therapy in HBV genotype C patients

    Institute of Scientific and Technical Information of China (English)

    Etsuro Orito; Kei Fujiwara; Hiroshi Kanie; Tesshin Ban; Tomonori Yamada; Katsumi Hayashi

    2012-01-01

    AIM:To analysis the factors that predict the response to entecavir therapy in chronic hepatitis patients with hepatitis B virus (HBV) genotype C.METHODS:Fifty patients [hepatitis B e antigen (HBeAg)-negative:HBeAg-positive =26:24] with HBV genotype C,who received na(i)ve entecavir therapy for > 2 years,were analyzed.Patients who showed HBV DNA levels ≥3.0 log viral copies/mL after 2 years of entecavir therapy were designated as slow-responders,while those that showed < 3.0 log copies/mL were termed rapidresponders.Quantitative hepatitis B surface antigen (HBsAg) levels (qHBsAg) were determined by the Architect HBsAg QT immunoassay.Hepatitis B core-related antigen was detected by enzyme immunoassay.Pre-C and Core promoter mutations were determined using by polymerase chain reaction (PCR).Drug-resistance mutations were detected by the PCR-Invader method.RESULTS:At year 2,HBV DNA levels in all patients in the HBeAg-negative group were < 3.0 log copies/mL.In contrast,in the HBeAg-positive group,41.7% were slow-responders,while 58.3% were rapid-responders.No entecavir-resistant mutants were detected in the slow-responders.When the pretreatment factors were compared between the slow-and rapid-responders;the median qHBsAg in the slow-responders was 4.57log IU/mL,compared with 3.63 log IU/mL in the rapidresponders (P < 0.01).When the pretreatment factors predictive of HBV DNA-negative status at year 2 in all 50 patients were analyzed,HBeAg-negative status,low HBV DNA levels,and low qHBsAg levels were significant (P < 0.01).Multivariate analysis revealed that the low qHBsAg level was the most significant predictive factor (P =0.03).CONCLUSION:Quantitation of HBsAg could be a useful indicator to predict response to entecavir therapy.

  5. Breast Cancer Spatial Heterogeneity in Near-Infrared Spectra and the Prediction of Neoadjuvant Chemotherapy Response

    Science.gov (United States)

    Santoro, Ylenia

    Breast cancer accounts for more than 20% of all female cancers. Many of these patients receive neoadjuvant chemotherapy (NAC) to reduce the size of the tumor before surgery and to anticipate the efficacy of treatments for after the procedure. Breast cancer is a heterogeneous disease that comes in several clinical and histological forms. The prediction of the efficacy of chemotherapy would potentially select good candidates who would respond while excluding poor candidates who would not benefit from treatment. In this work we investigate the possibility of noninvasively predicting chemotherapy response prior to treatment based on optical biomarkers obtained from tumor spatial heterogeneities of spectral features measured using Diffuse Optical Spectroscopy. We describe an algorithm to calculate an index that characterizes spatial differences in broadband near-infrared absorption spectra of tumor-containing breast tissue. Patient-specific tumor spatial heterogeneities are visualized through a Heterogeneity Spectrum (HS). HS is a biomarker that can be attributed to different molecular distributions within the tumor. To classify lesion heterogeneities, we built a Heterogeneity Index (HI) from the HS by weighing specific absorption bands. It has been shown that NAC response is potentially related to tumor heterogeneity. Therefore, we correlate the HI obtained prior to treatment with the final response to NAC. In this thesis we also present a novel digital parallel frequency domain system for tissue imaging. The systems employs a supercontinuum laser with high brightness, and a photomultiplier with a large detection area, both allowing a deep penetration with extremely low power on the sample. The digital parallel acquisition is performed through the use of the Flimbox and it decreases the time required for standard serial systems that need to scan through all modulation frequencies. The all-digital acquisition removes analog noise, avoids the analog mixer and it does not

  6. [Predictive response variables to recombinant human erythropoietin treatment in patients with anemia and cancer].

    Science.gov (United States)

    Lastiri, José M; Specterman, Sergio R; Rendo, Pablo; Pallotta, María G; Varela, Mirta S; Goldstein, Sofía

    2002-01-01

    The use of human recombinant erythropoietin (rHuEpo) has been approved by the Food and Drug Administration (FDA) in patients with anemia and cancer. Although good results have been obtained, it is too expensive to permit its use massively. For the purpose of evaluating the therapeutic effect of rHuEpo, including toxicity, predictive response variables and quality of life parameters, a prospective trial was carried out in patients with anemia and cancer. Hematimetric parameters, ferritin, Epo, cytokines, transfusions and quality of life were registered. A total of 36 patients were treated in the protocol (34 were evaluable): 16 men and 20 women, with a medium age 56.4 years; 27 patients were treated with chemotherapy (16 with cisplatinum); 15 patients presented medullar infiltration. In 73.5% patients an increase in the level of hemoglobin was registered, and in 64.7% its normalisation was attained. Transfusional requirements were reduced by 50%. The hemoglobin increase greater than 0.5 g/dl at the second week of treatment was the most significant variable of early response. Patients treated with cisplatinum, seric ferritin lower than 1,100 ng/dl and those without medullar tumoral infiltration responded best. Serum Epo, cytokines (IL-1, IL-6 and TNF) and reticulocyte count at the second week did not correlate with response. Quality of life parameters were better in patients with good response to rHuEpo. It can be concluded that good results in the treatment of patients with anemia and cancer are obtained with rHuEpo.

  7. Local predation pressure predicts the strength of mobbing responses in tropical birds

    Institute of Scientific and Technical Information of China (English)

    Luis SANDOVAL; David R.WILSON

    2012-01-01

    Many birds join cooperative mobbing aggregations and collectively harass predators.Individuals participating in these ephemeral associations benefit by deterring the predator,but also incur energetic costs and increased risk of predation.Explaining the evolution of mobbing is challenging because individuals could prevail by selfishly seeking safety while allowing others to mob.An important step in understanding the evolution of mobbing is to identify factors affecting its expression.The ecological constraints model suggests that animals are more likely to cooperate under adverse environmental conditions,such as when local predation pressure is high.We tested this prediction by comparing the mobbing responses of several species of birds to the local abundance of their primary predator,the ferruginous pygmy-owl Glaucidium brasilianum.We used acoustic playback to elicit mobbing responses in environments where owls were common,uncommon,or rare.Stimuli were either the song of a ferruginous pygmy-owl or the mobbing calls of three of the owl's common prey species.During each playback,we characterized mobbing responses by noting the number of species and individuals that approached the loudspeaker,as well as the closest approach by any bird.Mobbing responses to both stimuli were strong in locations where Ferruginous Pygmy-owls were common,intermediate where owls were uncommon,and weak where they were rare.This pattern persisted even after controlling for differences in species richness and composition among the three environments.Results support the ecological constraints model and provide strong evidence that intense predation pressure increases the expression of cooperative mobbing in tropical birds.

  8. Local predation pressure predicts the strength of mobbing responses in tropical birds

    Directory of Open Access Journals (Sweden)

    Luis SANDOVAL, David R. WILSON

    2012-10-01

    Full Text Available Many birds join cooperative mobbing aggregations and collectively harass predators. Individuals participating in these ephemeral associations benefit by deterring the predator, but also incur energetic costs and increased risk of predation. Explaining the evolution of mobbing is challenging because individuals could prevail by selfishly seeking safety while allowing others to mob. An important step in understanding the evolution of mobbing is to identify factors affecting its expression. The ecological constraints model suggests that animals are more likely to cooperate under adverse environmental conditions, such as when local predation pressure is high. We tested this prediction by comparing the mobbing responses of several species of birds to the local abundance of their primary predator, the ferruginous pygmy-owl Glaucidium brasilianum. We used acoustic playback to elicit mobbing responses in environments where owls were common, uncommon, or rare. Stimuli were either the song of a ferruginous pygmy-owl or the mobbing calls of three of the owl’s common prey species. During each playback, we characterized mobbing responses by noting the number of species and individuals that approached the loudspeaker, as well as the closest approach by any bird. Mobbing responses to both stimuli were strong in locations where Ferruginous Pygmy-owls were common, intermediate where owls were uncommon, and weak where they were rare. This pattern persisted even after controlling for differences in species richness and composition among the three environments. Results support the ecological constraints model and provide strong evidence that intense predation pressure increases the expression of cooperative mobbing in tropical birds [Current Zoology 58 (5: 781-790, 2012].

  9. Can we predict ectotherm responses to climate change using thermal performance curves and body temperatures?

    DEFF Research Database (Denmark)

    Sinclair, Brent J.; Marshall, Katie E.; Sewell, Mary A.;

    2016-01-01

    Thermal performance curves (TPCs), which quantify how an ectotherm's body temperature (T-b) affects its performance or fitness, are often used in an attempt to predict organismal responses to climate change. Here, we examine the key - but often biologically unreasonable - assumptions underlying...... this approach; for example, that physiology and thermal regimes are invariant over ontogeny, space and time, and also that TPCs are independent of previously experienced T-b. We show how a critical consideration of these assumptions can lead to biologically useful hypotheses and experimental designs....... For example, rather than assuming that TPCs are fixed during ontogeny, one can measure TPCs for each major life stage and incorporate these into stage-specific ecological models to reveal the life stage most likely to be vulnerable to climate change. Our overall goal is to explicitly examine the assumptions...

  10. NASA Langley developments in response calculations needed for failure and life prediction

    Science.gov (United States)

    Housner, Jerrold M.

    1993-10-01

    NASA Langley developments in response calculations needed for failure and life predictions are discussed. Topics covered include: structural failure analysis in concurrent engineering; accuracy of independent regional modeling demonstrated on classical example; functional interface method accurately joins incompatible finite element models; interface method for insertion of local detail modeling extended to curve pressurized fuselage window panel; interface concept for joining structural regions; motivation for coupled 2D-3D analysis; compression panel with discontinuous stiffener coupled 2D-3D model and axial surface strains at the middle of the hat stiffener; use of adaptive refinement with multiple methods; adaptive mesh refinement; and studies on quantity effect of bow-type initial imperfections on reliability of stiffened panels.

  11. Predicting bird response to alternative management scenarios on a ranch in Campeche, Mexico

    Science.gov (United States)

    Wood, P.A.; Dawson, D.K.; Sauer, J.R.; Wilson, M.H.; Ralph, C. John; Rich, Terrell D.

    2005-01-01

    We developed models to predict the potential response of wintering Neotropical migrant and resident bird species to alternative management scenarios, using data from point counts of birds along with habitat variables measured or estimated from remotely sensed data in a Geographic Information System. Expected numbers of occurrences at points were calculated for 100 species of birds, under current habitat conditions and under habitat conditions that would result from seven alternative management scenarios for Rancho Sandoval, a cattle ranch and private nature reserve in Campeche, Mexico. Most bird species of conservation concern would benefit from management scenarios that increase the amount of forest, but the highest priority resident species would not. To balance the somewhat conflicting habitat needs of these species and the concerns of ranch managers, we recommend that forest area and connectivity be increased, and pastures be maintained but more efficiently managed to support cattle and the priority resident and migrant birds that require open habitats.

  12. Power Prediction Model for Turning EN-31 Steel Using Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    M. Hameedullah

    2010-01-01

    Full Text Available Power consumption in turning EN-31 steel (a material that is most extensively used in automotive industry with tungstencarbide tool under different cutting conditions was experimentally investigated. The experimental runs were planned accordingto 24+8 added centre point factorial design of experiments, replicated thrice. The data collected was statisticallyanalyzed using Analysis of Variance technique and first order and second order power consumption prediction models weredeveloped by using response surface methodology (RSM. It is concluded that second-order model is more accurate than thefirst-order model and fit well with the experimental data. The model can be used in the automotive industries for decidingthe cutting parameters for minimum power consumption and hence maximum productivity

  13. Kalman filtering for neural prediction of response spectra from mining tremors

    Energy Technology Data Exchange (ETDEWEB)

    Krok, A.; Waszczyszyn, Z. [Cracow University of Technology, Krakow (Poland)

    2007-08-15

    Acceleration response spectra (ARS) for mining tremors in the Upper Silesian Coalfield, Poland are generated using neural networks trained by means of Kalman filtering. The target ARS were computed on the base of measured accelerograms. It was proved that the standard feed-forward, layered neural network, trained by the DEFK (decoupled extended Kalman filter) algorithm is numerically much less efficient than the standard recurrent NN learnt by Recurrent DEKF, cf. (Haykin S, (editor). Kalman filtering and neural networks. New York: John Wiley & Sons; 2001). It is also shown that the studied KF algorithms are better than the traditional Resilient-Propagation learning method. The improvement of the training process and neural prediction due to introduction of an autoregressive input is also discussed in the paper.

  14. Mechanisms of frequency-specific responses of omega neuron 1 in crickets (Teleogryllus oceanicus): a polysynaptic pathway for song?

    Science.gov (United States)

    Faulkes, Z; Pollack, G S

    2001-04-01

    In crickets (Teleogryllus oceanicus), the auditory interneuron omega neuron 1 (ON1) responds to sounds over a wide range of frequencies but is most sensitive to the frequency of conspecific songs (4.5 kHz). Response latency is longest for this same frequency. We investigate the mechanisms that might account for the longer latency of ON1 to cricket-like sounds. Intracellular recordings revealed no evidence for appropriately timed postsynaptic inhibition of ON1 that might increase its latency, nor was latency affected by picrotoxin. The onset of excitatory postsynaptic potentials (EPSPs) was delayed for 4.5 kHz stimuli compared with ultrasound stimuli, pointing to a presynaptic locus for the latency difference. When ON1 is stimulated with high frequencies, discrete, apparently unitary EPSPs can be recorded in its dendrite, and these are latency-locked to spikes recorded simultaneously in the auditory nerve. This suggests that input to ON1 from high-frequency-tuned auditory receptor neurons is monosynaptic. In agreement with this, brief ultrasound stimuli evoke a single, short-latency EPSP in ON1. In contrast, the EPSP evoked by a brief 4.5 kHz stimulus consists of an early component, similar in latency to that evoked by ultrasound and possibly evoked by ultrasound-tuned receptors, and a later, dominant component. We interpret the early peak as arising from a monosynaptic afferent pathway and the late peak from a polysynaptic afferent pathway. Multiple-peak EPSPs, with timing similar to those evoked by sound stimuli, were also evoked by electrical stimulation of the auditory nerve.

  15. Traditional clinical risk factors predict clopidogrel hypo-responsiveness in unselected patients undergoing non-emergent percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Ratcovich, Hanna; Holmvang, Lene; Johansson, Pär Inge

    2016-01-01

    High and low platelet reactivity, HPR and LPR respectively, to clopidogrel and aspirin have previously been associated with adverse events following percutaneous coronary intervention (PCI). The aim is to test the ability of a previously developed clinical risk-score, the PREDICT score, to identify...... of PREDICT score variables and the incidence of HPR for clopidogrel (HPR (ADP)) (p ... = 0.003); 7-9 points OR 9.84 (95% CI 3.49-27.7, p clopidogrel LPR (LPR (ADP)). On the other hand, there was no clear association between PREDICT score and AA response. The PREDICT...

  16. Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Riazy, Maziar; Kalloger, Steve E; Sheffield, Brandon S; Peixoto, Renata D; Li-Chang, Hector H; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-10-01

    Deficiencies in DNA mismatch repair have been associated with inferior response to 5-FU in colorectal cancer. Pancreatic ductal adenocarcinoma is similarly treated with pyrimidine analogs, yet the predictive value of mismatch repair status for response to these agents has not been examined in this malignancy. A tissue microarray with associated clinical outcome, comprising 254 resected pancreatic ductal adenocarcinoma patients was stained for four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Mismatch repair deficiency and proficiency was determined by the absence or presence of uniform nuclear staining in tumor cells, respectively. Cases identified as mismatch repair deficient on the tissue microarray were confirmed by immunohistochemistry on whole slide sections. Of the 265 cases, 78 (29%) received adjuvant treatment with a pyrimidine analog and 41 (15%) showed a mismatch repair-deficient immunoprofile. Multivariable disease-specific survival in the mismatch repair-proficient cohort demonstrated that adjuvant chemotherapy, regional lymph-node status, gender, and the presence of tumor budding were significant independent prognostic variables (P≤0.04); however, none of the eight clinico-pathologic covariates examined in the mismatch repair-deficient cohort were of independent prognostic significance. Univariable assessment of disease-specific survival revealed an almost identical survival profile for both treated and untreated patients with a mismatch repair-deficient profile, while treatment in the mismatch repair-proficient cohort conferred a greater than 10-month median disease-specific survival advantage over their untreated counterparts (P=0.0018). In this cohort, adjuvant chemotherapy with a pyrimidine analog conferred no survival advantage to mismatch repair-deficient pancreatic ductal adenocarcinoma patients. Mismatch repair immunoprofiling is a feasible predictive marker in pancreatic ductal adenocarcinoma patients, and further prospective

  17. Pretreatment Growth Rate Predicts Radiation Response in Vestibular Schwannomas

    Energy Technology Data Exchange (ETDEWEB)

    Niu, Nina N. [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); Harvard Medical School, Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Niemierko, Andrzej [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); Larvie, Mykol [Harvard Medical School, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Curtin, Hugh [Harvard Medical School, Department of Radiology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Loeffler, Jay S. [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); McKenna, Michael J. [Harvard Medical School, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-05-01

    Purpose: Vestibular schwannomas (VS) are often followed without initial therapeutic intervention because many tumors do not grow and radiation therapy is associated with potential adverse effects. In an effort to determine whether maximizing initial surveillance predicts for later treatment response, the predictive value of preirradiation growth rate of VS on response to radiation therapy was assessed. Methods and Materials: Sixty-four patients with 65 VS were treated with single-fraction stereotactic radiation surgery or fractionated stereotactic radiation therapy. Pre- and postirradiation linear expansion rates were estimated using volumetric measurements on sequential magnetic resonance images (MRIs). In addition, postirradiation tumor volume change was classified as demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months, respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were excluded from statistical analyses. Results: In the 58 non-NF2 patients, there was a trend of correlation between pre- and postirradiation volume change rates (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation expansion had a median preirradiation growth rate of 89%/year, and those without postirradiation expansion had a median preirradiation growth rate of 41%/year (P=.02). As the preirradiation growth rate increased, the probability of postirradiation expansion also increased. Overall, 24.1% of tumors were stable, 53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no postirradiation tumor expansion included no prior surgery (P=.01) and slower tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%. Conclusions: Radiation therapy is an effective treatment for VS, but tumors that grow quickly preirradiation may be

  18. Deep sequencing reveals microRNAs predictive of antiangiogenic drug response

    Science.gov (United States)

    García-Donas, Jesús; Beuselinck, Benoit; Inglada-Pérez, Lucía; Graña, Osvaldo; Schöffski, Patrick; Wozniak, Agnieszka; Bechter, Oliver; Apellániz-Ruiz, Maria; Leandro-García, Luis Javier; Esteban, Emilio; Castellano, Daniel E.; González del Alba, Aranzazu; Climent, Miguel Angel; Hernando, Susana; Arranz, José Angel; Morente, Manuel; Pisano, David G.; Robledo, Mercedes

    2016-01-01

    The majority of metastatic renal cell carcinoma (RCC) patients are treated with tyrosine kinase inhibitors (TKI) in first-line treatment; however, a fraction are refractory to these antiangiogenic drugs. MicroRNAs (miRNAs) are regulatory molecules proven to be accurate biomarkers in cancer. Here, we identified miRNAs predictive of progressive disease under TKI treatment through deep sequencing of 74 metastatic clear cell RCC cases uniformly treated with these drugs. Twenty-nine miRNAs were differentially expressed in the tumors of patients who progressed under TKI therapy (P values from 6 × 10–9 to 3 × 10–3). Among 6 miRNAs selected for validation in an independent series, the most relevant associations corresponded to miR–1307-3p, miR–155-5p, and miR–221-3p (P = 4.6 × 10–3, 6.5 × 10–3, and 3.4 × 10–2, respectively). Furthermore, a 2 miRNA–based classifier discriminated individuals with progressive disease upon TKI treatment (AUC = 0.75, 95% CI, 0.64–0.85; P = 1.3 × 10–4) with better predictive value than clinicopathological risk factors commonly used. We also identified miRNAs significantly associated with progression-free survival and overall survival (P = 6.8 × 10–8 and 7.8 × 10–7 for top hits, respectively), and 7 overlapped with early progressive disease. In conclusion, this is the first miRNome comprehensive study, to our knowledge, that demonstrates a predictive value of miRNAs for TKI response and provides a new set of relevant markers that can help rationalize metastatic RCC treatment. PMID:27699216

  19. MRI evaluation of anterior knee pain: predicting response to nonoperative treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wittstein, Jocelyn R.; Garrett, William E. [Duke University Medical Center, Division of Orthopaedic Surgery, Durham, NC (United States); O' Brien, Seth D. [Brooke Army Medical Center, Department of Radiology, San Antonio, TX (United States); Vinson, Emily N. [Duke University Medical Center, Department of Radiology, Durham, NC (United States)

    2009-09-15

    Tibial tubercle lateral deviation and patellofemoral chondromalacia are associated with anterior knee pain (AKP). We hypothesized that increased tibial tubercle lateral deviation and patellofemoral chondromalacia on magnetic resonance imaging correlates with the presence of AKP and with failure of nonoperative management. In this retrospective comparative study, a blinded musculoskeletal radiologist measured tibial tubercle lateral deviation relative to the trochlear groove in 15 controls, 15 physical therapy responders with AKP, and 15 physical therapy nonresponders with AKP. Patellar and trochlear cartilage was assessed for signal abnormality, irregularity, and defects. The mean tibial tubercle lateral deviation in controls, physical therapy responders, and physical therapy nonresponders were 9.32 {+-} 0.68, 13.01 {+-} 0.82, and 16.07 {+-} 1.16 mm, respectively (data are mean {+-} standard deviation). The correlation coefficients for tubercle deviation, chondromalacia patellae, and trochlear chondromalacia were 0.51 (P < 0.01), 0.44 (P < 0.01), and 0.28 (P < 0.05), respectively. On analysis of variance, tubercle deviation and chondromalacia patellae contributed significantly to prediction of AKP and response to physical therapy. The presence of chondromalacia patellae and a tubercle deviation greater than 14.6 mm is 100% specific and 67% sensitive with a positive predictive value of 100% and negative predictive value of 75% for failure of nonoperative management. Subjects with AKP have more laterally positioned tibial tubercles and are more likely to have patellar chondromalacia. Patients with AKP, chondromalacia patellae, and a tubercle deviation greater than 14.6 mm are unlikely to respond to nonoperative treatment. Knowledge of tibial tubercle lateralization and presence of chondromalacia patellae may assist clinicians in determining patient prognosis and selecting treatment options. (orig.)

  20. Impediments to predicting site response: Seismic property estimation and modeling simplifications

    Science.gov (United States)

    Thompson, E.M.; Baise, L.G.; Kayen, R.E.; Guzina, B.B.

    2009-01-01

    We compare estimates of the empirical transfer function (ETF) to the plane SH-wave theoretical transfer function (TTF) within a laterally constant medium for invasive and noninvasive estimates of the seismic shear-wave slownesses at 13 Kiban-Kyoshin network stations throughout Japan. The difference between the ETF and either of the TTFs is substantially larger than the difference between the two TTFs computed from different estimates of the seismic properties. We show that the plane SH-wave TTF through a laterally homogeneous medium at vertical incidence inadequately models observed amplifications at most sites for both slowness estimates, obtained via downhole measurements and the spectral analysis of surface waves. Strategies to improve the predictions can be separated into two broad categories: improving the measurement of soil properties and improving the theory that maps the 1D soil profile onto spectral amplification. Using an example site where the 1D plane SH-wave formulation poorly predicts the ETF, we find a more satisfactory fit to the ETF by modeling the full wavefield and incorporating spatially correlated variability of the seismic properties. We conclude that our ability to model the observed site response transfer function is limited largely by the assumptions of the theoretical formulation rather than the uncertainty of the soil property estimates.

  1. Differential Response of Coral Assemblages to Thermal Stress Underscores the Complexity in Predicting Bleaching Susceptibility.

    Science.gov (United States)

    Chou, Loke Ming; Toh, Tai Chong; Toh, Kok Ben; Ng, Chin Soon Lionel; Cabaitan, Patrick; Tun, Karenne; Goh, Eugene; Afiq-Rosli, Lutfi; Taira, Daisuke; Du, Rosa Celia Poquita; Loke, Hai Xin; Khalis, Aizat; Li, Jinghan; Song, Tiancheng

    2016-01-01

    Coral bleaching events have been predicted to occur more frequently in the coming decades with global warming. The susceptibility of corals to bleaching during thermal stress episodes is dependent on many factors and an understanding of these underlying drivers is crucial for conservation management. In 2013, a mild bleaching episode ensued in response to elevated sea temperature on the sediment-burdened reefs in Singapore. Surveys of seven sites highlighted variable bleaching susceptibility among coral genera-Pachyseris and Podabacia were the most impacted (31% of colonies of both genera bleached). The most susceptible genera such as Acropora and Pocillopora, which were expected to bleach, did not. Susceptibility varied between less than 6% and more than 11% of the corals bleached, at four and three sites respectively. Analysis of four of the most bleached genera revealed that a statistical model that included a combination of the factors (genus, colony size and site) provided a better explanation of the observed bleaching patterns than any single factor alone. This underscored the complexity in predicting the coral susceptibility to future thermal stress events and the importance of monitoring coral bleaching episodes to facilitate more effective management of coral reefs under climate change.

  2. Differential Response of Coral Assemblages to Thermal Stress Underscores the Complexity in Predicting Bleaching Susceptibility.

    Directory of Open Access Journals (Sweden)

    Loke Ming Chou

    Full Text Available Coral bleaching events have been predicted to occur more frequently in the coming decades with global warming. The susceptibility of corals to bleaching during thermal stress episodes is dependent on many factors and an understanding of these underlying drivers is crucial for conservation management. In 2013, a mild bleaching episode ensued in response to elevated sea temperature on the sediment-burdened reefs in Singapore. Surveys of seven sites highlighted variable bleaching susceptibility among coral genera-Pachyseris and Podabacia were the most impacted (31% of colonies of both genera bleached. The most susceptible genera such as Acropora and Pocillopora, which were expected to bleach, did not. Susceptibility varied between less than 6% and more than 11% of the corals bleached, at four and three sites respectively. Analysis of four of the most bleached genera revealed that a statistical model that included a combination of the factors (genus, colony size and site provided a better explanation of the observed bleaching patterns than any single factor alone. This underscored the complexity in predicting the coral susceptibility to future thermal stress events and the importance of monitoring coral bleaching episodes to facilitate more effective management of coral reefs under climate change.

  3. Use of reflectance spectrophotometry to predict the response of port wine stains to pulsed dye laser.

    Science.gov (United States)

    Halachmi, Shlomit; Azaria, Ron; Inbar, Roy; Ad-El, Dean; Lapidoth, Moshe

    2014-01-01

    Reflectance spectroscopy can be used to quantitate subtle differences in color. We applied a portable reflectance spectrometer to determine its utility in the evaluation of pulsed dye laser treatment of port wine stains (PWS) and in prediction of clinical outcome, in a prospective study. Forty-eight patients with PWS underwent one to nine pulsed dye laser treatments. Patient age and skin color as well as PWS surface area, anatomic location, and color were recorded. Pretreatment spectrophotometric measurements were performed. The subjective clinical results of treatment and the quantitative spectrophotometry results were evaluated by two independent teams, and the findings were correlated. The impact of the clinical characteristics on the response to treatment was assessed as well. Patients with excellent to good clinical results of laser treatments had pretreatment spectrophotometric measurements which differed by more than 10%, whereas patients with fair to poor results had spectrophotometric measurements with a difference of of less than 10%. The correlation between the spectrophotometric results and the clinical outcome was 73% (p Spectrophotometry has a higher correlation with clinical outcome and a better predictive value than other nonmeasurable, nonquantitative, dependent variables.

  4. Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rawstron, Andy C; Kennedy, Ben; Moreton, Paul; Dickinson, Anita J; Cullen, Matthew J; Richards, Stephen J; Jack, Andrew S; Hillmen, Peter

    2004-03-15

    Alemtuzumab therapy is effective for some refractory chronic lymphocytic leukemia (CLL), but identifying responders requires at least 8 weeks of therapy. Early identification of nonresponders would minimize toxicity and/or facilitate more effective strategies. The aim of this study was to identify a minimally invasive method for early prediction of response and relapse. Flow cytometric monitoring was performed in 887 blood samples and 201 marrow samples from 43 patients undergoing intravenous alemtuzumab therapy. Although the absolute lymphocytosis was resolved in all patients by week 4, significant depletion of bone marrow tumor only occurred if circulating B-lymphocyte counts were persistently less than 0.001 x 10(9)/L, which was rare in nonresponders. The majority of patients (16/28) who did not benefit from a full course of therapy were identified with 100% positive predictive value using the following algorithm: peripheral B-cell count greater than 0.001 x 10(9)/L at week 2 with less than 1 log depletion of circulating B cells between weeks 2 and 4. Monitoring CLL levels after treatment identified patients at risk of early disease progression and could potentially improve patient management. During alemtuzumab therapy, bone marrow CLL depletion only occurs after abrogation of circulating tumor, requiring close monitoring of circulating B-cell levels. If validated in prospective studies, blood monitoring at 2 and 4 weeks may be used to optimize therapy.

  5. The biology of developmental plasticity and the Predictive Adaptive Response hypothesis.

    Science.gov (United States)

    Bateson, Patrick; Gluckman, Peter; Hanson, Mark

    2014-06-01

    Many forms of developmental plasticity have been observed and these are usually beneficial to the organism. The Predictive Adaptive Response (PAR) hypothesis refers to a form of developmental plasticity in which cues received in early life influence the development of a phenotype that is normally adapted to the environmental conditions of later life. When the predicted and actual environments differ, the mismatch between the individual's phenotype and the conditions in which it finds itself can have adverse consequences for Darwinian fitness and, later, for health. Numerous examples exist of the long-term effects of cues indicating a threatening environment affecting the subsequent phenotype of the individual organism. Other examples consist of the long-term effects of variations in environment within a normal range, particularly in the individual's nutritional environment. In mammals the cues to developing offspring are often provided by the mother's plane of nutrition, her body composition or stress levels. This hypothetical effect in humans is thought to be important by some scientists and controversial by others. In resolving the conflict, distinctions should be drawn between PARs induced by normative variations in the developmental environment and the ill effects on development of extremes in environment such as a very poor or very rich nutritional environment. Tests to distinguish between different developmental processes impacting on adult characteristics are proposed. Many of the mechanisms underlying developmental plasticity involve molecular epigenetic processes, and their elucidation in the context of PARs and more widely has implications for the revision of classical evolutionary theory.

  6. Response surface and neural network based predictive models of cutting temperature in hard turning

    Directory of Open Access Journals (Sweden)

    Mozammel Mia

    2016-11-01

    Full Text Available The present study aimed to develop the predictive models of average tool-workpiece interface temperature in hard turning of AISI 1060 steels by coated carbide insert. The Response Surface Methodology (RSM and Artificial Neural Network (ANN were employed to predict the temperature in respect of cutting speed, feed rate and material hardness. The number and orientation of the experimental trials, conducted in both dry and high pressure coolant (HPC environments, were planned using full factorial design. The temperature was measured by using the tool-work thermocouple. In RSM model, two quadratic equations of temperature were derived from experimental data. The analysis of variance (ANOVA and mean absolute percentage error (MAPE were performed to suffice the adequacy of the models. In ANN model, 80% data were used to train and 20% data were employed for testing. Like RSM, herein, the error analysis was also conducted. The accuracy of the RSM and ANN model was found to be ⩾99%. The ANN models exhibit an error of ∼5% MAE for testing data. The regression coefficient was found to be greater than 99.9% for both dry and HPC. Both these models are acceptable, although the ANN model demonstrated a higher accuracy. These models, if employed, are expected to provide a better control of cutting temperature in turning of hardened steel.

  7. Probabilistic models of expectation violation predict psychophysiological emotional responses to live concert music.

    Science.gov (United States)

    Egermann, Hauke; Pearce, Marcus T; Wiggins, Geraint A; McAdams, Stephen

    2013-09-01

    We present the results of a study testing the often-theorized role of musical expectations in inducing listeners' emotions in a live flute concert experiment with 50 participants. Using an audience response system developed for this purpose, we measured subjective experience and peripheral psychophysiological changes continuously. To confirm the existence of the link between expectation and emotion, we used a threefold approach. (1) On the basis of an information-theoretic cognitive model, melodic pitch expectations were predicted by analyzing the musical stimuli used (six pieces of solo flute music). (2) A continuous rating scale was used by half of the audience to measure their experience of unexpectedness toward the music heard. (3) Emotional reactions were measured using a multicomponent approach: subjective feeling (valence and arousal rated continuously by the other half of the audience members), expressive behavior (facial EMG), and peripheral arousal (the latter two being measured in all 50 participants). Results confirmed the predicted relationship between high-information-content musical events, the violation of musical expectations (in corresponding ratings), and emotional reactions (psychologically and physiologically). Musical structures leading to expectation reactions were manifested in emotional reactions at different emotion component levels (increases in subjective arousal and autonomic nervous system activations). These results emphasize the role of musical structure in emotion induction, leading to a further understanding of the frequently experienced emotional effects of music.

  8. Response Assessment and Prediction in Esophageal Cancer Patients via F-18 FDG PET/CT Scans

    Science.gov (United States)

    Higgins, Kyle J.

    Purpose: The purpose of this study is to utilize F-18 FDG PET/CT scans to determine an indicator for the response of esophageal cancer patients during radiation therapy. There is a need for such an indicator since local failures are quite common in esophageal cancer patients despite modern treatment techniques. If an indicator is found, a patient's treatment strategy may be altered to possibly improve the outcome. This is investigated with various standard uptake volume (SUV) metrics along with image texture features. The metrics and features showing the most promise and indicating response are used in logistic regression analysis to find an equation for the prediction of response. Materials and Methods: 28 patients underwent F-18 FDG PET/CT scans prior to the start of radiation therapy (RT). A second PET/CT scan was administered following the delivery of ~32 Gray (Gy) of dose. A physician contoured gross tumor volume (GTV) was used to delineate a PET based GTV (GTV-pre-PET) based on a threshold of >40% and >20% of the maximum SUV value in the GTV. Deformable registration was used in VelocityAI software to register the pre-treatment and intra-treatment CT scans so that the GTV-pre-PET contours could be transferred from the pre to intra scans (GTV-intra-PET). The fractional decrease in the maximum, mean, volume to the highest intensity 10%-90%, and combination SUV metrics of the significant previous SUV metrics were compared to post-treatment pathologic response for an indication of response. Next for the >40% threshold, texture features based on a neighborhood gray-tone dimension matrix (NGTDM) were analyzed. The fractional decrease in coarseness, contrast, busyness, complexity, and texture strength were compared to the pathologic response of the patients. From these previous two types of analysis, SUV and texture features, the two most significant results were used in logistic regression analysis to find an equation to predict the probability of a non

  9. Electrophysiological indices of response inhibition in a Go/NoGo task predict self-control in a social context.

    Directory of Open Access Journals (Sweden)

    Kyle Nash

    Full Text Available Recent research demonstrates that response inhibition-a core executive function-may subserve self-regulation and self-control. However, it is unclear whether response inhibition also predicts self-control in the multifaceted, high-level phenomena of social decision-making. Here we examined whether electrophysiological indices of response inhibition would predict self-control in a social context. Electroencephalography was recorded as participants completed a widely used Go/NoGo task (the cued Continuous Performance Test. Participants then interacted with a partner in an economic exchange game that requires self-control. Results demonstrated that greater NoGo-Anteriorization and larger NoGo-P300 peak amplitudes-two established electrophysiological indices of response inhibition-both predicted more self-control in this social game. These findings support continued integration of executive function and self-regulation and help extend prior research into social decision-making processes.

  10. Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers.

    Directory of Open Access Journals (Sweden)

    Elena Pereira

    Full Text Available High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools.Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival.Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic dilemma and a potential

  11. Prediction of outcome in buccal cancers treated with radical radiotherapy based on the early tumor response

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    G V Giri

    2015-01-01

    Full Text Available Aim of the Study: Aim was to assess the clinical significance of the rate of tumor regression in carcinoma buccal mucosa undergoing radical radiotherapy. Materials and Methods: Sixty six patients were enrolled in the study with proven buccal cancers requiring radical radiotherapy, from 1990 to 1996. Radiotherapy was delivered using a combination of external beam and brachytherapy with preloaded cesium 137 needles. The response to the radiation was assessed at the completion of external beam radiation and 6 weeks after brachytherapy. An analysis correlating various parameters influencing the long term disease free survival and overall survival was done. Results: Response assessed at the end of external beam radiation correlated strongly with the overall survival and the disease free interval (P=0.000. No other factor influenced the survival. Conclusion: The rate of the tumor regression can predict the overall outcome in patients with buccal cancers treated with radiation. Completion of the planned course of radiation in patients who do not show a substantial reduction in size by 4.5 weeks of conventional radiation does not improve the results.

  12. Field Measurement-Based System Identification and Dynamic Response Prediction of a Unique MIT Building.

    Science.gov (United States)

    Cha, Young-Jin; Trocha, Peter; Büyüköztürk, Oral

    2016-07-01

    Tall buildings are ubiquitous in major cities and house the homes and workplaces of many individuals. However, relatively few studies have been carried out to study the dynamic characteristics of tall buildings based on field measurements. In this paper, the dynamic behavior of the Green Building, a unique 21-story tall structure located on the campus of the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA), was characterized and modeled as a simplified lumped-mass beam model (SLMM), using data from a network of accelerometers. The accelerometer network was used to record structural responses due to ambient vibrations, blast loading, and the October 16th 2012 earthquake near Hollis Center (ME, USA). Spectral and signal coherence analysis of the collected data was used to identify natural frequencies, modes, foundation rocking behavior, and structural asymmetries. A relation between foundation rocking and structural natural frequencies was also found. Natural frequencies and structural acceleration from the field measurements were compared with those predicted by the SLMM which was updated by inverse solving based on advanced multiobjective optimization methods using the measured structural responses and found to have good agreement.

  13. Multi-scale simulations predict responses to non-invasive nerve root stimulation

    Science.gov (United States)

    Laakso, Ilkka; Matsumoto, Hideyuki; Hirata, Akimasa; Terao, Yasuo; Hanajima, Ritsuko; Ugawa, Yoshikazu

    2014-10-01

    Objective. Established biophysical neurone models have achieved limited success in reproducing electrophysiological responses to non-invasive stimulation of the human nervous system. This is related to our insufficient knowledge of the induced electric currents inside the human body. Despite the numerous research and clinical applications of non-invasive stimulation, it is still unclear which internal sites are actually affected by it. Approach. We performed multi-scale computer simulations that, by making use of advances in computing power and numerical algorithms, combine a microscopic model of electrical excitation of neurones with a macroscopic electromagnetic model of the realistic whole-body anatomy. Main results. The simulations yield responses consistent with those experimentally recorded following magnetic and electrical motor root stimulation in human subjects, and reproduce the observed amplitudes and latencies for a wide variety of stimulation parameters. Significance. Our findings demonstrate that modern computational techniques can produce detailed predictions about which and where neurones are activated, leading to improved understanding of the physics and basic mechanisms of non-invasive stimulation and enabling potential new applications that make use of improved targeting of stimulation.

  14. Field Measurement-Based System Identification and Dynamic Response Prediction of a Unique MIT Building

    Directory of Open Access Journals (Sweden)

    Young-Jin Cha

    2016-07-01

    Full Text Available Tall buildings are ubiquitous in major cities and house the homes and workplaces of many individuals. However, relatively few studies have been carried out to study the dynamic characteristics of tall buildings based on field measurements. In this paper, the dynamic behavior of the Green Building, a unique 21-story tall structure located on the campus of the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA, was characterized and modeled as a simplified lumped-mass beam model (SLMM, using data from a network of accelerometers. The accelerometer network was used to record structural responses due to ambient vibrations, blast loading, and the October 16th 2012 earthquake near Hollis Center (ME, USA. Spectral and signal coherence analysis of the collected data was used to identify natural frequencies, modes, foundation rocking behavior, and structural asymmetries. A relation between foundation rocking and structural natural frequencies was also found. Natural frequencies and structural acceleration from the field measurements were compared with those predicted by the SLMM which was updated by inverse solving based on advanced multiobjective optimization methods using the measured structural responses and found to have good agreement.

  15. Can measurement of apparent diffusion coefficient before treatment predict the response to uterine artery embolization for adenomyosis?

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yaewon; Kim, Man Deuk; Jung, Dae Chul; Lee, Shin Jae; Kim, Gyoungmin; Park, Sung Il; Won, Jong Yun; Lee, Do Yun [Yonsei University College of Medicine, Department of Radiology, Severance Hospital, Seoul (Korea, Republic of)

    2015-05-01

    To determine the usefulness of the apparent diffusion coefficient (ADC) in predicting response to uterine artery embolization (UAE) for symptomatic adenomyosis. A prospective study was performed on 25 patients who underwent diffusion-weighted (DW) magnetic resonance imaging (MRI) before UAE between June 2011 and December 2012. All patients underwent 3-month follow-up MRI after UAE using non-spherical polyvinyl alcohol (PVA) particles ranging from 150 to 500 μm. Quantitative measurement of the ADC was performed for each adenomyosis. Complete response and incomplete response were defined as ≥90 % or <90 %, respectively, of the non-perfusion area with adenomyosis at the follow-up MRI. The ADC values were compared between patients who achieved complete or incomplete response which was assessed according to the MRI findings after UAE. Nineteen patients showed complete response, and six showed incomplete response. The ADC value ranged from 0.842 to 1.346 x 10{sup -3} mm{sup 2}/s (mean 1.075 ± 0.117). The mean ADC was 1.043 ± 0.237 in the complete response group and 1.176 ± 0.429 in the incomplete response group (0.012). Using a threshold of <1.147 x 10{sup -3} mm{sup 2}/s, the sensitivity and specificity of the ADC to predict success after UAE were 83.3 % and 84.2 %. The ADC of adenomyosis may potentially predict a successful response to UAE for adenomyosis. (orig.)

  16. Functional trade-offs in succulent stems predict responses to climate change in columnar cacti.

    Science.gov (United States)

    Williams, David G; Hultine, Kevin R; Dettman, David L

    2014-07-01

    Columnar cacti occur naturally in many habitats and environments in the Americas but are conspicuously dominant in very dry desert regions. These majestic plants are widely regarded for their cultural, economic, and ecological value and, in many ecosystems, support highly diverse communities of pollinators, seed dispersers, and frugivores. Massive amounts of water and other resources stored in the succulent photosynthetic stems of these species confer a remarkable ability to grow and reproduce during intensely hot and dry periods. Yet many columnar cacti are potentially under severe threat from environmental global changes, including climate change and loss of habitat. Stems in columnar cacti and other cylindrical-stemmed cacti are morphologically diverse; stem volume-to-surface area ratio (V:S) across these taxa varies by almost two orders of magnitude. Intrinsic functional trade-offs are examined here across a broad range of V:S in species of columnar cacti. It is proposed that variation in photosynthetic gas exchange, growth, and response to stress is highly constrained by stem V:S, establishing a mechanistic framework for understanding the sensitivity of columnar cacti to climate change and drought. Specifically, species that develop stems with low V:S, and thus have little storage capacity, are expected to express high mass specific photosynthesis and growth rates under favourable conditions compared with species with high V:S. But the trade-off of having little storage capacity is that low V:S species are likely to be less tolerant of intense or long-duration drought compared with high V:S species. The application of stable isotope measurements of cactus spines as recorders of growth, water relations, and metabolic responses to the environment across species of columnar cacti that vary in V:S is also reviewed. Taken together, our approach provides a coherent theory and required set of observations needed for predicting the responses of columnar cacti to

  17. Managing and predicting low response to standard in vitro fertilization therapy: a review of the options.

    Science.gov (United States)

    Karande, Visjhvanath C

    2003-01-01

    Low responders remain a difficult group of patients to manage in an in vitro fertilization (IVF) program. Such patients have low peak estradiol concentrations (strategies that have been utilized to manage low responders because the definition of a low responder varies widely. Also, very few large prospective randomized trials have compared different protocols. Two stimulation protocols involving varying doses of leuprorelin and high doses of gonadotropins appear to be the most promising. The early gonadotropin-releasing hormone (GnRH) agonist cessation protocol involves routine pituitary desensitization with luteal phase start of leuprorelin 0.5 mg for 10-14 days. With the onset of gonadotropin treatment, there is cessation of leuprorelin. The 'microdose flare' protocol utilizes oral contraceptive priming followed by diluted doses of leuprorelin 50 microg given twice daily. Two days later, stimulation is started by adding high doses of gonadotropins. The microdoses of leuprorelin and the high doses of gonadotropins are then continued until the day of chorionic gonadotropin administration. Patients who do not respond to these protocols or those with severely diminished ovarian reserve are candidates for donor oocytes. The role of GnRH antagonists and the in vitro maturation of oocytes are potentially exciting strategies that are still being investigated. Ultrasound measurements of ovarian volume, baseline antral follicle counts, and Doppler measurement of ovarian stromal blood flow now make it possible to predict low response to IVF therapy. Low response can be expected if the smaller ovary has a volume <3 cm3, or the mean ovarian diameter in the two longest planes is <20 mm. Antral follicle counts of < or = 3 in each ovary are also associated with low response. Data on ovarian stromal blood flow are still unclear, but an ovarian peak systolic velocity of <10 cm/sec is associated with low response. If low response is anticipated based on baseline ultrasound scan, a

  18. Recognition memory strength is predicted by pupillary responses at encoding while fixation patterns distinguish recollection from familiarity.

    Science.gov (United States)

    Kafkas, Alexandros; Montaldi, Daniela

    2011-10-01

    Thirty-five healthy participants incidentally encoded a set of man-made and natural object pictures, while their pupil response and eye movements were recorded. At retrieval, studied and new stimuli were rated as novel, familiar (strong, moderate, or weak), or recollected. We found that both pupil response and fixation patterns at encoding predict later recognition memory strength. The extent of pupillary response accompanying incidental encoding was found to be predictive of subsequent memory. In addition, the number of fixations was also predictive of later recognition memory strength, suggesting that the accumulation of greater visual detail, even for single objects, is critical for the creation of a strong memory. Moreover, fixation patterns at encoding distinguished between recollection and familiarity at retrieval, with more dispersed fixations predicting familiarity and more clustered fixations predicting recollection. These data reveal close links between the autonomic control of pupil responses and eye movement patterns on the one hand and memory encoding on the other. Moreover, the data illustrate quantitative as well as qualitative differences in the incidental visual processing of stimuli, which are differentially predictive of the strength and the kind of memory experienced at recognition.

  19. A temporal predictive code for voice motor control: Evidence from ERP and behavioral responses to pitch-shifted auditory feedback.

    Science.gov (United States)

    Behroozmand, Roozbeh; Sangtian, Stacey; Korzyukov, Oleg; Larson, Charles R

    2016-04-01

    The predictive coding model suggests that voice motor control is regulated by a process in which the mismatch (error) between feedforward predictions and sensory feedback is detected and used to correct vocal motor behavior. In this study, we investigated how predictions about timing of pitch perturbations in voice auditory feedback would modulate ERP and behavioral responses during vocal production. We designed six counterbalanced blocks in which a +100 cents pitch-shift stimulus perturbed voice auditory feedback during vowel sound vocalizations. In three blocks, there was a fixed delay (500, 750 or 1000 ms) between voice and pitch-shift stimulus onset (predictable), whereas in the other three blocks, stimulus onset delay was randomized between 500, 750 and 1000 ms (unpredictable). We found that subjects produced compensatory (opposing) vocal responses that started at 80 ms after the onset of the unpredictable stimuli. However, for predictable stimuli, subjects initiated vocal responses at 20 ms before and followed the direction of pitch shifts in voice feedback. Analysis of ERPs showed that the amplitudes of the N1 and P2 components were significantly reduced in response to predictable compared with unpredictable stimuli. These findings indicate that predictions about temporal features of sensory feedback can modulate vocal motor behavior. In the context of the predictive coding model, temporally-predictable stimuli are learned and reinforced by the internal feedforward system, and as indexed by the ERP suppression, the sensory feedback contribution is reduced for their processing. These findings provide new insights into the neural mechanisms of vocal production and motor control.

  20. Prediction of lip response to orthodontic treatment using a multivariable regression model

    Directory of Open Access Journals (Sweden)

    Amin Shirvani

    2016-01-01

    Conclusion: Within the limitation of this study, multiple regression technique was slightly more accurate than the ratio of mean prediction (Viewbox4.0 software and appears to be useful in the prediction of soft tissue changes. As the variability of the predicted individual outcome seems to be relatively high, caution should be taken in predicting hard and soft tissue positional changes.

  1. Prediction of response to neoadjuvant chemotherapy in osteosarcoma using dual-phase {sup 18}F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun [The Catholic University of Korea, Division of Nuclear Medicine, Department of Radiology, College of Medicine, Seoul (Korea, Republic of); Korea Institute of Radiological and Medical Sciences (KIRAMS), Departments of Nuclear Medicine, Seoul (Korea, Republic of); Kim, Sung Hoon; Chung, Soo Kyo [The Catholic University of Korea, Division of Nuclear Medicine, Department of Radiology, College of Medicine, Seoul (Korea, Republic of); Lim, Sang Moo; Lim, Ilhan [Korea Institute of Radiological and Medical Sciences (KIRAMS), Departments of Nuclear Medicine, Seoul (Korea, Republic of); Kong, Chang-Bae; Song, Won Seok; Cho, Wan Hyeong; Jeon, Dae-Geun; Lee, Soo-Yong [Korea Institute of Radiological and Medical Sciences (KIRAMS), Orthopedic Surgery, Seoul (Korea, Republic of); Koh, Jae-Soo [Korea Institute of Radiological and Medical Sciences (KIRAMS), Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2015-07-15

    We evaluated the ability of dual-phase {sup 18}F-FDG PET/CT to predict the histological response after neoadjuvant chemotherapy (NAC) in osteosarcoma. Thirty-one patients with osteosarcoma treated with NAC and surgery were prospectively enrolled. After injection of {sup 18}F-FDG, both early (∝60 min) and delayed (∝150 min) PET were acquired before and after the completion of NAC. SUVmax, early/delayed SUVmax change (RImax), and early/delayed SUVmean change (RImean) of tumour were measured before (SUV1, RImax1, and RImean1) and after NAC (SUV2, RImax2, and RImean2). Then, we calculated the percentage changes between SUV1 and SUV2 (%SUV). Twelve patients (39 %) exhibited good histological response after NAC. SUVmax, RImax, and RImean significantly decreased after NAC. Before NAC, only RImean1 predicted good histological response with the optimal criterion of < 10 %, sensitivity of 92 %, specificity of 57 %, and accuracy of 71 %. After NAC, %SUV, SUV2, and RImax2 predicted histological response. By using combined criterion of %SUV and RImax2 or SUV2 and RImean1 or SUV2 and RImax2, accuracies were 81 %, 77 %, and 77 %, respectively. The histological response after NAC could be predicted by using RImean1 before the initiation of NAC in osteosarcoma. The combined use of SUV and RI values may provide a better prediction. (orig.)

  2. ADAMTS13 predicts renal and cardiovascular events in type 2 diabetic patients and response to therapy.

    Science.gov (United States)

    Rurali, Erica; Noris, Marina; Chianca, Antonietta; Donadelli, Roberta; Banterla, Federica; Galbusera, Miriam; Gherardi, Giulia; Gastoldi, Sara; Parvanova, Aneliya; Iliev, Ilian; Bossi, Antonio; Haefliger, Carolina; Trevisan, Roberto; Remuzzi, Giuseppe; Ruggenenti, Piero

    2013-10-01

    In patients with diabetes, impaired ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) proteolysis of highly thrombogenic von Willebrand factor (VWF) multimers may accelerate renal and cardiovascular complications. Restoring physiological VWF handling might contribute to ACE inhibitors' (ACEi) reno- and cardioprotective effects. To assess how Pro618Ala ADAMTS13 variants and related proteolytic activity interact with ACEi therapy in predicting renal and cardiovascular complications, we genotyped 1,163 normoalbuminuric type 2 diabetic patients from BErgamo NEphrologic DIabetes Complications Trial (BENEDICT). Interaction between Pro618Ala and ACEi was significant in predicting both renal and combined renal and cardiovascular events. The risk for renal or combined events versus reference Ala carriers on ACEi progressively increased from Pro/Pro homozygotes on ACEi (hazard ratio 2.80 [95% CI 0.849-9.216] and 1.58 [0.737-3.379], respectively) to Pro/Pro homozygotes on non-ACEi (4.77 [1.484-15.357] and 1.99 [0.944-4.187]) to Ala carriers on non-ACEi (8.50 [2.416-29.962] and 4.00 [1.739-9.207]). In a substudy, serum ADAMTS13 activity was significantly lower in Ala carriers than in Pro/Pro homozygotes and in case subjects with renal, cardiovascular, or combined events than in diabetic control subjects without events. ADAMTS13 activity significantly and negatively correlated with all outcomes. In patients with diabetes, ADAMTS13 618Ala variant associated with less proteolytic activity, higher risk of chronic complications, and better response to ACEi therapy. Screening for Pro618Ala polymorphism may help identify patients with diabetes at highest risk who may benefit the most from early reno- and cardioprotective therapy.

  3. Organizational changes to thyroid regulation in Alligator mississippiensis: evidence for predictive adaptive responses.

    Directory of Open Access Journals (Sweden)

    Ashley S P Boggs

    Full Text Available During embryonic development, organisms are sensitive to changes in thyroid hormone signaling which can reset the hypothalamic-pituitary-thyroid axis. It has been hypothesized that this developmental programming is a 'predictive adaptive response', a physiological adjustment in accordance with the embryonic environment that will best aid an individual's survival in a similar postnatal environment. When the embryonic environment is a poor predictor of the external environment, the developmental changes are no longer adaptive and can result in disease states. We predicted that endocrine disrupting chemicals (EDCs and environmentally-based iodide imbalance could lead to developmental changes to the thyroid axis. To explore whether iodide or EDCs could alter developmental programming, we collected American alligator eggs from an estuarine environment with high iodide availability and elevated thyroid-specific EDCs, a freshwater environment contaminated with elevated agriculturally derived EDCs, and a reference freshwater environment. We then incubated them under identical conditions. We examined plasma thyroxine and triiodothyronine concentrations, thyroid gland histology, plasma inorganic iodide, and somatic growth at one week (before external nutrition and ten months after hatching (on identical diets. Neonates from the estuarine environment were thyrotoxic, expressing follicular cell hyperplasia (p = 0.01 and elevated plasma triiodothyronine concentrations (p = 0.0006 closely tied to plasma iodide concentrations (p = 0.003. Neonates from the freshwater contaminated site were hypothyroid, expressing thyroid follicular cell hyperplasia (p = 0.01 and depressed plasma thyroxine concentrations (p = 0.008. Following a ten month growth period under identical conditions, thyroid histology (hyperplasia p = 0.04; colloid depletion p = 0.01 and somatic growth (body mass p<0.0001; length p = 0.02 remained altered among the

  4. Optimal prediction of human postural response under anterior-posterior platform tilting

    Science.gov (United States)

    Naderi, D.; Miripour Fard, B.; Sadeghi-Mehr, M.

    2013-01-01

    Previous studies have suggested that human beings movements can be related to the problem of cost function minimization. But at the present time it is not clear that which objective function(s) and constraints are used by central nervous system (CNS) to produce optimal reactions under perturbations. Present study has been done experimentally and by numerical simulations to explore the stability constraints which should be used in combination with energy based cost function (weighted minimum torque) to estimate the motor planning criterion is used by CNS for disturbance rejections. The influence of three stability criterions (ZMP, extrapolated center of mass and a vertical force criterion) in combination with minimum torque model on the optimal trajectory formation is investigated. First, the response of 10 male healthy persons to platform oscillation was recorded by motion analysis system and the hip, knee and ankle angular trajectories were derived from recorded data. Second, the dynamic simulation of a four-segment, three actuated degrees of freedom mechanical model of the human body was performed using predictive dynamic method which leads to an optimization problem. The simulated trajectories were then compared to the experimental data. With comparison between experimental results, the weighting coefficients of the objective function were found to achieve best estimation. It was seen that the minimum torque objective function with weighting coefficients gives trajectories that are mostly matched with experimental observation. Moreover, the results showed that between stability criterions, the ZMP predictions are near to experimental results. Although by using vertical force criterion some nearness to experimental results are lost (in comparison with ZMP criterion) but a secured flat-foot posture for the model is obtained which this posture is more applicable than others in humanoid implementations.

  5. Predicting woodrat (Neotoma) responses to anthropogenic warming from studies of the palaeomidden record

    Science.gov (United States)

    Smith, Felisa A.; Betancourt, Julio L.

    2006-01-01

    Aim The influence of anthropogenic climate change on organisms is an area of great scientific concern. Increasingly there is recognition that abrupt climate transitions have occurred over the late Quaternary; studies of these shifts may yield insights into likely biotic responses to contemporary warming. Here, we review research undertaken over the past decade investigating the response of Neotoma (woodrats) body size and distribution to climate change over the late Quaternary (the last 40,000 years). By integrating information from woodrat palaeomiddens, historical museum specimens and field studies of modern populations, we identify potential evolutionary responses to climate change occurring over a variety of temporal and spatial scales. Specifically, we characterize climatic thresholds in the past that led to local species extirpation and/or range alterations rather than in situ adaptation, and apply them to anticipate potential biotic responses to anthropogenic climate change. Location Middens were collected at about 55 sites scattered across the western United States, ranging from about 34 to 46° N and about 104 to 116° W, respectively. Data for modern populations were drawn from studies conducted in Death Valley, California, Missoula, Montana and the Sevilleta LTER site in central New Mexico. Methods We analysed faecal pellets from midden series collected at numerous cave sites across the western United States. From these we estimated body mass using techniques validated in earlier studies. We compared body size fluctuations at different elevations in different regions and integrated these results with studies investigating temperature–body size tradeoffs in modern animals. We also quantify the rapidity of the size changes over the late Quaternary to estimate the evolutionary capacity of woodrats to deal with predicted rates of anthropogenic climate change over the next century. Results We find remarkable similarities across the geographical range to

  6. Quantitative analysis of nuclear shape in oral squamous cell carcinoma is useful for predicting the chemotherapeutic response.

    Science.gov (United States)

    Ogura, Maki; Yamamoto, Yoichiro; Miyashita, Hitoshi; Kumamoto, Hiroyuki; Fukumoto, Manabu

    2016-06-01

    The number of people afflicted with oral carcinoma in Japan has increased in recent years. Although preoperative neoadjuvant therapy with cisplatin and 5-fluorouracil are performed, chemotherapeutic response varies widely among the patients. With the aim of establishing novel indices to predict the therapeutic response to chemotherapy, we investigated the relationship between morphological features of pre-treatment oral carcinoma nuclei and the chemotherapeutic response using quantifying morphology of cell nuclei in pathological specimen images. We measured 4 morphological features of the nucleus of oral squamous cell carcinoma cases classified by the response to chemotherapy: No Change (NC) group, Partial Response (PR) group and Complete Response (CR) group. Furthermore, we performed immunohistochemical staining for p53 and Ki67 and calculated their positive rates in cancer tissues. Compactness and symmetry of the nucleus were significantly higher and nuclear edge response was significantly lower in cancer cells with lower chemotherapeutic responses compared high chemotherapeutic responders. As for positive rates of p53 and Ki67, there were no significant differences between any of the response groups. Morphological features of cancer cell nuclei in pathological specimens are sensitive predictive factors for the chemotherapeutic response to oral squamous cell carcinoma.

  7. From field to region yield predictions in response to pedo-climatic variations in Eastern Canada

    Science.gov (United States)

    JÉGO, G.; Pattey, E.; Liu, J.

    2013-12-01

    to improve regional crop modelling. Although several aspects of the coupling between crop models and RS data have been investigated (e.g., inversion of radiative transfer models and neural networks), extensive verification using multiple years and sites is required prior to implementation of the RS assimilation at the regional scale, in order to evaluate the model robustness and consistency in response to climatic variations. STICS performance was evaluated over several years for spring wheat, soybean and corn yield predictions over two small rainfed agricultural region of Eastern Canada exhibiting a high degree of pedodiversity when LAI derived from EO data was assimilated. Averaged yield predictions of the three crops compared well with measurements (10%

  8. Response of Himalayan debris-covered glaciers to climate warming: from observations to predictive modeling

    Science.gov (United States)

    Benn, D.; Lefeuvre, P.; Ng, F.; Nicholson, L. I.

    2012-12-01

    , temperature increases have a strong impact on glacier mass balance, increasing melt and the altitude of the rain-snow transition in the summer accumulation season. At a more detailed level, melt models can simulate evolving surface topography and backwasting in response to variations in debris thickness. Recent simulations using coupled mass-balance - flow models can mimic key aspects of the observed behavior of debris-covered glaciers, including debris thickness - melt rate feedbacks, asymmetric advance - retreat cycles, as well as detachment and stagnation of glacier tongues in response to ELA rise. Future modeling challenges include parameterization of lake expansion and deepening processes, developing criteria for switching between ablation regimes, and upscaling the effects of spatially and temporally variable local processes. In the foreseeable future, advanced modeling efforts informed closely by observational studies should enable quantitative predictions to be made about the fate of debris-covered glaciers in the Himalaya.

  9. A Cooperative Test of the Load/Unload Response Ratio Proposed Method of Earthquake Prediction

    Science.gov (United States)

    Trotta, J. E.; Tullis, T. E.

    2004-12-01

    The Load/Unload Response Ratio (LURR) method is a proposed technique to predict earthquakes that was first put forward by Yin in 1984 (Yin, 1987). LURR is based on the idea that when a region is near failure, there is an increase in the rate of seismic activity during loading of the tidal cycle relative to the rate of seismic activity during unloading of the tidal cycle. Typically the numerator of the LURR ratio is the number, or the sum of some measure of the size (e.g. Benioff strain), of small earthquakes that occur during loading of the tidal cycle, whereas the denominator is the same as the numerator except it is calculated during unloading. LURR method suggests this ratio should increase in the months to year preceding a large earthquake. Regions near failure have tectonic stresses nearly high enough for a large earthquake to occur, thus it seems more likely that smaller earthquakes in the region would be triggered when the tidal stresses add to the tectonic ones. However, until recently even the most careful studies suggested that the effect of tidal stresses on earthquake occurrence is very small and difficult to detect. New studies have shown that there is a tidal triggering effect on shallow thrust faults in areas with strong tides from ocean loading (Tanaka et al., 2002; Cochran et al., 2004). We have been conducting an independent test of the LURR method, since there would be important scientific and social implications if the LURR method were proven to be a robust method of earthquake prediction. Smith and Sammis (2003) also undertook a similar study. Following both the parameters of Yin et al. (2000) and the somewhat different ones of Smith and Sammis (2003), we have repeated calculations of LURR for the Northridge and Loma Prieta earthquakes in California. Though we have followed both sets of parameters closely, we have been unable to reproduce either set of results. A general agreement was made at the recent ACES Workshop in China between research

  10. Predicting the Responses of Soil Nitrite-Oxidizers to Multi-Factorial Global Change: A Trait-Based Approach

    DEFF Research Database (Denmark)

    Le Roux, Xavier; Bouskill, Nicholas J.; Niboyet, Audrey;

    2016-01-01

    change scenarios for central California) on the potential activity, abundance and dominant taxa of soil nitrite-oxidizing bacteria (NOB). Using a trait-based model, we then tested whether categorizing NOB into a few functional groups unified by physiological traits enables understanding and predicting......Soil microbial diversity is huge and a few grams of soil contain more bacterial taxa than there are bird species on Earth. This high diversity often makes predicting the responses of soil bacteria to environmental change intractable and restricts our capacity to predict the responses of soil...... how soil NOB respond to global environmental change. Contrasted responses to global change treatments were observed between three main NOB functional types. In particular, putatively mixotrophic Nitrobacter, rare under most treatments, became dominant under the 'High CO2+Nitrogen...

  11. The Factors That May Predict Response to Rituximab Therapy in Recurrent Focal Segmental Glomerulosclerosis: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Carlos E. Araya

    2011-01-01

    Full Text Available Recurrence of FSGS occurs in 30–40% of allografts. Therapies for recurrence are not well established. We retrieved all published reports depicting kidney transplant recipients with focal segmental glomerulosclerosis (FSGS recurrence, treated with rituximab, to determine factors associated with treatment response. We found 18 reports of 39 transplant recipients who received rituximab. By univariate analysis for two outcomes (no response versus any response, fewer rituximab infusions and normal serum albumin at recurrence were associated with treatment response. For 3 outcomes (no response, partial and complete remission, male gender, fewer rituximab infusions, shorter time to rituximab treatment, and normal serum albumin were associated with remission. Multivariate analysis for both models revealed that normal serum albumin at FSGS recurrence and lower age at transplant were associated with response. Rituximab for recurrence of FSGS may be beneficial for only some patients. A younger age at transplant and normal serum albumin level at recurrence diagnosis may predict response.

  12. NUMERICAL PREDICTION OF PROPELLER EXCITED ACOUSTIC RESPONSE OF SUBMARINE STRUCTURE BASED ON CFD, FEM AND BEM

    Institute of Scientific and Technical Information of China (English)

    WEI Ying-san; WANG Yong-sheng; CHANG Shu-ping; FU Jian

    2012-01-01

    A mesh-less Refined Integral Algorithm (RIA) of Boundary Element Method (BEM) is proposed to accurately solve the Helmholtz Integral Equation (HIE).The convergence behavior and the practicability of the method are validated.Computational Fluid Dynamics (CFD),Finite Element Method (FEM) and RIA are used to predict the propeller excited underwater noise of the submarine hull structure.Firstly the propeller and submarine's flows are independently validated,then the self propulsion of the “submarine+propeller” system is simulated via CFD and the balanced point of the system is determined as well as the self propulsion factors.Secondly,the transient response of the “submarine + propeller” system is analyzed at the balanced point,and the propeller thrust and torque excitations are calculated.Thirdly the thrust and the torque excitations of the propeller are loaded on the submarine,respectively,to calculate the acoustic response,and the sound pover and the main peak frequencies are obtained.Results show that:(1) the thrust mainly excites the submarine axial mode and the high frequency area appears at the two conical-type ends,while the torque mainly excites the circumferential mode and the high frequency area appears at the broadside of the cylindrical section,but with rather smaller sound power and radiation efficiency than the former,(2) the main sound source appears at BPF and 2BPF and comes from the harmonic propeller excitations.So,the main attention should be paid on the thrust excitation control for the sound reduction of the propeller excited submarine structure.

  13. Methylphenidate for the treatment of apathy in Alzheimer disease: prediction of response using dextroamphetamine challenge.

    Science.gov (United States)

    Herrmann, Nathan; Rothenburg, Lana S; Black, Sandra E; Ryan, Michelle; Liu, Barbara A; Busto, Usoa E; Lanctôt, Krista L

    2008-06-01

    Apathy is a common behavioral symptom of Alzheimer's disease (AD), being present in up to 70% of patients. Apathy in AD and non-AD populations has been associated with dysfunction in the dopaminergic brain reward system, suggesting that pharmacotherapeutic targeting of this system may be an effective treatment for apathy in AD. We therefore performed a randomized, double-blind, placebo-controlled crossover trial of methylphenidate in a sample of 13 apathetic AD patients (6 men, 7 women; age mean 77.9 years [SD, 7.8 years]; Mini Mental Status Examination score, 19.9 [SD, 4.7]). Patients were treated with methylphenidate (10 mg PO twice a day) or an identical placebo in two 2-week phases separated by a 1-week placebo washout. All patients participated in a dextroamphetamine challenge test (one 10-mg oral dose) before treatment with methylphenidate to gauge the functional integrity of the dopamine brain reward system. Overall, patients demonstrated greater improvement with methylphenidate compared with placebo according to Apathy Evaluation Scale total change scores (end of treatment - baseline: Wilcoxon Z = -2.00; P = 0.047). However, a significantly greater proportion of patients experienced at least 1 adverse event with methylphenidate compared with placebo (3 vs 1; chi = 4.33, P = 0.038). Two patients experienced serious adverse events with methylphenidate, consisting of delusions, agitation, anger, irritability, and insomnia, which resolved upon discontinuation of the medication. Response to methylphenidate was associated with increases in inattention on a continuous performance task after dextroamphetamine challenge. Psychostimulants may be effective in treating features of apathy in AD, and dopaminergic changes may predict response.

  14. In Silico Analysis of Microarray-Based Gene Expression Profiles Predicts Tumor Cell Response to Withanolides

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2012-05-01

    Full Text Available Withania somnifera (L. Dunal (Indian ginseng, winter cherry, Solanaceae is widely used in traditional medicine. Roots are either chewed or used to prepare beverages (aqueous decocts. The major secondary metabolites of Withania somnifera are the withanolides, which are C-28-steroidal lactone triterpenoids. Withania somnifera extracts exert chemopreventive and anticancer activities in vitro and in vivo. The aims of the present in silico study were, firstly, to investigate whether tumor cells develop cross-resistance between standard anticancer drugs and withanolides and, secondly, to elucidate the molecular determinants of sensitivity and resistance of tumor cells towards withanolides. Using IC50 concentrations of eight different withanolides (withaferin A, withaferin A diacetate, 3-azerininylwithaferin A, withafastuosin D diacetate, 4-B-hydroxy-withanolide E, isowithanololide E, withafastuosin E, and withaperuvin and 19 established anticancer drugs, we analyzed the cross-resistance profile of 60 tumor cell lines. The cell lines revealed cross-resistance between the eight withanolides. Consistent cross-resistance between withanolides and nitrosoureas (carmustin, lomustin, and semimustin was also observed. Then, we performed transcriptomic microarray-based COMPARE and hierarchical cluster analyses of mRNA expression to identify mRNA expression profiles predicting sensitivity or resistance towards withanolides. Genes from diverse functional groups were significantly associated with response of tumor cells to withaferin A diacetate, e.g. genes functioning in DNA damage and repair, stress response, cell growth regulation, extracellular matrix components, cell adhesion and cell migration, constituents of the ribosome, cytoskeletal organization and regulation, signal transduction, transcription factors, and others.

  15. Parametric response mapping of dynamic CT for predicting intrahepatic recurrence of hepatocellular carcinoma after conventional transcatheter arterial chemoembolization

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seung Joon; Kim, Hyung Sik [Gachon University Gil Hospital, Department of Radiology, Incheon (Korea, Republic of); Kim, Jonghoon [Sungkyunkwan University, Department of Electronic Electrical and Computer Engineering, Suwon (Korea, Republic of); Seo, Jongbum [Yonsei University, Department of Biomedical Engineering, Wonju (Korea, Republic of); Lee, Jong-min [Hanyang University, Department of Biomedical Engineering, Seoul (Korea, Republic of); Park, Hyunjin [Sungkyunwkan University, School of Electronic and Electrical Engineering, Suwon (Korea, Republic of)

    2016-01-15

    The aim of our study was to determine the diagnostic value of a novel image analysis method called parametric response mapping (PRM) for prediction of intrahepatic recurrence of hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (TACE). This retrospective study was approved by the IRB. We recruited 55 HCC patients who achieved complete remission (CR) after TACE and received longitudinal multiphasic liver computed tomography (CT). The patients fell into two groups: the recurrent tumour group (n = 29) and the non-recurrent tumour group (n = 26). We applied the PRM analysis to see if this technique could distinguish between the two groups. The results of the PRM analysis were incorporated into a prediction algorithm. We retrospectively removed data from the last time point and attempted to predict the response to therapy of the removed data. The PRM analysis was able to distinguish between the non-recurrent and recurrent groups successfully. The prediction algorithm detected response to therapy with an area under the curve (AUC) of 0.76, while the manual approach had AUC 0.64. Adopting PRM analysis can potentially distinguish between recurrent and non-recurrent HCCs and allow for prediction of response to therapy after TACE. (orig.)

  16. Artificial neural network and response surface methodology modeling in mass transfer parameters predictions during osmotic dehydration of Carica papaya L.

    Directory of Open Access Journals (Sweden)

    J. Prakash Maran

    2013-09-01

    Full Text Available In this study, a comparative approach was made between artificial neural network (ANN and response surface methodology (RSM to predict the mass transfer parameters of osmotic dehydration of papaya. The effects of process variables such as temperature, osmotic solution concentration and agitation speed on water loss, weight reduction, and solid gain during osmotic dehydration were investigated using a three-level three-factor Box-Behnken experimental design. Same design was utilized to train a feed-forward multilayered perceptron (MLP ANN with back-propagation algorithm. The predictive capabilities of the two methodologies were compared in terms of root mean square error (RMSE, mean absolute error (MAE, standard error of prediction (SEP, model predictive error (MPE, chi square statistic (χ2, and coefficient of determination (R2 based on the validation data set. The results showed that properly trained ANN model is found to be more accurate in prediction as compared to RSM model.

  17. Stroke volume variation does not predict fluid responsiveness in patients with septic shock on pressure support ventilation

    DEFF Research Database (Denmark)

    Perner, A; Faber, T

    2006-01-01

    Stroke volume variation (SVV)--as measured by the pulse contour cardiac output (PiCCO) system--predicts the cardiac output response to a fluid challenge in patients on controlled ventilation. Whether this applies to patients on pressure support ventilation is unknown.......Stroke volume variation (SVV)--as measured by the pulse contour cardiac output (PiCCO) system--predicts the cardiac output response to a fluid challenge in patients on controlled ventilation. Whether this applies to patients on pressure support ventilation is unknown....

  18. Validation and Use of a Predictive Modeling Tool: Employing Scientific Findings to Improve Responsible Conduct of Research Education.

    Science.gov (United States)

    Mulhearn, Tyler J; Watts, Logan L; Todd, E Michelle; Medeiros, Kelsey E; Connelly, Shane; Mumford, Michael D

    2017-01-01

    Although recent evidence suggests ethics education can be effective, the nature of specific training programs, and their effectiveness, varies considerably. Building on a recent path modeling effort, the present study developed and validated a predictive modeling tool for responsible conduct of research education. The predictive modeling tool allows users to enter ratings in relation to a given ethics training program and receive instantaneous evaluative information for course refinement. Validation work suggests the tool's predicted outcomes correlate strongly (r = 0.46) with objective course outcomes. Implications for training program development and refinement are discussed.

  19. Artificial Neural Network and Response Surface Methodology Modeling in Ionic Conductivity Predictions of Phthaloylchitosan-Based Gel Polymer Electrolyte

    Directory of Open Access Journals (Sweden)

    Ahmad Danial Azzahari

    2016-01-01

    Full Text Available A gel polymer electrolyte system based on phthaloylchitosan was prepared. The effects of process variables, such as lithium iodide, caesium iodide, and 1-butyl-3-methylimidazolium iodide were investigated using a distance-based ternary mixture experimental design. A comparative approach was made between response surface methodology (RSM and artificial neural network (ANN to predict the ionic conductivity. The predictive capabilities of the two methodologies were compared in terms of coefficient of determination R2 based on the validation data set. It was shown that the developed ANN model had better predictive outcome as compared to the RSM model.

  20. Neuromagnetic oscillations predict evoked-response latency delays and core language deficits in autism spectrum disorders.

    Science.gov (United States)

    Edgar, J Christopher; Khan, Sarah Y; Blaskey, Lisa; Chow, Vivian Y; Rey, Michael; Gaetz, William; Cannon, Katelyn M; Monroe, Justin F; Cornew, Lauren; Qasmieh, Saba; Liu, Song; Welsh, John P; Levy, Susan E; Roberts, Timothy P L

    2015-02-01

    Previous studies have observed evoked response latency as well as gamma band superior temporal gyrus (STG) auditory abnormalities in individuals with autism spectrum disorders (ASD). A limitation of these studies is that associations between these two abnormalities, as well as the full extent of oscillatory phenomena in ASD in terms of frequency and time, have not been examined. Subjects were presented pure tones at 200, 300, 500, and 1,000 Hz while magnetoencephalography assessed activity in STG auditory areas in a sample of 105 children with ASD and 36 typically developing controls (TD). Findings revealed a profile such that auditory STG processes in ASD were characterized by pre-stimulus abnormalities across multiple frequencies, then early high-frequency abnormalities followed by low-frequency abnormalities. Increased pre-stimulus activity was a 'core' abnormality, with pre-stimulus activity predicting post-stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4 Core Language Index). Deficits in synaptic integration in the auditory cortex are associated with oscillatory abnormalities in ASD as well as patient symptoms. Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal-to-noise deficit in individuals with ASD, with elevations in oscillatory activity suggesting an inability to maintain an appropriate 'neural tone' and an inability to rapidly return to a resting state prior to the next stimulus.

  1. Predictions replaced by facts: a keystone species' behavioural responses to declining arctic sea-ice.

    Science.gov (United States)

    Hamilton, Charmain D; Lydersen, Christian; Ims, Rolf A; Kovacs, Kit M

    2015-11-01

    Since the first documentation of climate-warming induced declines in arctic sea-ice, predictions have been made regarding the expected negative consequences for endemic marine mammals. But, several decades later, little hard evidence exists regarding the responses of these animals to the ongoing environmental changes. Herein, we report the first empirical evidence of a dramatic shift in movement patterns and foraging behaviour of the arctic endemic ringed seal (Pusa hispida), before and after a major collapse in sea-ice in Svalbard, Norway. Among other changes to the ice-regime, this collapse shifted the summer position of the marginal ice zone from over the continental shelf, northward to the deep Arctic Ocean Basin. Following this change, which is thought to be a 'tipping point', subadult ringed seals swam greater distances, showed less area-restricted search behaviour, dived for longer periods, exhibited shorter surface intervals, rested less on sea-ice and did less diving directly beneath the ice during post-moulting foraging excursions. In combination, these behavioural changes suggest increased foraging effort and thus also likely increases in the energetic costs of finding food. Continued declines in sea-ice are likely to result in distributional changes, range reductions and population declines in this keystone arctic species.

  2. Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies.

    Science.gov (United States)

    Webb, Nicholas E; Montefiori, David C; Lee, Benhur

    2015-09-29

    A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values (50 and 80% inhibitory concentrations) figure prominently into the selection of clinical candidates; however, much higher therapeutic levels will be required to reduce multiple logs of virus and impede escape. Here we predict bnAb potency at therapeutic levels by analysing dose-response curve slopes, and show that slope is independent of IC50/IC80 and specifically relates to bnAb epitope class. With few exceptions, CD4-binding site and V3-glycan bnAbs exhibit slopes >1, indicative of higher expected therapeutic effectiveness, whereas V2-glycan, gp41 membrane-proximal external region (MPER) and gp120-gp41 bnAbs exhibit less favourable slopes <1. Our results indicate that slope is one major predictor of both potency and breadth for bnAbs at clinically relevant concentrations, and may better coordinate the relationship between bnAb epitope structure and therapeutic expectations.

  3. Predicting gender differences as latent variables: summed scores, and individual item responses: a methods case study

    Directory of Open Access Journals (Sweden)

    Jacobs Danny O

    2004-10-01

    Full Text Available Abstract Background Modeling latent variables such as physical disability is challenging since its measurement is performed through proxies. This poses significant methodological challenges. The objective of this article is to present three different methods to predict latent variables based on classical summed scores, individual item responses, and latent variable models. Methods This is a review of the literature and data analysis using "layers of information". Data was collected from the North Carolina Back Pain Project, using a modified version of the Roland Questionnaire. Results The three models are compared in relation to their goals and underlying concepts, previous clinical applications, data requirements, statistical theory, and practical applications. Initial linear regression models demonstrated a difference in disability between genders of 1.32 points (95% CI 0.65, 2.00 on a scale from 0–23. Subsequent item analysis found contradictory results across items, with no clear pattern. Finally, IRT models demonstrated three items were demonstrated to present differential item functioning. After these items were removed, the difference between genders was reduced to 0.78 points (95% CI, -0.99, 1.23. These results were shown to be robust with re-sampling methods. Conclusions Purported differences in the levels of a latent variable should be tested using different models to verify whether these differences are real or simply distorted by model assumptions.

  4. Muscle fatigue experienced during maximal eccentric exercise is predictive of the plasma creatine kinase (CK) response.

    Science.gov (United States)

    Hody, S; Rogister, B; Leprince, P; Wang, F; Croisier, J-L

    2013-08-01

    Unaccustomed eccentric exercise may cause skeletal muscle damage with an increase in plasma creatine kinase (CK) activity. Although the wide variability among individuals in CK response to standardized lengthening contractions has been well described, the reasons underlying this phenomenon have not yet been understood. Therefore, this study investigated a possible correlation of the changes in muscle damage indirect markers after an eccentric exercise with the decline in muscle performance during the exercise. Twenty-seven healthy untrained male subjects performed three sets of 30 maximal isokinetic eccentric contractions of the knee extensors. The muscular work was recorded using an isokinetic dynamometer to assess muscle fatigue by means of various fatigue indices. Plasma CK activity, muscle soreness, and stiffness were measured before (pre) and one day after (post) exercise. The eccentric exercise bout induced significant changes of the three muscle damage indirect markers. Large inter-subject variability was observed for all criteria measured. More interestingly, the log (CK(post) /CK(pre)) and muscle stiffness appeared to be closely correlated with the relative work decrease (r = 0.84, r(2)  = 0.70 and r = 0.75, r(2)  = 0.56, respectively). This is the first study to propose that the muscle fatigue profile during maximal eccentric protocol could predict the magnitude of the symptoms associated with muscle damage in humans.

  5. Modeling light adaptation in circadian clock: prediction of the response that stabilizes entrainment.

    Science.gov (United States)

    Tsumoto, Kunichika; Kurosawa, Gen; Yoshinaga, Tetsuya; Aihara, Kazuyuki

    2011-01-01

    Periods of biological clocks are close to but often different from the rotation period of the earth. Thus, the clocks of organisms must be adjusted to synchronize with day-night cycles. The primary signal that adjusts the clocks is light. In Neurospora, light transiently up-regulates the expression of specific clock genes. This molecular response to light is called light adaptation. Does light adaptation occur in other organisms? Using published experimental data, we first estimated the time course of the up-regulation rate of gene expression by light. Intriguingly, the estimated up-regulation rate was transient during light period in mice as well as Neurospora. Next, we constructed a computational model to consider how light adaptation had an effect on the entrainment of circadian oscillation to 24-h light-dark cycles. We found that cellular oscillations are more likely to be destabilized without light adaption especially when light intensity is very high. From the present results, we predict that the instability of circadian oscillations under 24-h light-dark cycles can be experimentally observed if light adaptation is altered. We conclude that the functional consequence of light adaptation is to increase the adjustability to 24-h light-dark cycles and then adapt to fluctuating environments in nature.

  6. Neuroimaging biomarkers to predict treatment response in schizophrenia: the end of 30 years of solitude?

    Science.gov (United States)

    Dazzan, Paola

    2014-12-01

    Studies that have used structural magnetic resonance imaging (MRI) suggest that individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, and in the white matter tracts that connect them. Furthermore, these studies suggest that brain alterations may be particularly prominent, already at illness onset, in those individuals more likely to have poorer outcomes (eg, higher number of hospital admissions, and poorer symptom remission, level of functioning, and response to the first treatment with antipsychotic drugs). The fact that, even when present, these brain alterations are subtle and distributed in nature, has limited, until now, the utility of MRI in the clinical management of these disorders. More recently, MRI approaches, such as machine learning, have suggested that these neuroanatomical biomarkers can be used for direct clinical benefits. For example, using support vector machine, MRI data obtained at illness onset have been used to predict, with significant accuracy, whether a specific individual is likely to experience a remission of symptoms later on in the course of the illness. Taken together, this evidence suggests that validated, strong neuroanatomical markers could be used not only to inform tailored intervention strategies in a single individual, but also to allow patient stratification in clinical trials for new treatments.

  7. Modeling light adaptation in circadian clock: prediction of the response that stabilizes entrainment.

    Directory of Open Access Journals (Sweden)

    Kunichika Tsumoto

    Full Text Available Periods of biological clocks are close to but often different from the rotation period of the earth. Thus, the clocks of organisms must be adjusted to synchronize with day-night cycles. The primary signal that adjusts the clocks is light. In Neurospora, light transiently up-regulates the expression of specific clock genes. This molecular response to light is called light adaptation. Does light adaptation occur in other organisms? Using published experimental data, we first estimated the time course of the up-regulation rate of gene expression by light. Intriguingly, the estimated up-regulation rate was transient during light period in mice as well as Neurospora. Next, we constructed a computational model to consider how light adaptation had an effect on the entrainment of circadian oscillation to 24-h light-dark cycles. We found that cellular oscillations are more likely to be destabilized without light adaption especially when light intensity is very high. From the present results, we predict that the instability of circadian oscillations under 24-h light-dark cycles can be experimentally observed if light adaptation is altered. We conclude that the functional consequence of light adaptation is to increase the adjustability to 24-h light-dark cycles and then adapt to fluctuating environments in nature.

  8. Neural Network Based Response Prediction of rTMS in Major Depressive Disorder Using QEEG Cordance

    Science.gov (United States)

    Ozekes, Serhat; Gultekin, Selahattin; Tarhan, Nevzat; Hizli Sayar, Gokben; Bayram, Ali

    2015-01-01

    Objective The combination of repetitive transcranial magnetic stimulation (rTMS), a non-pharmacological form of therapy for treating major depressive disorder (MDD), and electroencephalogram (EEG) is a valuable tool for investigating the functional connectivity in the brain. This study aims to explore whether pre-treating frontal quantitative EEG (QEEG) cordance is associated with response to rTMS treatment among MDD patients by using an artificial intelligence approach, artificial neural network (ANN). Methods The artificial neural network using pre-treatment cordance of frontal QEEG classification was carried out to identify responder or non-responder to rTMS treatment among 55 MDD subjects. The classification performance was evaluated using k-fold cross-validation. Results The ANN classification identified responders to rTMS treatment with a sensitivity of 93.33%, and its overall accuracy reached to 89.09%. Area under Receiver Operating Characteristic (ROC) curve (AUC) value for responder detection using 6, 8 and 10 fold cross validation were 0.917, 0.823 and 0.894 respectively. Conclusion Potential utility of ANN approach method can be used as a clinical tool in administering rTMS therapy to a targeted group of subjects suffering from MDD. This methodology is more potentially useful to the clinician as prediction is possible using EEG data collected before this treatment process is initiated. It is worth using feature selection algorithms to raise the sensitivity and accuracy values. PMID:25670947

  9. Protein-DNA binding dynamics predict transcriptional response to nutrients in archaea.

    Science.gov (United States)

    Todor, Horia; Sharma, Kriti; Pittman, Adrianne M C; Schmid, Amy K

    2013-10-01

    Organisms across all three domains of life use gene regulatory networks (GRNs) to integrate varied stimuli into coherent transcriptional responses to environmental pressures. However, inferring GRN topology and regulatory causality remains a central challenge in systems biology. Previous work characterized TrmB as a global metabolic transcription factor in archaeal extremophiles. However, it remains unclear how TrmB dynamically regulates its ∼100 metabolic enzyme-coding gene targets. Using a dynamic perturbation approach, we elucidate the topology of the TrmB metabolic GRN in the model archaeon Halobacterium salinarum. Clustering of dynamic gene expression patterns reveals that TrmB functions alone to regulate central metabolic enzyme-coding genes but cooperates with various regulators to control peripheral metabolic pathways. Using a dynamical model, we predict gene expression patterns for some TrmB-dependent promoters and infer secondary regulators for others. Our data suggest feed-forward gene regulatory topology for cobalamin biosynthesis. In contrast, purine biosynthesis appears to require TrmB-independent regulators. We conclude that TrmB is an important component for mediating metabolic modularity, integrating nutrient status and regulating gene expression dynamics alone and in concert with secondary regulators.

  10. Protein–DNA binding dynamics predict transcriptional response to nutrients in archaea

    Science.gov (United States)

    Todor, Horia; Sharma, Kriti; Pittman, Adrianne M. C.; Schmid, Amy K.

    2013-01-01

    Organisms across all three domains of life use gene regulatory networks (GRNs) to integrate varied stimuli into coherent transcriptional responses to environmental pressures. However, inferring GRN topology and regulatory causality remains a central challenge in systems biology. Previous work characterized TrmB as a global metabolic transcription factor in archaeal extremophiles. However, it remains unclear how TrmB dynamically regulates its ∼100 metabolic enzyme-coding gene targets. Using a dynamic perturbation approach, we elucidate the topology of the TrmB metabolic GRN in the model archaeon Halobacterium salinarum. Clustering of dynamic gene expression patterns reveals that TrmB functions alone to regulate central metabolic enzyme-coding genes but cooperates with various regulators to control peripheral metabolic pathways. Using a dynamical model, we predict gene expression patterns for some TrmB-dependent promoters and infer secondary regulators for others. Our data suggest feed-forward gene regulatory topology for cobalamin biosynthesis. In contrast, purine biosynthesis appears to require TrmB-independent regulators. We conclude that TrmB is an important component for mediating metabolic modularity, integrating nutrient status and regulating gene expression dynamics alone and in concert with secondary regulators. PMID:23892291

  11. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Wu Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Chemaitilly, Wassim [Division of Endocrinology, Department of Pediatric Medicine, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Lukose, Renin C.; Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  12. Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

    Science.gov (United States)

    Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

    2015-01-01

    Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.

  13. Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

    Directory of Open Access Journals (Sweden)

    Mohamed Ahmed Khedr

    2015-01-01

    Full Text Available Background & Aims. The currently available treatment for chronic hepatitis C (CHC in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p<0.0001, p=0.071, and p=0.87, resp.. In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p<0.0001 and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p<0.0001 and p=0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p=0.044. Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.

  14. Identification of Predictive DNA Methylation Biomarkers for Chemotherapy Response in Colorectal Cancer

    Science.gov (United States)

    Baharudin, Rashidah; Ab Mutalib, Nurul-Syakima; Othman, Sri N.; Sagap, Ismail; Rose, Isa M.; Mohd Mokhtar, Norfilza; Jamal, Rahman

    2017-01-01

    Resistance to 5-Fluorouracil (5-FU) is a major obstacle to the successful treatment of colorectal cancer (CRC) and posed an increased risk of recurrence. DNA methylation has been suggested as one of the underlying mechanisms for recurrent disease and its contribution to the development of drug resistance remains to be clarified. This study aimed to determine the methylation phenotype in CRC for identification of predictive markers for chemotherapy response. We performed DNA methylation profiling on 43 non-recurrent and five recurrent CRC patients using the Illumina Infinium HumanMethylation450 Beadchip assay. In addition, CRC cells with different genetic backgrounds, response to 5-FU and global methylation levels (HT29 and SW48) were treated with 5-FU and DNA methylation inhibitor 5-aza-2′-deoxycytidine (5-azadC). The singular and combined effects of these two drug classes on cell viability and global methylation profiles were investigated. Our genome-wide methylation study on the clinical specimens showed that recurrent CRCs exhibited higher methylation levels compared to non-recurrent CRCs. We identified 4787 significantly differentially methylated genes (P < 0.05); 3112 genes were hyper- while 1675 genes were hypomethylated in the recurrent group compared to the non-recurrent. Fifty eight and 47 of the significantly hypermethylated and hypomethylated genes have an absolute recurrent/non-recurrent methylation difference of ≥20%. Most of the hypermethylated genes were involved in the MAPK signaling pathway which is a key regulator for apoptosis while the hypomethylated genes were involved in the PI3K-AKT signaling pathway and proliferation process. We also demonstrate that 5-azadC treatment enhanced response to 5-FU which resulted in significant growth inhibition compared to 5-FU alone in hypermethylated cell lines SW48. In conclusion, we found the evidence of five potentially biologically important genes in recurrent CRCs that could possibly serve as a new

  15. Predicting nutrient responses to mitigation at catchment to national scale: the UK research platform (Invited)

    Science.gov (United States)

    Johnes, P.

    2013-12-01

    Nutrient enrichment of waters from land-based and atmospheric sources presents a significant management challenge, requiring effective stakeholder engagement and policy development, properly underpinned by robust scientific evidence. The challenge is complex, raising significant questions about the specific sources, apportionment and pathways that determine nutrient enrichment and the key priorities for effective management and policy intervention. This paper presents outputs from 4 major UK research programmes: the Defra Demonstration Test Catchments programme (DTC), the Environment Agency's Catchment Sensitive Farming monitoring and evaluation programme (CSF), Natural Resources Wales Welsh Catchment Initiative (WCI) and the NERC Environmental Virtual Observatory programme (EVOp). Funded to meet this challenge, they are delivering new understanding of the rates and sources of pollutant fluxes from land to water, their impacts on ecosystem goods and services, and likely trends under future climate and land use change from field to national scale. DTC, a 12m investment by the UK Government, has set up long-term, high resolution research platforms equipped with novel telemetered sensor networks to monitor stream ecosystem responses to on-farm mitigation measures at a representative scale for catchment management. Ecosystem structural and functional responses and bulk hydrochemistry are also being monitored using standard protocols. CSF has set up long-term, enhanced monitoring in 8 priority catchments, with monthly monitoring in a further 72 English catchments and 6 Welsh priority catchments, to identify shifts in pollutant flux to waters resulting from mitigation measures in priority areas and farming sectors. CSF and WCI have contributed to >50 million of targeted farm improvements to date, representing a significant shift in farming practice. Each programme has generated detailed evidence on stream ecosystem responses to targeted mitigation. However, to provide

  16. Predicting the likely response of data-poor ecosystems to climate change using space-for-time substitution across domains.

    Science.gov (United States)

    Lester, Rebecca E; Close, Paul G; Barton, Jan L; Pope, Adam J; Brown, Stuart C

    2014-11-01

    Predicting ecological response to climate change is often limited by a lack of relevant local data from which directly applicable mechanistic models can be developed. This limits predictions to qualitative assessments or simplistic rules of thumb in data-poor regions, making management of the relevant systems difficult. We demonstrate a method for developing quantitative predictions of ecological response in data-poor ecosystems based on a space-for-time substitution, using distant, well-studied systems across an inherent climatic gradient to predict ecological response. Changes in biophysical data across the spatial gradient are used to generate quantitative hypotheses of temporal ecological responses that are then tested in a target region. Transferability of predictions among distant locations, the novel outcome of this method, is demonstrated via simple quantitative relationships that identify direct and indirect impacts of climate change on physical, chemical and ecological variables using commonly available data sources. Based on a limited subset of data, these relationships were demonstrably plausible in similar yet distant (>2000 km) ecosystems. Quantitative forecasts of ecological change based on climate-ecosystem relationships from distant regions provides a basis for research planning and informed management decisions, especially in the many ecosystems for which there are few data. This application of gradient studies across domains - to investigate ecological response to climate change - allows for the quantification of effects on potentially numerous, interacting and complex ecosystem components and how they may vary, especially over long time periods (e.g. decades). These quantitative and integrated long-term predictions will be of significant value to natural resource practitioners attempting to manage data-poor ecosystems to prevent or limit the loss of ecological value. The method is likely to be applicable to many ecosystem types, providing a

  17. Study of the prediction system for clinical response to M-VAC neoadjuvant chemotherapy for bladder cancer.

    Science.gov (United States)

    Takata, R; Obara, W; Fujioka, T

    2010-01-01

    Neoadjuvant chemotherapy for invasive bladder cancer, involving a regimen of M-VAC, can manage micrometastasis and improve the prognosis. However, some patients suffer from severe adverse drug reactions without any effect, and no method yet exists for predicting the response of an individual patient to chemotherapy. Our purpose in this study is to establish a method for predicting the response to the M-VAC therapy. We analyzed gene-expression profiles of biopsy materials from 40 invasive bladder cancers using a cDNA microarray consisting of 27 648 genes, after populations of cancer cells had been purified by laser-microbeam microdissection. We identified 14 predictive genes that were expressed differently between nine responder and nine non-responder tumors and devised a prediction-scoring system that clearly separated the responder group from the non-responder group. This system accurately predicted the clinical response for 19 of the 22 additional test cases. The group of patients with positive predictive scores had significantly longer survival times than that with negative scores. As real-time RT-PCR data were highly concordant with the cDNA microarray data for those 14 genes, we developed a quantitative RT-PCR-based prediction system that could be feasible for routine clinical use. Taken together, our results suggest that the sensitivity of an invasive bladder cancer to the M-VAC neoadjuvant chemotherapy can be predicted by expression patterns in this set of genes, a step toward achievement of "personalized therapy" for treatment of this disease.

  18. Model predictions of features in microsaccade-related neural responses in a feedforward network with short-term synaptic depression.

    Science.gov (United States)

    Zhou, Jian-Fang; Yuan, Wu-Jie; Zhou, Zhao; Zhou, Changsong

    2016-02-08

    Recently, the significant microsaccade-induced neural responses have been extensively observed in experiments. To explore the underlying mechanisms of the observed neural responses, a feedforward network model with short-term synaptic depression has been proposed [Yuan, W.-J., Dimigen, O., Sommer, W. and Zhou, C. Front. Comput. Neurosci. 7, 47 (2013)]. The depression model not only gave an explanation for microsaccades in counteracting visual fading, but also successfully reproduced several microsaccade-related features in experimental findings. These results strongly suggest that, the depression model is very useful to investigate microsaccade-related neural responses. In this paper, by using the model, we extensively study and predict the dependance of microsaccade-related neural responses on several key parameters, which could be tuned in experiments. Particularly, we provide a significant prediction that microsaccade-related neural response also complies with the property "sharper is better" observed in many contexts in neuroscience. Importantly, the property exhibits a power-law relationship between the width of input signal and the responsive effectiveness, which is robust against many parameters in the model. By using mean field theory, we analytically investigate the robust power-law property. Our predictions would give theoretical guidance for further experimental investigations of the functional role of microsaccades in visual information processing.

  19. Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression.

    Science.gov (United States)

    Williams, L M; Debattista, C; Duchemin, A-M; Schatzberg, A F; Nemeroff, C B

    2016-05-03

    Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors-overall trauma 'load' and specific type of abuse-on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer outcomes

  20. Specific predictive power of automatic spider-related affective associations for controllable and uncontrollable fear responses toward spiders

    NARCIS (Netherlands)

    J. Huijding (Jorg); P.J. de Jong (Peter)

    2006-01-01

    textabstractThis study examined the predictive power of automatically activated spider-related affective associations for automatic and controllable fear responses. The Extrinsic Affective Simon Task (EAST; De Houwer, 2003) was used to indirectly assess automatic spider fear-related associations. Th

  1. Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments

    DEFF Research Database (Denmark)

    Vicca, S.; Bahn, M.; Estiarte, M.

    2014-01-01

    dependencies of SCE. Hence, the most justified answer to the question of whether current moisture responses of SCE can be extrapolated to predict SCE under altered precipitation regimes is 'no' - as based on the most reliable data sets available. We strongly recommend that future experiments focus more...

  2. Utility of comprehensive assessment of strain dyssynchrony index by speckle tracking imaging for predicting response to cardiac resynchronization therapy.

    Science.gov (United States)

    Tatsumi, Kazuhiro; Tanaka, Hidekazu; Yamawaki, Kouhei; Ryo, Keiko; Omar, Alaa Mabrouk Salem; Fukuda, Yuko; Norisada, Kazuko; Matsumoto, Kensuke; Onishi, Tetsuari; Gorcsan, John; Yoshida, Akihiro; Kawai, Hiroya; Hirata, Ken-ichi

    2011-02-01

    The strain delay index is reportedly a marker of dyssynchrony and residual myocardial contractility. The aim of this study was to test the hypothesis that a relatively simple version of the strain dyssynchrony index (SDI) can predict response to cardiac resynchronization therapy (CRT) and that combining assessment of radial, circumferential, and longitudinal SDI can further improve the prediction of responders. A total of 52 patients who underwent CRT were studied. The SDI was calculated as the average difference between peak and end-systolic strain from 6 segments for radial and circumferential SDI and 18 segments for longitudinal SDI. Conventional dyssynchrony measures were assessed by interventricular mechanical delay, the Yu index, and radial dyssynchrony by speckle tracking strain. Response was defined as a ≥15% decrease in end-systolic volume after 3 months. Of the individual parameters, radial SDI ≥6.5% was the best predictor of response to CRT, with sensitivity of 81%, specificity of 81%, and an area under the curve of 0.87 (p SDIs was 100%. In contrast, rates in patients with either 1 or no positive SDIs were 42% and 22%, respectively (p SDIs). In conclusion, the SDI can successfully predict response to CRT, and the combined approach leads to more accurate prediction than using individual parameters.

  3. Stroke volume variation does not predict fluid responsiveness in patients with septic shock on pressure support ventilation

    DEFF Research Database (Denmark)

    Perner, A; Faber, T

    2006-01-01

    Stroke volume variation (SVV)--as measured by the pulse contour cardiac output (PiCCO) system--predicts the cardiac output response to a fluid challenge in patients on controlled ventilation. Whether this applies to patients on pressure support ventilation is unknown....

  4. Response prediction techniques and case studies of a path blocking system based on Global Transmissibility Direct Transmissibility method

    Science.gov (United States)

    Wang, Zengwei; Zhu, Ping; Zhao, Jianxuan

    2017-02-01

    In this paper, the prediction capabilities of the Global Transmissibility Direct Transmissibility (GTDT) method are further developed. Two path blocking techniques solely using the easily measured variables of the original system to predict the response of a path blocking system are generalized to finite element models of continuous systems. The proposed techniques are derived theoretically in a general form for the scenarios of setting the response of a subsystem to zero and of removing the link between two directly connected subsystems. The objective of this paper is to verify the reliability of the proposed techniques by finite element simulations. Two typical cases, the structural vibration transmission case and the structure-borne sound case, in two different configurations are employed to illustrate the validity of proposed techniques. The points of attention for each case have been discussed, and conclusions are given. It is shown that for the two cases of blocking a subsystem the proposed techniques are able to predict the new response using measured variables of the original system, even though operational forces are unknown. For the structural vibration transmission case of removing a connector between two components, the proposed techniques are available only when the rotational component responses of the connector are very small. The proposed techniques offer relative path measures and provide an alternative way to deal with NVH problems. The work in this paper provides guidance and reference for the engineering application of the GTDT prediction techniques.

  5. Can current moisture responses predict soil CO2 efflux under altered precipitation regimes? A synthesis of manipulation experiments

    DEFF Research Database (Denmark)

    Vicca, S.; Bahn, M.; Estiarte, M.;

    2014-01-01

    As a key component of the carbon cycle, soil CO2 efflux (SCE) is being increasingly studied to improve our mechanistic understanding of this important carbon flux. Predicting ecosystem responses to climate change often depends on extrapolation of current relationships between ecosystem processes ...

  6. Predicting the profile of nutrients available for absorption: from nutrient requirement to animal response and environmental impact

    NARCIS (Netherlands)

    Dijkstra, J.; Kebreab, E.; Mills, J.A.N.; Pellikaan, W.F.; López, S.; Bannink, A.; France, J.

    2007-01-01

    Current feed evaluation systems for dairy cattle aim to match nutrient requirements with nutrient intake at pre-defined production levels. These systems were not developed to address, and are not suitable to predict, the responses to dietary changes in terms of production level and product compositi

  7. Specific predictive power of automatic spider-related affective associations for controllable and uncontrollable fear responses toward spiders

    NARCIS (Netherlands)

    Huijdlng, J; de Jong, PJ; Huijding, J.

    2006-01-01

    This study examined the predictive power of automatically activated spider-related affective associations for automatic and controllable fear responses. The Extrinsic Affective Simon Task (EAST; De Houwer, 2003) was used to indirectly assess automatic spider fear-related associations. The EAST and t

  8. A Global Genomic and Genetic Strategy to Predict Pathway Activation of Xenobiotic Responsive Transcription Factors in the Mouse Liver

    Science.gov (United States)

    Many drugs and environmentally-relevant chemicals activate xenobiotic-responsive transcription factors(TF). Identification of target genes of these factors would be useful in predicting pathway activation in in vitro chemical screening. Starting with a large compendium of Affymet...

  9. Chlamydia trachomatis and chlamydial heat shock protein 60-specific antibody and cell-mediated responses predict tubal factor infertility

    DEFF Research Database (Denmark)

    Tiitinen, A.; Surcel, H.-M.; Halttunen, M.

    2006-01-01

    BACKGROUND: To evaluate the role of Chlamydia trachomatis-induced humoral and cell-mediated immune (CMI) responses in predicting tubal factor infertility (TFI). METHODS: Blood samples were taken from 88 women with TFI and 163 control women. C. trachomatis and chlamydial heat shock protein 60 (CHSP...

  10. Developing Predictive Approaches to Characterize Adaptive Responses of the Reproductive Endocrine Axis to Aromatase Inhibition: Computational Modeling

    Science.gov (United States)

    Exposure to endocrine disrupting chemicals can affect reproduction and development in both humans and wildlife. We developed a mechanistic mathematical model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows to predict dose-response and time-course (DRTC)...

  11. Prediction of Nitrogen Responses of Corn by Soil Nitrogen Mineralization Indicators

    Directory of Open Access Journals (Sweden)

    R.R. Simard

    2001-01-01

    Full Text Available Soil nitrogen mineralization potential (Nmin has to be spatially quantified to enable farmers to vary N fertilizer rates, optimize crop yields, and minimize N transfer from soils to the environment. The study objectives were to assess the spatial variability in soil Nmin potential based on clay and organic matter (OM contents and the impact of grouping soils using these criteria on corn grain (Zea mays L. yield, N uptake response curves to N fertilizer, and soil residual N. Four indicators were used: OM content and three equations involving OM and clay content. The study was conducted on a 15-ha field near Montreal, Quebec, Canada. In the spring 2000, soil samples (n = 150 were collected on a 30- x 30-m grid and six rates of N fertilizer (0 to 250 kg N ha-1 were applied. Kriged maps of particle size showed areas of clay, clay loam, and fine sandy loam soils. The Nmin indicators were spatially structured but soil nitrate (NO3– was not. The N fertilizer rate to reach maximum grain yield (Nmax, as estimated by a quadratic model, varied among textural classes and Nmin indicators, and ranged from 159 to 250 kg N ha-1. The proportion of variability (R2 and the standard error of the estimate (SE varied among textural groups and Nmin indicators. The R2 ranged from 0.53 to 0.91 and the SE from 0.13 to 1.62. Corn grain N uptake was significantly affected by N fertilizer and the pattern of response differed with soil texture. For the 50 kg N ha-1 rate, the apparent Nmin potential (ANM was significantly larger in the clay loam (122 kg ha-1 than in the fine sandy loam (80 kg ha-1 or clay (64 kg ha-1 soils. The fall soil residual N was not affected by N fertlizer inputs. Textural classes can be used to predict Nmax. The Nmin indicators may also assist the variable rate N fertilizer inputs for corn production.

  12. Polymer Optical Fiber Sensor and the Prediction of Sensor Response Utilizing Artificial Neural Networks

    Science.gov (United States)

    Haroglu, Derya

    characteristics: reproducibility, accuracy, selectivity, aging, and resolution. Artificial neural network (ANN), a mathematical model formed by mimicking the human nervous system, was used to predict the sensor response. Qwiknet (version 2.23) software was used to develop ANNs and according to the results of Qwiknet the prediction performances for training and testing data sets were 75%, and 83.33% respectively. In this dissertation, Chapter 1 describes the worldwide plastic optical fiber (POF) and fiber optic sensor markets, and the existing textile structures used in fiber optic sensing design particularly for the applications of biomedical and structural health monitoring (SHM). Chapter 2 provides a literature review in detail on polymer optical fibers, fiber optic sensors, and occupancy sensing in the passenger seats of automobiles. Chapter 3 includes the research objectives. Chapter 4 presents the response of POF to tensile loading, bending, and cyclic tensile loading with discussion parts. Chapter 5 includes an e-mail based survey to prioritize customer needs in a Quality Function Deployment (QFD) format utilizing Analytic Hierarchy Process (AHP) and survey results. Chapter 6 describes the POF sensor design and the behavior of it under pressure. Chapter 7 provides a data analysis based on the experimental results of Chapter 6. Chapter 8 presents the summary of this study and recommendations for future work.

  13. Predictive value of serum cholinesterase for the prognosis of aged patients with systemic inflammatory response syndrome

    Institute of Scientific and Technical Information of China (English)

    JIN Qi-hui; HE Xiao-jun; LI Tian-lang; CHEN Huai-hong

    2011-01-01

    Background Some studies found that cholinesterase (ChE) can be an independent risk factor for patients with multiple organ dysfunction syndrome.To assess aged patients with systemic inflammatory response syndrome (SIRS) early and predict their prognosis,the predictive value of ChE for the prognosis of aged patients with SIRS was analyzed.Methods From September 2009 to September 2010,all aged patients with SIRS in the ICU of the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed if they met inclusion criteria:patients aged >65 years and met American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria for SIRS.Serum ChE,albumin,D-dimer,lactic acid and C-reactive protein (CRP) were measured,and the Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ and Glasgow Coma Scale (GCS) scores were evaluated within the first 24 hours in the ICU.Fisher's exact test was used for comparison of the primary disease between the deceased group and surviving group.For comparison of study variables between the two groups,the Student's t test or Mann-Whitney U test was used.Multivariate significance was tested with binary Logistic regression analysis.Results The clinical data of 124 aged patients with SIRS were collected and analyzed.Sixty-six patients (46 male,20female,mean age (78.70±8.08) years) who died were included in the deceased group and 58 patients (34 male,24female,mean age (76.02±6.57) years) who survived were included in the surviving group.There were no significant differences in age,gender,APACHE Ⅱ score and GCS score between the deceased group and surviving group (all P>0.05),but there were significant differences in lactic acid (P=0.011),D-dimer (P=0.011),albumin (P=0.007),CRP (P=0.008),and ChE (P <0.0001).The correlation analysis showed that the APACHE Ⅱ score and CRP were not correlated with ChE (both P <0.05).D-dimer and albumin were correlated with Ch

  14. Application of Response Surface Methodolody to Prediction of Dilution in Plasma Transferred Arc Hardfacing of Stainless Steel on Carbon Steel

    Institute of Scientific and Technical Information of China (English)

    V Balasubramanian; A K Lakshminarayanan; R Varahamoorthy; S Babu

    2009-01-01

    The application of.response surface methodology was highlighted to predict and optimize the percentage of dilution of iron-based hardfaced surface produced by the PTA (plasma transferred arc welding) process.The experiments were conducted based on five-factor five-level central composite rotatable design with full replication technique and a mathematical model was developed using response surface methodology.Furthermore,the response surface methodology was also used to optimize the process parameters that yielded the lowest percentage of dilution.

  15. An Integrated Analysis of Heterogeneous Drug Responses in Acute Myeloid Leukemia That Enables the Discovery of Predictive Biomarkers.

    Science.gov (United States)

    Chen, Weihsu C; Yuan, Julie S; Xing, Yan; Mitchell, Amanda; Mbong, Nathan; Popescu, Andreea C; McLeod, Jessica; Gerhard, Gitte; Kennedy, James A; Bogdanoski, Goce; Lauriault, Stevan; Perdu, Sofie; Merkulova, Yulia; Minden, Mark D; Hogge, Donna E; Guidos, Cynthia; Dick, John E; Wang, Jean C Y

    2016-03-01

    Many promising new cancer drugs proceed through preclinical testing and early-phase trials only to fail in late-stage clinical testing. Thus, improved models that better predict survival outcomes and enable the development of biomarkers are needed to identify patients most likely to respond to and benefit from therapy. Here, we describe a comprehensive approach in which we incorporated biobanking, xenografting, and multiplexed phospho-flow (PF) cytometric profiling to study drug response and identify predictive biomarkers in acute myeloid leukemia (AML) patients. To test the efficacy of our approach, we evaluated the investigational JAK2 inhibitor fedratinib (FED) in 64 patient samples. FED robustly reduced leukemia in mouse xenograft models in 59% of cases and was also effective in limiting the protumorigenic activity of leukemia stem cells as shown by serial transplantation assays. In parallel, PF profiling identified FED-mediated reduction in phospho-STAT5 (pSTAT5) levels as a predictive biomarker of in vivo drug response with high specificity (92%) and strong positive predictive value (93%). Unexpectedly, another JAK inhibitor, ruxolitinib (RUX), was ineffective in 8 of 10 FED-responsive samples. Notably, this outcome could be predicted by the status of pSTAT5 signaling, which was unaffected by RUX treatment. Consistent with this observed discrepancy, PF analysis revealed that FED exerted its effects through multiple JAK2-independent mechanisms. Collectively, this work establishes an integrated approach for testing novel anticancer agents that captures the inherent variability of response caused by disease heterogeneity and in parallel, facilitates the identification of predictive biomarkers that can help stratify patients into appropriate clinical trials.

  16. Predictive value of neurological examination for early cortical responses to somatosensory evoked potentials in patients with postanoxic coma.

    Science.gov (United States)

    Bouwes, Aline; Binnekade, Jan M; Verbaan, Bart W; Zandbergen, Eveline G J; Koelman, Johannes H T M; Weinstein, Henry C; Hijdra, Albert; Horn, Janneke

    2012-03-01

    Bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SEP) predicts poor neurological outcome in postanoxic coma after cardiopulmonary resuscitation (CPR). Although SEP is easy to perform and available in most hospitals, it is worthwhile to know how neurological signs are associated with SEP results. The aim of this study was to investigate whether specific clinical neurological signs are associated with either an absent or a present median nerve SEP in patients after CPR. Data from the previously published multicenter prospective cohort study PROPAC (prognosis in postanoxic coma, 2000-2003) were used. Neurological examination, consisting of Glasgow Coma Score (GCS) and brain stem reflexes, and SEP were performed 24, 48, and 72 h after CPR. Positive predictive values for predicting absent and present SEP, as well as diagnostic accuracy were calculated. Data of 407 patients were included. Of the 781 SEPs performed, N20 s were present in 401, bilaterally absent in 299, and 81 SEPs were technically undeterminable. The highest positive predictive values (0.63-0.91) for an absent SEP were found for absent pupillary light responses. The highest positive predictive values (0.71-0.83) for a present SEP were found for motor scores of withdrawal to painful stimuli or better. Multivariate analyses showed a fair diagnostic accuracy (0.78) for neurological examination in predicting an absent or present SEP at 48 or 72 h after CPR. This study shows that neurological examination cannot reliably predict absent or present cortical N20 responses in median nerve SEPs in patients after CPR.

  17. Baseline {sup 18}F-FDG PET image-derived parameters for therapy response prediction in oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hatt, Mathieu; Visvikis, Dimitris; Cheze-le Rest, Catherine [CHU Morvan, LaTIM, INSERM U650, Brest (France); Pradier, Olivier [CHU Morvan, LaTIM, INSERM U650, Brest (France); CHU Morvan, Department of Radiotherapy, Brest (France)

    2011-09-15

    The objectives of this study were to investigate the predictive value of tumour measurements on 2-deoxy-2-[{sup 18}F]fluoro-D-glucose ({sup 18}F-FDG) positron emission tomography (PET) pretreatment scan regarding therapy response in oesophageal cancer and to evaluate the impact of tumour delineation strategies. Fifty patients with oesophageal cancer treated with concomitant radiochemotherapy between 2004 and 2008 were retrospectively considered and classified as complete, partial or non-responders (including stable and progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST). The classification of partial and complete responders was confirmed by biopsy. Tumours were delineated on the {sup 18}F-FDG pretreatment scan using an adaptive threshold and the automatic fuzzy locally adaptive Bayesian (FLAB) methodologies. Several parameters were then extracted: maximum and peak standardized uptake value (SUV), tumour longitudinal length (TL) and volume (TV), SUV{sub mean}, and total lesion glycolysis (TLG = TV x SUV{sub mean}). The correlation between each parameter and response was investigated using Kruskal-Wallis tests, and receiver-operating characteristic methodology was used to assess performance of the parameters to differentiate patients. Whereas commonly used parameters such as SUV measurements were not significant predictive factors of the response, parameters related to tumour functional spatial extent (TL, TV, TLG) allowed significant differentiation of all three groups of patients, independently of the delineation strategy, and could identify complete and non-responders with sensitivity above 75% and specificity above 85%. A systematic although not statistically significant trend was observed regarding the hierarchy of the delineation methodologies and the parameters considered, with slightly higher predictive value obtained with FLAB over adaptive thresholding, and TLG over TV and TL. TLG is a promising predictive factor of

  18. Are predictions of cancer response to targeted drugs, based on effects in unrelated tissues, the 'Black Swan' events?

    Science.gov (United States)

    Kurbel, Beatrica; Golem, Ante Zvonimir; Kurbel, Sven

    2015-01-01

    Adverse effects of targeted drugs on normal tissues can predict the cancer response. Rash correlates with efficacy of erlotinib, cetuximab and gefitinib and onset of arterial hypertension with response to bevacizumab, sunitinib, axitinib and sorafenib, possible examples of 'Black Swan' events, unexpected scientific observations, as described by Karl Popper in 1935. The proposition is that our patients have individual intrinsic variants of cell growth control, important for tumor response and adverse effects on tumor-unrelated tissue. This means that the lack of predictive side effects in healthy tissue is linked with poor results of tumor therapy when tumor resistance is caused by mechanisms that protect all cells of that patient from the targeted drug effects.

  19. Coupled prediction of flash flood response and debris flow occurrence in an alpine basin

    Science.gov (United States)

    Amponsah, William

    2015-04-01

    Coupled prediction of flash flood response and debris flow occurrence in an alpine basin Author(s): William Amponsah1, E.I. Nikolopoulos2, Lorenzo Marchi1, Roberto Dinale4, Francesco Marra3,Davide Zoccatelli2 , Marco Borga2 Affiliation(s): 1CNR - IRPI, Corso Stati Uniti 4, 35127, Padova, ITALY, 2Department of Land, Environment, Agriculture and Forestry, University of Padova,VialeDell'Università 16, 35020, Legnaro PD, ITALY 3Department of Geography, Hebrew University of Jerusalem, ISRAEL 4Ufficio Idrografico, Provincia Autonoma di Bolzano, Bolzano, Italy This contribution examines the main hydrologic and morphologic metrics responsible for widespread triggering of debris-flows associated with flash flood occurrences in headwater alpine catchments.To achieve this objective, we investigate the precipitation forcing, hydrologic responses and landslides and debris-flow occurrences that prevailed during the August 4-5, 2012 extreme flash flood on the 140 km2 Vizze basin in the Eastern Alps of Italy. An intensive post-event survey was carried out a few days after the flood. This included the surveys of cross-sectional geometry and flood marks for the estimation of the peak discharges at multiple river sections and of the initiation and deposition areas of several debris flows. Rainfall estimates are based on careful analysis of weather radar observations and raingauge data. These data and observations permitted the implementation and calibration of a spatially distributed hydrological model, which was used to derive simulated flood hydrographs in 58 tributaries of the Vizze basin. Of these, 33 generated debris-flows, with area ranging from 0.02 km2 to 10 km2, with an average of 1.5 km2. With 130 mm peak event rainfall and a duration of 4 hours (with a max intensity of 90 mm h-1 for 10 min), model-simulated unit peak discharges range from 4 m3 s-1 km-2for elementary catchments up to 10 km2 to 2 m3 s-1 km-2 for catchments in the range of 50 - 100 km2. These are very high

  20. Precise prediction of optical responses of liquid-crystal display products using a behavioral model of liquid crystal

    Science.gov (United States)

    Park, Chansoo; Cho, Youngmin; Kim, Jong-Man; Kim, Jongbin; Lee, Seung-Woo

    2012-01-01

    We propose a precise circuit model to estimate transient optical responses of an active-matrix liquid crystal display (AMLCD). Liquid crystal (LC) molecules in the pixel is behaviorally modeled by using the first-order system that is described by Verilog-A. Capacitance-voltage (C-V) characteristics of a pixel determine the accuracy of the dynamic responses. Measuring C-V characteristics is impossible because pixels are driven by switching transistors in the AMLCD. We propose a method to obtain the C-V data from natural optical responses. Estimated optical responses based on the C-V data extracted by our proposal show more accurate results than those based on C-V data obtained by using transmittance-voltage data. It is demonstrated that our behavioral model enables us to predict very accurate transient responses, which makes it possible to design LCD products with lower costs.

  1. Dynamic contrast-enhanced magnetic resonance imaging for prediction of response to neoadjuvant chemotherapy in breast cancer

    Science.gov (United States)

    Fu, Juzhong; Fan, Ming; Zheng, Bin; Shao, Guoliang; Zhang, Juan; Li, Lihua

    2016-03-01

    Breast cancer is the second leading cause of women death in the United States. Currently, Neoadjuvant Chemotherapy (NAC) has become standard treatment paradigms for breast cancer patients. Therefore, it is important to find a reliable non-invasive assessment and prediction method which can evaluate and predict the response of NAC on breast cancer. The Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) approach can reflect dynamic distribution of contrast agent in tumor vessels, providing important basis for clinical diagnosis. In this study, the efficacy of DCE-MRI on evaluation and prediction of response to NAC in breast cancer was investigated. To this end, fifty-seven cases of malignant breast cancers with MRI examination both before and after two cycle of NAC were analyzed. After pre-processing approach for segmenting breast lesions and background regions, 126-dimensional imaging features were extracted from DCE-MRI. Statistical analyses were then performed to evaluate the associations between the extracted DCE-MRI features and the response to NAC. Specifically, pairwise t test was used to calculate differences of imaging features between MRI examinations before-and-after NAC. Moreover, the associations of these image features with response to NAC were assessed using logistic regression. Significant association are found between response to NAC and the features of lesion morphology and background parenchymal enhancement, especially the feature of background enhancement in normal side of breast (P=0.011). Our study indicate that DCE-MRI features can provide candidate imaging markers to predict response of NAC in breast cancer.

  2. Predicting maize phenology: Intercomparison of functions for developmental response to temperature

    Science.gov (United States)

    Accurate prediction of phenological development in maize is fundamental to determining crop adaptation and yield potential. A number of thermal functions are used in crop models, but their relative precision in predicting maize development has not been quantified. The objectives of this study were t...

  3. Can a mathematical model predict an individual's trait-like response to both total and partial sleep loss?

    Science.gov (United States)

    Ramakrishnan, Sridhar; Lu, Wei; Laxminarayan, Srinivas; Wesensten, Nancy J; Rupp, Tracy L; Balkin, Thomas J; Reifman, Jaques

    2015-06-01

    Humans display a trait-like response to sleep loss. However, it is not known whether this trait-like response can be captured by a mathematical model from only one sleep-loss condition to facilitate neurobehavioural performance prediction of the same individual during a different sleep-loss condition. In this paper, we investigated the extent to which the recently developed unified mathematical model of performance (UMP) captured such trait-like features for different sleep-loss conditions. We used the UMP to develop two sets of individual-specific models for 15 healthy adults who underwent two different sleep-loss challenges (order counterbalanced; separated by 2-4 weeks): (i) 64 h of total sleep deprivation (TSD) and (ii) chronic sleep restriction (CSR) of 7 days of 3 h nightly time in bed. We then quantified the extent to which models developed using psychomotor vigilance task data under TSD predicted performance data under CSR, and vice versa. The results showed that the models customized to an individual under one sleep-loss condition accurately predicted performance of the same individual under the other condition, yielding, on average, up to 50% improvement over non-individualized, group-average model predictions. This finding supports the notion that the UMP captures an individual's trait-like response to different sleep-loss conditions.

  4. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.

    2014-11-11

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the H