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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. Copyright © 2011 Elsevier B.V. All

  2. Modeling auditory-nerve responses to electrical stimulation

    DEFF Research Database (Denmark)

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

    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

    , 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...... 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...

  4. Wiener-Kernel Analysis of Responses to Noise of Chinchilla Auditory-Nerve Fibers

    National Research Council Canada - National Science Library

    Alberto Recio-Spinoso; Andrei N. Temchin; Pim van Dijk; Yun-Hui Fan; Mario A. Ruggero

    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...

  5. Noise-induced hearing loss alters the temporal dynamics of auditory-nerve responses.

    Science.gov (United States)

    Scheidt, Ryan E; Kale, Sushrut; Heinz, Michael G

    2010-10-01

    Auditory-nerve fibers demonstrate dynamic response properties in that they adapt to rapid changes in sound level, both at the onset and offset of a sound. These dynamic response properties affect temporal coding of stimulus modulations that are perceptually relevant for many sounds such as speech and music. Temporal dynamics have been well characterized in auditory-nerve fibers from normal-hearing animals, but little is known about the effects of sensorineural hearing loss on these dynamics. This study examined the effects of noise-induced hearing loss on the temporal dynamics in auditory-nerve fiber responses from anesthetized chinchillas. Post-stimulus-time histograms were computed from responses to 50-ms tones presented at characteristic frequency and 30 dB above fiber threshold. Several response metrics related to temporal dynamics were computed from post-stimulus-time histograms and were compared between normal-hearing and noise-exposed animals. Results indicate that noise-exposed auditory-nerve fibers show significantly reduced response latency, increased onset response and percent adaptation, faster adaptation after onset, and slower recovery after offset. The decrease in response latency only occurred in noise-exposed fibers with significantly reduced frequency selectivity. These changes in temporal dynamics have important implications for temporal envelope coding in hearing-impaired ears, as well as for the design of dynamic compression algorithms for hearing aids.

  6. 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

    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

  7. 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

    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

  8. Predicted effects of sensorineural hearing loss on across-fiber envelope coding in the auditory nerve.

    Science.gov (United States)

    Swaminathan, Jayaganesh; Heinz, Michael G

    2011-06-01

    Cross-channel envelope correlations are hypothesized to influence speech intelligibility, particularly in adverse conditions. Acoustic analyses suggest speech envelope correlations differ for syllabic and phonemic ranges of modulation frequency. The influence of cochlear filtering was examined here by predicting cross-channel envelope correlations in different speech modulation ranges for normal and impaired auditory-nerve (AN) responses. Neural cross-correlation coefficients quantified across-fiber envelope coding in syllabic (0-5 Hz), phonemic (5-64 Hz), and periodicity (64-300 Hz) modulation ranges. Spike trains were generated from a physiologically based AN model. Correlations were also computed using the model with selective hair-cell damage. Neural predictions revealed that envelope cross-correlation decreased with increased characteristic-frequency separation for all modulation ranges (with greater syllabic-envelope correlation than phonemic or periodicity). Syllabic envelope was highly correlated across many spectral channels, whereas phonemic and periodicity envelopes were correlated mainly between adjacent channels. Outer-hair-cell impairment increased the degree of cross-channel correlation for phonemic and periodicity ranges for speech in quiet and in noise, thereby reducing the number of independent neural information channels for envelope coding. In contrast, outer-hair-cell impairment was predicted to decrease cross-channel correlation for syllabic envelopes in noise, which may partially account for the reduced ability of hearing-impaired listeners to segregate speech in complex backgrounds. © 2011 Acoustical Society of America

  9. Modeling auditory-nerve responses to electrical stimulation

    DEFF Research Database (Denmark)

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

    2014-01-01

    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 stimulationof the AN [1, 2, 3] were considered in terms of their efficacy to predict the spike timing for anodic...... andcathodic stimulation of the AN of cat [4]. The models' responses to the electrical pulses of variousshapes [5] were also analyzed. It was found that, while the models can account for the ring rates inresponse to various biphasic pulse shapes, they fail to correctly describe the timing of AP in response...

  10. Temporal modulation transfer functions measured from auditory-nerve responses following sensorineural hearing loss.

    Science.gov (United States)

    Kale, Sushrut; Heinz, Michael G

    2012-04-01

    The ability of auditory-nerve (AN) fibers to encode modulation frequencies, as characterized by temporal modulation transfer functions (TMTFs), generally shows a low-pass shape with a cut-off frequency that increases with fiber characteristic frequency (CF). Because AN-fiber bandwidth increases with CF, this result has been interpreted to suggest that peripheral filtering has a significant effect on limiting the encoding of higher modulation frequencies. Sensorineural hearing loss (SNHL), which is typically associated with broadened tuning, is thus predicted to increase the range of modulation frequencies encoded; however, perceptual studies have generally not supported this prediction. The present study sought to determine whether the range of modulation frequencies encoded by AN fibers is affected by SNHL, and whether the effects of SNHL on envelope coding are similar at all modulation frequencies within the TMTF passband. Modulation response gain for sinusoidally amplitude modulated (SAM) tones was measured as a function of modulation frequency, with the carrier frequency placed at fiber CF. TMTFs were compared between normal-hearing chinchillas and chinchillas with a noise-induced hearing loss for which AN fibers had significantly broadened tuning. Synchrony and phase responses for individual SAM tone components were quantified to explore a variety of factors that can influence modulation coding. Modulation gain was found to be higher than normal in noise-exposed fibers across the entire range of modulation frequencies encoded by AN fibers. The range of modulation frequencies encoded by noise-exposed AN fibers was not affected by SNHL, as quantified by TMTF 3- and 10-dB cut-off frequencies. These results suggest that physiological factors other than peripheral filtering may have a significant role in determining the range of modulation frequencies encoded in AN fibers. Furthermore, these neural data may help to explain the lack of a consistent association

  11. Temporal Modulation Transfer Functions Measured From Auditory-Nerve Responses Following Sensorineural Hearing Loss

    Science.gov (United States)

    Kale, Sushrut; Heinz, Michael G.

    2012-01-01

    The ability of auditory-nerve (AN) fibers to encode modulation frequencies, as characterized by temporal modulation transfer functions (TMTFs), generally shows a low-pass shape with a cut-off frequency that increases with fiber characteristic frequency (CF). Because AN-fiber bandwidth increases with CF, this result has been interpreted to suggest that peripheral filtering has a significant effect on limiting the encoding of higher modulation frequencies. Sensorineural hearing loss (SNHL), which is typically associated with broadened tuning, is thus predicted to increase the range of modulation frequencies encoded; however, perceptual studies have generally not supported this prediction. The present study sought to determine whether the range of modulation frequencies encoded by AN fibers is affected by SNHL, and whether the effects of SNHL on envelope coding are similar at all modulation frequencies within the TMTF passband. Modulation response gain for sinusoidally amplitude modulated (SAM) tones was measured as a function of modulation frequency, with the carrier frequency placed at fiber CF. TMTFs were compared between normal-hearing chinchillas and chinchillas with a noise-induced hearing loss for which AN fibers had significantly broadened tuning. Synchrony and phase responses for individual SAM-tone components were quantified to explore a variety of factors that can influence modulation coding. Modulation gain was found to be higher than normal in noise-exposed fibers across the entire range of modulation frequencies encoded by AN fibers. The range of modulation frequencies encoded by noise-exposed AN fibers was not affected by SNHL, as quantified by TMTF 3- and 10-dB cut-off frequencies. These results suggest that physiological factors other than peripheral filtering may have a significant role in determining the range of modulation frequencies encoded in AN fibers. Furthermore, these neural data may help to explain the lack of a consistent association

  12. A Model of Electrically Stimulated Auditory Nerve Fiber Responses with Peripheral and Central Sites of Spike Generation

    DEFF Research Database (Denmark)

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

    2017-01-01

    A computational model of cat auditory nerve fiber (ANF) responses to electrical stimulation is presented. The model assumes that (1) there exist at least two sites of spike generation along the ANF and (2) both an anodic (positive) and a cathodic (negative) charge in isolation can evoke a spike. ...

  13. 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 ...

  14. 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

    cause auditory nerve fiber (ANF) deafferentation in predominantly low-spontaneous rate (SR) fibers. In the present study, auditory steadystate response (ASSR) level growth functions were measured to evaluate the applicability of ASSR to assess compression and the ability to code intensity fluctuations...... at high stimulus levels. Level growth functions were measured in normal-hearing adults at stimulus levels ranging from 20 to 90 dB SPL. To evaluate compression, ASSR were measured for multiple carrier frequencies simultaneously. To evaluate intensity coding at high intensities, ASSR were measured using....... The results indicate that the slope of the ASSR level growth function can be used to estimate peripheral compression simultaneously at four frequencies below 60 dB SPL, while the slope above 60 dB SPL may provide information about the integrity of intensity coding of low-SR fibers....

  15. Modeling binaural responses in the auditory brainstem to electric stimulation of the auditory nerve.

    Science.gov (United States)

    Chung, Yoojin; Delgutte, Bertrand; Colburn, H Steven

    2015-02-01

    Bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs. However, the benefits arise mainly from the perception of interaural level differences, while bilateral CI listeners' sensitivity to interaural time difference (ITD) is poorer than normal. To help understand this limitation, a set of ITD-sensitive neural models was developed to study binaural responses to electric stimulation. Our working hypothesis was that central auditory processing is normal with bilateral CIs so that the abnormality in the response to electric stimulation at the level of the auditory nerve fibers (ANFs) is the source of the limited ITD sensitivity. A descriptive model of ANF response to both acoustic and electric stimulation was implemented and used to drive a simplified biophysical model of neurons in the medial superior olive (MSO). The model's ITD sensitivity was found to depend strongly on the specific configurations of membrane and synaptic parameters for different stimulation rates. Specifically, stronger excitatory synaptic inputs and faster membrane responses were required for the model neurons to be ITD-sensitive at high stimulation rates, whereas weaker excitatory synaptic input and slower membrane responses were necessary at low stimulation rates, for both electric and acoustic stimulation. This finding raises the possibility of frequency-dependent differences in neural mechanisms of binaural processing; limitations in ITD sensitivity with bilateral CIs may be due to a mismatch between stimulation rate and cell parameters in ITD-sensitive neurons.

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

    Science.gov (United States)

    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.

  17. The Corticofugal Effects of Auditory Cortex Microstimulation on Auditory Nerve and Superior Olivary Complex Responses Are Mediated via Alpha-9 Nicotinic Receptor Subunit.

    Directory of Open Access Journals (Sweden)

    Cristian Aedo

    Full Text Available The auditory efferent system is a complex network of descending pathways, which mainly originate in the primary auditory cortex and are directed to several auditory subcortical nuclei. These descending pathways are connected to olivocochlear neurons, which in turn make synapses with auditory nerve neurons and outer hair cells (OHC of the cochlea. The olivocochlear function can be studied using contralateral acoustic stimulation, which suppresses auditory nerve and cochlear responses. In the present work, we tested the proposal that the corticofugal effects that modulate the strength of the olivocochlear reflex on auditory nerve responses are produced through cholinergic synapses between medial olivocochlear (MOC neurons and OHCs via alpha-9/10 nicotinic receptors.We used wild type (WT and alpha-9 nicotinic receptor knock-out (KO mice, which lack cholinergic transmission between MOC neurons and OHC, to record auditory cortex evoked potentials and to evaluate the consequences of auditory cortex electrical microstimulation in the effects produced by contralateral acoustic stimulation on auditory brainstem responses (ABR.Auditory cortex evoked potentials at 15 kHz were similar in WT and KO mice. We found that auditory cortex microstimulation produces an enhancement of contralateral noise suppression of ABR waves I and III in WT mice but not in KO mice. On the other hand, corticofugal modulations of wave V amplitudes were significant in both genotypes.These findings show that the corticofugal modulation of contralateral acoustic suppressions of auditory nerve (ABR wave I and superior olivary complex (ABR wave III responses are mediated through MOC synapses.

  18. 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

    Responses to free-field sound of 401 fibers from the VIIIth nerve of the grassfrog, Rana temporaria, are described. The spontaneous activities of the fibers ranged from 0 to 75 spikes/s, showing only weak correlation with frequency or sensitivity of the fibers. The highest spontaneous activities...... were approximately twice as high as reported previously for frogs. Best frequencies ranged from 100 to 1600 Hz and thresholds ranged from 21 to 80 dB SPL. The median dynamic range was 20 dB and the slopes of the rate-level curves ranged from 5 to 20 spikes/(s-dB). Most of the units showed post......-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...

  19. A point process framework for modeling electrical stimulation of the auditory nerve

    Science.gov (United States)

    Rubinstein, Jay T.; Shea-Brown, Eric

    2012-01-01

    Model-based studies of responses of auditory nerve fibers to electrical stimulation can provide insight into the functioning of cochlear implants. Ideally, these studies can identify limitations in sound processing strategies and lead to improved methods for providing sound information to cochlear implant users. To accomplish this, models must accurately describe spiking activity while avoiding excessive complexity that would preclude large-scale simulations of populations of auditory nerve fibers and obscure insight into the mechanisms that influence neural encoding of sound information. In this spirit, we develop a point process model of individual auditory nerve fibers that provides a compact and accurate description of neural responses to electric stimulation. Inspired by the framework of generalized linear models, the proposed model consists of a cascade of linear and nonlinear stages. We show how each of these stages can be associated with biophysical mechanisms and related to models of neuronal dynamics. Moreover, we derive a semianalytical procedure that uniquely determines each parameter in the model on the basis of fundamental statistics from recordings of single fiber responses to electric stimulation, including threshold, relative spread, jitter, and chronaxie. The model also accounts for refractory and summation effects that influence the responses of auditory nerve fibers to high pulse rate stimulation. Throughout, we compare model predictions to published physiological data of response to high and low pulse rate stimulation. We find that the model, although constructed to fit data from single and paired pulse experiments, can accurately predict responses to unmodulated and modulated pulse train stimuli. We close by performing an ideal observer analysis of simulated spike trains in response to sinusoidally amplitude modulated stimuli and find that carrier pulse rate does not affect modulation detection thresholds. PMID:22673331

  20. Traveling waves on the organ of corti of the chinchilla cochlea: spatial trajectories of inner hair cell depolarization inferred from responses of auditory-nerve fibers.

    Science.gov (United States)

    Temchin, Andrei N; Recio-Spinoso, Alberto; Cai, Hongxue; Ruggero, Mario A

    2012-08-01

    Spatial magnitude and phase profiles for inner hair cell (IHC) depolarization throughout the chinchilla cochlea were inferred from responses of auditory-nerve fibers (ANFs) to threshold- and moderate-level tones and tone complexes. Firing-rate profiles for frequencies ≤2 kHz are bimodal, with the major peak at the characteristic place and a secondary peak at 3-5 mm from the extreme base. Response-phase trajectories are synchronous with peak outward stapes displacement at the extreme cochlear base and accumulate 1.5 period lags at the characteristic places. High-frequency phase trajectories are very similar to the trajectories of basilar-membrane peak velocity toward scala tympani. Low-frequency phase trajectories undergo a polarity flip in a region, 6.5-9 mm from the cochlear base, where traveling-wave phase velocity attains a local minimum and a local maximum and where the onset latencies of near-threshold impulse responses computed from responses to near-threshold white noise exhibit a local minimum. That region is the same where frequency-threshold tuning curves of ANFs undergo a shape transition. Since depolarization of IHCs presumably indicates the mechanical stimulus to their stereocilia, the present results suggest that distinct low-frequency forward waves of organ of Corti vibration are launched simultaneously at the extreme base of the cochlea and at the 6.5-9 mm transition region, from where antiphasic reflections arise.

  1. Temporal Response Properties of the Auditory Nerve in Implanted Children with Auditory Neuropathy Spectrum Disorder and Implanted Children with Sensorineural Hearing Loss.

    Science.gov (United States)

    He, Shuman; Abbas, Paul J; Doyle, Danielle V; McFayden, Tyler C; Mulherin, Stephen

    2016-01-01

    This study aimed to (1) characterize temporal response properties of the auditory nerve in implanted children with auditory neuropathy spectrum disorder (ANSD), and (2) compare results recorded in implanted children with ANSD with those measured in implanted children with sensorineural hearing loss (SNHL). Participants included 28 children with ANSD and 29 children with SNHL. All subjects used cochlear nucleus devices in their test ears. Both ears were tested in 6 children with ANSD and 3 children with SNHL. For all other subjects, only one ear was tested. The electrically evoked compound action potential (ECAP) was measured in response to each of the 33 pulses in a pulse train (excluding the second pulse) for one apical, one middle-array, and one basal electrode. The pulse train was presented in a monopolar-coupled stimulation mode at 4 pulse rates: 500, 900, 1800, and 2400 pulses per second. Response metrics included the averaged amplitude, latencies of response components and response width, the alternating depth and the amount of neural adaptation. These dependent variables were quantified based on the last six ECAPs or the six ECAPs occurring within a time window centered around 11 to 12 msec. A generalized linear mixed model was used to compare these dependent variables between the 2 subject groups. The slope of the linear fit of the normalized ECAP amplitudes (re. amplitude of the first ECAP response) over the duration of the pulse train was used to quantify the amount of ECAP increment over time for a subgroup of 9 subjects. Pulse train-evoked ECAPs were measured in all but 8 subjects (5 with ANSD and 3 with SNHL). ECAPs measured in children with ANSD had smaller amplitude, longer averaged P2 latency and greater response width than children with SNHL. However, differences in these two groups were only observed for some electrodes. No differences in averaged N1 latency or in the alternating depth were observed between children with ANSD and children with

  2. Suppression Measured from Chinchilla Auditory-Nerve-Fiber Responses Following Noise-Induced Hearing Loss: Adaptive-Tracking and Systems-Identification Approaches.

    Science.gov (United States)

    Sayles, Mark; Walls, Michael K; Heinz, Michael G

    2016-01-01

    The compressive nonlinearity of cochlear signal transduction, reflecting outer-hair-cell function, manifests as suppressive spectral interactions; e.g., two-tone suppression. Moreover, for broadband sounds, there are multiple interactions between frequency components. These frequency-dependent nonlinearities are important for neural coding of complex sounds, such as speech. Acoustic-trauma-induced outer-hair-cell damage is associated with loss of nonlinearity, which auditory prostheses attempt to restore with, e.g., "multi-channel dynamic compression" algorithms.Neurophysiological data on suppression in hearing-impaired (HI) mammals are limited. We present data on firing-rate suppression measured in auditory-nerve-fiber responses in a chinchilla model of noise-induced hearing loss, and in normal-hearing (NH) controls at equal sensation level. Hearing-impaired (HI) animals had elevated single-fiber excitatory thresholds (by ~ 20-40 dB), broadened frequency tuning, and reduced-magnitude distortion-product otoacoustic emissions; consistent with mixed inner- and outer-hair-cell pathology. We characterized suppression using two approaches: adaptive tracking of two-tone-suppression threshold (62 NH, and 35 HI fibers), and Wiener-kernel analyses of responses to broadband noise (91 NH, and 148 HI fibers). Suppression-threshold tuning curves showed sensitive low-side suppression for NH and HI animals. High-side suppression thresholds were elevated in HI animals, to the same extent as excitatory thresholds. We factored second-order Wiener-kernels into excitatory and suppressive sub-kernels to quantify the relative strength of suppression. We found a small decrease in suppression in HI fibers, which correlated with broadened tuning. These data will help guide novel amplification strategies, particularly for complex listening situations (e.g., speech in noise), in which current hearing aids struggle to restore intelligibility.

  3. Computational modeling of the effects of auditory nerve dysmyelination

    Directory of Open Access Journals (Sweden)

    Angus M Brown

    2014-08-01

    Full Text Available Our previous study showed that exposure to loud sound leading to hearing loss elongated the auditory nerve nodes of Ranvier and triggered notable morphological changes at paranodes and juxtaparanodes. Here we used computational modeling to examine how theoretical redistribution of voltage gated Na+, Kv3.1 and Kv1.1 channels along the auditory nerve may be responsible for the alterations of conduction property following acoustic over-exposure. Our modeling study infers that changes related to Na+ channel density (rather than the redistribution of voltage gated Na+, Kv3.1 and Kv1.1 channels is the likely cause of the decreased conduction velocity and the conduction block observed after acoustic overexposure.

  4. Time course of dynamic range adaptation in the auditory nerve

    Science.gov (United States)

    Wang, Grace I.; Dean, Isabel; Delgutte, Bertrand

    2012-01-01

    Auditory adaptation to sound-level statistics occurs as early as in the auditory nerve (AN), the first stage of neural auditory processing. In addition to firing rate adaptation characterized by a rate decrement dependent on previous spike activity, AN fibers show dynamic range adaptation, which is characterized by a shift of the rate-level function or dynamic range toward the most frequently occurring levels in a dynamic stimulus, thereby improving the precision of coding of the most common sound levels (Wen B, Wang GI, Dean I, Delgutte B. J Neurosci 29: 13797–13808, 2009). We investigated the time course of dynamic range adaptation by recording from AN fibers with a stimulus in which the sound levels periodically switch from one nonuniform level distribution to another (Dean I, Robinson BL, Harper NS, McAlpine D. J Neurosci 28: 6430–6438, 2008). Dynamic range adaptation occurred rapidly, but its exact time course was difficult to determine directly from the data because of the concomitant firing rate adaptation. To characterize the time course of dynamic range adaptation without the confound of firing rate adaptation, we developed a phenomenological “dual adaptation” model that accounts for both forms of AN adaptation. When fitted to the data, the model predicts that dynamic range adaptation occurs as rapidly as firing rate adaptation, over 100–400 ms, and the time constants of the two forms of adaptation are correlated. These findings suggest that adaptive processing in the auditory periphery in response to changes in mean sound level occurs rapidly enough to have significant impact on the coding of natural sounds. PMID:22457465

  5. The development of biophysical models of the electrically stimulated auditory nerve: Single-node and cable models.

    Science.gov (United States)

    O'Brien, Gabrielle E; Rubinstein, Jay T

    2016-01-01

    In the last few decades, biophysical models have emerged as a prominent tool in the study and improvement of cochlear implants, a neural prosthetic that restores a degree of sound perception to the profoundly deaf. Owing to the spatial phenomena associated with extracellular stimulation, these models have evolved to a relatively high degree of morphological and physiological detail: single-node models in the tradition of Hodgkin-Huxley are paired with cable descriptions of the auditory nerve fiber. No singular model has emerged as a frontrunner to the field; rather, parameter sets deriving from the channel kinetics and morphologies of numerous organisms (mammalian and otherwise) are combined and tuned to foster strong agreement with response properties observed in vivo, such as refractoriness, summation, and strength-duration relationships. Recently, biophysical models of the electrically stimulated auditory nerve have begun to incorporate adaptation and stochastic mechanisms, in order to better realize the goal of predicting realistic neural responses to a wide array of stimuli.

  6. Cortical perfusion response to an electrical stimulation of the auditory nerve in profoundly deaf patients: Study with technetium-99m hexamethylpropylene amine oxime single photon emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Le Scao, Y.; Robier, A.; Beuter, P. (Centre Hospitalier Universitaire, 37 - Tours (France). Dept. of Otorhinolaryngology); Baulieu, J.L.; Pourcelot, L. (Centre Hospitalier Universitaire, 37 - Tours (France). Dept. of Nuclear Medicine)

    1992-04-01

    Brain activation procedures associated with single photon emission tomography (SPET) have recently been developed in healthy controls and diseased patients in order to help in their diagnosis and treatment. We investigated the effects of a promontory test (PT) on the cerebral distribution of technetium-99m hexamethyl-propylene amine oxime ({sup 99m}Tc-HMPAO) in 7 profoundly deaf patients, 6 PT+ and PT-. The count variation in the temporal lobe was calculated on 6 coronal slices using the ratio (R{sub stimulation}-R{sub deprivation})/R{sub deprivation} where R=counts in the temporal lobe was observed in all patients and was higher in all patients with PT+ than in the patient with PT-. The problems of head positioning and resolution of the system were taken into account, and we considered that the maximal count increment was related to the auditory cortex response to the stimulus. Further clinical investigations with high-resolution systems have to be performed in order to validate this presurgery test in cochlear implant assessment. (orig.).

  7. Comparison of three spike detectors dedicated to single unit action potentials of the auditory nerve.

    Science.gov (United States)

    Bourien, J; Ruel, J; Senhadji, L; Puel, J L

    2007-01-01

    This paper compares three methods for the detection of single unit action potentials in auditory nerve. The detector structures are similar consisting of a filtering procedure in the first stage and a decision rule in the second stage. The detection accuracy of each detector is characterized by the couple probability of a true detection vs. rates of false detection with synthetic data. The performance comparison between detectors shows that the detector using a band-pass finite-impulse-response filter with complex coefficients offers the best performance. This observation was especially evident for low signal to noise ratios. This finding is confirmed with real data and leads us to revise the protocol of spike detection in auditory nerve.

  8. Pitch representations in the auditory nerve: two concurrent complex tones.

    Science.gov (United States)

    Larsen, Erik; Cedolin, Leonardo; Delgutte, Bertrand

    2008-09-01

    Pitch differences between concurrent sounds are important cues used in auditory scene analysis and also play a major role in music perception. To investigate the neural codes underlying these perceptual abilities, we recorded from single fibers in the cat auditory nerve in response to two concurrent harmonic complex tones with missing fundamentals and equal-amplitude harmonics. We investigated the efficacy of rate-place and interspike-interval codes to represent both pitches of the two tones, which had fundamental frequency (F0) ratios of 15/14 or 11/9. We relied on the principle of scaling invariance in cochlear mechanics to infer the spatiotemporal response patterns to a given stimulus from a series of measurements made in a single fiber as a function of F0. Templates created by a peripheral auditory model were used to estimate the F0s of double complex tones from the inferred distribution of firing rate along the tonotopic axis. This rate-place representation was accurate for F0s greater, similar900 Hz. Surprisingly, rate-based F0 estimates were accurate even when the two-tone mixture contained no resolved harmonics, so long as some harmonics were resolved prior to mixing. We also extended methods used previously for single complex tones to estimate the F0s of concurrent complex tones from interspike-interval distributions pooled over the tonotopic axis. The interval-based representation was accurate for F0s less, similar900 Hz, where the two-tone mixture contained no resolved harmonics. Together, the rate-place and interval-based representations allow accurate pitch perception for concurrent sounds over the entire range of human voice and cat vocalizations.

  9. The robustness of speech representations obtained from simulated auditory nerve fibers under different noise conditions.

    Science.gov (United States)

    Jürgens, Tim; Brand, Thomas; Clark, Nicholas R; Meddis, Ray; Brown, Guy J

    2013-09-01

    Different methods of extracting speech features from an auditory model were systematically investigated in terms of their robustness to different noises. The methods either computed the average firing rate within frequency channels (spectral features) or inter-spike-intervals (timing features) from the simulated auditory nerve response. When used as the front-end for an automatic speech recognizer, timing features outperformed spectral features in Gaussian noise. However, this advantage was lost in babble, because timing features extracted the spectro-temporal structure of babble noise, which is similar to the target speaker. This suggests that different feature extraction methods are optimal depending on the background noise.

  10. Nanofibrous scaffolds for the guidance of stem cell-derived neurons for auditory nerve regeneration.

    Directory of Open Access Journals (Sweden)

    Sandra Hackelberg

    Full Text Available Impairment of spiral ganglion neurons (SGNs of the auditory nerve is a major cause for hearing loss occurring independently or in addition to sensory hair cell damage. Unfortunately, mammalian SGNs lack the potential for autonomous regeneration. Stem cell based therapy is a promising approach for auditory nerve regeneration, but proper integration of exogenous cells into the auditory circuit remains a fundamental challenge. Here, we present novel nanofibrous scaffolds designed to guide the integration of human stem cell-derived neurons in the internal auditory meatus (IAM, the foramen allowing passage of the spiral ganglion to the auditory brainstem. Human embryonic stem cells (hESC were differentiated into neural precursor cells (NPCs and seeded onto aligned nanofiber mats. The NPCs terminally differentiated into glutamatergic neurons with high efficiency, and neurite projections aligned with nanofibers in vitro. Scaffolds were assembled by seeding GFP-labeled NPCs on nanofibers integrated in a polymer sheath. Biocompatibility and functionality of the NPC-seeded scaffolds were evaluated in vivo in deafened guinea pigs (Cavia porcellus. To this end, we established an ouabain-based deafening procedure that depleted an average 72% of SGNs from apex to base of the cochleae and caused profound hearing loss. Further, we developed a surgical procedure to implant seeded scaffolds directly into the guinea pig IAM. No evidence of an inflammatory response was observed, but post-surgery tissue repair appeared to be facilitated by infiltrating Schwann cells. While NPC survival was found to be poor, both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically-evoked auditory brainstem thresholds. Thus, while future studies must address cell survival, nanofibrous scaffolds pose a promising strategy for auditory nerve regeneration.

  11. 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.

  12. Prediction and control of neural responses to pulsatile electrical stimulation

    Science.gov (United States)

    Campbell, Luke J.; Sly, David James; O'Leary, Stephen John

    2012-04-01

    This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s-1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s-1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

  13. Degeneration of auditory nerve fibers in guinea pigs with severe sensorineural hearing loss

    NARCIS (Netherlands)

    Kroon, Steven; Ramekers, Dyan; Smeets, Emma M; Hendriksen, Ferry G J; Klis, Sjaak F L; Versnel, Huib

    Damage to and loss of the organ of Corti leads to secondary degeneration of the spiral ganglion cell (SGC) somata of the auditory nerve. Extensively examined in animal models, this degeneration process of SGC somata following deafening is well known. However, degeneration of auditory nerve axons,

  14. Representation of voice pitch in discharge patterns of auditory-nerve fibers.

    Science.gov (United States)

    Miller, M I; Sachs, M B

    1984-06-01

    Responses of populations of auditory-nerve fibers were measured for synthesized consonant-vowel stimuli. This paper explores the encoding of fundamental frequency (pitch) in these responses. Post-stimulus time (PST) histograms were computed from 25 ms segments of the spike trains. Discrete Fourier transforms with a 40 Hz resolution were computed from the histograms. Two representations of pitch are considered. The first representation is based on the pitch-related temporal properties of the speech signal. Histograms for individual units can show envelope modulations directly related to the pitch period. These modulations reflect the responses of these fibers to a number of stimulus harmonics near fiber CF. Responses of fibers near formant frequencies are dominated by a single large harmonic component, and thus show small or no pitch-related enveloped modulations. Envelope modulations are reduced in the presence of background noise. The second representation uses both temporal properties of auditory-nerve responses and cochlear place to encode the pitch-related harmonic structure of speech. As a measure of the response of the population of fibers to each harmonic of 40 Hz the magnitude of the component of the Fourier transform at that frequency was averaged across all fibers whose characteristic frequencies were within one-fourth octave of that harmonic. We call this measure the average localized synchronized rate (ALSR). The ALSR provides a good representation of stimulus spectrum, even in the presence of background noise. From the harmonic structure of the ALSR, we are able to extract the stimulus pitch frequency. The relationship of these two representations to pitch perception in both acoustic and electrical stimulation (via cochlear implants) is discussed.

  15. Changes in Properties of Auditory Nerve Synapses following Conductive Hearing Loss.

    Science.gov (United States)

    Zhuang, Xiaowen; Sun, Wei; Xu-Friedman, Matthew A

    2017-01-11

    Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization. We examined the effects of CHL at auditory nerve synapses onto bushy cells in the mouse anteroventral cochlear nucleus following occlusion of the ear canal. These synapses, called endbulbs of Held, normally show strong depression in voltage-clamp recordings in brain slices. After 1 week of CHL, endbulbs showed even greater depression, reflecting higher release probability. We observed no differences in quantal size between control and occluded mice. We confirmed these observations using mean-variance analysis and the integration method, which also revealed that the number of release sites decreased after occlusion. Consistent with this, synaptic puncta immunopositive for VGLUT1 decreased in area after occlusion. The level of depression and number of release sites both showed recovery after returning to normal conditions. Finally, bushy cells fired fewer action potentials in response to evoked synaptic activity after occlusion, likely because of increased depression and decreased input resistance. These effects appear to reflect a homeostatic, adaptive response of auditory nerve synapses to reduced activity. These effects may have important implications for perceptual changes following CHL. Normal hearing is important to everyday life, but abnormal auditory experience during development can lead to processing disorders. For example, otitis media reduces sound to the ear, which can cause long-lasting deficits in language skills and verbal

  16. Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

    Science.gov (United States)

    Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

    2016-01-01

    The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  17. 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.

  18. 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.

  19. Noise-induced hearing loss increases the temporal precision of complex envelope coding by auditory-nerve fibers

    Directory of Open Access Journals (Sweden)

    Kenneth Stuart Henry

    2014-02-01

    Full Text Available While changes in cochlear frequency tuning are thought to play an important role in the perceptual difficulties of people with sensorineural hearing loss (SNHL, the possible role of temporal processing deficits remains less clear. Our knowledge of temporal envelope coding in the impaired cochlea is limited to two studies that examined auditory-nerve fiber responses to narrowband amplitude modulated stimuli. In the present study, we used Wiener-kernel analyses of auditory-nerve fiber responses to broadband Gaussian noise in anesthetized chinchillas to quantify changes in temporal envelope coding with noise-induced SNHL. Temporal modulation transfer functions (TMTFs and temporal windows of sensitivity to acoustic stimulation were computed from 2nd-order Wiener kernels and analyzed to estimate the temporal precision, amplitude, and latency of envelope coding. Noise overexposure was associated with slower (less negative TMTF roll-off with increasing modulation frequency and reduced temporal window duration. The results show that at equal stimulus sensation level, SNHL increases the temporal precision of envelope coding by 20-30%. Furthermore, SNHL increased the amplitude of envelope coding by 50% in fibers with CFs from 1-2 kHz and decreased mean response latency by 0.4 ms. While a previous study of envelope coding demonstrated a similar increase in response amplitude, the present study is the first to show enhanced temporal precision. This new finding may relate to the use of a more complex stimulus with broad frequency bandwidth and a dynamic temporal envelope. Exaggerated neural coding of fast envelope modulations may contribute to perceptual difficulties in people with SNHL by acting as a distraction from more relevant acoustic cues, especially in fluctuating background noise. Finally, the results underscore the value of studying sensory systems with more natural, real-world stimuli.

  20. Stapes Vibration in the Chinchilla Middle Ear: Relation to Behavioral and Auditory-Nerve Thresholds.

    Science.gov (United States)

    Robles, Luis; Temchin, Andrei N; Fan, Yun-Hui; Ruggero, Mario A

    2015-08-01

    The vibratory responses to tones of the stapes and incus were measured in the middle ears of deeply anesthetized chinchillas using a wide-band acoustic-stimulus system and a laser velocimeter coupled to a microscope. With the laser beam at an angle of about 40 ° relative to the axis of stapes piston-like motion, the sensitivity-vs.-frequency curves of vibrations at the head of the stapes and the incus lenticular process were very similar to each other but larger, in the range 15-30 kHz, than the vibrations of the incus just peripheral to the pedicle. With the laser beam aligned with the axis of piston-like stapes motion, vibrations of the incus just peripheral to its pedicle were very similar to the vibrations of the lenticular process or the stapes head measured at the 40 ° angle. Thus, the pedicle prevents transmission to the stapes of components of incus vibration not aligned with the axis of stapes piston-like motion. The mean magnitude curve of stapes velocities is fairly flat over a wide frequency range, with a mean value of about 0.19 mm(.)(s Pa(-1)), has a high-frequency cutoff of 25 kHz (measured at -3 dB re the mean value), and decreases with a slope of about -60 dB/octave at higher frequencies. According to our measurements, the chinchilla middle ear transmits acoustic signals into the cochlea at frequencies exceeding both the bandwidth of responses of auditory-nerve fibers and the upper cutoff of hearing. The phase lags of stapes velocity relative to ear-canal pressure increase approximately linearly, with slopes equivalent to pure delays of about 57-76 μs.

  1. Envelope coding in auditory nerve fibers following noise-induced hearing loss.

    Science.gov (United States)

    Kale, Sushrut; Heinz, Michael G

    2010-12-01

    Recent perceptual studies suggest that listeners with sensorineural hearing loss (SNHL) have a reduced ability to use temporal fine-structure cues, whereas the effects of SNHL on temporal envelope cues are generally thought to be minimal. Several perceptual studies suggest that envelope coding may actually be enhanced following SNHL and that this effect may actually degrade listening in modulated maskers (e.g., competing talkers). The present study examined physiological effects of SNHL on envelope coding in auditory nerve (AN) fibers in relation to fine-structure coding. Responses were compared between anesthetized chinchillas with normal hearing and those with a mild-moderate noise-induced hearing loss. Temporal envelope coding of narrowband-modulated stimuli (sinusoidally amplitude-modulated tones and single-formant stimuli) was quantified with several neural metrics. The relative strength of envelope and fine-structure coding was compared using shuffled correlogram analyses. On average, the strength of envelope coding was enhanced in noise-exposed AN fibers. A high degree of enhanced envelope coding was observed in AN fibers with high thresholds and very steep rate-level functions, which were likely associated with severe outer and inner hair cell damage. Degradation in fine-structure coding was observed in that the transition between AN fibers coding primarily fine structure or envelope occurred at lower characteristic frequencies following SNHL. This relative fine-structure degradation occurred despite no degradation in the fundamental ability of AN fibers to encode fine structure and did not depend on reduced frequency selectivity. Overall, these data suggest the need to consider the relative effects of SNHL on envelope and fine-structure coding in evaluating perceptual deficits in temporal processing of complex stimuli.

  2. 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.

  3. 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...

  4. 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...... for optimal benefit from a CI. Diffusion tensor MRI (DTI) may provide such a measure, by allowing noninvasive investigations of the nerve's microstructure. In this pilot study, we show the first use of DTI to image the auditory nerve in five normal-hearing subjects and five patients with long-term profound...... single-sided sensorineural hearing loss. A specialized acquisition protocol was designed for a 3 T MRI scanner to image the small nerve bundle. The nerve was reconstructed using fiber tractography and DTI metrics - which reflect the nerve's microstructural properties - were computed per tract. Comparing...

  5. Auditory nerve frequency tuning measured with forward-masked compound action potentials.

    Science.gov (United States)

    Verschooten, Eric; Robles, Luis; Kovačić, Damir; Joris, Philip X

    2012-12-01

    Frequency selectivity is a fundamental cochlear property. Recent studies using otoacoustic emissions and psychophysical forward masking suggest that frequency selectivity is sharper in human than in common laboratory species. This has been disputed based on reports using compound action potentials (CAPs), which reflect activity in the auditory nerve and can be measured in humans. Comparative data of CAPs, obtained with a variety of simultaneous masking protocols, have been interpreted to indicate similarity of frequency tuning across mammals and even birds. Unfortunately, there are several issues with the available CAP measurements which hamper a straightforward comparison across species. We investigate sharpness of CAP tuning in cat and chinchilla using a forward masking notched-noise paradigm--which is less confounded by cochlear nonlinearities than simultaneous masking paradigms and similar to what was used in the psychophysical study reporting sharper tuning in humans. Our parametric study, using different probe frequencies and notch widths, shows relationships consistent with those of auditory nerve fibers (ANFs). The sharpness of tuning, quantified by Q(10) factors, is negatively correlated with probe level and increases with probe frequency, but the Q(10) values are generally lower than the average trend for ANFs. Like the single fiber data, tuning for CAPs is sharper in cat than in chinchilla, but the two species are similar in the dependence of tuning on probe frequency and in the relationship between tuning in ANFs and CAP. Growth-of-maskability functions show slopes <1 indicating that with increasing probe level the probe is more susceptible to cochlear compression than the masker. The results support the use of forward-masked CAPs as an alternative measure to estimate ANF tuning and to compare frequency tuning across species.

  6. Fractal auditory-nerve firing patterns may derive from fractal switching in sensory hair-cell ion channels

    Science.gov (United States)

    Lowen, S. B.; Teich, M. C.

    1993-08-01

    Hair-cell ion channels, which provide a crucial link in the transformation of incoming acoustic information to neural action-potential trains, switch between open and closed states with power-law-distributed (fractal) dwell times. Trains of action potentials recorded from auditory nerves in mammals always exhibit fractal behavior, including a 1/f-type spectrum, for long time scales. We provide a mathematical model linking these two fractal behaviors within a common framework.

  7. Effects of sensorineural hearing loss on temporal coding of harmonic and inharmonic tone complexes in the auditory nerve.

    Science.gov (United States)

    Kale, Sushrut; Micheyl, Christophe; Heinz, Michael G

    2013-01-01

    Listeners with sensorineural hearing loss (SNHL) often show poorer thresholds for fundamental-frequency (F0) discrimination and poorer discrimination between harmonic and frequency-shifted (inharmonic) complex tones, than normal-hearing (NH) listeners-especially when these tones contain resolved or partially resolved components. It has been suggested that these perceptual deficits reflect reduced access to temporal-fine-structure (TFS) information and could be due to degraded phase locking in the auditory nerve (AN) with SNHL. In the present study, TFS and temporal-envelope (ENV) cues in single AN-fiber responses to band-pass-filtered harmonic and inharmonic complex tones were -measured in chinchillas with either normal-hearing or noise-induced SNHL. The stimuli were comparable to those used in recent psychophysical studies of F0 and harmonic/inharmonic discrimination. As in those studies, the rank of the center component was manipulated to produce -different resolvability conditions, different phase relationships (cosine and random phase) were tested, and background noise was present. Neural TFS and ENV cues were quantified using cross-correlation coefficients computed using shuffled cross correlograms between neural responses to REF (harmonic) and TEST (F0- or frequency-shifted) stimuli. In animals with SNHL, AN-fiber tuning curves showed elevated thresholds, broadened tuning, best-frequency shifts, and downward shifts in the dominant TFS response component; however, no significant degradation in the ability of AN fibers to encode TFS or ENV cues was found. Consistent with optimal-observer analyses, the results indicate that TFS and ENV cues depended only on the relevant frequency shift in Hz and thus were not degraded because phase locking remained intact. These results suggest that perceptual "TFS-processing" deficits do not simply reflect degraded phase locking at the level of the AN. To the extent that performance in F0- and harmonic/inharmonic discrimination

  8. Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus.

    Science.gov (United States)

    Clarkson, Cheryl; Antunes, Flora M; Rubio, Maria E

    2016-09-28

    Sound deprivation by conductive hearing loss increases hearing thresholds, but little is known about the response of the auditory brainstem during and after conductive hearing loss. Here, we show in young adult rats that 10 d of monaural conductive hearing loss (i.e., earplugging) leads to hearing deficits that persist after sound levels are restored. Hearing thresholds in response to clicks and frequencies higher than 8 kHz remain increased after a 10 d recovery period. Neural output from the cochlear nucleus measured at 10 dB above threshold is reduced and followed by an overcompensation at the level of the lateral lemniscus. We assessed whether structural and molecular substrates at auditory nerve (endbulb of Held) synapses in the cochlear nucleus could explain these long-lasting changes in hearing processing. During earplugging, vGluT1 expression in the presynaptic terminal decreased and synaptic vesicles were smaller. Together, there was an increase in postsynaptic density (PSD) thickness and an upregulation of GluA3 AMPA receptor subunits on bushy cells. After earplug removal and a 10 d recovery period, the density of synaptic vesicles increased, vesicles were also larger, and the PSD of endbulb synapses was larger and thicker. The upregulation of the GluA3 AMPAR subunit observed during earplugging was maintained after the recovery period. This suggests that GluA3 plays a role in plasticity in the cochlear nucleus. Our study demonstrates that sound deprivation has long-lasting alterations on structural and molecular presynaptic and postsynaptic components at the level of the first auditory nerve synapse in the auditory brainstem. Despite being the second most prevalent form of hearing loss, conductive hearing loss and its effects on central synapses have received relatively little attention. Here, we show that 10 d of monaural conductive hearing loss leads to an increase in hearing thresholds, to an increased central gain upstream of the cochlear nucleus at

  9. Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus.

    Science.gov (United States)

    Sedlacek, Miloslav; Brenowitz, Stephan D

    2014-01-01

    Feed-forward inhibition (FFI) represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs), principal neurons of the dorsal cochlear nucleus (DCN) that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs) on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and FFI in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of FFI had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition, we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs) in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

  10. Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus

    Directory of Open Access Journals (Sweden)

    Miloslav eSedlacek

    2014-07-01

    Full Text Available Feedforward inhibition represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs, principal neurons of the dorsal cochlear nucleus (DCN that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and feed-forward inhibition in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven feed-forward inhibition (FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of feed-forward inhibition had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

  11. Hidden Hearing Loss and Computational Models of the Auditory Pathway: Predicting Speech Intelligibility Decline

    Science.gov (United States)

    2016-11-28

    Thomas F. Quatieri* *Massachusetts Institute of Technology Lincoln Laboratory, Lexington MA, USA A common complaint of listeners with normal...auditory nerve (AN) responses to speech stimuli under a variety of difficult listening conditions. The resulting cochlear neurogram, a spectrogram

  12. Towards Clinical Application of Neurotrophic Factors to the Auditory Nerve; Assessment of Safety and Efficacy by a Systematic Review of Neurotrophic Treatments in Humans

    Directory of Open Access Journals (Sweden)

    Aren Bezdjian

    2016-11-01

    Full Text Available Animal studies have evidenced protection of the auditory nerve by exogenous neurotrophic factors. In order to assess clinical applicability of neurotrophic treatment of the auditory nerve, the safety and efficacy of neurotrophic therapies in various human disorders were systematically reviewed. Outcomes of our literature search included disorder, neurotrophic factor, administration route, therapeutic outcome, and adverse event. From 2103 articles retrieved, 20 randomized controlled trials including 3974 patients were selected. Amyotrophic lateral sclerosis (53% was the most frequently reported indication for neurotrophic therapy followed by diabetic polyneuropathy (28%. Ciliary neurotrophic factor (50%, nerve growth factor (24% and insulin-like growth factor (21% were most often used. Injection site reaction was a frequently occurring adverse event (61% followed by asthenia (24% and gastrointestinal disturbances (20%. Eighteen out of 20 trials deemed neurotrophic therapy to be safe, and six out of 17 studies concluded the neurotrophic therapy to be effective. Positive outcomes were generally small or contradicted by other studies. Most non-neurodegenerative diseases treated by targeted deliveries of neurotrophic factors were considered safe and effective. Hence, since local delivery to the cochlea is feasible, translation from animal studies to human trials in treating auditory nerve degeneration seems promising.

  13. Prediction of flap response.

    Science.gov (United States)

    Potgieter, Frederik J; Roberts, Cynthia; Cox, Ian G; Mahmoud, Ashraf M; Herderick, Edward E; Roetz, Marlize; Steenkamp, Wouter

    2005-01-01

    To find predictors of the induced biomechanical and optical effects of lamellar flap creation on the cornea. Optimed Eye and Laser Clinic, Pretoria, South Africa, and the Department of Ophthalmology and Biomedical Engineering Center, The Ohio State University, Columbus, Ohio, and Bausch & Lomb Vision Research Laboratory, Rochester, New York, USA. This prospective study monitored the refractive, wavefront aberration, and corneal topographic changes in 29 eyes of 15 patients for 3 months after the creation of a corneal lamellar flap. The main outcome measures for statistical analysis were refraction, total corneal thickness, residual corneal bed thickness, horizontal white-to-white corneal diameter, horizontal flap diameter, topography data, and wavefront data. Statistically significant changes were seen in the autorefraction mode. Wavefront data showed significant change in 4 Zernike modes-90/180-degree astigmatism, vertical coma, horizontal coma, and spherical aberration. The topography data indicated the corneal biomechanical response was significantly predicted by stromal bed thickness in the early follow-up period and by total corneal pachymetry and flap diameter in a 2-parameter statistical model in the late follow-up period. Uncomplicated lamellar flap creation is responsible for systematic changes in corneal topography and induction of higher-order optical aberrations. Predictors of this response include stromal bed thickness, flap diameter, and total corneal pachymetry.

  14. Spontaneous activity of auditory nerve fibers in the barn owl (Tyto alba): analyses of interspike interval distributions.

    Science.gov (United States)

    Neubauer, Heinrich; Köppl, Christine; Heil, Peter

    2009-06-01

    In vertebrate auditory systems, the conversion from graded receptor potentials across the hair-cell membrane into stochastic spike trains of the auditory nerve (AN) fibers is performed by ribbon synapses. The statistics underlying this process constrain auditory coding but are not precisely known. Here, we examine the distributions of interspike intervals (ISIs) from spontaneous activity of AN fibers of the barn owl (Tyto alba), a nocturnal avian predator whose auditory system is specialized for precise temporal coding. The spontaneous activity of AN fibers, with the exception of those showing preferred intervals, is commonly thought to result from excitatory events generated by a homogeneous Poisson point process, which lead to spikes unless the fiber is refractory. We show that the ISI distributions in the owl are better explained as resulting from the action of a brief refractory period ( approximately 0.5 ms) on excitatory events generated by a homogeneous stochastic process where the distribution of interevent intervals is a mixture of an exponential and a gamma distribution with shape factor 2, both with the same scaling parameter. The same model was previously shown to apply to AN fibers in the cat. However, the mean proportions of exponentially versus gamma-distributed intervals in the mixture were different for cat and owl. Furthermore, those proportions were constant across fibers in the cat, whereas they covaried with mean spontaneous rate and with characteristic frequency in the owl. We hypothesize that in birds, unlike in mammals, more than one ribbon may provide excitation to most fibers, accounting for the different proportions, and that variation in the number of ribbons may underlie the variation in the proportions.

  15. Auditory nerve fiber representation of cues to voicing in syllable-final stop consonants

    Energy Technology Data Exchange (ETDEWEB)

    Sinex, D.G. (Boys Town National Research Hospital, Omaha, NE (United States))

    1993-09-01

    Acoustic cues to the identity of consonants such as d and t vary according to contextual factors such as the position of the consonant within a syllable. However, investigations of the neural coding of consonants have almost always used stimuli in which the consonant occurs in the syllable-initial position. The present experiments examined the peripheral neural representation of spectral and temporal cues that can distinguish between stop consonants d and t in syllable-final position. Stimulus sets consisting of the syllables hid, hit, hud, and hut were recorded by three different talkers. During the consonant closure interval, the spectrum of d was characterized by the presence of a low-frequency voice bar. Most neurons responses were characterized by discharge rate decreases at the beginning of the closure interval and by rate increases that marked the release of the consonant closure. Exceptions were seen in the responses of neurons with characteristics frequencies (CFs) below approximately 0.7 kHz to syllables ending in d. These neurons responded to the voice bar with discharge rates that could approach the rates elicited by the vowel. The latencies of prominent discharge rate changes were measured for all neurons and used to compute the length of the encoded closure interval. The encoded interval was clearly longer for syllables ending in t than in d. The encoded interval increased with CF for both consonants but more rapidly for t. Differences in the encoded closure interval were small for syllables with different vowels or syllables produced by different talkers. 29 refs., 10 figs.

  16. 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.

  17. [Exposing the rabbit cerebellopontine angle through post-sigmoid sinus approach and recording the direct compound action potential of the auditory nerve].

    Science.gov (United States)

    Zhu, Ming; Wu, Hao; Li, Zhaoji; Chen, Xiangping; Cao, Rongping; Shen, Min; Zhu, Chunsheng; Zhou, Jingfeng

    2005-04-01

    To study the way of exposing the rabbit cerebellopontine angle through post-sigmoid sinus approach and recording the direct compound action potential of the auditory nerve, and to investigate the stability of DCAP N1 wave latency. Fifteen New Zealand rabbits which had normal Preyer's auricle reflex were selected. Each one was studied in the left ear. After anaesthetized,the cerebellopontine angle of rabbits were exposed through post-sigmoid sinus approach under aseptic status,then the needle-shaped pole were inserted into the facial-acoustic nerve complex. The DCAP was recorded at the immediateness, 2 h and 5 h after the insertino sequentially. At last, DCAP N1 wave latencies of 15 rabbits were statisticed and analyzed using paired-samples t-test. To the 15 sides, the distinct curves with well differentiated waves were induced in the all three times. No significant difference in any N1 wave latency had been found among the 3 times. The rabbit cerebellopontine angle could be exposed and the direct compound action potential of the auditory nerve could be recorded successfully by the way studied in this experiment. In normal state, the individual value of DCAP N1 wave latency is stable. During the process of surgery in which the cerebellopontine angle has been exposed, the DCAP N1 wave latency is a practical index for monitoring of hearing impairment.

  18. Predicting response to epigenetic therapy

    DEFF Research Database (Denmark)

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

    2014-01-01

    of good pretreatment predictors of response is of great value. Many clinical parameters and molecular targets have been tested in preclinical and clinical studies with varying results, leaving room for optimization. Here we provide an overview of markers that may predict the efficacy of FDA- and EMA...

  19. Analysis of a purely conductance-based stochastic nerve fibre model as applied to compound models of populations of human auditory nerve fibres used in cochlear implant simulations.

    Science.gov (United States)

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

    2017-12-01

    The study presents the application of a purely conductance-based stochastic nerve fibre model to human auditory nerve fibres within finite element volume conduction models of a semi-generic head and user-specific cochleae. The stochastic, threshold and temporal characteristics of the human model are compared and successfully validated against physiological feline results with the application of a mono-polar, bi-phasic, cathodic first stimulus. Stochastic characteristics validated include: (i) the log(Relative Spread) versus log(fibre diameter) distribution for the discharge probability versus stimulus intensity plots and (ii) the required exponential membrane noise versus transmembrane voltage distribution. Intra-user, and to a lesser degree inter-user, comparisons are made with respect to threshold and dynamic range at short and long pulse widths for full versus degenerate single fibres as well as for populations of degenerate fibres of a single user having distributed and aligned somas with varying and equal diameters. Temporal characteristics validated through application of different stimulus pulse rates and different stimulus intensities include: (i) discharge rate, latency and latency standard deviation versus stimulus intensity, (ii) period histograms and (iii) interspike interval histograms. Although the stochastic population model does not reduce the modelled single deterministic fibre threshold, the simulated stochastic and temporal characteristics show that it could be used in future studies to model user-specific temporally encoded information, which influences the speech perception of CI users.

  20. Auditory brainstem response latency in forward masking, a marker of sensory deficits in listeners with normal hearing thresholds

    DEFF Research Database (Denmark)

    Mehraei, Golbarg; Paredes Gallardo, Andreu; Shinn-Cunningham, Barbara G.

    2017-01-01

    In rodent models, acoustic exposure too modest to elevate hearing thresholds can nonetheless cause auditory nerve fiber deafferentation, interfering with the coding of supra-threshold sound. Low-spontaneous rate nerve fibers, important for encoding acoustic information at supra-threshold levels...... and in noise, are more susceptible to degeneration than high-spontaneous rate fibers. The change in auditory brainstem response (ABR) wave-V latency with noise level has been shown to be associated with auditory nerve deafferentation. Here, we measured ABR in a forward masking paradigm and evaluated wave......-V latency changes with increasing masker-to-probe intervals. In the same listeners, behavioral forward masking detection thresholds were measured. We hypothesized that 1) auditory nerve fiber deafferentation increases forward masking thresholds and increases wave-V latency and 2) a preferential loss of low...

  1. 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 ...

  2. 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.

  3. Low-frequency versus high-frequency synchronisation in chirp-evoked auditory brainstem responses

    DEFF Research Database (Denmark)

    Rønne, Filip Munch; Gøtsche-Rasmussen, Kristian

    2011-01-01

    This study investigates the frequency specific contribution to the auditory brainstem response (ABR) of chirp stimuli. Frequency rising chirps were designed to compensate for the cochlear traveling wave delay, and lead to larger wave-V amplitudes than for click stimuli as more auditory nerve fibres...

  4. Difference in response reliability predicted by spectrotemporal tuning in the cochlear nuclei of barn owls

    Science.gov (United States)

    Steinberg, Louisa J.; Peña, Jose L.

    2011-01-01

    The brainstem auditory pathway is obligatory for all aural information. Brainstem auditory neurons must encode the level and timing of sounds, as well as their time-dependent spectral properties, the fine structure and envelope, which are essential for sound discrimination. This study focused on envelope coding in the two cochlear nuclei of the barn owl, nucleus angularis (NA) and nucleus magnocellularis (NM). NA and NM receive input from bifurcating auditory nerve fibers and initiate processing pathways specialized in encoding interaural time (ITD) and level (ILD) differences, respectively. We found that NA neurons, though unable to accurately encode stimulus phase, lock more strongly to the stimulus envelope than NM units. The spectrotemporal receptive fields (STRFs) of NA neurons exhibit a pre-excitatory suppressive field. Using multilinear regression analysis and computational modeling, we show that this feature of STRFs can account for enhanced across-trial response reliability, by locking spikes to the stimulus envelope. Our findings indicate a dichotomy in envelope coding between the time and intensity processing pathways as early as at the level of the cochlear nuclei. This allows the ILD processing pathway to encode envelope information with greater fidelity than the ITD processing pathway. Furthermore, we demonstrate that the properties of the neurons’ STRFs can be quantitatively related to spike timing reliability. PMID:21368035

  5. 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

  6. Prediction of treatment response to adalimumab

    DEFF Research Database (Denmark)

    Krintel, S. 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 algori...... of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.The Pharmacogenomics Journal advance online publication, 5 May 2015; doi:10.1038/tpj.2015.30....

  7. Response predictions using the observed autocorrelation function

    DEFF Research Database (Denmark)

    Nielsen, Ulrik Dam; H. Brodtkorb, Astrid; Jensen, Jørgen Juncher

    2018-01-01

    This article studies a procedure that facilitates short-time, deterministic predictions of the wave-induced motion of a marine vessel, where it is understood that the future motion of the vessel is calculated ahead of time. Such predictions are valuable to assist in the execution of many marine......-induced response in study. Thus, predicted (future) values ahead of time for a given time history recording are computed through a mathematical combination of the sample autocorrelation function and previous measurements recorded just prior to the moment of action. Importantly, the procedure does not need input...

  8. 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.

  9. Responses of Auditory Nerve and Anteroventral Cochlear Nucleus Fibers to Broadband and Narrowband Noise: Implications for the Sensitivity to Interaural Delays

    NARCIS (Netherlands)

    M. van der Heijden (Marcel); D.H.G. Louage (Dries H.G.); P.X. Joris (Philip)

    2011-01-01

    textabstractThe quality of temporal coding of sound waveforms in the monaural afferents that converge on binaural neurons in the brainstem limits the sensitivity to temporal differences at the two ears. The anteroventral cochlear nucleus (AVCN) houses the cells that project to the binaural nuclei,

  10. Suppression Measured from Chinchilla Auditory-Nerve-Fiber Responses Following Noise-Induced Hearing Loss: Adaptive-Tracking and Systems-Identification Approaches

    OpenAIRE

    Sayles, Mark; Walls, Michael K.; Heinz, Michael G.

    2016-01-01

    The compressive nonlinearity of cochlear signal transduction, reflecting outer-hair-cell function, manifests as suppressive spectral interactions; e.g., two-tone suppression. Moreover, for broadband sounds, there are multiple interactions between frequency components. These frequency-dependent nonlinearities are important for neural coding of complex sounds, such as speech. Acoustic-trauma-induced outer-hair-cell damage is associated with loss of nonlinearity, which auditory prostheses attemp...

  11. Prediction Models for Dynamic Demand Response

    Energy Technology Data Exchange (ETDEWEB)

    Aman, Saima; Frincu, Marc; Chelmis, Charalampos; Noor, Muhammad; Simmhan, Yogesh; Prasanna, Viktor K.

    2015-11-02

    As Smart Grids move closer to dynamic curtailment programs, Demand Response (DR) events will become necessary not only on fixed time intervals and weekdays predetermined by static policies, but also during changing decision periods and weekends to react to real-time demand signals. Unique challenges arise in this context vis-a-vis demand prediction and curtailment estimation and the transformation of such tasks into an automated, efficient dynamic demand response (D2R) process. While existing work has concentrated on increasing the accuracy of prediction models for DR, there is a lack of studies for prediction models for D2R, which we address in this paper. Our first contribution is the formal definition of D2R, and the description of its challenges and requirements. Our second contribution is a feasibility analysis of very-short-term prediction of electricity consumption for D2R over a diverse, large-scale dataset that includes both small residential customers and large buildings. Our third, and major contribution is a set of insights into the predictability of electricity consumption in the context of D2R. Specifically, we focus on prediction models that can operate at a very small data granularity (here 15-min intervals), for both weekdays and weekends - all conditions that characterize scenarios for D2R. We find that short-term time series and simple averaging models used by Independent Service Operators and utilities achieve superior prediction accuracy. We also observe that workdays are more predictable than weekends and holiday. Also, smaller customers have large variation in consumption and are less predictable than larger buildings. Key implications of our findings are that better models are required for small customers and for non-workdays, both of which are critical for D2R. Also, prediction models require just few days’ worth of data indicating that small amounts of

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Predicted effects of sensorineural hearing loss on across-fiber envelope coding in the auditory nervea

    Science.gov (United States)

    Swaminathan, Jayaganesh; Heinz, Michael G.

    2011-01-01

    Cross-channel envelope correlations are hypothesized to influence speech intelligibility, particularly in adverse conditions. Acoustic analyses suggest speech envelope correlations differ for syllabic and phonemic ranges of modulation frequency. The influence of cochlear filtering was examined here by predicting cross-channel envelope correlations in different speech modulation ranges for normal and impaired auditory-nerve (AN) responses. Neural cross-correlation coefficients quantified across-fiber envelope coding in syllabic (0–5 Hz), phonemic (5–64 Hz), and periodicity (64–300 Hz) modulation ranges. Spike trains were generated from a physiologically based AN model. Correlations were also computed using the model with selective hair-cell damage. Neural predictions revealed that envelope cross-correlation decreased with increased characteristic-frequency separation for all modulation ranges (with greater syllabic-envelope correlation than phonemic or periodicity). Syllabic envelope was highly correlated across many spectral channels, whereas phonemic and periodicity envelopes were correlated mainly between adjacent channels. Outer-hair-cell impairment increased the degree of cross-channel correlation for phonemic and periodicity ranges for speech in quiet and in noise, thereby reducing the number of independent neural information channels for envelope coding. In contrast, outer-hair-cell impairment was predicted to decrease cross-channel correlation for syllabic envelopes in noise, which may partially account for the reduced ability of hearing-impaired listeners to segregate speech in complex backgrounds. PMID:21682421

  17. Resting state functional connectivity predicts neurofeedback response

    Directory of Open Access Journals (Sweden)

    Dustin eScheinost

    2014-09-01

    Full Text Available Tailoring treatments to the specific needs and biology of individual patients – personalized medicine – requires delineation of reliable predictors of response. Unfortunately, these have been slow to emerge, especially in neuropsychiatric disorders. We have recently described a real-time functional magnetic resonance imaging (rt-fMRI neurofeedback protocol that can reduce contamination-related anxiety, a prominent symptom of many cases of obsessive-compulsive disorder (OCD. Individual response to this intervention is variable. Here we used patterns of brain functional connectivity, as measured by baseline resting-state fMRI (rs-fMRI, to predict improvements in contamination anxiety after neurofeedback training. Activity of a region of the orbitofrontal cortex (OFC and anterior prefrontal cortex, Brodmann area (BA 10, associated with contamination anxiety in each subject was measured in real time and presented as a neurofeedback signal, permitting subjects to learn to modulate this target brain region. We have previously reported both enhanced OFC/BA 10 control and improved anxiety in a group of subclinically anxious subjects after neurofeedback. Five individuals with contamination-related OCD who underwent the same protocol also showed improved clinical symptomatology. In both groups, these behavioral improvements were strongly correlated with baseline whole-brain connectivity in the OFC/BA 10, computed from rs-fMRI collected several days prior to neurofeedback training. These pilot data suggest that rs-fMRI can be used to identify individuals likely to benefit from rt-fMRI neurofeedback training to control contamination anxiety.

  18. 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. Copyright © 2014 the authors 0270-6474/14/3415097-13$15.00/0.

  19. The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells.

    Science.gov (United States)

    Rubio, María E; Matsui, Ko; Fukazawa, Yugo; Kamasawa, Naomi; Harada, Harumi; Itakura, Makoto; Molnár, Elek; Abe, Manabu; Sakimura, Kenji; Shigemoto, Ryuichi

    2017-11-01

    The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner.

  20. Personality predicts brain responses to cognitive demands.

    Science.gov (United States)

    Kumari, Veena; ffytche, Dominic H; Williams, Steven C R; Gray, Jeffrey A

    2004-11-24

    Eysenck (1981) proposed that the personality dimension of introversion- extraversion (E) reflects individual differences in a cortical arousal system modulated by reticulothalamic- cortical pathways: it is chronically more active in introverts relative to extraverts and influences cognitive performance in interaction with task parameters. A circuit with connections to this system, including the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate (AC) cortex, has been identified in studies applying functional magnetic resonance imaging (fMRI) to a broad range of cognitive tasks. We examined the influence of E, assessed with the Eysenck Personality Questionnaire-Revised (Eysenck and Eysenck, 1991), in fMRI activity during an "n-back" task involving four memory loads (0-, 1-, 2-, and 3-back) and a rest condition in healthy men. To confirm the specificity of E effects, we also examined the effects of neuroticism and psychoticism (P) scores. We observed that, as predicted by Eysenck's model, the higher the E score, the greater the change in fMRI signal from rest to the 3-back condition in the DLPFC and AC. In addition, E scores were negatively associated with resting fMRI signals in the thalamus and Broca's area extending to Wernicke's area, supporting the hypothesized (negative) relationship between E and resting arousal. P scores negatively correlated with resting fMRI signal in the globus pallidus-putamen, extending previous findings of a negative relationship of schizotypy to striatal activity seen with older neuroimaging modalities to fMRI. These observations suggest that individual differences affect brain responses during cognitive activity and at rest and provide evidence for the hypothesized neurobiological basis of personality.

  1. Response predictions using the observed autocorrelation function

    DEFF Research Database (Denmark)

    Nielsen, Ulrik Dam; H. Brodtkorb, Astrid; Jensen, Jørgen Juncher

    2017-01-01

    operations (crane lifts, helicopter landings, etc.), as a specic prediction can be used to inform whether it is safe, or not, to carry out the particular operation within the nearest time horizon. The examined prediction procedure relies on observations of the correlation structure of the wave...

  2. A Robust Speaker Identification System Using the Responses from a Model of the Auditory Periphery.

    Science.gov (United States)

    Islam, Md Atiqul; Jassim, Wissam A; Cheok, Ng Siew; Zilany, Muhammad Shamsul Arefeen

    2016-01-01

    Speaker identification under noisy conditions is one of the challenging topics in the field of speech processing applications. Motivated by the fact that the neural responses are robust against noise, this paper proposes a new speaker identification system using 2-D neurograms constructed from the responses of a physiologically-based computational model of the auditory periphery. The responses of auditory-nerve fibers for a wide range of characteristic frequency were simulated to speech signals to construct neurograms. The neurogram coefficients were trained using the well-known Gaussian mixture model-universal background model classification technique to generate an identity model for each speaker. In this study, three text-independent and one text-dependent speaker databases were employed to test the identification performance of the proposed method. Also, the robustness of the proposed method was investigated using speech signals distorted by three types of noise such as the white Gaussian, pink, and street noises with different signal-to-noise ratios. The identification results of the proposed neural-response-based method were compared to the performances of the traditional speaker identification methods using features such as the Mel-frequency cepstral coefficients, Gamma-tone frequency cepstral coefficients and frequency domain linear prediction. Although the classification accuracy achieved by the proposed method was comparable to the performance of those traditional techniques in quiet, the new feature was found to provide lower error rates of classification under noisy environments.

  3. A Robust Speaker Identification System Using the Responses from a Model of the Auditory Periphery.

    Directory of Open Access Journals (Sweden)

    Md Atiqul Islam

    Full Text Available Speaker identification under noisy conditions is one of the challenging topics in the field of speech processing applications. Motivated by the fact that the neural responses are robust against noise, this paper proposes a new speaker identification system using 2-D neurograms constructed from the responses of a physiologically-based computational model of the auditory periphery. The responses of auditory-nerve fibers for a wide range of characteristic frequency were simulated to speech signals to construct neurograms. The neurogram coefficients were trained using the well-known Gaussian mixture model-universal background model classification technique to generate an identity model for each speaker. In this study, three text-independent and one text-dependent speaker databases were employed to test the identification performance of the proposed method. Also, the robustness of the proposed method was investigated using speech signals distorted by three types of noise such as the white Gaussian, pink, and street noises with different signal-to-noise ratios. The identification results of the proposed neural-response-based method were compared to the performances of the traditional speaker identification methods using features such as the Mel-frequency cepstral coefficients, Gamma-tone frequency cepstral coefficients and frequency domain linear prediction. Although the classification accuracy achieved by the proposed method was comparable to the performance of those traditional techniques in quiet, the new feature was found to provide lower error rates of classification under noisy environments.

  4. A Robust Speaker Identification System Using the Responses from a Model of the Auditory Periphery

    Science.gov (United States)

    Islam, Md. Atiqul; Jassim, Wissam A.; Cheok, Ng Siew; Zilany, Muhammad Shamsul Arefeen

    2016-01-01

    Speaker identification under noisy conditions is one of the challenging topics in the field of speech processing applications. Motivated by the fact that the neural responses are robust against noise, this paper proposes a new speaker identification system using 2-D neurograms constructed from the responses of a physiologically-based computational model of the auditory periphery. The responses of auditory-nerve fibers for a wide range of characteristic frequency were simulated to speech signals to construct neurograms. The neurogram coefficients were trained using the well-known Gaussian mixture model-universal background model classification technique to generate an identity model for each speaker. In this study, three text-independent and one text-dependent speaker databases were employed to test the identification performance of the proposed method. Also, the robustness of the proposed method was investigated using speech signals distorted by three types of noise such as the white Gaussian, pink, and street noises with different signal-to-noise ratios. The identification results of the proposed neural-response-based method were compared to the performances of the traditional speaker identification methods using features such as the Mel-frequency cepstral coefficients, Gamma-tone frequency cepstral coefficients and frequency domain linear prediction. Although the classification accuracy achieved by the proposed method was comparable to the performance of those traditional techniques in quiet, the new feature was found to provide lower error rates of classification under noisy environments. PMID:27392046

  5. An observation on the variance of a predicted response in ...

    African Journals Online (AJOL)

    In studying individual parameters and the predicted response in regression analysis, three important properties are usually distinguished. These are bias, variance and mean-square error. The choice of a predicted response has to be made on a balance of these properties and computational simplicity. To avoid over fitting, ...

  6. The combined effects of forward masking by noise and high click rate on monaural and binaural human auditory nerve and brainstem potentials.

    Science.gov (United States)

    Pratt, Hillel; Polyakov, Andrey; Bleich, Naomi; Mittelman, Naomi

    2004-07-01

    To study effects of forward masking and rapid stimulation on human monaurally- and binaurally-evoked brainstem potentials and suggest their relation to synaptic fatigue and recovery and to neuronal action potential refractoriness. Auditory brainstem evoked potentials (ABEPs) were recorded from 12 normally- and symmetrically hearing adults, in response to each click (50 dB nHL, condensation and rarefaction) in a train of nine, with an inter-click interval of 11 ms, that followed a white noise burst of 100 ms duration (50 dB nHL). Sequences of white noise and click train were repeated at a rate of 2.89 s(-1). The interval between noise and first click in the train was 2, 11, 22, 44, 66 or 88 ms in different runs. ABEPs were averaged (8000 repetitions) using a dwell time of 25 micros/address/channel. The binaural interaction components (BICs) of ABEPs were derived and the single, centrally located equivalent dipoles of ABEP waves I and V and of the BIC major wave were estimated. The latencies of dipoles I and V of ABEP, their inter-dipole interval and the dipole magnitude of component V were significantly affected by the interval between noise and clicks and by the serial position of the click in the train. The latency and dipole magnitude of the major BIC component were significantly affected by the interval between noise and clicks. Interval from noise and the click's serial position in the train interacted to affect dipole V latency, dipole V magnitude, BIC latencies and the V-I inter-dipole latency difference. Most of the effects were fully apparent by the first few clicks in the train, and the trend (increase or decrease) was affected by the interval between noise and clicks. The changes in latency and magnitude of ABEP and BIC components with advancing position in the click train and the interactions of click position in the train with the intervals from noise indicate an interaction of fatigue and recovery, compatible with synaptic depletion and replenishing

  7. 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...

  8. Prediction of psilocybin response in healthy volunteers

    National Research Council Canada - National Science Library

    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...

  9. 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...

  10. Usefulness of Electrical Auditory Brainstem Responses to Assess the Functionality of the Cochlear Nerve Using an Intracochlear Test Electrode.

    Science.gov (United States)

    Lassaletta, Luis; Polak, Marek; Huesers, Jan; Díaz-Gómez, Miguel; Calvino, Miryam; Varela-Nieto, Isabel; Gavilán, Javier

    2017-12-01

    To use an intracochlear test electrode to assess the integrity and the functionality of the auditory nerve in cochlear implant (CI) recipients and to compare electrical auditory brainstem responses (eABR) via the test electrode with the eABR responses with the CI. Otolaryngology department, tertiary referral hospital. Ten subjects (age at implantation 55 yr, range, 19-72) were subsequently implanted with a MED-EL CONCERTO CI on the side without any useful residual hearing. Following identification of the round window (RW), the test electrode was inserted in the cochlea previous to cochlear implantation. To assess the quality of an eABR waveform, scoring criteria from Walton et al. (2008) were chosen. The waveforms in each session were classified by detecting waves III and V by the algorithm and visual assessment of the waveform. Speech performance was evaluated with monosyllables, disyllables, and sentence recognition tests. It was possible to evoke electrical stimulation responses along with both the test electrode and the CI in all subjects. No significant differences in latencies or amplitudes after stimulation were found between the test electrode and the CI. All subjects obtained useful hearing with their CI and use their implants daily. The intracochlear test electrode may be suitable to test the integrity of the auditory nerve by recording eABR signals. This allows for further research on the status of the auditory nerve after tumor removal and correlation with auditory performance.

  11. Field Response Prediction: Framing the problem.

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera-Palmer, Belkis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-06-01

    Predicting the performance of radiation detection systems at field sites based on measured performance acquired under controlled conditions at test locations, e.g., the Nevada National Security Site (NNSS), remains an unsolved and standing issue within DNDO’s testing methodology. Detector performance can be defined in terms of the system’s ability to detect and/or identify a given source or set of sources, and depends on the signal generated by the detector for the given measurement configuration (i.e., source strength, distance, time, surrounding materials, etc.) and on the quality of the detection algorithm. Detector performance is usually evaluated in the performance and operational testing phases, where the measurement configurations are selected to represent radiation source and background configurations of interest to security applications.

  12. Pre-treatment amygdala volume predicts electroconvulsive therapy response

    NARCIS (Netherlands)

    ten Doesschate, Freek; van Eijndhoven, Philip; Tendolkar, Indira; van Wingen, Guido A.; van Waarde, Jeroen A.

    2014-01-01

    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

  13. Radiation response prediction of single mode fibers

    Science.gov (United States)

    Friebele, E. J.; Askins, Charles G.; Brambani, Louise A.; Dorsey, Kenneth L.; Griscom, David L.; Gingerich, Michael E.; Harrington, Calvin C.; Shaw, Cathy M.; Tsai, Tsung-Ein; Paek, Un-Chul

    1988-03-01

    Fiber optic transmission systems, because of their extraordinary channel capacity and decreasing cost, are rapidly becoming the preferred terrestrial transmission media of the nation's long distance, inter-city telecommunications infrastructure. Since the commercial telephone network forms the foundation for emergency communication in the event of a national crisis or emergency, additional requirements are placed on the fibers and components being installed. One of the most stressing environments for the fiber consists of fallout subsequent to a nuclear attack. The susceptibility of some of types of commercially available fiber optic cable to optical darkening (and hence increased signal loss) from exposure to ionizing radiation raises serious questions about the survivability of such systems in the reconstitution phase of a nuclear conflict. There is a large body of knowledge available on the effects of gamma radiation on the older multimode fiber cables. However, there are critically important knowledge gaps with respect to the newer single mode cables which are employed in the inter-city fiber transmission links being installed today. This document is a final report of a two year program funded by NCS at NRL, which was the first systematic study of the interrelationship of fiber fabrication parameters and radiation-induced loss. A rudimentary regression model was developed for predicting the loss induced by a fallout exposure at -35 C.

  14. Deterministic Predictions of Vessel Responses Based on Past Measurements

    DEFF Research Database (Denmark)

    Nielsen, Ulrik Dam; Jensen, Jørgen Juncher

    2017-01-01

    The paper deals with a prediction procedure from which global wave-induced responses can be deterministically predicted a short time, 10-50 s, ahead of current time. The procedure relies on the autocorrelation function and takes into account prior measurements only; i.e. knowledge about wave cond...

  15. 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...

  16. Early prediction of blonanserin response in Japanese patients with schizophrenia.

    Science.gov (United States)

    Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

    2014-01-01

    Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (Pblonanserin response at week 4 could predict the later response at week 8.

  17. Posterior Predictive Model Checking for Multidimensionality in Item Response Theory

    Science.gov (United States)

    Levy, Roy; Mislevy, Robert J.; Sinharay, Sandip

    2009-01-01

    If data exhibit multidimensionality, key conditional independence assumptions of unidimensional models do not hold. The current work pursues posterior predictive model checking, a flexible family of model-checking procedures, as a tool for criticizing models due to unaccounted for dimensions in the context of item response theory. Factors…

  18. Predicting responsiveness to intervention in dyslexia using dynamic assessment

    NARCIS (Netherlands)

    Aravena, S.; Tijms, J.; Snellings, P.; van der Molen, M.W.

    In the current study we examined the value of a dynamic test for predicting responsiveness to reading intervention for children diagnosedwith dyslexia. The test consisted of a 20-minute training aimed at learning eight basic letter–speech sound correspondences within an artificial orthography,

  19. Prediction of Clinical Response in Children Taking Methylphenidate.

    Science.gov (United States)

    Aman, Michael G.; Turbott, Sarah H.

    1991-01-01

    Twenty-six children (ages 5-12) with attention deficit hyperactivity disorder were tested before and after treatment with methylphenidate. Few performance tests predicted clinical response to medication. Chronological age and performance on a memory distraction task and the Graduated Holes Task were moderately correlated with clinical outcome.…

  20. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    A Drug Response Prediction (DRP) score was developed based on gene expression profiling (GEP) from cell lines and tumor samples. Twenty percent of high-risk patients by GEP70 treated in Total Therapy 2 and 3A have a progression-free survival (PFS) of more than 10years. We used available GEP data ...

  1. 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.

  2. Prenatal Cortisol Exposure Predicts Infant Cortisol Response to Acute Stress

    Science.gov (United States)

    O’Connor, Thomas G; Bergman, Kristin; Sarkar, Pampa; Glover, Vivette

    2012-01-01

    Summary Experimental animal findings suggest that early stress and glucocorticoid exposure may program the function of the Hypothalamic-pituitary-adrenal (HPA) axis in the offspring. The extension of these findings to human development is not yet clear. A prospective longitudinal study was conducted on 125 mothers and their normally developing children. Amniotic fluid was obtained at, on average, 17.2 weeks gestation; infant behavior and cortisol response to a separation-reunion stress was assessed at 17 months. Amniotic fluid cortisol predicted infant cortisol response to separation-reunion stress: infants who were exposed to higher levels of cortisol in utero showed higher pre-stress cortisol values and blunted response to stress exposure. The association was independent of prenatal, obstetric, and socioeconomic factors and child-parent attachment. The findings provide some of the strongest data in humans that HPA axis functioning in the child may be predicted from prenatal cortisol exposure. PMID:22315044

  3. Early prediction of blonanserin response in Japanese patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Kishi T

    2014-09-01

    Full Text Available Taro Kishi,1 Yuki Matsuda,1 Kiyoshi Fujita,2,3 Nakao Iwata1 1Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Department of Psychiatry, Okehazama Hospital, Toyoake, Aichi, Japan; 3The Neuroscience Research Center, Toyoake, Aichi, Japan Background: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. Methods: An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8.Results: Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia, and 28 (75.7% completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS total score (P<0.0001 and in positive (P<0.0001, negative (P<0.0001, and general subscale scores (P<0.0001. In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores were 88.9% and 94.1%, respectively. The specificities were 80.0% and

  4. 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.)

  5. Predicting aquifer response time for application in catchment modeling.

    Science.gov (United States)

    Walker, Glen R; Gilfedder, Mat; Dawes, Warrick R; Rassam, David W

    2015-01-01

    It is well established that changes in catchment land use can lead to significant impacts on water resources. Where land-use changes increase evapotranspiration there is a resultant decrease in groundwater recharge, which in turn decreases groundwater discharge to streams. The response time of changes in groundwater discharge to a change in recharge is a key aspect of predicting impacts of land-use change on catchment water yield. Predicting these impacts across the large catchments relevant to water resource planning can require the estimation of groundwater response times from hundreds of aquifers. At this scale, detailed site-specific measured data are often absent, and available spatial data are limited. While numerical models can be applied, there is little advantage if there are no detailed data to parameterize them. Simple analytical methods are useful in this situation, as they allow the variability in groundwater response to be incorporated into catchment hydrological models, with minimal modeling overhead. This paper describes an analytical model which has been developed to capture some of the features of real, sloping aquifer systems. The derived groundwater response timescale can be used to parameterize a groundwater discharge function, allowing groundwater response to be predicted in relation to different broad catchment characteristics at a level of complexity which matches the available data. The results from the analytical model are compared to published field data and numerical model results, and provide an approach with broad application to inform water resource planning in other large, data-scarce catchments. © 2014, CommonWealth of Australia. Groundwater © 2014, National Ground Water Association.

  6. 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

    BACKGROUND: Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response...

  7. Gene-expression profiling to predict responsiveness to immunotherapy.

    Science.gov (United States)

    Jamieson, N B; Maker, A V

    2017-03-01

    Recent clinical successes with immunotherapy have resulted in expanding indications for cancer therapy. To enhance antitumor immune responses, and to better choose specific strategies matched to patient and tumor characteristics, genomic-driven precision immunotherapy will be necessary. Herein, we explore the role that tumor gene-expression profiling (GEP) may have in the prediction of an immunotherapeutic response. Genetic markers associated with response to immunotherapy are addressed as they pertain to the tumor genomic landscape, the extent of DNA damage, tumor mutational load and tumor-specific neoantigens. Furthermore, genetic markers associated with resistance to checkpoint blockade and relapse are reviewed. Finally, the utility of GEP to identify new tumor types for immunotherapy and implications for combinatorial strategies are summarized.

  8. Development of agent based model for predicting emergency response time

    Directory of Open Access Journals (Sweden)

    Mainak Bandyopadhyay

    2016-09-01

    Full Text Available Determining the time to reach any incident location by an emergency service is a very important aspect for emergency management. In most of the developing countries road network is considered as a main infrastructure for transporting emergency services. Therefore in order to predict the response time consideration must be given to the characteristics of road segments and driving behaviour of emergency vehicle drivers. In this paper real time driving data by Fire emergency service of Allahabad city is collected using GPS logger HOLUX M1000C. The spatial trajectories collected from GPS logger are analysed in GIS along with road network, population density and landuse data to determine the driver's route deciding behaviour. Based on the integrated analysis the Fire Emergency Vehicle Agent is designed. The Agent based model is simulated to determine the response time which is subsequently compared with the real response time.

  9. Clinical predictive factors of sildenafil response: a penile hemodynamic study.

    Science.gov (United States)

    Elhanbly, S M; Elkholy, A A-M; Alghobary, M; Abou Al-Ghar, M

    2015-03-01

    Phosphodiestrase-5 inhibitors are an important line of treatment for erectile dysfunction (ED). To detect the clinical and hemodynamic predictors of sildenafil response, we conducted this study on 124 Egyptian men with ED. All patients were evaluated by thorough history and clinical assessment with measurement of the abridged international index of erectile function-5 (IIEF-5) score. All patients were then subjected to intracavernosal injection (ICI) of trimix and pharmaco-penile duplex ultrasonography (PPDU). Patients were then classified into sildenafil responders and non-responders after six consecutive doses of 100 mg sildenafil. On doing the binary logistic stepwise regression analysis, only ED duration, IIEF-5 score, and response to ICI were the significant independent predictors of sildenafil response. These three parameters together correctly predicted the sildenafil response by 81.5% (p value <0.001). With the receiver operator characteristic curve analysis, the cut-off value of ED duration was 2.5 years and it was 14 for the IIEF-5 score. These findings indicate that ED duration, the IIEF-5 score and response to ICI are more significant predictors of sildenafil response than the more expensive and time-consuming PPDU testing. © 2015 American Society of Andrology and European Academy of Andrology.

  10. Predicting response to antimicrobial therapy in children with acute sinusitis

    Science.gov (United States)

    Shaikh, Nader; Wald, Ellen R.; Jeong, Jong H.; Kurs-Lasky, Marcia; Bowen, A’Delbert; Flom, Lynda L.; Hoberman, Alejandro

    2014-01-01

    Objective To determine prognostic factors that independently predict response to antimicrobial therapy in children with acute sinusitis. Study design 206 children meeting a priori clinical criteria for acute sinusitis who were given antimicrobial therapy by their primary care provider were included. The severity of symptoms in the 8 to 12 days after treatment was initiated was followed using a validated scale. We examined the univariate and multivariate association between factors present at the time of diagnosis (symptoms, signs, nasopharyngeal culture result, radiograph results) and time to resolution of symptoms. This study was conducted 8 to 10 years after 7-valent pneumococcal conjugate vaccination was introduced, but before introduction of the 13-valent pneumococcal conjugate vaccination. Results Children with proven nasopharyngeal colonization with Streptococcus pneumoniae improved more rapidly (6.5 vs. 8.5 median days to symptom resolution) than those who were not colonized with S. pneumoniae. Age and radiograph findings did not predict time to symptom resolution. Conclusions In children with acute sinusitis, proven nasopharyngeal colonization with S. pneumoniae at presentation independently predicted time to symptom resolution. Future randomized, placebo-controlled trials could investigate the usefulness of testing for the presence of nasopharyngeal pathogens as a predictor of response to treatment. PMID:24367985

  11. Predicting response to antimicrobial therapy in children with acute sinusitis.

    Science.gov (United States)

    Shaikh, Nader; Wald, Ellen R; Jeong, Jong H; Kurs-Lasky, Marcia; Bowen, A'delbert; Flom, Lynda L; Hoberman, Alejandro

    2014-03-01

    To determine prognostic factors that independently predict response to antimicrobial therapy in children with acute sinusitis. A total of 206 children meeting a priori clinical criteria for acute sinusitis who were prescribed antimicrobial therapy by their primary care provider were included. The severity of symptoms in the 8-12 days after treatment was initiated was followed with the use of a validated scale. We examined the univariate and multivariate association between factors present at the time of diagnosis (symptoms, signs, nasopharyngeal culture result, radiograph results) and time to resolution of symptoms. This study was conducted 8-10 years after the 7-valent pneumococcal conjugate vaccination was introduced but before introduction of the 13-valent pneumococcal conjugate vaccination. Children with proven nasopharyngeal colonization with Streptococcus pneumoniae improved more rapidly (6.5 vs 8.5 median days to symptom resolution) than those who were not colonized with S pneumoniae. Age and radiograph findings did not predict time to symptom resolution. In children with acute sinusitis, proven nasopharyngeal colonization with S pneumoniae at presentation independently predicted time to symptom resolution. Future randomized, placebo-controlled trials could investigate the usefulness of testing for the presence of nasopharyngeal pathogens as a predictor of response to treatment. Copyright © 2014 Mosby, Inc. All rights reserved.

  12. 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.

  13. Can we predict the blood pressure response to renal denervation?

    Science.gov (United States)

    Fink, Gregory D; Phelps, Jeremiah T

    2017-05-01

    Renal denervation (RDN) is a new therapy used to treat drug-resistant hypertension in the clinical setting. Published human trials show substantial inter-individual variability in the blood pressure (BP) response to RDN, even when technical aspects of the treatment are standardized as much as possible between patients. Widespread acceptance of RDN for treating hypertension will require accurate identification of patients likely to respond to RDN with a fall in BP that is clinically significant in magnitude, well-maintained over time and does not cause adverse consequences. In this paper we review and evaluate clinical studies that address possible predictors of the BP response to RDN. We conclude that only one generally reliable predictor has been identified to date, namely pre-RDN BP level, although there is some evidence for a few other factors. Experimental interventions in laboratory animals provide the opportunity to explore potential predictors that are difficult to investigate in human patients. Therefore we also describe results (from our lab and others) with RDN in spontaneously hypertensive rats. Since virtually all patients receiving RDN are taking three or more antihypertensive drugs, a particular focus of our work was on how ongoing antihypertensive drug treatment might alter the BP response to RDN. We conclude that patient age (or duration of hypertension) and concomitant treatment with certain drugs can affect the blood pressure response to RDN and that this information could help predict a favorable clinical response. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Fluid responsiveness is predicted by analysis of extra systoles

    DEFF Research Database (Denmark)

    Vistisen, Simon Tilma

    .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. Response to intravenous fentanyl infusion predicts subsequent response to transdermal fentanyl.

    Science.gov (United States)

    Hayashi, Norihito; Kanai, Akifumi; Suzuki, Asaha; Nagahara, Yuki; Okamoto, Hirotsugu

    2016-04-01

    Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 µg/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p 0.04, each). The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl.

  16. Auditory brainstem responses to stop consonants predict literacy.

    Science.gov (United States)

    Neef, Nicole E; Schaadt, Gesa; Friederici, Angela D

    2017-03-01

    Precise temporal coding of speech plays a pivotal role in sound processing throughout the central auditory system, which, in turn, influences literacy acquisition. The current study tests whether an electrophysiological measure of this precision predicts literacy skills. Complex auditory brainstem responses were analysed from 62 native German-speaking children aged 11-13years. We employed the cross-phaseogram approach to compute the quality of the electrophysiological stimulus contrast [da] and [ba]. Phase shifts were expected to vary with literacy. Receiver operating curves demonstrated a feasible sensitivity and specificity of the electrophysiological measure. A multiple regression analysis resulted in a significant prediction of literacy by delta cross-phase as well as phonological awareness. A further commonality analysis separated a unique variance that was explained by the physiological measure, from a unique variance that was explained by the behavioral measure, and common effects of both. Despite multicollinearities between literacy, phonological awareness, and subcortical differentiation of stop consonants, a combined assessment of behavior and physiology strongly increases the ability to predict literacy skills. The strong link between the neurophysiological signature of sound encoding and literacy outcome suggests that the delta cross-phase could indicate the risk of dyslexia and thereby complement subjective psychometric measures for early diagnoses. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  17. Brain stem evoked response to forward and reversed speech in humans.

    Science.gov (United States)

    Galbraith, Gary C; Amaya, Elizabeth M; de Rivera, Jacinta M Diaz; Donan, Namee M; Duong, Mylien T; Hsu, Jeffrey N; Tran, Kim; Tsang, Lian P

    2004-09-15

    Speech stimuli played in reverse are perceived as unfamiliar and alien-sounding, even though phoneme duration and fundamental voicing frequency are preserved. Although language perception ultimately resides in the neocortex, the brain stem plays a vital role in processing auditory information, including speech. The present study measured brain stem frequency-following responses (FFR) evoked by forward and reverse speech stimuli recorded from electrodes oriented horizontally and vertically to measure signals with putative origins in auditory nerve and rostral brain stem, respectively. The vertical FFR showed increased amplitude due to forward speech. It is concluded that familiar phonological and prosodic properties of forward speech selectively activate central brain stem neurons.

  18. Music-related reward responses predict episodic memory performance.

    Science.gov (United States)

    Ferreri, Laura; Rodriguez-Fornells, Antoni

    2017-12-01

    Music represents a special type of reward involving the recruitment of the mesolimbic dopaminergic system. According to recent theories on episodic memory formation, as dopamine strengthens the synaptic potentiation produced by learning, stimuli triggering dopamine release could result in long-term memory improvements. Here, we behaviourally test whether music-related reward responses could modulate episodic memory performance. Thirty participants rated (in terms of arousal, familiarity, emotional valence, and reward) and encoded unfamiliar classical music excerpts. Twenty-four hours later, their episodic memory was tested (old/new recognition and remember/know paradigm). Results revealed an influence of music-related reward responses on memory: excerpts rated as more rewarding were significantly better recognized and remembered. Furthermore, inter-individual differences in the ability to experience musical reward, measured through the Barcelona Music Reward Questionnaire, positively predicted memory performance. Taken together, these findings shed new light on the relationship between music, reward and memory, showing for the first time that music-driven reward responses are directly implicated in higher cognitive functions and can account for individual differences in memory performance.

  19. Block factorization of step response model predictive control problems

    DEFF Research Database (Denmark)

    Kufoalor, D. K.M.; Frison, Gianluca; Imsland, L.

    2017-01-01

    in a traditional manner and use the computationally efficient block factorization facilities in QP solution methods. In order to solve the MPC problem efficiently, both tailored Riccati recursion and condensing algorithms are proposed and embedded into an interior-point method. The proposed algorithms were...... implemented in the HPMPC framework, and the performance is evaluated through simulation studies. The results confirm that a computationally fast controller is achieved, compared to the traditional step response MPC scheme that relies on an explicit prediction formulation. Moreover, the tailored condensing...... algorithm exhibits superior performance and produces solution times comparable to that achieved when using a condensing scheme for an equivalent (but much smaller) state-space model derived from first-principles. Implementation aspects necessary for high performance on embedded platforms are discussed...

  20. The evolution of predictive adaptive responses in human life history.

    Science.gov (United States)

    Nettle, Daniel; Frankenhuis, Willem E; Rickard, Ian J

    2013-09-07

    Many studies in humans have shown that adverse experience in early life is associated with accelerated reproductive timing, and there is comparative evidence for similar effects in other animals. There are two different classes of adaptive explanation for associations between early-life adversity and accelerated reproduction, both based on the idea of predictive adaptive responses (PARs). According to external PAR hypotheses, early-life adversity provides a 'weather forecast' of the environmental conditions into which the individual will mature, and it is adaptive for the individual to develop an appropriate phenotype for this anticipated environment. In internal PAR hypotheses, early-life adversity has a lasting negative impact on the individual's somatic state, such that her health is likely to fail more rapidly as she gets older, and there is an advantage to adjusting her reproductive schedule accordingly. We use a model of fluctuating environments to derive evolveability conditions for acceleration of reproductive timing in response to early-life adversity in a long-lived organism. For acceleration to evolve via the external PAR process, early-life cues must have a high degree of validity and the level of annual autocorrelation in the individual's environment must be almost perfect. For acceleration to evolve via the internal PAR process requires that early-life experience must determine a significant fraction of the variance in survival prospects in adulthood. The two processes are not mutually exclusive, and mechanisms for calibrating reproductive timing on the basis of early experience could evolve through a combination of the predictive value of early-life adversity for the later environment and its negative impact on somatic state.

  1. Neural responses to exclusion predict susceptibility to social influence.

    Science.gov (United States)

    Falk, Emily B; Cascio, Christopher N; O'Donnell, Matthew Brook; Carp, Joshua; Tinney, Francis J; Bingham, C Raymond; Shope, Jean T; Ouimet, Marie Claude; Pradhan, Anuj K; Simons-Morton, Bruce G

    2014-05-01

    Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American adolescents, traffic-related crashes are leading causes of nonfatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents' vulnerability to peer influence. We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately 1 week after the neuroimaging session. Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside the neuroimaging laboratory 1 week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion. These results address the neural bases of social influence and risk taking; contribute to our understanding of social and emotional function in the adolescent brain; and link neural activity in specific, hypothesized, regions to risk-relevant outcomes beyond the neuroimaging laboratory. Results of this investigation are discussed in terms of the mechanisms underlying risk taking in adolescents and the public health implications for adolescent driving. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

  2. Aggression predicts Cortisol Awakening Response in healthy young adults

    Directory of Open Access Journals (Sweden)

    Patricia Sariñana-González

    2015-10-01

    Full Text Available It seems that aggressive behavior is negatively related to cortisol (C, but this relationship has been established considering the evening C levels. On the other hand, the relationship with the C awakening response (CAR and the influence of gender and menstrual cycle phase are not well understood. This study analyzed this relationship in 83 women (38 in the luteal and 45 in the follicular phase of their menstrual cycle and 20 men. CAR was assessed by measuring salivary free cortisol levels in samples taken immediately following awakening and 30, 45, and 60 minutes later. Additionally, participants completed a self-report of aggression. Men presented lower CAR than women in the luteal phase. Moreover, they also had higher levels of physical aggression than women, independently of their menstrual phase. Regarding the relationships between variables, in men general aggression and verbal aggression predicted the CAR. In women, verbal aggression predicted the CAR during the follicular phase, whereas anger and physical aggression were predictors during the luteal phase. Our data support the view that there is a negative relationship between C and aggressive behavior, even during the morning, this relationship being moderated by gender and menstrual cycle phase in the women. These findings may help improve our understanding of the biological mechanisms involved in violence.

  3. Predictive parameters of response to desmopressin in primary nocturnal enuresis.

    Science.gov (United States)

    Van Herzeele, Charlotte; Evans, Jonathan; Eggert, Paul; Lottmann, Henri; Norgaard, Jens Peter; Vande Walle, Johan

    2015-08-01

    Many recent treatment guidelines have advocated the importance of a full noninvasive medical evaluation. To individualize treatment, special emphasis must be put on recording of the maximum voided volume (MVV) and nocturnal diuresis in a diary or frequency/volume chart. The aim of this study was to identify any possible predictive factors to desmopressin response. This study is a re-analysis of a prospective, open-label, multinational, phase-IV study evaluating ≤6 months of treatment with desmopressin tablets for children with primary nocturnal enuresis. The children were enrolled between April 2002 and December 2004 from 86 centers in four countries: UK, Canada, Germany and France. A total of 936 children were screened; 744 children aged 5-15 years participated in the study. Of these, 471 children completed the study with 6 months follow-up and recording in a frequency/volume chart. All children experienced six or more wet nights during the 14-day screening period. Exclusion criteria were: organic pathology, treatment for enuresis within the past year, previous treatment for enuresis for >4 weeks, diurnal symptoms, renal or central diabetes insipidus and the use of systemic antibiotics or other drugs known to affect desmopressin activity. The predictive value of number of wet nights a week, fluid intake, daytime voiding frequency and diuresis was investigated by performing a multinomial logistic regression. Of the demographic variables, age was the only significant predictor for response to desmopressin. Controlling for age, the significant predictive variables were: number of wet nights a week, average voided volume daytime, maximum voided volume daytime, total daytime diuresis, nocturnal diuresis (see Figure), maximum voided volume 24 h and total 24 h diuresis. More than 80% of the children had no nocturnal polyuria and a low maximum voided volume. Performing a secondary analysis is a limitation because the original study was not designed for that. A new

  4. Executive Functioning at Baseline Prospectively Predicts Depression Treatment Response.

    Science.gov (United States)

    Dawson, Erica L; Caveney, Angela F; Meyers, Kortni K; Weisenbach, Sara L; Giordani, Bruno; Avery, Erich T; Schallmo, Michael-Paul; Bahadori, Armita; Bieliauskas, Linas A; Mordhorst, Matthew; Marcus, Sheila M; Kerber, Kevin; Zubieta, Jon-Kar; Langenecker, Scott A

    2017-02-09

    Existing cognitive and clinical predictors of treatment response to date are not of sufficient strength to meaningfully impact treatment decision making and are not readily employed in clinical settings. This study investigated whether clinical and cognitive markers used in a tertiary care clinic could predict response to usual treatment over a period of 4 to 6 months in a sample of 75 depressed adults. Patients (N = 384) were sequentially tested in 2 half-day clinics as part of a quality improvement project at an outpatient tertiary care center between August 2003 and September 2007; additional subjects evaluated in the clinic between 2007 and 2009 were also included. Diagnosis was according to DSM-IV-TR criteria and completed by residents and attending faculty. Test scores obtained at intake visits on a computerized neuropsychological screening battery were the Parametric Go/No-Go task and Facial Emotion Perception Task. Treatment outcome was assessed using 9-item Patient Health Questionnaire (PHQ-9) self-ratings at follow-up (n = 75). Usual treatment included psychotropic medication and psychotherapy. Decline in PHQ-9 scores was predicted on the basis of baseline PHQ-9 score and education, with neuropsychological variables entered in the second step. PHQ-9 scores declined by 46% at follow-up (56% responders). Using 2-step multiple regression, baseline PHQ-9 score (P ≤ .05) and education (P ≤ .01) were significant step 1 predictors of percent change in PHQ-9 follow-up scores. In step 2 of the model, faster processing speed with interference resolution (go reaction time) independently explained a significant amount of variance over and above variables in step 1 (12% of variance, P < .01), while other cognitive and affective skills did not. This 2-step model accounted for 28% of the variance in treatment change in PHQ-9 scores. Processing speed with interference resolution also accounted for 12% variance in treatment and follow-up attrition. Use of executive

  5. 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.

  6. Predicting the vibroacoustic response of satellite equipment panels.

    Science.gov (United States)

    Conlon, S C; Hambric, S A

    2003-03-01

    Modern satellites are constructed of large, lightweight equipment panels that are strongly excited by acoustic pressures during launch. During design, performing vibroacoustic analyses to evaluate and ensure the integrity of the complex electronics mounted on the panels is critical. In this study the attached equipment is explicitly addressed and how its properties affect the panel responses is characterized. FEA and BEA methods are used to derive realistic parameters to input to a SEA hybrid model of a panel with multiple attachments. Specifically, conductance/modal density and radiation efficiency for nonhomogeneous panel structures with and without mass loading are computed. The validity of using the spatially averaged conductance of panels with irregular features for deriving the structure modal density is demonstrated. Maidanik's proposed method of modifying the traditional SEA input power is implemented, illustrating the importance of accounting for system internal couplings when calculating the external input power. The predictions using the SEA hybrid model agree with the measured data trends, and are found to be most sensitive to the assumed dynamic mass ratio (attachments/structure) and the attachment internal loss factor. Additional experimental and analytical investigations are recommended to better characterize dynamic masses, modal densities and loss factors.

  7. Seasonal Climate Extremes : Mechanism, Predictability and Responses to Global Warming

    Science.gov (United States)

    Shongwe, M. E.

    2010-01-01

    Climate extremes are rarely occurring natural phenomena in the climate system. They often pose one of the greatest environmental threats to human and natural systems. Statistical methods are commonly used to investigate characteristics of climate extremes. The fitted statistical properties are often interpolated or extrapolated to give an indication of the likelihood of a certain event within a given period or interval. Under changing climatic conditions, the statistical properties of climate extremes are also changing. It is an important scientific goal to predict how the properties of extreme events change. To achieve this goal, observational and model studies aimed at revealing important features are a necessary prerequisite. Notable progress has been made in understanding mechanisms that influence climate variability and extremes in many parts of the globe including Europe. However, some of the recently observed unprecedented extremes cannot be fully explained from the already identified forcing factors. A better understanding of why these extreme events occur and their sensitivity to certain reinforcing and/or competing factors is useful. Understanding their basic form as well as their temporal variability is also vital and can contribute to global scientific efforts directed at advancing climate prediction capabilities, particularly making skilful forecasts and realistic projections of extremes. In this thesis temperature and precipitation extremes in Europe and Africa, respectively, are investigated. Emphasis is placed on the mechanisms underlying the occurrence of the extremes, their predictability and their likely response to global warming. The focus is on some selected seasons when extremes typically occur. An atmospheric energy budget analysis for the record-breaking European Autumn 2006 event has been carried out with the goal to identify the sources of energy for the extreme event. Net radiational heating is compared to surface turbulent fluxes of

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

    Directory of Open Access Journals (Sweden)

    Carvalho, Bettina

    2014-04-01

    Full Text Available 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.

  9. 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

  10. 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

  11. The Use of Factorial Forecasting to Predict Public Response

    Science.gov (United States)

    Weiss, David J.

    2012-01-01

    Policies that call for members of the public to change their behavior fail if people don't change; predictions of whether the requisite changes will take place are needed prior to implementation. I propose to solve the prediction problem with Factorial Forecasting, a version of functional measurement methodology that employs group designs. Aspects…

  12. 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.

  13. The Reduced Cochlear Output and the Failure to Adapt the Central Auditory Response Causes Tinnitus in Noise Exposed Rats

    Science.gov (United States)

    Matsumoto, Masahiro; Lee, Sze Chim; Zuccotti, Annalisa; Zimmermann, Ulrike; Jaumann, Mirko; Rohbock, Karin; Xiong, Hao; Knipper, Marlies

    2013-01-01

    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. PMID:23516401

  14. Apoptosis and other immune biomarkers predict influenza vaccine responsiveness

    National Research Council Canada - National Science Library

    Furman, David; Jojic, Vladimir; Kidd, Brian; Shen‐Orr, Shai; Price, Jordan; Jarrell, Justin; Tse, Tiffany; Huang, Huang; Lund, Peder; Maecker, Holden T; Utz, Paul J; Dekker, Cornelia L; Koller, Daphne; Davis, Mark M

    ... (60 to >89 years) as models for strong and weak immune responses, respectively, and assayed their serological responses to influenza strains as well as a wide variety of other parameters, including gene expression...

  15. 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…

  16. Alkaline phosphatase predicts response in polycystic liver disease during somatostatin analogue therapy: a pooled analysis

    NARCIS (Netherlands)

    Gevers, T.J.; Nevens, F.; Torres, V.E.; Hogan, M.C.; Drenth, J.P.

    2016-01-01

    BACKGROUND & AIMS: Somatostatin analogues reduce liver volumes in polycystic liver disease. However, patients show considerable variability in treatment responses. Our aim was to identify specific patient, disease or treatment characteristics that predict response in polycystic liver disease during

  17. Evaluating the molecule-based prediction of clinical drug responses in cancer.

    Science.gov (United States)

    Ding, Zijian; Zu, Songpeng; Gu, Jin

    2016-10-01

    Molecule-based prediction of drug response is one major task of precision oncology. Recently, large-scale cancer genomic studies, such as The Cancer Genome Atlas (TCGA), provide the opportunity to evaluate the predictive utility of molecular data for clinical drug responses in multiple cancer types. Here, we first curated the drug treatment information from TCGA. Four chemotherapeutic drugs had more than 180 clinical response records. Then, we developed a computational framework to evaluate the molecule based predictions of clinical responses of the four drugs and to identify the corresponding molecular signatures. Results show that mRNA or miRNA expressions can predict drug responses significantly better than random classifiers in specific cancer types. A few signature genes are involved in drug response related pathways, such as DDB1 in DNA repair pathway and DLL4 in Notch signaling pathway. Finally, we applied the framework to predict responses across multiple cancer types and found that the prediction performances get improved for cisplatin based on miRNA expressions. Integrative analysis of clinical drug response data and molecular data offers opportunities for discovering predictive markers in cancer. This study provides a starting point to objectively evaluate the molecule-based predictions of clinical drug responses. jgu@tsinghua.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. PREDICTING MICROEVOLUTIONARY RESPONSES TO DIRECTIONAL SELECTION ON HERITABLE VARIATION.

    Science.gov (United States)

    Grant, Peter R; Grant, B Rosemary

    1995-04-01

    Microevolution of quantitative traits in the wild can be predicted from a knowledge of selection and genetic parameters. Testing the predictions requires measurement of the offspring of the selected group, a requirement that is difficult to meet. We present the results of a study of Darwin's finches on the Galápagos island of Daphne Major where this requirement is met. The study demonstrates microevolutionary consequences of natural selection. © 1995 The Society for the Study of Evolution.

  19. Predicting binaural responses from monaural responses in the gerbil medial superior olive.

    Science.gov (United States)

    Plauška, Andrius; Borst, J Gerard; van der Heijden, Marcel

    2016-06-01

    Accurate sound source localization of low-frequency sounds in the horizontal plane depends critically on the comparison of arrival times at both ears. A specialized brainstem circuit containing the principal neurons of the medial superior olive (MSO) is dedicated to this comparison. MSO neurons are innervated by segregated inputs from both ears. The coincident arrival of excitatory inputs from both ears is thought to trigger action potentials, with differences in internal delays creating a unique sensitivity to interaural time differences (ITDs) for each cell. How the inputs from both ears are integrated by the MSO neurons is still debated. Using juxtacellular recordings, we tested to what extent MSO neurons from anesthetized Mongolian gerbils function as simple cross-correlators of their bilateral inputs. From the measured subthreshold responses to monaural wideband stimuli we predicted the rate-ITD functions obtained from the same MSO neuron, which have a damped oscillatory shape. The rate of the oscillations and the position of the peaks and troughs were accurately predicted. The amplitude ratio between dominant and secondary peaks of the rate-ITD function, captured in the width of its envelope, was not always exactly reproduced. This minor imperfection pointed to the methodological limitation of using a linear representation of the monaural inputs, which disregards any temporal sharpening occurring in the cochlear nucleus. The successful prediction of the major aspects of rate-ITD curves supports a simple scheme in which the ITD sensitivity of MSO neurons is realized by the coincidence detection of excitatory monaural inputs. Copyright © 2016 the American Physiological Society.

  20. Presbycusis and auditory brainstem responses: a review

    Directory of Open Access Journals (Sweden)

    Shilpa Khullar

    2011-06-01

    Full Text Available Age-related hearing loss or presbycusis is a complex phenomenon consisting of elevation of hearing levels as well as changes in the auditory processing. It is commonly classified into four categories depending on the cause. Auditory brainstem responses (ABRs are a type of early evoked potentials recorded within the first 10 ms of stimulation. They represent the synchronized activity of the auditory nerve and the brainstem. Some of the changes that occur in the aging auditory system may significantly influence the interpretation of the ABRs in comparison with the ABRs of the young adults. The waves of ABRs are described in terms of amplitude, latencies and interpeak latency of the different waves. There is a tendency of the amplitude to decrease and the absolute latencies to increase with advancing age but these trends are not always clear due to increase in threshold with advancing age that act a major confounding factor in the interpretation of ABRs.

  1. Novel transformation-based response prediction of shear building ...

    Indian Academy of Sciences (India)

    Present paper uses powerful technique of interval neural network (INN) to simulate and estimate structural response of multi-storey shear buildings subject to earthquake motion. The INN is first trained for a real earthquake data, viz., the ground acceleration as input and the numerically generated responses of different ...

  2. Impaired neural response to negative prediction errors in cocaine addiction.

    Science.gov (United States)

    Parvaz, Muhammad A; Konova, Anna B; Proudfit, Greg H; Dunning, Jonathan P; Malaker, Pias; Moeller, Scott J; Maloney, Tom; Alia-Klein, Nelly; Goldstein, Rita Z

    2015-02-04

    Learning can be guided by unexpected success or failure, signaled via dopaminergic positive reward prediction error (+RPE) and negative reward-prediction error (-RPE) signals, respectively. Despite conflicting empirical evidence, RPE signaling is thought to be impaired in drug addiction. To resolve this outstanding question, we studied as a measure of RPE the feedback negativity (FN) that is sensitive to both reward and the violation of expectation. We examined FN in 25 healthy controls; 25 individuals with cocaine-use disorder (CUD) who tested positive for cocaine on the study day (CUD+), indicating cocaine use within the past 72 h; and in 25 individuals with CUD who tested negative for cocaine (CUD-). EEG was acquired while the participants performed a gambling task predicting whether they would win or lose money on each trial given three known win probabilities (25, 50, or 75%). FN was scored for the period in each trial when the actual outcome (win or loss) was revealed. A significant interaction between prediction, outcome, and group revealed that controls showed increased FN to unpredicted compared with predicted wins (i.e., intact +RPE) and decreased FN to unpredicted compared with predicted losses (i.e., intact -RPE). However, neither CUD subgroup showed FN modulation to loss (i.e., impaired -RPE), and unlike CUD+ individuals, CUD- individuals also did not show FN modulation to win (i.e., impaired +RPE). Thus, using FN, the current study directly documents -RPE deficits in CUD individuals. The mechanisms underlying -RPE signaling impairments in addiction may contribute to the disadvantageous nature of excessive drug use, which can persist despite repeated unfavorable life experiences (e.g., frequent incarcerations). Copyright © 2015 the authors 0270-6474/15/351872-08$15.00/0.

  3. Mechanistic Modeling Framework for Predicting Extreme Battery Response

    Energy Technology Data Exchange (ETDEWEB)

    Moffat, Harry K.; Geller, Anthony S.; R. Kee (CSM); S. Allu (ORNL)

    2017-03-01

    The objective of this project was to Address root cause and 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.

  4. Can brain responses to movie trailers predict success?

    NARCIS (Netherlands)

    M.A.S. Boksem (Maarten)

    2015-01-01

    textabstractDecades of research have shown that much of our mental processing occurs at the subconscious level, including the decisions we make as consumers. These subconscious processes explain why we so often fail to accurately predict our own future choices. Often what we think we want has

  5. Surrogate decision makers' responses to physicians' predictions of medical futility.

    Science.gov (United States)

    Zier, Lucas S; Burack, Jeffrey H; Micco, Guy; Chipman, Anne K; Frank, James A; White, Douglas B

    2009-07-01

    Although physicians sometimes use the futility rationale to limit the use of life-sustaining treatments, little is known about how surrogate decision makers view this rationale. We sought to determine the attitudes of surrogates of patients who are critically ill toward whether physicians can predict futility and whether these attitudes predict surrogates' willingness to discontinue life support when faced with predictions of futility. This multicenter, mixed qualitative and quantitative study took place at three hospitals in California from 2006 to 2007. We conducted semistructured interviews with surrogate decision makers for 50 patients who were critically ill and incapacitated that addressed their beliefs about medical futility and inductively developed an organizing framework to describe these beliefs. We used a hypothetical scenario with a modified time-trade-off design to examine the relationship between a patient's prognosis and a surrogate's willingness to withdraw life support. We used a mixed-effects regression model to examine the association between surrogates' attitudes about futility and their willingness to limit life support in the face of a very poor prognosis. Validation methods included the use and integration of multiple data sources, multidisciplinary analysis, and member checking. Sixty-four percent of surrogates (n = 32; 95% confidence interval [CI], 49 to 77%) expressed doubt about the accuracy of physicians' futility predictions, 32% of surrogates (n = 16; 95% CI, 20 to 47%) elected to continue life support with a decision makers. The nature of the doubt may have implications for responding to conflicts about futility in clinical practice.

  6. Reduced-Order Models for Acoustic Response Prediction

    Science.gov (United States)

    2011-07-01

    predicted frequencies from a FEM. The first two axial natural frequencies were measured using a pair of small piezoelectric strain actuators, one...test. Displacement and velocity relative to the shaker head were measured with a Polytec Model OVF-512 Differential Fiber Optic Vibrometer . The...The vibrometer controller processes the object and reference beams to produce differential velocity and displacement. Dynamic strains were

  7. Model prediction of maize yield responses to climate change in ...

    African Journals Online (AJOL)

    Observed data of the last three decades (1971 to 2000) from several climatological stations in north-eastern Zimbabwe and outputs from several global climate models were used. The downscaled model simulations consistently predicted a warming of between 1 and 2 ºC above the baseline period (1971-2000) at most of ...

  8. 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.

  9. 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

    .0009) and high expression of a HLA class II gene (2-fold increase in HLA-DQA1; OR = 1.22; 95% CI: 1.01-1.47; P = 0.04). These two genes were included in a model that is able predict response to bevacizumab combination therapy in clinical practice. When stratified for a validated prognostic index, the predictive...... model for response was significantly associated with improved overall survival. Conclusion: Two genes (low angiotensinogen and high HLA-class II expression) were predictive for bevacizumab response and were included in a predictive model for response. This model can be used in clinical practice...... 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...

  10. Predicting bee community responses to land-use changes

    NARCIS (Netherlands)

    Palma, De Adriana; Abrahamczyk, Stefan; Aizen, Marcelo A.; Albrecht, Matthias; Basset, Yves; Bates, Adam; Blake, Robin J.; Boutin, Céline; Bugter, Rob; Connop, Stuart; Cruz-López, Leopoldo; Cunningham, Saul A.; Darvill, Ben; Diekötter, Tim; Dorn, Silvia; Downing, Nicola; Entling, Martin H.; Farwig, Nina; Felicioli, Antonio; Fonte, Steven J.; Fowler, Robert; Franzén, Markus; Goulson, Dave; Grass, Ingo; Hanley, Mick E.; Hendrix, Stephen D.; Herrmann, Farina; Herzog, Felix; Holzschuh, Andrea; Jauker, Birgit; Kessler, Michael; Knight, M.E.; Kruess, Andreas; Lavelle, Patrick; Féon, Le Violette; Lentini, Pia; Malone, Louise A.; Marshall, Jon; Pachón, Eliana Martínez; McFrederick, Quinn S.; Morales, Carolina L.; Mudri-Stojnic, Sonja; Nates-Parra, Guiomar; Nilsson, Sven G.; Öckinger, Erik; Osgathorpe, Lynne; Parra-H, Alejandro; Peres, Carlos A.; Persson, Anna S.; Petanidou, Theodora; Poveda, Katja; Power, Eileen F.; Quaranta, Marino; Quintero, Carolina; Rader, Romina; Richards, Miriam H.; Roulston, Tai; Rousseau, Laurent; Sadler, Jonathan P.; Samnegård, Ulrika; Schellhorn, Nancy A.; Schüepp, Christof; Schweiger, Oliver; Smith-Pardo, Allan H.; Steffan-Dewenter, Ingolf; Stout, Jane C.; Tonietto, Rebecca K.; Tscharntke, Teja; Tylianakis, Jason M.; Verboven, Hans A.F.; Vergara, Carlos H.; Verhulst, Jort; Westphal, Catrin; Yoon, Hyung Joo; Purvis, Andy

    2016-01-01

    Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically

  11. Nuclear medicine imaging to predict response to radiotherapy: a review.

    NARCIS (Netherlands)

    Wiele, C. van de; Lahorte, C.; Oyen, W.J.G.; Boerman, O.C.; Goethals, I.; Slegers, G.; Dierckx, R.A.

    2003-01-01

    PURPOSE: To review available literature on positron emission tomography (PET) and single photon emission computerized tomography (SPECT) for the measurement of tumor metabolism, hypoxia, growth factor receptor expression, and apoptosis as predictors of response to radiotherapy. METHODS AND

  12. Development of finite element models to predict dynamic bridge response.

    Science.gov (United States)

    1997-10-01

    Dynamic response has long been recognized as one of the significant factors affecting the service life and safety of bridge structures. Even though considerable research, both analytical and experimental, has been devoted to dynamic bridge behavior, ...

  13. 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...... filtering, is performed. The results show that the controller achieves a good performance while keeping the temperature inside the predefined comfort limits. Fuzzy predictive filtering has shown to be an effective tool which is capable of reducing the computational burden and increasing the performance...

  14. 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

    The effects of the 5-HTTLPR polymorphism on neural responses to emotionally salient faces have been studied extensively, focusing on amygdala reactivity and amygdala-prefrontal interactions. Despite compelling evidence that emotional face paradigms engage a distributed network of brain regions...... 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...

  15. Error consciousness predicts physiological response to an acute psychosocial stressor in men

    NARCIS (Netherlands)

    Wu, J.; Sun, X.; Wang, L.; Zhang, L.; Fernandez, G.; Yao, Z.

    2017-01-01

    There are substantial individual differences in the response towards acute stressor. The aim of the current study was to examine how the neural activity after an error response during a non-stressful state, prospectively predicts the magnitude of physiological stress response (e.g., cortisol

  16. Incident experience predicts freezing-like responses in firefighters

    NARCIS (Netherlands)

    Ly, V. (Verena); Roijendijk, Linsey; Hazebroek, Hans; Tonnaer, Clemon; Hagenaars, Muriel A

    2017-01-01

    Freezing is a defensive response to acute stress that is associated with coping and alterations in attentional processing. However, it remains unclear whether individuals in high risk professions, who are skilled at making rapid decisions in emergency situations, show altered threat-induced

  17. Novel transformation-based response prediction of shear building ...

    Indian Academy of Sciences (India)

    Conte and Durrani (1994) gave a neural network-based approach to model the seismic response of multi-storey frame build- ings. Pandey and Barai (1995) detected damage in a bridge truss by applying ANN to numerically simulated data. A counter-propagation neural net- work (NN) to locate damage in beams and frames.

  18. Uninvolved immunoglobulins predicting hematological response in newly diagnosed AL amyloidosis.

    Science.gov (United States)

    Muchtar, Eli; Magen, Hila; Itchaki, Gilad; Cohen, Amos; Rosenfeld, Ra'ama; Shochat, Tzippy; Kornowski, Ran; Iakobishvili, Zaza; Raanani, Pia

    2016-02-01

    Immunoparesis serves as a marker for elevated risk for progression in plasma cell proliferative disorders. However, the impact of immunoparesis in AL amyloidosis has not been addressed. Immunoparesis was defined qualitatively as any decrease below the low reference levels of the uninvolved immunoglobulins and quantitatively, as the relative difference between the uninvolved immunoglobulins and the lower reference values. Forty-one newly diagnosed AL amyloidosis patients were included. Sixty-six percent of patients had a suppression of the uninvolved immunoglobulins. The median relative difference of the uninvolved immunoglobulins was 18% above the low reference levels [range (-71%)-210%]. Ninety percent of the patients were treated with novel agents-based regimens, mostly bortezomib-containing regimens. Nineteen percent of the patients did not attain response to first line treatment. Patients with relative difference of uninvolved immunoglobulins below -25% of the low reference levels were less likely to respond to first line treatment compared to patients with a relative difference of -25% and above [odds ratio for no response vs. partial response and better 30 [(95% CI 4.1-222.2), P=0.0004]. Patients who failed first line treatment were successfully salvaged with lenalidomide-based treatment. Immunoparesis, if assessed quantitatively, may serve as a predictor of response in AL amyloidosis patients treated with bortezomib-containing regimens. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. 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....

  20. 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...

  1. 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...

  2. Aggression predicts Cortisol Awakening Response in healthy young adults

    OpenAIRE

    Patricia Sariñana-González; Ángel Romero-Martínez; Luis Moya-Albiol

    2015-01-01

    It seems that aggressive behavior is negatively related to cortisol (C), but this relationship has been established considering the evening C levels. On the other hand, the relationship with the C awakening response (CAR) and the influence of gender and menstrual cycle phase are not well understood. This study analyzed this relationship in 83 women (38 in the luteal and 45 in the follicular phase of their menstrual cycle) and 20 men. CAR was assessed by measuring salivary free cortisol levels...

  3. Nutritional Risk Screening Predicts Tumor Response in Lung Cancer Patients.

    Science.gov (United States)

    Illa, Petr; Tomiskova, Marcela; Skrickova, Jana

    2015-01-01

    Malnutrition in cancer patients may be associated with poor tolerance of chemotherapy and lower response rate after oncological treatment. Nutritional Risk Screening 2002 (NRS) adapted for oncological patients was used to assess the risk of undernutrition in a group of 188 patients with lung cancer. The risk was evaluated on a 6-point scale according to common signs of nutritional status (weight loss, body mass index, and dietary intake), tumor, and its treatment risk factors. A score of 3 or more (called "nutritional risk") means significant risk of malnutrition and poor outcome. Acceptable NRS score was found in 50.6%, and in 45.3% a score of 3-5 suggested the risk of malnutrition (nutritional risk). Unexpectedly, the toxicity of anticancer treatment was not significantly different between the subgroups (acceptable score vs nutritional risk). The rate of treatment response evaluated by imaging techniques was significantly higher in patients with an acceptable score compared to nutritional risk. Overall survival rate was significantly higher in cytostatically treated patients with lung cancer with an acceptable score. Nutritional risk screening is a significant predictor of tumor response in patients with lung cancer. Early detection of malnutrition is important to determine the prognosis of cancer patients as well as to plan effective supportive care.

  4. Negative-Margin Criterion for Impact-Response Prediction

    Science.gov (United States)

    Anderson, Denton

    2006-01-01

    Some space missions require a nuclear-power source to generate electrical power to meet mission objectives. At present, the nuclear-power source is an assembly of modular heat sources called the general purpose heat source (GPHS) modules. Each module comprises graphite shells designed to protect iridium-alloy clads which serve as the primary containment shells for the radioactive, heat-producing material. In the course of launching the space vehicle to perform its mission the nuclear heat source may be exposed to severe accident environments. One particular environment is a primary impact event where individual GPHS modules impact hard surfaces at speeds in the range of 50 meters per second or more. Tests have shown that some clads may be breached in particularly severe impacts and release a small fraction of their contents. This paper presents an empirical model for predicting essential ingredients for assessing the risk associated with primary impact events. The ingredients include: clad failure probability, release fraction of clad contents, characterization of the released material in terms of particle-size distribution and a means to estimate uncertainty in the prediction process. The empirical model focuses on the deformation of the clads and their capability to withstand deformation without breaching, measured by ductility. The basic criterion used to estimate all ingredients is called ``negative margin''. The procedure for estimating risk factors entails calculation of clad distortion by, e.g. hydrocode simulation, and high-strain-rate ductility of the iridium alloy. Negative margin is a linear combination of distortion and ductility. Regression equations derived from test data are used to calculate the clad failure probability and the fractional activity release as functions of negative margin. The mass-based particle-size distribution is calculated as a function of release fraction. Cumulative uncertainty in this computing process is evaluated using

  5. Response of dorsomedial prefrontal cortex predicts altruistic behavior.

    Science.gov (United States)

    Waytz, Adam; Zaki, Jamil; Mitchell, Jason P

    2012-05-30

    Human beings have an unusual proclivity for altruistic behavior, and recent commentators have suggested that these prosocial tendencies arise from our unique capacity to understand the minds of others (i.e., to mentalize). The current studies test this hypothesis by examining the relation between altruistic behavior and the reflexive engagement of a neural system reliably associated with mentalizing. Results indicated that activity in the dorsomedial prefrontal cortex--a region consistently involved in understanding others' mental states--predicts both monetary donations to others and time spent helping others. These findings address long-standing questions about the proximate source of human altruism by suggesting that prosocial behavior results, in part, from our broader tendency for social-cognitive thought.

  6. The utility of the ASI factors in predicting response to voluntary hyperventilation among nonclinical participants.

    Science.gov (United States)

    Carter, M M; Suchday, S; Gore, K L

    2001-01-01

    Empirical research has demonstrated that the Anxiety Sensitivity Index (ASI) contains three separable factors and that ASI total scores are useful in predicting response to physiological challenge procedures. Little is known, however, of the predictive capability of the ASI factors. This study investigated the utility of the three factors of the ASI compared to ASI total scores and the STAI-T, a more general measure of trait anxiety, in predicting response to hyperventilation. As expected, the ASI total score was a significant predictor of response to hyperventilation, while the STAI-T was not. Using multiple regression, when the physical concerns factor was entered first, the social concerns and mental incapacitation factors of the ASI were not significant predictors of response to hyperventilation. Furthermore, when the physical concerns factor was entered into a regression equation followed by the remainder of the ASI items, only the physical concerns factor remained a significant predictor of response to hyperventilation. These results suggest that while response to physiological challenge procedures is predicted by ASI total scores, it may be best predicted by the physical concerns factor, and that the mental incapacitation and social concerns subscales do not play key roles in predicting response to physiological challenge procedures.

  7. Response variability in rapid automatized naming predicts reading comprehension.

    Science.gov (United States)

    Li, James J; Cutting, Laurie E; Ryan, Matthew; Zilioli, Monica; Denckla, Martha B; Mahone, E Mark

    2009-10-01

    A total of 37 children ages 8 to 14 years, screened for word-reading difficulties (23 with attention-deficit/hyperactivity disorder, ADHD; 14 controls) completed oral reading and rapid automatized naming (RAN) tests. RAN trials were segmented into pause and articulation time and intraindividual variability. There were no group differences on reading or RAN variables. Color- and letter-naming pause times and number-naming articulation time were significant predictors of reading fluency. In contrast, number and letter pause variability were predictors of comprehension. Results support analysis of subcomponents of RAN and add to literature emphasizing intraindividual variability as a marker for response preparation, which has relevance to reading comprehension.

  8. 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...... prospectively after the initiation of their first treatment with IFN-β. RESULTS: 62% of patients experienced relapses during the first 2 years of treatment, and 32% had disability progression during the first 5 years of treatment. Patients with a pretreatment annualized relapse rate >1 had an increased risk...

  9. A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound

    Science.gov (United States)

    Tadayyon, Hadi; Sannachi, Lakshmanan; Gangeh, Mehrdad J.; Kim, Christina; Ghandi, Sonal; Trudeau, Maureen; Pritchard, Kathleen; Tran, William T.; Slodkowska, Elzbieta; Sadeghi-Naini, Ali; Czarnota, Gregory J.

    2017-04-01

    Quantitative ultrasound (QUS) can probe tissue structure and analyze tumour characteristics. Using a 6-MHz ultrasound system, radiofrequency data were acquired from 56 locally advanced breast cancer patients prior to their neoadjuvant chemotherapy (NAC) and QUS texture features were computed from regions of interest in tumour cores and their margins as potential predictive and prognostic indicators. Breast tumour molecular features were also collected and used for analysis. A multiparametric QUS model was constructed, which demonstrated a response prediction accuracy of 88% and ability to predict patient 5-year survival rates (p = 0.01). QUS features demonstrated superior performance in comparison to molecular markers and the combination of QUS and molecular markers did not improve response prediction. This study demonstrates, for the first time, that non-invasive QUS features in the core and margin of breast tumours can indicate breast cancer response to neoadjuvant chemotherapy (NAC) and predict five-year recurrence-free survival.

  10. 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.

  11. Incident experience predicts freezing-like responses in firefighters.

    Directory of Open Access Journals (Sweden)

    Verena Ly

    Full Text Available Freezing is a defensive response to acute stress that is associated with coping and alterations in attentional processing. However, it remains unclear whether individuals in high risk professions, who are skilled at making rapid decisions in emergency situations, show altered threat-induced freezing. Here we investigated the effect of incident experience in a high risk profession on freezing. Additionally, we explored whether any effect of incident experience on freezing would be different for profession-related and -unrelated threat. Forty experienced and inexperienced firefighters were presented neutral, pleasant, related-unpleasant, and unrelated-unpleasant pictures in a passive viewing task. Postural sway and heart rate were assessed to determine freezing. Both postural and heart rate data evidenced reduced freezing upon unpleasant pictures in the experienced versus the inexperienced group. Relatedness of the unpleasant pictures did not modulate these effects. These findings indicate that higher incident experience relates to decreased threat-induced freezing, at least in a passive task context. This might suggest that primary defense responses are malleable through experience. Finally, these findings demonstrate the potential of using animal to human translational approaches to investigate defensive behaviors in relation to incident experience in high risk professions and stimulate future research on the role of freezing in resilience and coping.

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

    National Research Council Canada - National Science Library

    Carruthers, Helen R; Morris, Julie; Tarrier, Nicholas; Whorwell, Peter J

    2010-01-01

    .... 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...

  13. Data to establish the optimal standard regimen and predicting the response to docetaxel therapy

    Directory of Open Access Journals (Sweden)

    Emad Y. Moawad

    2015-12-01

    Full Text Available This paper contains data to establish the optimal standard regimen and predicting the response to docetaxel therapy (Moawad, 2014 [1]. Docetaxel has been in use for over a decade without demonstrating data indicates a predictable response in the treatment of cancer. Data of puzzling response to docetaxel therapy was due to its cell cycle specific effect. Although several administered schedules were investigated, the relative therapeutic advantage of high versus low doses has not been identified yet. Also the antitumor target of docetaxel has not yet been identified to optimize therapy by predicting the response of patients prior to therapy to provide a protection against treatment failure. In the present paper, we demonstrate the data used to optimize docetaxel therapy and investigate the possibility of predicting for the first time the antitumor target of docetaxel.

  14. Dopamine reward prediction-error signalling: a two-component response

    Science.gov (United States)

    Schultz, Wolfram

    2017-01-01

    Environmental stimuli and objects, including rewards, are often processed sequentially in the brain. Recent work suggests that the phasic dopamine reward prediction-error response follows a similar sequential pattern. An initial brief, unselective and highly sensitive increase in activity unspecifically detects a wide range of environmental stimuli, then quickly evolves into the main response component, which reflects subjective reward value and utility. This temporal evolution allows the dopamine reward prediction-error signal to optimally combine speed and accuracy. PMID:26865020

  15. 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.

  16. 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 ...

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

    NARCIS (Netherlands)

    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; Day, Julie; Echeverría-Londoño, Susy; Emerson, Susan R; Gao, Di; Garon, Morgan; Harrison, Michelle L K; Ingram, Daniel J; Jung, Martin; Kemp, Victoria; Kirkpatrick, Lucinda; Martin, Callum D; Pan, Yuan; Pask-Hale, Gwilym D; Pynegar, Edwin L; Robinson, Alexandra N; Sanchez-Ortiz, Katia; Senior, Rebecca A; Simmons, Benno I; White, Hannah J; Zhang, Hanbin; Aben, Job; Abrahamczyk, Stefan; Adum, Gilbert B; Aguilar-Barquero, Virginia; Aizen, Marcelo A; Albertos, Belén; Alcala, E L; Del Mar Alguacil, Maria; Alignier, Audrey; Ancrenaz, Marc; Andersen, Alan N; Arbeláez-Cortés, Enrique; Armbrecht, Inge; Arroyo-Rodríguez, Víctor; Aumann, Tom; Axmacher, Jan C; Azhar, Badrul; Azpiroz, Adrián B; Baeten, Lander; Bakayoko, Adama; Báldi, András; Banks, John E; Baral, Sharad K; Barlow, Jos; Barratt, Barbara I P; Barrico, Lurdes; Bartolommei, Paola; Barton, Diane M; Basset, Yves; Batáry, Péter; Bates, Adam J; Baur, Bruno; Bayne, Erin M; Beja, Pedro; Benedick, Suzan; Berg, Åke; Bernard, Henry; Berry, Nicholas J; Bhatt, Dinesh; Bicknell, Jake E; Bihn, Jochen H; Blake, Robin J; Bobo, Kadiri S; Bóçon, Roberto; Boekhout, Teun; Böhning-Gaese, Katrin; Bonham, Kevin J; Borges, Paulo A V; Borges, Sérgio H; Boutin, Céline; Bouyer, Jérémy; Bragagnolo, Cibele; Brandt, Jodi S; Brearley, Francis Q; Brito, Isabel; Bros, Vicenç; Brunet, Jörg; Buczkowski, Grzegorz; Buddle, Christopher M; Bugter, Rob; Buscardo, Erika; Buse, Jörn; Cabra-García, Jimmy; Cáceres, Nilton C; Cagle, Nicolette L; Calviño-Cancela, María; Cameron, Sydney A; Cancello, Eliana M; Caparrós, Rut; Cardoso, Pedro; Carpenter, Dan; Carrijo, Tiago F; Carvalho, Anelena L; Cassano, Camila R; Castro, Helena; Castro-Luna, Alejandro A; Rolando, Cerda B; Cerezo, Alexis; Chapman, Kim Alan; Chauvat, Matthieu; Christensen, Morten; Clarke, Francis M; Cleary, Daniel F R; Colombo, Giorgio; Connop, Stuart P; Craig, Michael D; Cruz-López, Leopoldo; Cunningham, Saul A; D'Aniello, Biagio; D'Cruze, Neil; da Silva, Pedro Giovâni; Dallimer, Martin; Danquah, Emmanuel; Darvill, Ben; Dauber, Jens; Davis, Adrian L V; Dawson, Jeff; de Sassi, Claudio; de Thoisy, Benoit; Deheuvels, Olivier; Dejean, Alain; Devineau, Jean-Louis; Diekötter, Tim; Dolia, Jignasu V; Domínguez, Erwin; Dominguez-Haydar, Yamileth; Dorn, Silvia; Draper, Isabel; Dreber, Niels; Dumont, Bertrand; Dures, Simon G; Dynesius, Mats; Edenius, Lars; Eggleton, Paul; Eigenbrod, Felix; Elek, Zoltán; Entling, Martin H; Esler, Karen J; de Lima, Ricardo F; Faruk, Aisyah; Farwig, Nina; Fayle, Tom M; Felicioli, Antonio; Felton, Annika M; Fensham, Roderick J; Fernandez, Ignacio C; Ferreira, Catarina C; Ficetola, Gentile F; Fiera, Cristina; Filgueiras, Bruno K C; Fırıncıoğlu, Hüseyin K; Flaspohler, David; Floren, Andreas; Fonte, Steven J; Fournier, Anne; Fowler, Robert E; Franzén, Markus; Fraser, Lauchlan H; Fredriksson, Gabriella M; Freire, Geraldo B; Frizzo, Tiago L M; Fukuda, Daisuke; Furlani, Dario; Gaigher, René; Ganzhorn, Jörg U; García, Karla P; Garcia-R, Juan C; Garden, Jenni G; Garilleti, Ricardo; Ge, Bao-Ming; Gendreau-Berthiaume, Benoit; Gerard, Philippa J; Gheler-Costa, Carla; Gilbert, Benjamin; Giordani, Paolo; Giordano, Simonetta; Golodets, Carly; Gomes, Laurens G L; Gould, Rachelle K; Goulson, Dave; Gove, Aaron D; Granjon, Laurent; Grass, Ingo; Gray, Claudia L; Grogan, James; Gu, Weibin; Guardiola, Moisès; Gunawardene, Nihara R; Gutierrez, Alvaro G; Gutiérrez-Lamus, Doris L; Haarmeyer, Daniela H; Hanley, Mick E; Hanson, Thor; Hashim, Nor R; Hassan, Shombe N; Hatfield, Richard G; Hawes, Joseph E; Hayward, Matt W; Hébert, Christian; Helden, Alvin J; Henden, John-André; Henschel, Philipp; Hernández, Lionel; Herrera, James P; Herrmann, Farina; Herzog, Felix; Higuera-Diaz, Diego; Hilje, Branko; Höfer, Hubert; Hoffmann, Anke; Horgan, Finbarr G; Hornung, Elisabeth; Horváth, Roland; Hylander, Kristoffer; Isaacs-Cubides, Paola; Ishida, Hiroaki; Ishitani, Masahiro; Jacobs, Carmen T; Jaramillo, Víctor J; Jauker, Birgit; Hernández, F Jiménez; Johnson, McKenzie F; Jolli, Virat; Jonsell, Mats; Juliani, S Nur; Jung, Thomas S; Kapoor, Vena; Kappes, Heike; Kati, Vassiliki; Katovai, Eric; Kellner, Klaus; Kessler, Michael; Kirby, Kathryn R; Kittle, Andrew M; Knight, Mairi E; Knop, Eva; Kohler, Florian; Koivula, Matti; Kolb, Annette; Kone, Mouhamadou; Kőrösi, Ádám; Krauss, Jochen; Kumar, Ajith; Kumar, Raman; Kurz, David J; Kutt, Alex S; Lachat, Thibault; Lantschner, Victoria; Lara, Francisco; Lasky, Jesse R; Latta, Steven C; Laurance, William F; Lavelle, Patrick; Le Féon, Violette; LeBuhn, Gretchen; Légaré, Jean-Philippe; Lehouck, Valérie; Lencinas, María V; Lentini, Pia E; Letcher, Susan G; Li, Qi; Litchwark, Simon A; Littlewood, Nick A; Liu, Yunhui; Lo-Man-Hung, Nancy; López-Quintero, Carlos A; Louhaichi, Mounir; Lövei, Gabor L; Lucas-Borja, Manuel Esteban; Luja, Victor H; Luskin, Matthew S; MacSwiney G, M Cristina; Maeto, Kaoru; Magura, Tibor; Mallari, Neil Aldrin; Malone, Louise A; Malonza, Patrick K; Malumbres-Olarte, Jagoba; Mandujano, Salvador; Måren, Inger E; Marin-Spiotta, Erika; Marsh, Charles J; Marshall, E J P; Martínez, Eliana; Martínez Pastur, Guillermo; Moreno Mateos, David; Mayfield, Margaret M; Mazimpaka, Vicente; McCarthy, Jennifer L; McCarthy, Kyle P; McFrederick, Quinn S; McNamara, Sean; Medina, Nagore G; Medina, Rafael; Mena, Jose L; Mico, Estefania; Mikusinski, Grzegorz; Milder, Jeffrey C; Miller, James R; Miranda-Esquivel, Daniel R; Moir, Melinda L; Morales, Carolina L; Muchane, Mary N; Muchane, Muchai; Mudri-Stojnic, Sonja; Munira, A Nur; Muoñz-Alonso, Antonio; Munyekenye, B F; Naidoo, Robin; Naithani, A; Nakagawa, Michiko; Nakamura, Akihiro; Nakashima, Yoshihiro; Naoe, Shoji; Nates-Parra, Guiomar; Navarrete Gutierrez, Dario A; Navarro-Iriarte, Luis; Ndang'ang'a, Paul K; Neuschulz, Eike L; Ngai, Jacqueline T; Nicolas, Violaine; Nilsson, Sven G; Noreika, Norbertas; Norfolk, Olivia; Noriega, Jorge Ari; Norton, David A; Nöske, Nicole M; Nowakowski, A Justin; Numa, Catherine; O'Dea, Niall; O'Farrell, Patrick J; Oduro, William; Oertli, Sabine; Ofori-Boateng, Caleb; Oke, Christopher Omamoke; Oostra, Vicencio; Osgathorpe, Lynne M; Otavo, Samuel Eduardo; Page, Navendu V; Paritsis, Juan; Parra-H, Alejandro; Parry, Luke; Pe'er, Guy; Pearman, Peter B; Pelegrin, Nicolás; Pélissier, Raphaël; Peres, Carlos A; Peri, Pablo L; Persson, Anna S; Petanidou, Theodora; Peters, Marcell K; Pethiyagoda, Rohan S; Phalan, Ben; Philips, T Keith; Pillsbury, Finn C; Pincheira-Ulbrich, Jimmy; Pineda, Eduardo; Pino, Joan; Pizarro-Araya, Jaime; Plumptre, A J; Poggio, Santiago L; Politi, Natalia; Pons, Pere; Poveda, Katja; Power, Eileen F; Presley, Steven J; Proença, Vânia; Quaranta, Marino; Quintero, Carolina; Rader, Romina; Ramesh, B R; Ramirez-Pinilla, Martha P; Ranganathan, Jai; Rasmussen, Claus; Redpath-Downing, Nicola A; Reid, J Leighton; Reis, Yana T; Rey Benayas, José M; Rey-Velasco, Juan Carlos; Reynolds, Chevonne; Ribeiro, Danilo Bandini; Richards, Miriam H; Richardson, Barbara A; Richardson, Michael J; Ríos, Rodrigo Macip; Robinson, Richard; Robles, Carolina A; Römbke, Jörg; Romero-Duque, Luz Piedad; Rös, Matthias; Rosselli, Loreta; Rossiter, Stephen J; Roth, Dana S; Roulston, T'ai H; Rousseau, Laurent; Rubio, André V; Ruel, Jean-Claude; Sadler, Jonathan P; Sáfián, Szabolcs; Saldaña-Vázquez, Romeo A; Sam, Katerina; Samnegård, Ulrika; Santana, Joana; Santos, Xavier; Savage, Jade; Schellhorn, Nancy A; Schilthuizen, Menno; Schmiedel, Ute; Schmitt, Christine B; Schon, Nicole L; Schüepp, Christof; Schumann, Katharina; Schweiger, Oliver; Scott, Dawn M; Scott, Kenneth A; Sedlock, Jodi L; Seefeldt, Steven S; Shahabuddin, Ghazala; Shannon, Graeme; Sheil, Douglas; Sheldon, Frederick H; Shochat, Eyal; Siebert, Stefan J; Silva, Fernando A B; Simonetti, Javier A; Slade, Eleanor M; Smith, Jo; Smith-Pardo, Allan H; Sodhi, Navjot S; Somarriba, Eduardo J; Sosa, Ramón A; Soto Quiroga, Grimaldo; St-Laurent, Martin-Hugues; Starzomski, Brian M; Stefanescu, Constanti; Steffan-Dewenter, Ingolf; Stouffer, Philip C; Stout, Jane C; Strauch, Ayron M; Struebig, Matthew J; Su, Zhimin; Suarez-Rubio, Marcela; Sugiura, Shinji; Summerville, Keith S; Sung, Yik-Hei; Sutrisno, Hari; Svenning, Jens-Christian; Teder, Tiit; Threlfall, Caragh G; Tiitsaar, Anu; Todd, Jacqui H; Tonietto, Rebecca K; Torre, Ignasi; Tóthmérész, Béla; Tscharntke, Teja; Turner, Edgar C; Tylianakis, Jason M; Uehara-Prado, Marcio; Urbina-Cardona, Nicolas; Vallan, Denis; Vanbergen, Adam J; Vasconcelos, Heraldo L; Vassilev, Kiril; Verboven, Hans A F; Verdasca, Maria João; Verdú, José R; Vergara, Carlos H; Vergara, Pablo M; Verhulst, Jort; Virgilio, Massimiliano; Vu, Lien Van; Waite, Edward M; Walker, Tony R; Wang, Hua-Feng; Wang, Yanping; Watling, James I; Weller, Britta; Wells, Konstans; Westphal, Catrin; Wiafe, Edward D; Williams, Christopher D; Willig, Michael R; Woinarski, John C Z; Wolf, Jan H D; Wolters, Volkmar; Woodcock, Ben A; Wu, Jihua; Wunderle, Joseph M; Yamaura, Yuichi; Yoshikura, Satoko; Yu, Douglas W; Zaitsev, Andrey S; Zeidler, Juliane; Zou, Fasheng; Collen, Ben; Ewers, Rob M; Mace, Georgina M; Purves, Drew W; Scharlemann, Jörn P W; Purvis, Andy

    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

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

    Science.gov (United States)

    Lawrence N. Hudson; Joseph Wunderle M.; And Others

    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...

  19. Assessment of Predictive Markers of Response to Neoadjuvant Chemotherapy in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mallika Tewari

    2010-10-01

    Conclusion: Of all parameters examined, only the apoptosis-related genes (Bcl-2 and BAX seemed to exert some influence on the response to NACT, and neither by itself was sufficient to predict pCR; however, 50 patients is not sufficient to simultaneously analyse several predictive markers.

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

    Science.gov (United States)

    Holmlund, A; Lampa, E; Lind, L

    2017-07-01

    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.

  1. Baseline hepatitis B surface antigen quantitation can predict virologic response in entecavir-treated chronic hepatitis B patients

    Directory of Open Access Journals (Sweden)

    Chia-Chi Wang

    2014-11-01

    Conclusion: The baseline serum qHBsAg level can predict virologic response in entecavir-treated CHB patients. However, a significant decline in the qHBsAg level cannot predict serologic or virologic response of entecavir treatment.

  2. Can Nutritional Assessment Tools Predict Response to Nutritional Therapy?

    Science.gov (United States)

    Patel, Chirag; Omer, Endashaw; Diamond, Sarah J; McClave, Stephen A

    2016-04-01

    Traditional tools and scoring systems for nutritional assessment have focused solely on parameters of poor nutritional status in the past, in an effort to define the elusive concept of malnutrition. Such tools fail to account for the contribution of disease severity to overall nutritional risk. High nutritional risk, caused by either deterioration of nutritional status or greater disease severity (or a combination of both factors), puts the patient in a metabolic stress state characterized by adverse outcome and increased complications. Newer scoring systems for determining nutritional risk, such as the Nutric Score and the Nutritional Risk Score-2002 have created a paradigm shift connecting assessment and treatment with quality outcome measures of success. Clinicians now have the opportunity to identify high risk patients through their initial assessment, provide adequate or sufficient nutrition therapy, and expect improved patient outcomes as a result. These concepts are supported by observational and prospective interventional trials. Greater clinical experience and refinement in these scoring systems are needed in the future to optimize patient response to nutrition therapy.

  3. 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. © 2016 John Wiley & Sons Ltd.

  4. Proton MRS may predict AED response in patients with TLE.

    Science.gov (United States)

    Campos, Bruno A G; Yasuda, Clarissa L; Castellano, Gabriela; Bilevicius, Elizabeth; Li, Li M; Cendes, Fernando

    2010-05-01

    To compare relative N-acetylaspartate (NAA) measurements in temporal lobe epilepsy (TLE) patients with good response to the first trial of antiepileptic drugs (AEDs) (an important prognostic factor) to TLE patients who failed the first AED monotherapy and required further AED trials with monotherapy or polytherapy. We studied 25 consecutive TLE patients who responded to first AED (responders) and 21 who did not (failure-group), as well as 27 controls. Patients were seen regularly in our Epilepsy Service and underwent electroencephalography (EEG) investigation, high-resolution magnetic resonance imaging (MRI), and single-voxel proton MR spectroscopy. Voxels were tailored to the medial temporal region on each side and involved the anterior hippocampus. Analysis of variance (ANOVA) demonstrated significant variation of NAA/creatine (NAA/Cr) values in both hippocampi, ipsilateral and contralateral to the EEG focus (p AED have significantly less evidence of neuronal and axonal damage/dysfunction compared to those who are refractory to the first AED trial.

  5. Association of Elevated Reward Prediction Error Response With Weight Gain in Adolescent Anorexia Nervosa.

    Science.gov (United States)

    DeGuzman, Marisa; Shott, Megan E; Yang, Tony T; Riederer, Justin; Frank, Guido K W

    2017-06-01

    Anorexia nervosa is a psychiatric disorder of unknown etiology. Understanding associations between behavior and neurobiology is important in treatment development. Using a novel monetary reward task during functional magnetic resonance brain imaging, the authors tested how brain reward learning in adolescent anorexia nervosa changes with weight restoration. Female adolescents with anorexia nervosa (N=21; mean age, 16.4 years [SD=1.9]) underwent functional MRI (fMRI) before and after treatment; similarly, healthy female control adolescents (N=21; mean age, 15.2 years [SD=2.4]) underwent fMRI on two occasions. Brain function was tested using the reward prediction error construct, a computational model for reward receipt and omission related to motivation and neural dopamine responsiveness. Compared with the control group, the anorexia nervosa group exhibited greater brain response 1) for prediction error regression within the caudate, ventral caudate/nucleus accumbens, and anterior and posterior insula, 2) to unexpected reward receipt in the anterior and posterior insula, and 3) to unexpected reward omission in the caudate body. Prediction error and unexpected reward omission response tended to normalize with treatment, while unexpected reward receipt response remained significantly elevated. Greater caudate prediction error response when underweight was associated with lower weight gain during treatment. Punishment sensitivity correlated positively with ventral caudate prediction error response. Reward system responsiveness is elevated in adolescent anorexia nervosa when underweight and after weight restoration. Heightened prediction error activity in brain reward regions may represent a phenotype of adolescent anorexia nervosa that does not respond well to treatment. Prediction error response could be a neurobiological marker of illness severity that can indicate individual treatment needs.

  6. Predicting individual differences in response to sleep loss: application of current techniques.

    Science.gov (United States)

    Chandler, Joseph F; Arnold, Richard D; Phillips, Jeffrey B; Turnmire, Ashley E

    2013-09-01

    Fatigue's negative impact on safety represents one of the top threats to military transportation. Biomathematical models have been developed to predict the response to fatigue; however, current models do not take into account stable individual differences in fatigue susceptibility. Readiness Screening Tools (RSTs) can capture individual differences in fatigue response, but cannot predict performance long-term. The objective of this study was to combine an existing biomathematical model of fatigue with existing RST-derived measures to determine current ability to predict individual differences in fatigue response. We hypothesized that the predictive ability of the biomathematical model could be significantly improved by incorporating cognitive and oculometric measures shown to be sensitive to individual differences in fatigue response. Data on multiple cognitive and oculometric measures were collected at rested baseline and then every 3 h across 25 h of continual wakefulness. Results characterized actual fatigued performance at the group and individual levels. Actual performance was compared to predicted performance decrements over the same time period. The unique variance explained by each approach was then combined to determine if RST-derived individual difference measures added significant predictive power to the model. Addition of individual-difference sensitive RST measures to an existing fatigue model significantly increased the amount of variance in performance explained by the model from 13.8 to 35.7%. Simply leveraging RSTs' ability to capture individual differences in fatigue susceptibility can substantially improve biomathematical prediction of fatigued performance.

  7. Can personality traits predict pathological responses to audiovisual stimulation?

    Science.gov (United States)

    Yambe, Tomoyuki; Yoshizawa, Makoto; Fukudo, Shin; Fukuda, Hiroshi; Kawashima, Ryuta; Shizuka, Kazuhiko; Nanka, Shunsuke; Tanaka, Akira; Abe, Ken-ichi; Shouji, Tomonori; Hongo, Michio; Tabayashi, Kouichi; Nitta, Shin-ichi

    2003-10-01

    pathophysiological reaction to the audiovisual stimulations. As for the photo sensitive epilepsy, it was reported to be only 5-10% for all patients. Therefore, 90% or more of the cause could not be determined in patients who started a morbid response. The results in this study suggest that the autonomic function was connected to the mental tendency of the objects. By examining such directivity, it is expected that subjects, which show morbid reaction to an audiovisual stimulation, can be screened beforehand.

  8. Posterior predictive checks for conditional independence between response time and accuracy

    NARCIS (Netherlands)

    Bolsinova, Maria; Tijmstra, J.

    2016-01-01

    Conditional independence (CI) between response time and response accuracy is a fundamental assumption of many joint models for time and accuracy used in educational measurement. In this study, posterior predictive checks (PPCs) are proposed for testing this assumption. These PPCs are based on three

  9. 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

    % CI 73-100) and an area under the receiver operating curve of 0.90 (95% CI 0.73-0.98). Only one study of TTE-based methods fulfilled the criteria for valid assessment of fluid responsiveness. Before recommending the use of TTE in predicting fluid responsiveness, proper evaluation including...

  10. Demographic and phenotypic responses of juvenile steelhead trout to spatial predictability of food resources

    Science.gov (United States)

    Matthew R. Sloat; Gordon H. Reeves

    2014-01-01

    We manipulated food inputs among patches within experimental streams to determine how variation in foraging behavior influenced demographic and phenotypic responses of juvenile steelhead trout (Oncorhynchus mykiss) to the spatial predictability of food resources. Demographic responses included compensatory adjustments in fish abundance, mean fish...

  11. 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

  12. The Predictive Adaptive Response: Modeling the Life-History Evolution of the Butterfly

    NARCIS (Netherlands)

    Heuvel, van den J.; Saastamoinen, M.; Brakefield, P.M.; Kirkwood, T.B.; Zwaan, B.J.; Shanley, D.P.

    2013-01-01

    A predictive adaptive response (PAR) is a type of developmental plasticity where the response to an environmental cue is not immediately advantageous but instead is later in life. The PAR is a way for organisms to maximize fitness in varying environments. Insects living in seasonal environments are

  13. Predictive clinical model of tumor response after chemoradiation in rectal cancer.

    Science.gov (United States)

    Santos, Marisa D; Silva, Cristina; Rocha, Anabela; Nogueira, Carlos; Castro-Poças, Fernando; Araujo, António; Matos, Eduarda; Pereira, Carina; Medeiros, Rui; Lopes, Carlos

    2017-08-29

    Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery. Blood cell counts in peripheral blood were analyzed. Pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and protein 21 were assessed. A total of 61 single nucleotide polymorphisms were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specimens were classified according to Mandard TRG. The patients were divided as: "good responders" (Mandard TRG1-2) and "poor responders" (Mandard TGR3-5). We examined predictive factors for Mandard response and performed statistical analysis. In univariate analysis, distance from anal verge, neutrophil lymphocyte ratio (NLR), cyclin D1, VEGF, EGFR, protein 21 and rs1810871 interleukin 10 (IL10) gene polymorphism are the pretreatment variables with predictive value for Mandard response. In multivariable analysis, NLR, cyclin D1, protein 21 and rs1800871 in IL10 gene maintain predictive value, allowing a clinical model design. It seems possible to use pretreatment expression of blood and tissue biomarkers, and build a model of tumor response prediction to neoadjuvant chemoradiation in rectal cancer.

  14. 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

  15. RAMAN SPECTROSCOPIC STUDY ON PREDICTION OF TREATMENT RESPONSE IN CERVICAL CANCERS

    Directory of Open Access Journals (Sweden)

    S. RUBINA

    2013-04-01

    Full Text Available Concurrent chemoradiotherapy (CCRT is the choice of treatment for locally advanced cervical cancers; however, tumors exhibit diverse response to treatment. Early prediction of tumor response leads to individualizing treatment regimen. Response evaluation criteria in solid tumors (RECIST, the current modality of tumor response assessment, is often subjective and carried out at the first visit after treatment, which is about four months. Hence, there is a need for better predictive tool for radioresponse. Optical spectroscopic techniques, sensitive to molecular alteration, are being pursued as potential diagnostic tools. Present pilot study aims to explore the fiber-optic-based Raman spectroscopy approach in prediction of tumor response to CCRT, before taking up extensive in vivo studies. Ex vivo Raman spectra were acquired from biopsies collected from 11 normal (148 spectra, 16 tumor (201 spectra and 13 complete response (151 CR spectra, one partial response (8 PR spectra and one nonresponder (8 NR spectra subjects. Data was analyzed using principal component linear discriminant analysis (PC-LDA followed by leave-one-out cross-validation (LOO-CV. Findings suggest that normal tissues can be efficiently classified from both pre- and post-treated tumor biopsies, while there is an overlap between pre- and post-CCRT tumor tissues. Spectra of CR, PR and NR tissues were subjected to principal component analysis (PCA and a tendency of classification was observed, corroborating previous studies. Thus, this study further supports the feasibility of Raman spectroscopy in prediction of tumor radioresponse and prospective noninvasive in vivo applications.

  16. Gut Microbiota Signatures Predict Host and Microbiota Responses to Dietary Interventions in Obese Individuals

    Science.gov (United States)

    Korpela, Katri; Flint, Harry J.; Johnstone, Alexandra M.; Lappi, Jenni; Poutanen, Kaisa; Dewulf, Evelyne; Delzenne, Nathalie; de Vos, Willem M.; Salonen, Anne

    2014-01-01

    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 potential of

  17. 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.

  18. Resting lateralized activity predicts the cortical response and appraisal of emotions: an fNIRS study.

    Science.gov (United States)

    Balconi, Michela; Grippa, Elisabetta; Vanutelli, Maria Elide

    2015-12-01

    This study explored the effect of lateralized left-right resting brain activity on prefrontal cortical responsiveness to emotional cues and on the explicit appraisal (stimulus evaluation) of emotions based on their valence. Indeed subjective responses to different emotional stimuli should be predicted by brain resting activity and should be lateralized and valence-related (positive vs negative valence). A hemodynamic measure was considered (functional near-infrared spectroscopy). Indeed hemodynamic resting activity and brain response to emotional cues were registered when subjects (N = 19) viewed emotional positive vs negative stimuli (IAPS). Lateralized index response during resting state, LI (lateralized index) during emotional processing and self-assessment manikin rating were considered. Regression analysis showed the significant predictive effect of resting activity (more left or right lateralized) on both brain response and appraisal of emotional cues based on stimuli valence. Moreover, significant effects were found as a function of valence (more right response to negative stimuli; more left response to positive stimuli) during emotion processing. Therefore, resting state may be considered a predictive marker of the successive cortical responsiveness to emotions. The significance of resting condition for emotional behavior was discussed. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  19. Evaluation of stroke volume variation obtained by arterial pulse contour analysis to predict fluid responsiveness intraoperatively.

    Science.gov (United States)

    Lahner, D; Kabon, B; Marschalek, C; Chiari, A; Pestel, G; Kaider, A; Fleischmann, E; Hetz, H

    2009-09-01

    Fluid management guided by oesophageal Doppler monitor has been reported to improve perioperative outcome. Stroke volume variation (SVV) is considered a reliable clinical predictor of fluid responsiveness. Consequently, the aim of the present trial was to evaluate the accuracy of SVV determined by arterial pulse contour (APCO) analysis, using the FloTrac/Vigileo system, to predict fluid responsiveness as measured by the oesophageal Doppler. Patients undergoing major abdominal surgery received intraoperative fluid management guided by oesophageal Doppler monitoring. Fluid boluses of 250 ml each were administered in case of a decrease in corrected flow time (FTc) to 10%. The ability of SVV to predict fluid responsiveness was assessed by calculation of the area under the receiver operating characteristic (ROC) curve. Twenty patients received 67 fluid boluses. Fifty-two of the 67 fluid boluses administered resulted in fluid responsiveness. SVV achieved an area under the ROC curve of 0.512 [confidence interval (CI) 0.32-0.70]. A cut-off point for fluid responsiveness was found for SVV > or =8.5% (sensitivity: 77%; specificity: 43%; positive predictive value: 84%; and negative predictive value: 33%). This prospective, interventional observer-blinded study demonstrates that SVV obtained by APCO, using the FloTrac/Vigileo system, is not a reliable predictor of fluid responsiveness in the setting of major abdominal surgery.

  20. 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. PMID:25184672

  1. 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.

  2. 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.

  3. 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.

  4. Physiological thermal limits predict differential responses of bees to urban heat-island effects.

    Science.gov (United States)

    Hamblin, April L; Youngsteadt, Elsa; López-Uribe, Margarita M; Frank, Steven D

    2017-06-01

    Changes in community composition are an important, but hard to predict, effect of climate change. Here, we use a wild-bee study system to test the ability of critical thermal maxima (CTmax, a measure of heat tolerance) to predict community responses to urban heat-island effects in Raleigh, NC, USA. Among 15 focal species, CTmax ranged from 44.6 to 51.3°C, and was strongly predictive of population responses to urban warming across 18 study sites (r(2) = 0.44). Species with low CTmax declined the most. After phylogenetic correction, solitary species and cavity-nesting species (bumblebees) had the lowest CTmax, suggesting that these groups may be most sensitive to climate change. Community responses to urban and global warming will likely retain strong physiological signal, even after decades of warming during which time lags and interspecific interactions could modulate direct effects of temperature. © 2017 The Author(s).

  5. Spouses’ Attachment Pairings Predict Neuroendocrine, Behavioral, and Psychological Responses to Marital Conflict

    Science.gov (United States)

    Beck, Lindsey A.; Pietromonaco, Paula R.; DeBuse, Casey J.; Powers, Sally I.; Sayer, Aline G.

    2014-01-01

    This research investigated how spouses’ attachment styles jointly contributed to their stress responses. Newlywed couples discussed relationship conflicts. Salivary cortisol indexed physiological stress; observer-rated behaviors indexed behavioral stress; self-reported distress indexed psychological stress. Multilevel modeling tested predictions that couples including one anxious and one avoidant partner or two anxious partners would show distinctive stress responses. As predicted, couples with anxious wives and avoidant husbands showed physiological reactivity in anticipation of conflict: Both spouses showed sharp increases in cortisol, followed by rapid declines. These couples also showed distinctive behaviors during conflict: Anxious wives had difficulty recognizing avoidant husbands’ distress, and avoidant husbands had difficulty approaching anxious wives for support. Contrary to predictions, couples including two anxious partners did not show distinctive stress responses. Findings suggest that the fit between partners’ attachment styles can improve understanding of relationships by specifying conditions under which partners’ attachment characteristics jointly influence individual and relationship outcomes. PMID:23773048

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

    OpenAIRE

    Tarrier Nicholas; Morris Julie; Carruthers Helen R; Whorwell Peter J

    2010-01-01

    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 ha...

  7. Prediction of Individual Response to Electroconvulsive Therapy via Machine Learning on Structural Magnetic Resonance Imaging Data.

    Science.gov (United States)

    Redlich, Ronny; Opel, Nils; Grotegerd, Dominik; Dohm, Katharina; Zaremba, Dario; Bürger, Christian; Münker, Sandra; Mühlmann, Lisa; Wahl, Patricia; Heindel, Walter; Arolt, Volker; Alferink, Judith; Zwanzger, Peter; Zavorotnyy, Maxim; Kugel, Harald; Dannlowski, Udo

    2016-06-01

    Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, biomarkers that accurately predict a response to ECT remain unidentified. To investigate whether certain factors identified by structural magnetic resonance imaging (MRI) techniques are able to predict ECT response. In this nonrandomized prospective study, gray matter structure was assessed twice at approximately 6 weeks apart using 3-T MRI and voxel-based morphometry. Patients were recruited through the inpatient service of the Department of Psychiatry, University of Muenster, from March 11, 2010, to March 27, 2015. Two patient groups with acute major depressive disorder were included. One group received an ECT series in addition to antidepressants (n = 24); a comparison sample was treated solely with antidepressants (n = 23). Both groups were compared with a sample of healthy control participants (n = 21). Binary pattern classification was used to predict ECT response by structural MRI that was performed before treatment. In addition, univariate analysis was conducted to predict reduction of the Hamilton Depression Rating Scale score by pretreatment gray matter volumes and to investigate ECT-related structural changes. One participant in the ECT sample was excluded from the analysis, leaving 67 participants (27 men and 40 women; mean [SD] age, 43.7 [10.6] years). The binary pattern classification yielded a successful prediction of ECT response, with accuracy rates of 78.3% (18 of 23 patients in the ECT sample) and sensitivity rates of 100% (13 of 13 who responded to ECT). Furthermore, a support vector regression yielded a significant prediction of relative reduction in the Hamilton Depression Rating Scale score. The principal findings of the univariate model indicated a positive association between pretreatment subgenual cingulate volume and individual ECT response (Montreal Neurological Institute [MNI] coordinates x = 8, y = 21, z = -18

  8. Prediction of accommodative optical response in prepresbyopic subjects using ultrasound biomicroscopy.

    Science.gov (United States)

    Ramasubramanian, Viswanathan; Glasser, Adrian

    2015-05-01

    To determine whether relatively low-resolution ultrasound biomicroscopy (UBM) can be used to predict the accommodative optical response in prepresbyopic eyes as well as in a previous study of young phakic subjects, despite lower accommodative amplitudes. College of Optometry, University of Houston, Houston, USA. Observational cross-sectional study. Static accommodative optical response was measured with infrared photorefraction and an autorefractor (WR-5100K) in subjects aged 36 to 46 years. A 35 MHz UBM device (Vumax, Sonomed Escalon) was used to image the left eye, while the right eye viewed accommodative stimuli. Custom-developed Matlab image-analysis software was used to perform automated analysis of UBM images to measure the ocular biometry parameters. The accommodative optical response was predicted from biometry parameters using linear regression, 95% confidence intervals (CIs), and 95% prediction intervals. The study evaluated 25 subjects. Per-diopter (D) accommodative changes in anterior chamber depth (ACD), lens thickness, anterior and posterior lens radii of curvature, and anterior segment length were similar to previous values from young subjects. The standard deviations (SDs) of accommodative optical response predicted from linear regressions for UBM-measured biometry parameters were ACD, 0.15 D; lens thickness, 0.25 D; anterior lens radii of curvature, 0.09 D; posterior lens radii of curvature, 0.37 D; and anterior segment length, 0.42 D. Ultrasound biomicroscopy parameters can, on average, predict accommodative optical responses with SDs of less than 0.55 D using linear regressions and 95% CIs. Ultrasound biomicroscopy can be used to visualize and quantify accommodative biometric changes and predict accommodative optical response in prepresbyopic eyes. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  9. Response surface model predictions of emergence and response to pain in the recovery room: an evaluation of patients emerging from an isoflurane and fentanyl anesthetic

    Science.gov (United States)

    Syroid, Noah D.; Johnson, Ken B.; Pace, Nathan L.; Westenskow, Dwayne R.; Tyler, Diane; Brühschwein, Frederike; Albert, Robert W.; Roalstad, Shelly; Costy-Bennett, Samuel; Egan, Talmage D.

    2009-01-01

    Introduction Sevoflurane - remifentanil interaction models that predict responsiveness and response to painful stimuli have been evaluated in patients undergoing elective surgery. Preliminary evaluations of model predictions were found to be consistent with observations in patients anesthetized with sevoflurane, remifentanil and fentanyl. The present study explored the feasibility of adapting the predictions of sevoflurane-remifentanil interaction models to an isoflurane-fentanyl anesthetic. We hypothesized that model predictions adapted for isoflurane and fentanyl are consistent with observed patient responses and are similar to the predictions observed in our prior work with sevoflurane-remifentanil/fentanyl anesthetics. Methods Twenty-five patients scheduled for elective surgery received a fentanyl-isoflurane anesthetic. Model predictions of unresponsiveness were recorded at emergence and predictions of a response to noxious stimulus were recorded when patients first required analgesics in the recovery room. Model predictions were compared to observations with graphical and temporal analyses. Results were also compared to our prior predictions following a sevoflurane-remifentanil/fentanyl anesthetic. Results While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (≥ 99%). Following termination of the anesthetic, model predictions of responsiveness well described the actual fraction of patients observed to be responsive during emergence. Half of the patients awoke within 2 minutes of the 50% model predicted probability of unresponsiveness; 70% awoke within 4 minutes. Similarly, predictions of a response to a noxious stimulus were consistent with the number of patients who required fentanyl in the recovery room. Model predictions following an isoflurane-fentanyl anesthetic were similar to model predictions following a sevoflurane-remifentanil/fentanyl anesthetic. Discussion Results confirmed our study

  10. Bayesian Mapping Reveals That Attention Boosts Neural Responses to Predicted and Unpredicted Stimuli.

    Science.gov (United States)

    Garrido, Marta I; Rowe, Elise G; Halász, Veronika; Mattingley, Jason B

    2017-04-10

    Predictive coding posits that the human brain continually monitors the environment for regularities and detects inconsistencies. It is unclear, however, what effect attention has on expectation processes, as there have been relatively few studies and the results of these have yielded contradictory findings. Here, we employed Bayesian model comparison to adjudicate between 2 alternative computational models. The "Opposition" model states that attention boosts neural responses equally to predicted and unpredicted stimuli, whereas the "Interaction" model assumes that attentional boosting of neural signals depends on the level of predictability. We designed a novel, audiospatial attention task that orthogonally manipulated attention and prediction by playing oddball sequences in either the attended or unattended ear. We observed sensory prediction error responses, with electroencephalography, across all attentional manipulations. Crucially, posterior probability maps revealed that, overall, the Opposition model better explained scalp and source data, suggesting that attention boosts responses to predicted and unpredicted stimuli equally. Furthermore, Dynamic Causal Modeling showed that these Opposition effects were expressed in plastic changes within the mismatch negativity network. Our findings provide empirical evidence for a computational model of the opposing interplay of attention and expectation in the brain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Weight Stigma Predicts Poorer Psychological Well-Being Through Internalized Weight Bias and Maladaptive Coping Responses.

    Science.gov (United States)

    Hayward, Lydia E; Vartanian, Lenny R; Pinkus, Rebecca T

    2018-02-10

    Weight-based stigmatization is associated with negative psychological and behavioral consequences, but individuals respond to stigma in different ways. The present study aimed to understand some of the factors that predict how one will cope with weight stigma and how different coping responses predict psychological well-being. Across four samples, 1,391 individuals who identified as having overweight or obesity completed surveys assessing the frequency of weight stigma experiences, internalized weight bias, coping responses to weight stigma, and psychological distress. Frequency of weight stigma predicted greater internalized weight bias, which predicted more frequent use of maladaptive coping responses ("disengagement coping") and less frequent use of adaptive coping responses ("reappraisal coping"), in turn predicting more depression, anxiety, and stress symptoms. The more that individuals with overweight or obesity experience weight stigma and internalize weight bias, the more they report using maladaptive coping and the less they report using adaptive coping when dealing with weight stigma. Maladaptive coping is strongly associated with poorer psychological well-being. Thus, those who experience more frequent weight stigma may be more vulnerable to psychological distress because they appear to be at greater risk of employing maladaptive coping strategies. © 2018 The Obesity Society.

  12. Predicting biomaterial property-dendritic cell phenotype relationships from the multivariate analysis of responses to polymethacrylates

    Science.gov (United States)

    Kou, Peng Meng; Pallassana, Narayanan; Bowden, Rebeca; Cunningham, Barry; Joy, Abraham; Kohn, Joachim; Babensee, Julia E.

    2011-01-01

    Dendritic cells (DCs) play a critical role in orchestrating the host responses to a wide variety of foreign antigens and are essential in maintaining immune tolerance. Distinct biomaterials have been shown to differentially affect the phenotype of DCs, which suggested that biomaterials may be used to modulate immune response towards the biologic component in combination products. The elucidation of biomaterial property-DC phenotype relationships is expected to inform rational design of immuno-modulatory biomaterials. In this study, DC response to a set of 12 polymethacrylates (pMAs) was assessed in terms of surface marker expression and cytokine profile. Principal component analysis (PCA) determined that surface carbon correlated with enhanced DC maturation, while surface oxygen was associated with an immature DC phenotype. Partial square linear regression, a multivariate modeling approach, was implemented and successfully predicted biomaterial-induced DC phenotype in terms of surface marker expression from biomaterial properties with R2prediction = 0.76. Furthermore, prediction of DC phenotype was effective based on only theoretical chemical composition of the bulk polymers with R2prediction = 0.80. These results demonstrated that immune cell response can be predicted from biomaterial properties, and computational models will expedite future biomaterial design and selection. PMID:22136715

  13. Predicting biomaterial property-dendritic cell phenotype relationships from the multivariate analysis of responses to polymethacrylates.

    Science.gov (United States)

    Kou, Peng Meng; Pallassana, Narayanan; Bowden, Rebeca; Cunningham, Barry; Joy, Abraham; Kohn, Joachim; Babensee, Julia E

    2012-02-01

    Dendritic cells (DCs) play a critical role in orchestrating the host responses to a wide variety of foreign antigens and are essential in maintaining immune tolerance. Distinct biomaterials have been shown to differentially affect the phenotype of DCs, which suggested that biomaterials may be used to modulate immune response toward the biologic component in combination products. The elucidation of biomaterial property-DC phenotype relationships is expected to inform rational design of immuno-modulatory biomaterials. In this study, DC response to a set of 12 polymethacrylates (pMAs) was assessed in terms of surface marker expression and cytokine profile. Principal component analysis (PCA) determined that surface carbon correlated with enhanced DC maturation, while surface oxygen was associated with an immature DC phenotype. Partial square linear regression, a multivariate modeling approach, was implemented and successfully predicted biomaterial-induced DC phenotype in terms of surface marker expression from biomaterial properties with R(prediction)(2) = 0.76. Furthermore, prediction of DC phenotype was effective based on only theoretical chemical composition of the bulk polymers with R(prediction)(2) = 0.80. These results demonstrated that immune cell response can be predicted from biomaterial properties, and computational models will expedite future biomaterial design and selection. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. 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.)

  15. Systemic inflammation response index (SIRI) predicts prognosis in hepatocellular carcinoma patients

    Science.gov (United States)

    Xu, Litao; Yu, Shulin; Zhuang, Liping; Wang, Peng; Shen, Yehua; Lin, Junhua; Meng, Zhiqiang

    2017-01-01

    The systemic inflammation response index (SIRI) is a useful tool for predicting prognosis in some types of cancer. In this retrospective study, we evaluated the efficacy of SIRI in predicting overall survival in hepatocellular carcinoma (HCC) patients following local or systemic therapy. A cutoff value of 1.05 was identified for SIRI using ROC analysis in a training patient cohort. In the validation cohort, survival analysis revealed that median overall survival was longer in HCC patients with SIRI scores SIRI was associated with overall survival and was more predictive of overall survival that the AFP level or Child-Pugh score. However, SIRI and Barcelona Clinic Liver Cancer (BCLC) stage were equally effective for predicting survival. In addition, HCC patients with BCLC stage C had higher SIRI scores and poorer overall survival. SIRI also correlated with liver function parameters. Thus SIRI may be a convenient, low cost and reliable tumor marker for predicting prognosis in HCC patients. PMID:28430597

  16. 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 response...... is not calculated by FIELD II. This work investigates the usability of combining a one-dimensional multilayer transducer modeling principle with the FIELD II software. Multilayer here refers to a transducer composed of several material layers. Measurements of pressure and current from Pz27 piezoceramic disks...... transducer model and the FIELD II software in combination give good agreement with measurements....

  17. 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...

  18. 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.

  19. Sleep spindles may predict response to cognitive-behavioral therapy for chronic insomnia.

    Science.gov (United States)

    Dang-Vu, Thien Thanh; Hatch, Benjamin; Salimi, Ali; Mograss, Melodee; Boucetta, Soufiane; O'Byrne, Jordan; Brandewinder, Marie; Berthomier, Christian; Gouin, Jean-Philippe

    2017-11-01

    While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed to determine whether pre-treatment sleep spindle density predicts treatment response to cognitive-behavioral therapy for insomnia. Twenty-four participants with chronic primary insomnia participated in a 6-week cognitive-behavioral therapy for insomnia performed in groups of 4-6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre- and post-treatment, and at 3- and 12-months' follow-up assessments. Secondary outcome measures were extracted from sleep diaries over 7 days and overnight polysomnography, obtained at pre- and post-treatment. Spindle density during stage N2-N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive-behavioral therapy. After adjusting for age, sex, and education level, lower spindle density at pre-treatment predicted poorer response over the 12-month follow-up, as reflected by a smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. These preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive-behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia subtype characterized by a neurophysiological vulnerability to sleep disruption associated with impaired responsiveness to

  20. Dealing with feeling: Specific emotion regulation skills predict responses to stress in psychosis.

    Science.gov (United States)

    Lincoln, Tania M; Hartmann, Maike; Köther, Ulf; Moritz, Steffen

    2015-08-15

    Elevated negative affect is an established link between minor stressors and psychotic symptoms. Less clear is why people with psychosis fail to regulate distressing emotions effectively. This study tests whether subjective, psychophysiological and symptomatic responses to stress can be predicted by specific emotion regulation (ER) difficulties. Participants with psychotic disorders (n=35) and healthy controls (n=28) were assessed for ER-skills at baseline. They were then exposed to a noise versus no stressor on different days, during which self-reported stress responses, state paranoia and skin conductance levels (SCL) were assessed. Participants with psychosis showed a stronger increase in self-reported stress and SCL in response to the stressor than healthy controls. Stronger increases in self-reported stress were predicted by a reduced ability to be aware of and tolerate distressing emotions, whereas increases in SCL were predicted by a reduced ability to be aware of, tolerate, accept and modify them. Although paranoid symptoms were not significantly affected by the stressors, individual variation in paranoid responses was also predicted by a reduced ability to be aware of and tolerate emotions. Differences in stress responses in the samples were no longer significant after controlling for ER skills. Thus, interventions that improve ER-skills could reduce stress-sensitivity in psychosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Anterior cingulate volume predicts response to cognitive behavioral therapy in major depressive disorder.

    Science.gov (United States)

    Fujino, Junya; Yamasaki, Nobuyuki; Miyata, Jun; Sasaki, Hitoshi; Matsukawa, Noriko; Takemura, Ariyoshi; Tei, Shisei; Sugihara, Genichi; Aso, Toshihiko; Fukuyama, Hidenao; Takahashi, Hidehiko; Inoue, Kazuomi; Murai, Toshiya

    2015-03-15

    Cognitive behavioral therapy (CBT) is widely used to treat major depressive disorder (MDD). Although improved response prediction could facilitate the development of individualized treatment plans, few studies have investigated whether underlying brain structure is related to CBT response in MDD. Ten MDD patients who received individual CBT were studied in this study. We investigated the relationship between the regional gray matter (GM) volume and subsequent responses to CBT using voxel-based morphometry. The degree of improvement in depressive symptoms was positively correlated with GM volume in the caudal portion of the anterior cingulate cortex. The sample size was small, and the effects of medication on the results could not be excluded. Our results, although preliminary, suggest that the anterior cingulate cortex is a key structure whose volume can be used to predict responses to CBT and is thus a potential prognostic marker in MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. 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.

  3. Emotional Responses during Reading: Physiological Responses Predict Real-Time Reading Comprehension

    Science.gov (United States)

    Daley, Samantha G.; Willett, John B.; Fischer, Kurt W.

    2014-01-01

    This study investigated the relationship between emotional responses and reading performance in middle-school students. Although a large number of prior studies have investigated the relationship between emotion and reading, those studies have concentrated primarily on relatively static and distal measures of emotion. In this research, we measured…

  4. Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders

    OpenAIRE

    Lester, Kathryn J; Eley, Thalia C

    2013-01-01

    Abstract Considerable variation is evident in response to psychological therapies for mood and anxiety disorders. Genetic factors alongside environmental variables and gene-environment interactions are implicated in the etiology of these disorders and it is plausible that these same factors may also be important in predicting individual differences in response to psychological treatment. In this article, we review the evidence that genetic variation influences psychological treatment outcomes...

  5. Infants, mothers, and dyadic contributions to stability and prediction of social stress response at 6 months.

    Science.gov (United States)

    Provenzi, Livio; Olson, Karen L; Montirosso, Rosario; Tronick, Ed

    2016-01-01

    The study of infants' interactive style and social stress response to repeated stress exposures is of great interest for developmental and clinical psychologists. Stable maternal and dyadic behavior is critical to sustain infants' development of an adaptive social stress response, but the association between infants' interactive style and social stress response has received scant attention in previous literature. In the present article, overtime stability of infant, maternal, and dyadic behaviors was measured across 2 social stress (i.e., Face-to-Face Still-Face, FFSF) exposures, separated by 15 days. Moreover, infant, maternal, and dyadic behaviors were simultaneously assessed as predictors of infants' social stress to both FFSF exposures. Eighty-one mother-infant dyads underwent the FFSF twice, at 6 months (Exposure 1: the first social stress) and at 6 months and 15 days (Exposure 2: repeated social stress). Infant and mother behavior and dyadic synchrony were microanalytically coded. Overall, individual behavioral stability emerged between FFSF exposures. Infants' response to the first stress was predicted by infant behavior during Exposure 1 Play. Infants' response to the repeated social stress was predicted by infants' response to the first exposure to the Still-Face and by infants' behavior and dyadic synchrony during Exposure 2 Play. Findings reveal stability for individual, but not for dyadic, behavior between 2 social stress exposures at 6 months. Infants' response to repeated social stress was predicted by infants' earlier stress response, infants' own behavior in play, and dyadic synchrony. No predictive effects of maternal behavior were found. Insights for research and clinical work are discussed. (c) 2015 APA, all rights reserved).

  6. Circulating Biomarkers for Predicting Infliximab Response in Rheumatoid Arthritis: A Systematic Bioinformatics Analysis.

    Science.gov (United States)

    Huang, Qiu-Lan; Zhou, Fu-Jiang; Wu, Cheng-Bin; Xu, Chao; Qian, Wen-Ying; Fan, De-Ping; Cai, Xu-Shan

    2017-04-17

    BACKGROUND Infliximab shows good efficacy in treating refractory rheumatoid arthritis (RA). However, many patients responded poorly and related studies were inconsistent in predictive biomarkers. This study aimed to identify circulating biomarkers for predicting infliximab response in RA. MATERIAL AND METHODS Public databases of Gene Expression Omnibus (GEO) and ArrayExpress were searched for related microarray datasets, focused on the response to infliximab in RA. All peripheral blood samples were collected before infliximab treatment and gene expression profiles were measured using microarray. Differential genes associated with infliximab efficacy were analyzed. The genes recognized by half of the datasets were regarded as candidate biomarkers and validated by prospective datasets. RESULTS Eight microarray datasets were identified with 374 blood samples of RA patients, among which 191 (51.1%) were diagnosed as non-responders in the subsequent infliximab treatment. Five genes (FKBP1A, FGF12, ANO1, LRRC31, and AKR1D1) were associated with the efficacy and recognized by half of the datasets. The 5-gene model showed a good predictive power in random- and prospective-designed studies, with AUC (area under receiver operating characteristic [ROC] curve)=0.963 and 1.000, and it was also applicable at the early phase of treatment (at week 2) for predicting the response at week 14 (AUC=1.000). In the placebo group, the model failed to predict the response (AUC=0.697), indicating the model's specificity in infliximab treatment. CONCLUSIONS The model of FKBP1A, FGF12, ANO1, LRRC31, and AKR1D1 in peripheral blood is useful for efficiently predicting the response to infliximab treatment in rheumatoid arthritis.

  7. 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.)

  8. 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.

  9. A prediction model for the response to oral labetalol for the treatment of antenatal hypertension.

    Science.gov (United States)

    Stott, D; Bolten, M; Salman, M; Paraschiv, D; Douiri, A; Kametas, N A

    2017-02-01

    This prospective observational study aimed to identify at presentation the maternal hemodynamic and demographic variables associated with a therapeutic response to oral labetalol and to use these variables to develop a prediction model to anticipate the response to labetalol monotherapy in women with hypertension. It was set at a maternity unit in a UK teaching hospital. Maternal demographic data from 50 pregnant women, presenting with hypertension between January and August 2013, was collected and blood pressure measured with a device validated for pregnancy and pre-eclampsia. Maternal haemodynamics were assessed with a bioreactance monitor. Participants were commenced on oral labetalol, and reviewed until delivery and discharge home. Logistic regression analysis was performed to assess the prediction of response to labetalol according to the maternal demographic and hemodynamic variables. Main outcome measures were the response to labetalol monotherapy up to delivery and discharge home, defined as sustained blood pressure control labetalol monotherapy, 13 (26%) failed to achieve control with labetalol alone, of whom 9 developed severe hypertension. Multivariate logistic regression showed that heart rate, ethnicity and stroke volume index were independent predictors of the response to labetalol. The predictive accuracy of the model was 96% (95% confidence interval (CI) 86-99%). Maternal demographics and haemodynamics are potent predictors for the response to labetalol, and these parameters may guide therapy to enable effective blood pressure control and a lowering of severe hypertension rates.

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

    Science.gov (United States)

    Pena, Michelle J; Heinzel, Andreas; Rossing, Peter; Parving, Hans-Henrik; Dallmann, Guido; Rossing, Kasper; Andersen, Steen; Mayer, Bernd; Heerspink, Hiddo J L

    2016-07-05

    Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria. 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 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. In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1-Q3: -69 to -8]. The classifier, consisting of 21 metabolites, was significantly associated with UAE response to irbesartan (p diabetes mellitus.

  11. Single-subject prediction of response inhibition behavior by event-related potentials.

    Science.gov (United States)

    Stock, Ann-Kathrin; Popescu, Florin; Neuhaus, Andres H; Beste, Christian

    2016-03-01

    Much research has been devoted to investigating response inhibition and the neuronal processes constituting this essential cognitive faculty. However, the nexus between cognitive subprocesses, behavior, and electrophysiological processes remains associative in nature. We therefore investigated whether neurophysiological correlates of inhibition subprocesses merely correlate with behavioral performance or actually provide information expedient to the prediction of behavior on a single-subject level. Tackling this question, we used different data-driven classification approaches in a sample of n = 262 healthy young subjects who completed a standard Go/Nogo task while an EEG was recorded. On the basis of median-split response inhibition performance, subjects were classified as "accurate/slow" and "less accurate/fast." Even though these behavioral group differences were associated with significant amplitude variations in classical electrophysiological correlates of response inhibition (i.e., N2 and P3), they were not predictive for group membership on a single-subject level. Instead, amplitude differences in the Go-P2 originating in the precuneus (BA7) were shown to predict group membership on a single-subject level with up to 64% accuracy. These findings strongly suggest that the behavioral outcome of response inhibition greatly depends on the amount of cognitive resources allocated to early stages of stimulus-response activation during responding. This suggests that research should focus more on early processing steps during responding when trying to understand the origin of interindividual differences in response inhibition processes. Copyright © 2016 the American Physiological Society.

  12. Prediction of anti-cancer drug response by kernelized multi-task learning.

    Science.gov (United States)

    Tan, Mehmet

    2016-10-01

    Chemotherapy or targeted therapy are two of the main treatment options for many types of cancer. Due to the heterogeneous nature of cancer, the success of the therapeutic agents differs among patients. In this sense, determination of chemotherapeutic response of the malign cells is essential for establishing a personalized treatment protocol and designing new drugs. With the recent technological advances in producing large amounts of pharmacogenomic data, in silico methods have become important tools to achieve this aim. Data produced by using cancer cell lines provide a test bed for machine learning algorithms that try to predict the response of cancer cells to different agents. The potential use of these algorithms in drug discovery/repositioning and personalized treatments motivated us in this study to work on predicting drug response by exploiting the recent pharmacogenomic databases. We aim to improve the prediction of drug response of cancer cell lines. We propose to use a method that employs multi-task learning to improve learning by transfer, and kernels to extract non-linear relationships to predict drug response. The method outperforms three state-of-the-art algorithms on three anti-cancer drug screen datasets. We achieved a mean squared error of 3.305 and 0.501 on two different large scale screen data sets. On a recent challenge dataset, we obtained an error of 0.556. We report the methodological comparison results as well as the performance of the proposed algorithm on each single drug. The results show that the proposed method is a strong candidate to predict drug response of cancer cell lines in silico for pre-clinical studies. The source code of the algorithm and data used can be obtained from http://mtan.etu.edu.tr/Supplementary/kMTrace/. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Performance of Remotely Controlled Mandibular Protrusion Sleep Studies for Prediction of Oral Appliance Treatment Response.

    Science.gov (United States)

    Sutherland, Kate; Ngiam, Joachim; Cistulli, Peter A

    2017-03-15

    Mandibular protrusion during sleep monitoring has been proposed as a method to predict oral appliance treatment outcome. A commercial remotely controlled mandibular protrusion (RCMP) device has become available for this purpose with predictive accuracy demonstrated in an initial study. Our aim was to validate this RCMP method for oral appliance treatment outcome prediction in a clinical sleep laboratory setting. Forty-two obstructive sleep apnea (OSA) patients (apnea-hypopnea index [AHI] > 10 events/h) were recruited to undergo a RCMP sleep study before commencing oral appliance treatment. The RCMP study was used to make a prediction of treatment "Success" or "Failure" based on a rule of ≤ 1 respiratory event per 5 min supine rapid eye movement sleep. Oral appliance treatment response was verified by polysomonography and defined as treatment AHI 30 events/h). Two participants (5%) were not able to tolerate the RCMP study. Oral appliance treatment outcome was verified in 33 participants (RCMP results: "Success" n = 10, "Failure" n = 15, "Inconclusive" n = 8). In those with a treatment outcome prediction (n = 25) the diagnostic characteristics of the RCMP test were sensitivity 81.8%, specificity 92.9%, positive predictive value 90%, and negative predictive value 86.7% (n = 3 misclassified). The RCMP device was well tolerated by patients and successfully used to perform mandibular protrusion sleep studies in our sleep laboratory. The RCMP sleep study showed good accuracy as a prediction technique for oral appliance treatment outcome, although there was a high rate of inconclusive tests.

  14. Psychological stress as a measure for treatment response prediction in idiopathic sudden hearing loss.

    Science.gov (United States)

    Roh, Daeyoung; Chao, Janet Ren; Kim, Do Hoon; Yoon, Kyung Hee; Jung, Jae Hoon; Lee, Chang Hyun; Shin, Ji-Hyeon; Kim, Min Jae; Park, Chan Hum; Lee, Jun Ho

    2017-11-01

    Early prediction of therapeutic outcomes could reduce exposure to ineffective treatments and optimize clinical outcomes. However, none of the known otologic predictors is amenable to therapeutic intervention for idiopathic sudden sensorineural hearing loss (ISSNHL). The aims of this study were to investigate psychological stress as a potential predictor to discriminate outcomes in ISSNHL. Various psychological measures were conducted including structured interview assessment tools in patients with recently diagnosed ISSNHL before initiating treatment. Using logistic regression analysis, we identified the predictors of treatment response and estimated the probability of treatment response in 50 ISSNHL patients who participated in a clinical trial. Treatment non-responders were significantly differentiated from responders by various psychological problems. The depression subscore of Modified form of Stress Response Inventory (SRI-MF) (p=0.007) and duration of hearing loss (p=0.045) significantly predicted treatment response after controlling other clinical correlates. The same predictors were identified from different treatment response measured using Siegel's criteria. The most discriminative measure for treatment response was SRI-MF depression score with an overall classification accuracy of 73%. We found depressive stress response to be the strong predictor of treatment response in patients with ISSNHL. Our results highlight the potential use of the psychiatric approach as a tool for enhancing therapeutic outcomes. Future stress intervention studies with larger number of ISSNHL patients are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Texture analysis on MR images helps predicting non-response to NAC in breast cancer.

    Science.gov (United States)

    Michoux, N; Van den Broeck, S; Lacoste, L; Fellah, L; Galant, C; Berlière, M; Leconte, I

    2015-08-05

    To assess the performance of a predictive model of non-response to neoadjuvant chemotherapy (NAC) in patients with breast cancer based on texture, kinetic, and BI-RADS parameters measured from dynamic MRI. Sixty-nine patients with invasive ductal carcinoma of the breast who underwent pre-treatment MRI were studied. Morphological parameters and biological markers were measured. Pathological complete response was defined as the absence of invasive and in situ cancer in breast and nodes. Pathological non-responders, partial and complete responders were identified. Dynamic imaging was performed at 1.5 T with a 3D axial T1W GRE fat-suppressed sequence. Visual texture, kinetic and BI-RADS parameters were measured in each lesion. ROC analysis and leave-one-out cross-validation were used to assess the performance of individual parameters, then the performance of multi-parametric models in predicting non-response to NAC. A model based on four pre-NAC parameters (inverse difference moment, GLN, LRHGE, wash-in) and k-means clustering as statistical classifier identified non-responders with 84 % sensitivity. BI-RADS mass/non-mass enhancement, biological markers and histological grade did not contribute significantly to the prediction. Pre-NAC texture and kinetic parameters help predicting non-benefit to NAC. Further testing including larger groups of patients with different tumor subtypes is needed to improve the generalization properties and validate the performance of the predictive model.

  16. Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

    Science.gov (United States)

    Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

    2015-12-01

    Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Added value of pharmacogenetic testing in predicting statin response: Results from the REGRESS trial

    NARCIS (Netherlands)

    Van Der Baan, F.H.; Knol, M.J.; Maitland-Van Der Zee, A.H.; Regieli, J.J.; Van Iperen, E.P.A.; Egberts, A.C.G.; Klungel, O.H.; Grobbee, D.E.; Jukema, J.W.

    2013-01-01

    It was investigated whether pharmacogenetic factors, both as single polymorphism and as gene-gene interactions, have an added value over non-genetic factors in predicting statin response. Five common polymorphisms were selected in apolipoprotein E, angiotensin-converting enzyme, hepatic lipase and

  18. 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.…

  19. 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

  20. Can a single dose response predict the effect of montelukast on exercise-induced bronchoconstriction?

    NARCIS (Netherlands)

    Kersten, Elin T. G.; Akkerman-Nijland, Anne M.; Driessen, Jean M. M.; Diamant, Zuzana; Thio, Bernard J.

    RationaleExercise-induced bronchoconstriction (EIB) can be prevented by a single dose of montelukast (MLK). The effect is variable, similar to the variable responsiveness observed after daily treatment with MLK. We hypothesized that the effect of a single MLK-dose (5 or 10mg) on EIB could predict

  1. Nonrandom Acts of Kindness: Parasympathetic and Subjective Empathic Responses to Sadness Predict Children's Prosociality

    Science.gov (United States)

    Miller, Jonas G.; Nuselovici, Jacob N.; Hastings, Paul D.

    2016-01-01

    How does empathic physiology unfold as a dynamic process, and which aspect of empathy predicts children's kindness? In response to empathy induction videos, 4- to 6-year-old children (N = 180) showed an average pattern of dynamic respiratory sinus arrhythmia (RSA) change characterized by early RSA suppression, followed by RSA recovery, and modest…

  2. 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,…

  3. Accurate Prediction and Validation of Response to Endocrine Therapy in Breast Cancer.

    Science.gov (United States)

    Turnbull, Arran K; Arthur, Laura M; Renshaw, Lorna; Larionov, Alexey A; Kay, Charlene; Dunbier, Anita K; Thomas, Jeremy S; Dowsett, Mitch; Sims, Andrew H; Dixon, J Michael

    2015-07-10

    Aromatase inhibitors (AIs) have an established role in the treatment of breast cancer. Response rates are only 50% to 70% in the neoadjuvant setting and lower in advanced disease. Accurate biomarkers are urgently needed to predict response in these settings and to determine which individuals will benefit from adjuvant AI therapy. Pretreatment and on-treatment (after 2 weeks and 3 months) biopsies were obtained from 89 postmenopausal women who had estrogen receptor-alpha positive breast cancer and were receiving neoadjuvant letrozole for transcript profiling. Dynamic clinical response was assessed with use of three-dimensional ultrasound measurements. The molecular response to letrozole was characterized and a four-gene classifier of clinical response was established (accuracy of 96%) on the basis of the level of two genes before treatment (one gene [IL6ST] was associated with immune signaling, and the other [NGFRAP1] was associated with apoptosis) and the level of two proliferation genes (ASPM, MCM4) after 2 weeks of therapy. The four-gene signature was found to be 91% accurate in a blinded, completely independent validation data set of patients treated with anastrozole. Matched 2-week on-treatment biopsies were associated with improved predictive power as compared with pretreatment biopsies alone. This signature also significantly predicted recurrence-free survival (P = .029) and breast cancer -specific survival (P = .009). We demonstrate that the test can also be performed with use of quantitative polymerase chain reaction or immunohistochemistry. A four-gene predictive model of clinical response to AIs by 2 weeks has been generated and validated. Deregulated immune and apoptotic responses before treatment and cell proliferation that is not reduced 2 weeks after initiation of treatment are functional characteristics of breast tumors that do not respond to AIs. © 2015 by American Society of Clinical Oncology.

  4. Predicting breast cancer response to neoadjuvant chemotherapy using pretreatment diffuse optical spectroscopic texture analysis.

    Science.gov (United States)

    Tran, William T; Gangeh, Mehrdad J; Sannachi, Lakshmanan; Chin, Lee; Watkins, Elyse; Bruni, Silvio G; Rastegar, Rashin Fallah; Curpen, Belinda; Trudeau, Maureen; Gandhi, Sonal; Yaffe, Martin; Slodkowska, Elzbieta; Childs, Charmaine; Sadeghi-Naini, Ali; Czarnota, Gregory J

    2017-05-09

    Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC) patients. In this study, we evaluate texture features of pretreatment DOS functional maps for predicting LABC response to NAC. Locally advanced breast cancer patients (n=37) underwent DOS breast imaging before starting NAC. Breast tissue parametric maps were constructed and texture analyses were performed based on grey-level co-occurrence matrices for feature extraction. Ground truth labels as responders (R) or non-responders (NR) were assigned to patients based on Miller-Payne pathological response criteria. The capability of DOS textural features computed on volumetric tumour data before the start of treatment (i.e., 'pretreatment') to predict patient responses to NAC was evaluated using a leave-one-out validation scheme at subject level. Data were analysed using a logistic regression, naive Bayes, and k-nearest neighbour classifiers. Data indicated that textural characteristics of pretreatment DOS parametric maps can differentiate between treatment response outcomes. The HbO2 homogeneity resulted in the highest accuracy among univariate parameters in predicting response to chemotherapy: sensitivity (%Sn) and specificity (%Sp) were 86.5% and 89.0%, respectively, and accuracy was 87.8%. The highest predictors using multivariate (binary) combination features were the Hb-contrast+HbO2-homogeneity, which resulted in a %Sn/%Sp=78.0/81.0% and an accuracy of 79.5%. This study demonstrated that the pretreatment DOS texture features can predict breast cancer response to NAC and potentially guide treatments.

  5. An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Benjamin L Ebert

    2008-02-01

    Full Text Available Lenalidomide is an effective new agent for the treatment of patients with myelodysplastic syndrome (MDS, an acquired hematopoietic disorder characterized by ineffective blood cell production and a predisposition to the development of leukemia. Patients with an interstitial deletion of Chromosome 5q have a high rate of response to lenalidomide, but most MDS patients lack this deletion. Approximately 25% of patients without 5q deletions also benefit from lenalidomide therapy, but response in these patients cannot be predicted by any currently available diagnostic assays. The aim of this study was to develop a method to predict lenalidomide response in order to avoid unnecessary toxicity in patients unlikely to benefit from treatment.Using gene expression profiling, we identified a molecular signature that predicts lenalidomide response. The signature was defined in a set of 16 pretreatment bone marrow aspirates from MDS patients without 5q deletions, and validated in an independent set of 26 samples. The response signature consisted of a cohesive set of erythroid-specific genes with decreased expression in responders, suggesting that a defect in erythroid differentiation underlies lenalidomide response. Consistent with this observation, treatment with lenalidomide promoted erythroid differentiation of primary hematopoietic progenitor cells grown in vitro.These studies indicate that lenalidomide-responsive patients have a defect in erythroid differentiation, and suggest a strategy for a clinical test to predict patients most likely to respond to the drug. The experiments further suggest that the efficacy of lenalidomide, whose mechanism of action in MDS is unknown, may be due to its ability to induce erythroid differentiation.

  6. Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

    Science.gov (United States)

    Szczepanik, Joanna; Nugent, Allison C; Drevets, Wayne C; Khanna, Ashish; Zarate, Carlos A; Furey, Maura L

    2016-08-30

    The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Temporal Prediction Errors Affect Short-Term Memory Scanning Response Time.

    Science.gov (United States)

    Limongi, Roberto; Silva, Angélica M

    2016-11-01

    The Sternberg short-term memory scanning task has been used to unveil cognitive operations involved in time perception. Participants produce time intervals during the task, and the researcher explores how task performance affects interval production - where time estimation error is the dependent variable of interest. The perspective of predictive behavior regards time estimation error as a temporal prediction error (PE), an independent variable that controls cognition, behavior, and learning. Based on this perspective, we investigated whether temporal PEs affect short-term memory scanning. Participants performed temporal predictions while they maintained information in memory. Model inference revealed that PEs affected memory scanning response time independently of the memory-set size effect. We discuss the results within the context of formal and mechanistic models of short-term memory scanning and predictive coding, a Bayes-based theory of brain function. We state the hypothesis that our finding could be associated with weak frontostriatal connections and weak striatal activity.

  8. 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. Published 2012. This article is a US Government work and is in the public domain in the USA.

  9. 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.)

  10. Does stroke volume variation predict fluid responsiveness in children: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ling Yi

    Full Text Available Stroke volume variation (SVV is a reliable predictor of fluid responsiveness in adult patients. However, the predictive value of SVV is uncertain in pediatric patients. We performed the first systematic meta-analysis to evaluate the diagnostic value of SVV in predicting fluid responsiveness in children.PUBMED, EMBASE, and Cochrane Central Register of Controlled Trials were searched up to December 2016. Original studies assessing the diagnostic accuracy of SVV in predicting fluid responsiveness in children were considered to be eligible. A random-effects model was used to calculate pooled values of sensitivity, specificity and diagnostic odds ratio with 95% CI. The summary receiver operating characteristic curve was estimated and area under the curve was calculated. Quality of the studies was assessed with the QUADAS-2 tool.Six studies with a total of 279 fluid boluses in 224 children were included. The analysis demonstrated a pooled sensitivity of 0.68 (95% CI,0.59-0.76, pooled specificity of 0.65 (95% CI, 0.57-0.73, pooled diagnostic odds ratio of 8.24 (95% CI, 2.58-26.30, and the summary area under the summary receiver operating characteristic curve of 0.81. However, significant inter-study heterogeneity was found (p<0.05, I2 = 61.3%, likely due to small sample size and diverse study characteristics.Current evidence suggests that SVV was of diagnostic value in predicting fluid responsiveness in children under mechanical ventilation. Given the high heterogeneity of published data, further studies are needed to confirm the diagnostic accuracy of SVV in predicting fluid responsiveness in pediatric patients.

  11. Can Ki-67 Play a Role in Prediction of Breast Cancer Patients' Response to Neoadjuvant Chemotherapy?

    Directory of Open Access Journals (Sweden)

    Juhasz-Böss Ingolf

    2014-01-01

    Full Text Available Background. Currently the choice of breast cancer therapy is based on prognostic factors. The proliferation marker Ki-67 is used increasingly to determine the method of therapy. The current study analyses the predictive value of Ki-67 in foreseeing breast cancer patients’ responses to neoadjuvant chemotherapy. Methods. This study includes patients with invasive breast cancer treated between 2008 and 2013. The clinical response was assessed by correlating Ki-67 to histological examination, mammography, and ultrasonography findings. Results. The average Ki-67 value in our patients collectively (n=77 is 34.9 ± 24.6%. The average Ki-67 value is the highest with 37.4 ± 24.0% in patients with a pCR. The Ki-67 values do not differ significantly among the 3 groups: pCR versus partial pathological response versus stable disease/progress (P=0.896. However, Ki-67 values of patients with luminal, Her2 enriched, and basal-like cancers differed significantly from each other. Furthermore, within the group of luminal tumors Ki-67 values of patients with versus without pCR also differed significantly. Conclusion. Our data shows that the Ki-67 value predicts the response to neoadjuvant chemotherapy as a function of the molecular subtype, reflecting the daily routine concerning Ki-67 and its impressing potential and limitation as a predictive marker for neoadjuvant chemotherapy response.

  12. Response to anticipated reward in the nucleus accumbens predicts behavior in an independent test of honesty.

    Science.gov (United States)

    Abe, Nobuhito; Greene, Joshua D

    2014-08-06

    This study examines the cognitive and neural determinants of honesty and dishonesty. Human subjects undergoing fMRI completed a monetary incentive delay task eliciting responses to anticipated reward in the nucleus accumbens. Subjects next performed an incentivized prediction task, giving them real and repeated opportunities for dishonest gain. Subjects attempted to predict the outcomes of random computerized coin-flips and were financially rewarded for accuracy. In some trials, subjects were rewarded based on self-reported accuracy, allowing them to gain money dishonestly by lying. Dishonest behavior was indexed by improbably high levels of self-reported accuracy. Nucleus accumbens response in the first task, involving only honest rewards, accounted for ∼25% of the variance in dishonest behavior in the prediction task. Individuals showing relatively strong nucleus accumbens responses to anticipated reward also exhibited increased dorsolateral prefrontal activity (bilateral) in response to opportunities for dishonest gain. These results address two hypotheses concerning (dis)honesty. According to the "Will" hypothesis, honesty results from the active deployment of self-control. According to the "Grace" hypothesis, honesty flows more automatically. The present results suggest a reconciliation between these two hypotheses while explaining (dis)honesty in terms of more basic neural mechanisms: relatively weak responses to anticipated rewards make people morally "Graceful," but individuals who respond more strongly may resist temptation by force of Will. Copyright © 2014 the authors 0270-6474/14/3410564-09$15.00/0.

  13. Neural Reactivity to Angry Faces Predicts Treatment Response in Pediatric Anxiety.

    Science.gov (United States)

    Bunford, Nora; Kujawa, Autumn; Fitzgerald, Kate D; Swain, James E; Hanna, Gregory L; Koschmann, Elizabeth; Simpson, David; Connolly, Sucheta; Monk, Christopher S; Phan, K Luan

    2017-02-01

    Although cognitive-behavioral psychotherapy (CBT) and pharmacotherapy are evidence-based treatments for pediatric anxiety, many youth with anxiety disorders fail to respond to these treatments. Given limitations of clinical measures in predicting treatment response, identifying neural predictors is timely. In this study, 35 anxious youth (ages 7-19 years) completed an emotional face-matching task during which the late positive potential (LPP), an event-related potential (ERP) component that indexes sustained attention towards emotional stimuli, was measured. Following the ERP measurement, youth received CBT or selective serotonin reuptake inhibitor (SSRI) treatment, and the LPP was examined as a predictor of treatment response. Findings indicated that, accounting for pre-treatment anxiety severity, neural reactivity to emotional faces predicted anxiety severity post- CBT and SSRI treatment such that enhanced electrocortical response to angry faces was associated with better treatment response. An enhanced LPP to angry faces may predict treatment response insofar as it may reflect greater emotion dysregulation or less avoidance and/or enhanced engagement with environmental stimuli in general, including with treatment.

  14. 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.

  15. Predictive feedback can account for biphasic responses in the lateral geniculate nucleus.

    Directory of Open Access Journals (Sweden)

    Janneke F M Jehee

    2009-05-01

    Full Text Available Biphasic neural response properties, where the optimal stimulus for driving a neural response changes from one stimulus pattern to the opposite stimulus pattern over short periods of time, have been described in several visual areas, including lateral geniculate nucleus (LGN, primary visual cortex (V1, and middle temporal area (MT. We describe a hierarchical model of predictive coding and simulations that capture these temporal variations in neuronal response properties. We focus on the LGN-V1 circuit and find that after training on natural images the model exhibits the brain's LGN-V1 connectivity structure, in which the structure of V1 receptive fields is linked to the spatial alignment and properties of center-surround cells in the LGN. In addition, the spatio-temporal response profile of LGN model neurons is biphasic in structure, resembling the biphasic response structure of neurons in cat LGN. Moreover, the model displays a specific pattern of influence of feedback, where LGN receptive fields that are aligned over a simple cell receptive field zone of the same polarity decrease their responses while neurons of opposite polarity increase their responses with feedback. This phase-reversed pattern of influence was recently observed in neurophysiology. These results corroborate the idea that predictive feedback is a general coding strategy in the brain.

  16. Attenuation of Frontostriatal Connectivity During Reward Processing Predicts Response to Psychotherapy in Major Depressive Disorder.

    Science.gov (United States)

    Walsh, Erin; Carl, Hannah; Eisenlohr-Moul, Tory; Minkel, Jared; Crowther, Andrew; Moore, Tyler; Gibbs, Devin; Petty, Chris; Bizzell, Josh; Smoski, Moria J; Dichter, Gabriel S

    2017-03-01

    There are few reliable predictors of response to antidepressant treatments. In the present investigation, we examined pretreatment functional brain connectivity during reward processing as a potential predictor of response to Behavioral Activation Treatment for Depression (BATD), a validated psychotherapy that promotes engagement with rewarding stimuli and reduces avoidance behaviors. Thirty-three outpatients with major depressive disorder (MDD) and 20 matched controls completed two runs of the monetary incentive delay task during functional magnetic resonance imaging after which participants with MDD received up to 15 sessions of BATD. Seed-based generalized psychophysiological interaction analyses focused on task-based connectivity across task runs, as well as the attenuation of connectivity from the first to the second run of the task. The average change in Beck Depression Inventory-II scores due to treatment was 10.54 points, a clinically meaningful response. Groups differed in seed-based functional connectivity among multiple frontostriatal regions. Hierarchical linear modeling revealed that improved treatment response to BATD was predicted by greater connectivity between the left putamen and paracingulate gyrus during reward anticipation. In addition, MDD participants with greater attenuation of connectivity between several frontostriatal seeds, and midline subcallosal cortex and left paracingulate gyrus demonstrated improved response to BATD. These findings indicate that pretreatment frontostriatal functional connectivity during reward processing is predictive of response to a psychotherapy modality that promotes improving approach-related behaviors in MDD. Furthermore, connectivity attenuation among reward-processing regions may be a particularly powerful endophenotypic predictor of response to BATD in MDD.

  17. Prediction of postoperative pain by preoperative pain response to heat stimulation in total knee arthroplasty

    DEFF Research Database (Denmark)

    Lunn, Troels H; Gaarn-Larsen, Lissi; Kehlet, Henrik

    2013-01-01

    : From 6-24hrs (primary), from postoperative day (POD) 1-7 (secondary), and from POD14-30 (tertiary). Two preoperative tonic heat stimuli with 47°C were used; short (5sec) and long (7min) stimulation upon which patients rated their pain response on an electronic VAS. Multivariate stepwise linear......It has been estimated that up to 54% of the variance in postoperative pain experience may be predicted with preoperative pain responses to experimental stimuli, with suprathreshold heat pain as the most consistent test modality. We aimed to explore if 2 heat test paradigms could predict...... and logistic regressions analyses were carried out including 8 potential preoperative explanatory variables (among these anxiety, depression, preoperative pain and pain catastrophizing) to assess pain response to preoperative heat pain stimulation as independent predictor for postoperative pain. 100 patients...

  18. rpartOrdinal: An R Package for Deriving a Classification Tree for Predicting an Ordinal Response

    Directory of Open Access Journals (Sweden)

    Kellie J. Archer

    2010-10-01

    Full Text Available This paper describes an R package, rpartOrdinal, that implements alternative splitting functions for fitting a classification tree when interest lies in predicting an ordinal response. This includes the generalized Gini impurity function, which was introduced as a method for predicting an ordinal response by including costs of misclassification into the impurity function, as well as an alternative ordinal impurity function due to Piccarreta (2008 that does not require the assignment of misclassification costs. The ordered twoing splitting method, which is not defined as a decrease in node impurity, is also included in the package. Since, in the ordinal response setting, misclassifying observations to adjacent categories is a less egregious error than misclassifying observations to distant categories, this package also includes a function for estimating an ordinal measure of association, the gamma statistic.

  19. Predicting Reading Growth with Event-Related Potentials: Thinking Differently about Indexing "Responsiveness"

    Science.gov (United States)

    Lemons, Christopher J; Key, Alexandra P F; Fuchs, Douglas; Yoder, Paul J; Fuchs, Lynn S; Compton, Donald L; Williams, Susan M; Bouton, Bobette

    2010-06-01

    The purpose of this study was to determine if event-related potential (ERP) data collected during three reading-related tasks (Letter Sound Matching, Nonword Rhyming, and Nonword Reading) could be used to predict short-term reading growth on a curriculum-based measure of word identification fluency over 19 weeks in a sample of 29 first-grade children. Results indicate that ERP responses to the Letter Sound Matching task were predictive of reading change and remained so after controlling for two previously validated behavioral predictors of reading, Rapid Letter Naming and Segmenting. ERP data for the other tasks were not correlated with reading change. The potential for cognitive neuroscience to enhance current methods of indexing responsiveness in a response-to-intervention (RTI) model is discussed.

  20. What predicts outcome, response, and drop-out in CBT of depressive adults? a naturalistic study.

    Science.gov (United States)

    Schindler, Amrei; Hiller, Wolfgang; Witthöft, Michael

    2013-05-01

    The efficacy of CBT for unipolar depressive disorders is well established, yet not all patients improve or tolerate treatment. To identify factors associated with symptomatic outcome, response, and drop-out in depressive patients under naturalistic CBT. 193 patients with major depression or dysthymia were tested. Sociodemographic and clinical variables were entered as predictors in hierarchical regression analyses. A higher degree of pretreatment depression, early improvement, and completion of therapy were identified as predictors for symptomatic change and response. Drop-out was predicted by concurrent personality disorder, less positive outcome expectancies, and by failure to improve early in treatment. Our results highlight the importance of early response to predict improvement in routine CBT. Attempts to refine the quality of treatment programs should focus on avoiding premature termination (drop-out) and consider motivational factors in more depth. Routinely administered standardized assessments would enhance symptom monitoring and help to identify persons at risk of not improving under therapy.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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. Transcription-based prediction of response to IFNbeta using supervised computational methods.

    Directory of Open Access Journals (Sweden)

    Sergio E Baranzini

    2005-01-01

    Full Text Available Changes in cellular functions in response to drug therapy are mediated by specific transcriptional profiles resulting from the induction or repression in the activity of a number of genes, thereby modifying the preexisting gene activity pattern of the drug-targeted cell(s. Recombinant human interferon beta (rIFNbeta is routinely used to control exacerbations in multiple sclerosis patients with only partial success, mainly because of adverse effects and a relatively large proportion of nonresponders. We applied advanced data-mining and predictive modeling tools to a longitudinal 70-gene expression dataset generated by kinetic reverse-transcription PCR from 52 multiple sclerosis patients treated with rIFNbeta to discover higher-order predictive patterns associated with treatment outcome and to define the molecular footprint that rIFNbeta engraves on peripheral blood mononuclear cells. We identified nine sets of gene triplets whose expression, when tested before the initiation of therapy, can predict the response to interferon beta with up to 86% accuracy. In addition, time-series analysis revealed potential key players involved in a good or poor response to interferon beta. Statistical testing of a random outcome class and tolerance to noise was carried out to establish the robustness of the predictive models. Large-scale kinetic reverse-transcription PCR, coupled with advanced data-mining efforts, can effectively reveal preexisting and drug-induced gene expression signatures associated with therapeutic effects.

  4. Predicting community responses to perturbations in the face of imperfect knowledge and network complexity

    Science.gov (United States)

    Novak, Mark; Wootton, J. Timothy; Doak, Daniel F.; Emmerson, Mark; Estes, James A.; Tinker, M. Timothy

    2011-01-01

    How best to predict the effects of perturbations to ecological communities has been a long-standing goal for both applied and basic ecology. This quest has recently been revived by new empirical data, new analysis methods, and increased computing speed, with the promise that ecologically important insights may be obtainable from a limited knowledge of community interactions. We use empirically based and simulated networks of varying size and connectance to assess two limitations to predicting perturbation responses in multispecies communities: (1) the inaccuracy by which species interaction strengths are empirically quantified and (2) the indeterminacy of species responses due to indirect effects associated with network size and structure. We find that even modest levels of species richness and connectance (∼25 pairwise interactions) impose high requirements for interaction strength estimates because system indeterminacy rapidly overwhelms predictive insights. Nevertheless, even poorly estimated interaction strengths provide greater average predictive certainty than an approach that uses only the sign of each interaction. Our simulations provide guidance in dealing with the trade-offs involved in maximizing the utility of network approaches for predicting dynamics in multispecies communities.

  5. Perseverance time of informal caregivers for people with dementia: construct validity, responsiveness and predictive validity.

    Science.gov (United States)

    Richters, Anke; Melis, René J F; van Exel, N Job; Olde Rikkert, Marcel G M; van der Marck, Marjolein A

    2017-04-04

    Informal care is essential for many people with dementia (PwD), but it often results in a considerable burden for the caregiver. The perseverance time instrument integrates the aspect of perceived burden with the caregiver's capacity to cope with the burden, in contrast to most available instruments, which measure solely the burden of caregiving. The aim of this study was to extend insight into psychometric properties of the perseverance time instrument, specifically the construct validity, responsiveness, and predictive validity, within the population of informal caregivers for PwD. Data from two studies among informal caregivers of community-dwelling PwD in the Netherlands were used. The first study included 198 caregivers from a single region in the Netherlands and lasted 1 year. The second was a cross-sectional nationwide study with 166 caregivers for PwD. Questionnaires of both studies included questions regarding demographics and informal care, perseverance time, and other informal caregiver outcomes (Caregiver Strain Index, Self-rated Burden scale, Care-related Quality of Life instrument, and visual analogue scale health scores). Construct validity and responsiveness were assessed using a hypothesis-testing approach. The predictive validity of demographic characteristics and perseverance time for living situation after 1 year (living at home, institutionalized, or deceased) was assessed with multivariable multinomial regression. All but one of the hypotheses regarding construct validity were met. Three of five hypotheses regarding responsiveness were met. Perseverance time scores at baseline were associated with living situation after 1 year (p validity of the perseverance time instrument and adds new evidence of good construct validity, responsiveness, and predictive validity. The predictive power of perseverance time scores for living situation exceeds the predictive power of other burden measures and indicates informal care as an important factor for

  6. Elevated Serum Interleukin-6 Predicts Favorable Response to Immunosuppressive Therapy in Children With Aplastic Anemia.

    Science.gov (United States)

    Lu, Shuanglong; Qiao, Xiaohong; Xie, Xiaotian

    2017-11-01

    Immunosuppressive therapy (IST) is the standard treatment for aplastic anemia (AA) children who lack a sibling donor, but the clinical response rate to IST varies. Predictors of response to IST are valuable for stratifying AA patients and making clinical decisions. The serum interleukin (IL)-6 levels of 41 AA patients were measured at the time of diagnosis and the response rate of the patients to IST was evaluated at 3, 6, and 12 months after IST. Receiver-operator characteristic (ROC) analysis was used to calculate the predictive value of initial IL-6 levels in determining response at 6 months after IST. The initial IL-6 levels were significant higher in responders than nonresponders at 6 months after IST (211.89 vs. 18.09 pg/mL; P=0.005), using 36.8 pg/mL as a threshold, there were 80% sensitivity and 81% specificity for discriminating responders and nonresponders to IST. Patients with initial high IL-6 level (>36.8 pg/mL) have favorable response rates than those with initial low IL-6 level (<36.8 pg/mL) at 3, 6, and 12 months after IST (P<0.01). High levels of IL-6 at the time of diagnosis predict a favorable response to IST in children with AA and this may be helpful for patient's stratification and clinical decisions.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Predicting the Perceptual Consequences of Hidden Hearing Loss

    Directory of Open Access Journals (Sweden)

    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.

  9. Comparing the performance of 11 crop simulation models in predicting yield response to nitrogen fertilization

    DEFF Research Database (Denmark)

    Salo, T J; Palosuo, T; Kersebaum, K C

    2016-01-01

    Eleven widely used crop simulation models (APSIM, CERES, CROPSYST, COUP, DAISY, EPIC, FASSET, HERMES, MONICA, STICS and WOFOST) were tested using spring barley (Hordeum vulgare L.) data set under varying nitrogen (N) fertilizer rates from three experimental years in the boreal climate of Jokioinen...... ranged from 170 to 870 kg/ha. During the test year 2009, most models failed to accurately reproduce the observed low yield without N fertilizer as well as the steep yield response to N applications. The multi-model predictions were closer to observations than most single-model predictions, but multi...

  10. Brain responses to regular and octave-scrambled melodies: A case of predictive-coding?

    Science.gov (United States)

    Globerson, Eitan; Granot, Roni; Tal, Idan; Harpaz, Yuval; Zeev-Wolf, Maor; Golstein, Abraham

    2017-03-01

    Melody recognition is an online process of evaluating incoming information and comparing this information to an existing internal corpus, thereby reducing prediction error. The predictive-coding model postulates top-down control on sensory processing accompanying reduction in prediction error. To investigate the relevancy of this model to melody processing, the current study examined early magnetoencephalogram (MEG) auditory responses to familiar and unfamiliar melodies in 25 participants. The familiar melodies followed and primed an octave-scrambled version of the same melody. The retrograde version of theses melodies served as the unfamiliar control condition. Octave-transposed melodies were included to examine the influence of pitch representation (pitch-height/pitch-chroma representation) on brain responses to melody recognition. Results demonstrate a reduction of the M100 auditory response to familiar, as compared with unfamiliar, melodies regardless of their form of presentation (condensed vs. octave-scrambled). This trend appeared to begin after the third tone of the melody. An additional behavioral study with the same melody corpus showed a similar trend-namely, a significant difference between familiarity rating for familiar and unfamiliar melodies, beginning with the third tone of the melody. These results may indicate a top-down inhibition of early auditory responses to melodies that is influenced by pitch representation. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Consumer Factors Predicting Level of Treatment Response to Illness Management and Recovery.

    Science.gov (United States)

    White, Dominique A; McGuire, Alan B; Luther, Lauren; Anderson, Adrienne I; Phalen, Peter; McGrew, John H

    2017-09-14

    This study aims to identify consumer-level predictors of level of treatment response to illness management and recovery (IMR) to target the appropriate consumers and aid psychiatric rehabilitation settings in developing intervention adaptations. Secondary analyses from a multisite study of IMR were conducted. Self-report data from consumer participants of the parent study (n = 236) were analyzed for the current study. Consumers completed prepost surveys assessing illness management, coping, goal-related hope, social support, medication adherence, and working alliance. Correlations and multiple regression analyses were run to identify self-report variables that predicted level of treatment response to IMR. Analyses revealed that goal-related hope significantly predicted level of improved illness self-management, F(1, 164) = 10.93, p consumer-level predictors of level of treatment response have not been explored for IMR. Although 2 significant predictors were identified, study findings suggest more work is needed. Future research is needed to identify additional consumer-level factors predictive of IMR treatment response in order to identify who would benefit most from this treatment program. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Exploring the Limitations of Peripheral Blood Transcriptional Biomarkers in Predicting Influenza Vaccine Responsiveness

    Directory of Open Access Journals (Sweden)

    Luca Marchetti

    2017-01-01

    Full Text Available Systems biology has been recently applied to vaccinology to better understand immunological responses to the influenza vaccine. Particular attention has been paid to the identification of early signatures capable of predicting vaccine immunogenicity. Building from previous studies, we employed a recently established algorithm for signature-based clustering of expression profiles, SCUDO, to provide new insights into why blood-derived transcriptome biomarkers often fail to predict the seroresponse to the influenza virus vaccination. Specifically, preexisting immunity against one or more vaccine antigens, which was found to negatively affect the seroresponse, was identified as a confounding factor able to decouple early transcriptome from later antibody responses, resulting in the degradation of a biomarker predictive power. Finally, the broadly accepted definition of seroresponse to influenza virus vaccine, represented by the maximum response across the vaccine-targeted strains, was compared to a composite measure integrating the responses against all strains. This analysis revealed that composite measures provide a more accurate assessment of the seroresponse to multicomponent influenza vaccines.

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

    Science.gov (United States)

    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

  15. Mood Linked Responses in Medial Prefrontal Cortex Predict Relapse in Patients with Recurrent Unipolar Depression

    Science.gov (United States)

    Farb, Norman A. S.; Anderson, Adam K.; Bloch, Richard T.; Segal, Zindel V.

    2011-01-01

    Background Altered cognitive processing following mood challenge is associated with elevated relapse risk in remitted unipolar depressed patients, but little is known about the neural basis of this reactivity and its link to depressive relapse and prophylaxis. Methods Remitted unipolar depressed participants (n = 16) and healthy controls (n = 16) underwent functional magnetic resonance imaging (fMRI) while viewing sad and neutral film clips. Correlations were determined between emotional reactivity (neural responses to sad vs. neutral films) in remitted patients and subsequent relapse status over an 18 month follow-up period. An ROC analysis was used to determine signal cutoffs for predicting relapse. Emotional reactivity in relapse prognostic areas was compared between groups. Results Within the remitted group, relapse was predicted by medial prefrontal cortical activity (MPFC, BA 32), and contraindicated by visual cortical activity (BA 17). MPFC reactivity predicted rumination, whereas visual cortical reactivity predicted distress tolerance (acceptance). Compared to control participants, remitted depressed patients who sustained remission demonstrated a more pronounced tradeoff between MPFC and visual cortex reactivity. The difference score between MPFC and visual reactivity yielded excellent prediction of depressive relapse. Conclusions Medial prefrontal cortical reactivity to mood provocation in remitted unipolar depressed patients serves as a marker of relapse risk rather than successful emotion regulation. Enduring remission is characterized by a normalization of the MPFC to the level of healthy controls. Further, visual cortex reactivity predicts resilience against depressive relapse, indicating a prophylactic role for sensory rather than ruminative cognitive reactivity in the processing of negative emotion. PMID:21531382

  16. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

    Science.gov (United States)

    Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

    2017-09-01

    Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. Skin Conductance Response to the Pain of Others Predicts Later Costly Helping

    Science.gov (United States)

    Brodbeck, Christian; Singer, Tania

    2011-01-01

    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. PMID:21826205

  1. Predicting individual responses to pravastatin using a physiologically based kinetic model for plasma cholesterol concentrations.

    Science.gov (United States)

    van de Pas, Niek C A; Rullmann, Johan A C; Woutersen, Ruud A; van Ommen, Ben; Rietjens, Ivonne M C M; de Graaf, Albert A

    2014-08-01

    We used a previously developed physiologically based kinetic (PBK) model to analyze the effect of individual variations in metabolism and transport of cholesterol on pravastatin response. The PBK model is based on kinetic expressions for 21 reactions that interconnect eight different body cholesterol pools including plasma HDL and non-HDL cholesterol. A pravastatin pharmacokinetic model was constructed and the simulated hepatic pravastatin concentration was used to modulate the reaction rate constant of hepatic free cholesterol synthesis in the PBK model. The integrated model was then used to predict plasma cholesterol concentrations as a function of pravastatin dose. Predicted versus observed values at 40 mg/d pravastatin were 15 versus 22 % reduction of total plasma cholesterol, and 10 versus 5.6 % increase of HDL cholesterol. A population of 7,609 virtual subjects was generated using a Monte Carlo approach, and the response to a 40 mg/d pravastatin dose was simulated for each subject. Linear regression analysis of the pravastatin response in this virtual population showed that hepatic and peripheral cholesterol synthesis had the largest regression coefficients for the non-HDL-C response. However, the modeling also showed that these processes alone did not suffice to predict non-HDL-C response to pravastatin, contradicting the hypothesis that people with high cholesterol synthesis rates are good statin responders. In conclusion, we have developed a PBK model that is able to accurately describe the effect of pravastatin treatment on plasma cholesterol concentrations and can be used to provide insight in the mechanisms behind individual variation in statin response.

  2. Predicting invasive species impacts: a community module functional response approach reveals context dependencies.

    Science.gov (United States)

    Paterson, Rachel A; Dick, Jaimie T A; Pritchard, Daniel W; Ennis, Marilyn; Hatcher, Melanie J; Dunn, Alison M

    2015-03-01

    Predatory functional responses play integral roles in predator-prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species. Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator-prey interactions and thus the predictive capability of the comparative functional response approach. We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses. Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator. Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator. This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

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

    Science.gov (United States)

    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; Heiner-Fokkema, M Rebecca; van Spronsen, Francjan J

    2013-07-10

    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. Data of the 48-hour BH4 loading test (20 mg BH4/kg/day) were collected at six Dutch university hospitals. Patients with ≥30% phenylalanine reduction at ≥1 time points during the 48 hours (potential responders) were invited for the BH4 extension phase, designed to establish true-positive BH4 responsiveness. This is defined as long-term ≥30% reduction in mean phenylalanine concentration and/or ≥4 g/day and/or ≥50% increase of natural protein intake. Genotype was collected if available. 177/183 patients successfully completed the 48-hour BH4 loading test. 80/177 were potential responders and 67/80 completed the BH4 extension phase. In 58/67 true-positive BH4 responsiveness was confirmed (PPV 87%). The genotype was available for 120/177 patients. 41/44 patients with ≥1 mutation associated with long-term BH4 responsiveness showed potential BH4 responsiveness in the 48-hour test and 34/41 completed the BH4 extension phase. In 33/34 true-positive BH4 responsiveness was confirmed. 4/40 patients with two known putative null mutations were potential responders; 2/4 performed the BH4 extension phase but showed no true-positive BH4 responsiveness. The 48-hour BH4 loading test in combination with a classified genotype is a good parameter in predicting true-positive BH4 responsiveness. We propose assessing genotype first, particularly in the neonatal period. Patients with two known putative null mutations can be excluded from BH4 testing.

  4. Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells.

    Science.gov (United States)

    Rashidian, Mohammad; Ingram, Jessica R; Dougan, Michael; Dongre, Anushka; Whang, Katherine A; LeGall, Camille; Cragnolini, Juan J; Bierie, Brian; Gostissa, Monica; Gorman, James; Grotenbreg, Gijsbert M; Bhan, Atul; Weinberg, Robert A; Ploegh, Hidde L

    2017-08-07

    Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used 89Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8+ T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A 89Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies. © 2017 Rashidian et al.

  5. Spike-train variability of auditory neurons in vivo: dynamic responses follow predictions from constant stimuli.

    Science.gov (United States)

    Schaette, Roland; Gollisch, Tim; Herz, Andreas V M

    2005-06-01

    Reliable accounts of the variability observed in neural spike trains are a prerequisite for the proper interpretation of neural dynamics and coding principles. Models that accurately describe neural variability over a wide range of stimulation and response patterns are therefore highly desirable, especially if they can explain this variability in terms of basic neural observables and parameters such as firing rate and refractory period. In this work, we analyze the response variability recorded in vivo from locust auditory receptor neurons under acoustic stimulation. In agreement with results from other systems, our data suggest that neural refractoriness has a strong influence on spike-train variability. We therefore explore a stochastic model of spike generation that includes refractoriness through a recovery function. Because our experimental data are consistent with a renewal process, the recovery function can be derived from a single interspike-interval histogram obtained under constant stimulation. The resulting description yields quantitatively accurate predictions of the response variability over the whole range of firing rates for constant-intensity as well as amplitude-modulated sound stimuli. Model parameters obtained from constant stimulation can be used to predict the variability in response to dynamic stimuli. These results demonstrate that key ingredients of the stochastic response dynamics of a sensory neuron are faithfully captured by a simple stochastic model framework.

  6. 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.

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

    Science.gov (United States)

    Lima, Aurea; Bernardes, Miguel; Azevedo, Rita; Medeiros, Rui; Seabra, Vitor

    2015-01-01

    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. PMID:26086825

  8. Empirical Model Development for Predicting Shock Response on Composite Materials Subjected to Pyroshock Loading

    Science.gov (United States)

    Gentz, Steven J.; Ordway, David O; Parsons, David S.; Garrison, Craig M.; Rodgers, C. Steven; Collins, Brian W.

    2015-01-01

    The NASA Engineering and Safety Center (NESC) received a request to develop an analysis model based on both frequency response and wave propagation analyses for predicting shock response spectrum (SRS) on composite materials subjected to pyroshock loading. The model would account for near-field environment (approx. 9 inches from the source) dominated by direct wave propagation, mid-field environment (approx. 2 feet from the source) characterized by wave propagation and structural resonances, and far-field environment dominated by lower frequency bending waves in the structure. This report documents the outcome of the assessment.

  9. Empirical Model Development for Predicting Shock Response on Composite Materials Subjected to Pyroshock Loading: Appendices

    Science.gov (United States)

    Gentz, Steven J.; Ordway, David O.; Parsons, David S.; Garrison, Craig M.; Rodgers, C. Steven; Collins, Brian W.

    2015-01-01

    The NASA Engineering and Safety Center (NESC) received a request to develop an analysis model based on both frequency response and wave propagation analyses for predicting shock response spectrum (SRS) on composite materials subjected to pyroshock loading. The model would account for near-field environment (approx. 9 inches from the source) dominated by direct wave propagation, mid-field environment (approx. 2 feet from the source) characterized by wave propagation and structural resonances, and far-field environment dominated by lower frequency bending waves in the structure. This document contains appendices to the Volume I report.

  10. Empirical Model Development for Predicting Shock Response on Composite Materials Subjected to Pyroshock Loading. [Appendices

    Science.gov (United States)

    Gentz, Steven J.; Ordway, David O.; Parsons, David S.; Garrison, Craig M.; Rodgers, C. Steven; Collins, Brian W.

    2015-01-01

    The NASA Engineering and Safety Center (NESC) received a request to develop an analysis model based on both frequency response and wave propagation analyses for predicting shock response spectrum (SRS) on composite materials subjected to pyroshock loading. The model would account for near-field environment (9 inches from the source) dominated by direct wave propagation, mid-field environment (approximately 2 feet from the source) characterized by wave propagation and structural resonances, and far-field environment dominated by lower frequency bending waves in the structure. This document contains appendices to the Volume I report.

  11. Predicting anxious response to a social challenge and hyperventilation: comparison of the ASI and ASI-3.

    Science.gov (United States)

    Carter, Michele M; Sbrocco, Tracy; Ayati, Firouzeh

    2009-09-01

    This study compared the predictive ability of the original ASI to the ASI-3 and measures of trait and social anxiety in two challenge conditions; hyperventilation or a social challenge. During hyperventilation, the ASI-3 social concerns subscale was a better predictor than the subscales of the original ASI and measures of general trait and social anxiety. During the social manipulation, results indicated the ASI-3 social concerns subscale and the social anxiety measure were significant predictors of anxious response. Results provide evidence that the ASI-3 is an improvement over the original ASI and is a sound overall measure of response to challenge procedures.

  12. 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...... suggest that sexual selection could help to understand this variation, since early spring arrival of males is favoured by female choice. Climate change could weaken the strength of natural selection opposing sexual selection for early migration, which would predict greatest advancement in species...... 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...

  13. PREDICTION OF SURFACE ROUGHNESS IN END MILLING OPERATION OF DUPLEX STAINLESS STEEL USING RESPONSE SURFACE METHODOLOGY

    Directory of Open Access Journals (Sweden)

    S. D. PHILIP

    2015-03-01

    Full Text Available Response surface methodology has been used to study the effects of the machining parameters such as spindle speed, feed rate and axial depth of cut on surface roughness of duplex stainless steel in end milling operation. Dry milling experiments were conducted with three levels of spindle speed, feed rate and axial depth of cut. A mathematical model has been developed to predict the surface roughness in terms of the machining parameters using Box-Behnken design response surface methodology. The adequacy of the model was verified using analysis of variance. The prediction equation shows that the feed rate is the most important factor that influences the surface roughness followed by axial depth of cut and spindle speed. The validity of the model was verified by conducting the confirmation experiment.

  14. Prediction of the Vibroacoustic Response of the Equipment Mounted on the Infrared Space Telescope "SPICA"

    Science.gov (United States)

    Akagi, Hiroki; Ando, Shigemasa; Shi, Qinzhong; Yamawaki, Toshiko

    2014-06-01

    The infrared space telescope "SPICA" (Space Infrared Telescope for Cosmology and Astrophysics) is a structurally-complex spacecraft, which requires the less conservative prediction of the random vibration at interface in order to reduce the over-margin issue for designing the strength on critical structure of optical instrument in the early stage of development, and to relieve the risk of overweight designing. This paper proposes Combination of FEA and SEA Methods to predict the vibroacoustic response of the equipment mounted on SPICA, and less conservative specification of the random vibration environments. Furthermore, a method of force-limiting to notch the specification over a certain frequency range during designing and a random vibration test is shown. Force-limiting specification is calculated using a simplified approach by multiplying the article's apparent mass to the equivalent of vibroacoustic response at interface.

  15. Nonrandom Acts of Kindness: Parasympathetic and Subjective Empathic Responses to Sadness Predict Children’s Prosociality

    Science.gov (United States)

    Miller, Jonas G.; Nuselovici, Jacob N.; Hastings, Paul D.

    2016-01-01

    How does empathic physiology unfold as a dynamic process, and which aspect of empathy predicts children’s kindness? In response to empathy induction videos, 4–6 year-old children (N = 180) showed an average pattern of dynamic respiratory sinus arrhythmia (RSA) change characterized by early RSA suppression followed by RSA recovery, and modest subsequent suppression during positive resolution of the empathic event. Children’s capacity for this pattern of flexible RSA change was associated with their subjective empathic feelings, which were concurrently associated with more sympathetic and prosocial responses to others. Conversely, only children’s dynamic RSA change longitudinally predicted prosocial behavior two years later. These findings have implications for understanding the dynamic and multifaceted nature of empathy, and its relation with prosocial development. PMID:28262932

  16. 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.

  17. Predicting responses to climate change requires all life-history stages.

    Science.gov (United States)

    Zeigler, Sara

    2013-01-01

    In Focus: Radchuk, V., Turlure, C. & Schtickzelle, N. (2013) Each life stage matters: the importance of assessing response to climate change over the complete life cycle in butterflies. Journal of Animal Ecology, 82, 275-285. Population-level responses to climate change depend on many factors, including unexpected interactions among life history attributes; however, few studies examine climate change impacts over complete life cycles of focal species. Radchuk, Turlure & Schtickzelle () used experimental and modelling approaches to predict population dynamics for the bog fritillary butterfly under warming scenarios. Although they found that warming improved fertility and survival of all stages with one exception, populations were predicted to decline because overwintering larvae, whose survival declined with warming, were disproportionately important contributors to population growth. This underscores the importance of considering all life history stages in analyses of climate change's effects on population dynamics. © 2012 The Authors. Journal of Animal Ecology © 2012 British Ecological Society.

  18. Unbalance Response Prediction for Accelerating Rotors With Load-Dependent Nonlinear Bearing Stiffness

    Science.gov (United States)

    Fleming, David P.; Sawicki, Jaezy T.; Poplawski, J. V.

    2005-01-01

    Rolling-element bearing forces vary nonlinearly with bearing deflection. Thus an accurate rotordynamic analysis requires that bearing forces corresponding to the actual bearing deflection be utilized. Previous papers have explored the transient effect of suddenly applied imbalance and the steady-state unbalance response, using bearing forces calculated by the rolling-element bearing analysis code COBRA-AHS. The present work considers the acceleration of a rotor through one or more critical speeds. The rotordynamic analysis showed that for rapid acceleration rates the maximum response amplitude may be considerably less than predicted by steady-state analysis. Above the critical speed, transient vibration at the rotor natural frequency occurs, similar to that predicted for a Jeffcott rotor with constant-stiffness bearings. A moderate amount of damping will markedly reduce the vibration amplitude, but this damping is not inherent in ball bearings.

  19. Discrimination of amygdala response predicts future separation anxiety in youth with early deprivation.

    Science.gov (United States)

    Green, Shulamite A; Goff, Bonnie; Gee, Dylan G; Gabard-Durnam, Laurel; Flannery, Jessica; Telzer, Eva H; Humphreys, Kathryn L; Louie, Jennifer; Tottenham, Nim

    2016-10-01

    Significant disruption in caregiving is associated with increased internalizing symptoms, most notably heightened separation anxiety symptoms during childhood. It is also associated with altered functional development of the amygdala, a neurobiological correlate of anxious behavior. However, much less is known about how functional alterations of amygdala predict individual differences in anxiety. Here, we probed amygdala function following institutional caregiving using very subtle social-affective stimuli (trustworthy and untrustworthy faces), which typically result in large differences in amygdala signal, and change in separation anxiety behaviors over a 2-year period. We hypothesized that the degree of differentiation of amygdala signal to trustworthy versus untrustworthy face stimuli would predict separation anxiety symptoms. Seventy-four youths mean (SD) age = 9.7 years (2.64) with and without previous institutional care, who were all living in families at the time of testing, participated in an fMRI task designed to examine differential amygdala response to trustworthy versus untrustworthy faces. Parents reported on their children's separation anxiety symptoms at the time of scan and again 2 years later. Previous institutional care was associated with diminished amygdala signal differences and behavioral differences to the contrast of untrustworthy and trustworthy faces. Diminished differentiation of these stimuli types predicted more severe separation anxiety symptoms 2 years later. Older age at adoption was associated with diminished differentiation of amygdala responses. A history of institutional care is associated with reduced differential amygdala responses to social-affective cues of trustworthiness that are typically exhibited by comparison samples. Individual differences in the degree of amygdala differential responding to these cues predict the severity of separation anxiety symptoms over a 2-year period. These findings provide a biological

  20. Applying Quantitative CT Image Feature Analysis to Predict Response of Ovarian Cancer Patients to Chemotherapy.

    Science.gov (United States)

    Danala, Gopichandh; Thai, Theresa; Gunderson, Camille C; Moxley, Katherine M; Moore, Kathleen; Mannel, Robert S; Liu, Hong; Zheng, Bin; Qiu, Yuchen

    2017-10-01

    The study aimed to investigate the role of applying quantitative image features computed from computed tomography (CT) images for early prediction of tumor response to chemotherapy in the clinical trials for treating ovarian cancer patients. A dataset involving 91 patients was retrospectively assembled. Each patient had two sets of pre- and post-therapy CT images. A computer-aided detection scheme was applied to segment metastatic tumors previously tracked by radiologists on CT images and computed image features. Two initial feature pools were built using image features computed from pre-therapy CT images only and image feature difference computed from both pre- and post-therapy images. A feature selection method was applied to select optimal features, and an equal-weighted fusion method was used to generate a new quantitative imaging marker from each pool to predict 6-month progression-free survival. The prediction accuracy between quantitative imaging markers and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria was also compared. The highest areas under the receiver operating characteristic curve are 0.684 ± 0.056 and 0.771 ± 0.050 when using a single image feature computed from pre-therapy CT images and feature difference computed from pre- and post-therapy CT images, respectively. Using two corresponding fusion-based image markers, the areas under the receiver operating characteristic curve significantly increased to 0.810 ± 0.045 and 0.829 ± 0.043 (P imaging markers and RECIST, respectively. This study demonstrated the feasibility of predicting patients' response to chemotherapy using quantitative imaging markers computed from pre-therapy CT images. However, using image feature difference computed between pre- and post-therapy CT images yielded higher prediction accuracy. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. Genetic Tests To Evaluate Prognosis and Predict Therapeutic Response in Acute Myeloid Leukemia

    OpenAIRE

    Gulley, Margaret L; Shea, Thomas C.; Fedoriw, Yuri

    2010-01-01

    Management of patients with acute myeloid leukemia relies on genetic tests that inform diagnosis and prognosis, predict response to therapy, and measure minimal residual disease. The value of genetics is reinforced in the revised 2008 World Health Organization acute myeloid leukemia classification scheme. The various analytic procedures—karyotype, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, DNA sequencing, and microarray technology—each have advantages...

  3. Fluconazole treatment of Candida albicans infection in mice: does in vitro susceptibility predict in vivo response?

    OpenAIRE

    Graybill, J R; Najvar, L K; Holmberg, J D; Correa, A.; Luther, M F

    1995-01-01

    A series of fluconazole-susceptible and-fluconazole resistant Candida albicans fungal isolates were used to infect mice intravenously. Mice were treated with varying doses of fluconazole beginning one day after infection. For all of the 6 fluconazole-susceptible isolates, fluconazole was highly effective at or = 40 mg/kg twice daily in 4 fluconazole-resistant isolates. Although the correlation is not precise, in vitro susceptibility testing of C. albicans can predict in vivo response to fluc...

  4. Abdominal electromyography may predict the response to tocolysis in preterm labor.

    Science.gov (United States)

    Kandil, Mohamed A; Abdel-Sattar, Mehany M; Abdel-Salam, Sherif M; Saleh, Saida; Khalafallah, Mohamed M

    2012-01-01

    To determine whether abdominal electromyography can predict the response to tocolysis in pregnant women in preterm labor. This study was carried out at the Department of Obstetrics and Gynecology, Menofyia University Hospital in Egypt. Fifty pregnant women in preterm labor who fulfilled the inclusion criteria were enrolled. Baseline abdominal electromyography was performed. Tocolysis in the form of hexoprenaline sulphate infusion was started for all women and electromyography was repeated after 24h in responders but only after 6h in non responders. The receiver operating characteristics curve was drawn to calculate specificity of the electromyography at 100% sensitivity. Results were tabulated and statistically analyzed. Forty women responded to tocolysis by delaying delivery for more than 48 h. There was a significant reduction in the frequency of uterine contractions after tocolysis (3.76 ± 0.92 versus 2.32 ± 2.05 contractions per 10 min; Pelectromyography of amplitude of 82 mV lasting for 30s or more had a specificity of 90%, positive and negative predictive values of 67% and 95%, and a diagnostic accuracy of 88% in predicting preterm labor. Abdominal electromyography may predict the response to tocolysis in preterm labor. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Assessment of Predictive Response Factors to Intragastric Balloon Therapy for the Treatment of Obesity.

    Science.gov (United States)

    Madeira, Eduardo; Madeira, Miguel; Guedes, Erika Paniago; Mafort, Thiago Thomaz; Neto, Leonardo Vieira; de Oliveira Moreira, Rodrigo; de Pinho, Paulo Roberto Alves; Lopes, Agnaldo José; Farias, Maria Lucia Fleiuss

    2016-03-01

    Obesity is a worldwide epidemic that is difficult to control with non-invasive treatments, which usually present poor results. In this context, the intragastric balloon (IGB) is an important tool that presents a mean body weight loss (BWL) estimated at approximately 12%, although individual responses are highly variable. This study assesses whether there are factors that can predict responses to IGB therapy either before or early after placement of the device. A total of 50 obese patients underwent insertion of IGB placed endoscopically, and patients were monitored for 6 months. The evaluated predictive factors involved general characteristics and psychological, social, and dyspeptic aspects, and the preliminary results obtained in the first month after balloon placement. The mean weight loss was 11.5%, and 48% of the participants presented BWL >10%. Among the factors analyzed before IGB placement, only advanced age (P = .04) and higher scores obtained in the social relationships domain of a shorter version of the World Health Organization's Quality of Life questionnaire (P = .02) were significant. Analysis of the factors evaluated after IGB placement revealed that the BWL amounts observed in week 2 (P = .001) and week 4 (P < .001) and the intensity of dyspeptic symptoms in week 2 (P < .001) were positive predictive factors. The assessment of predictive factors may help to manage patients with IGB.

  6. Algorithms to Improve the Prediction of Postprandial Insulinaemia in Response to Common Foods.

    Science.gov (United States)

    Bell, Kirstine J; Petocz, Peter; Colagiuri, Stephen; Brand-Miller, Jennie C

    2016-04-08

    Dietary patterns that induce excessive insulin secretion may contribute to worsening insulin resistance and beta-cell dysfunction. Our aim was to generate mathematical algorithms to improve the prediction of postprandial glycaemia and insulinaemia for foods of known nutrient composition, glycemic index (GI) and glycemic load (GL). We used an expanded database of food insulin index (FII) values generated by testing 1000 kJ portions of 147 common foods relative to a reference food in lean, young, healthy volunteers. Simple and multiple linear regression analyses were applied to validate previously generated equations for predicting insulinaemia, and develop improved predictive models. Large differences in insulinaemic responses within and between food groups were evident. GL, GI and available carbohydrate content were the strongest predictors of the FII, explaining 55%, 51% and 47% of variation respectively. Fat, protein and sugar were significant but relatively weak predictors, accounting for only 31%, 7% and 13% of the variation respectively. Nutritional composition alone explained only 50% of variability. The best algorithm included a measure of glycemic response, sugar and protein content and explained 78% of variation. Knowledge of the GI or glycaemic response to 1000 kJ portions together with nutrient composition therefore provides a good approximation for ranking of foods according to their "insulin demand".

  7. Psychic and somatic anxiety differentially predict response to light therapy in women with seasonal affective disorder.

    Science.gov (United States)

    MacKenzie, Bronwyn; Levitan, Robert D

    2005-10-01

    To examine whether psychic and/or somatic anxiety predict responsiveness to light therapy in women with winter Seasonal Affective Disorder (SAD). Eighty-one women with SAD were administered a standard 10-day trial of light therapy administered for one-half hour in the early morning. Using a multiple regression model, baseline somatic and psychic anxiety item scores were used to predict percentage change scores on the 29-item SIGH-SAD post treatment. Baseline scores for weight gain, hypersomnia and the total SIGH-SAD were also included as predictor variables. The regression model was highly significant (F=4.63, df=5,75; p=.001; model R(2)=.236), with both psychic anxiety and somatic anxiety contributing significantly to the model. Consistent with prior work using anti-depressant medication in non-seasonal depression, psychic anxiety was positively correlated with outcome, while somatic anxiety negatively predicted outcome. In SAD, psychic and somatic anxiety scores at baseline appear to be independent and opposite predictors of light therapy response. These effects were independent of baseline scores for weight gain and hypersomnia, two previously established predictors of response to light. These findings may be an important consideration in the design and interpretation of light therapy studies of SAD.

  8. Response-driven Imaging Biomarkers for Predicting Radiation Necrosis of the Brain

    Science.gov (United States)

    Nazem-Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-01-01

    Purpose Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy. Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Methods and Materials Twenty-nine patients with glioblastoma received six weeks of intensity modulated radiation therapy (RT) and concurrent temozolamide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Results Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p=0.05 and p=0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Conclusions Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid in predicting delayed radiation necrosis, which could provide guidance in dose-escalation trials. PMID:24778364

  9. Clinical application of fluctuation dissipation theory - Prediction of heart rate response to spontaneous breathing trial

    Science.gov (United States)

    Niestemski, Liang R.; Chen, Man; Prevost, Robert; McRae, Michael; Cholleti, Sharath; Najarro, Gabriel; Buchman, Timothy G.; Deem, Michael W.

    2013-03-01

    Contrary to the traditional view of the healthy physiological state as being a single static state, variation in physiologic variables has more recently been suggested to be a key component of the healthy state. Indeed, aging and disease are characterized by a loss of such variability. We apply the conceptual framework of fluctuation-dissipation theory (FDT) to predict the response to a common clinical intervention from historical fluctuations in physiologic time series data. The non-equilibrium FDT relates the response of a system to a perturbation to natural fluctuations in the stationary state of the system. We seek to understand with the FDT a common clinical perturbation, the spontaneous breathing trial (SBT), in which mechanical ventilation is briefly suspended while the patient breathes freely for a period of time. As a stress upon the heart of the patient, the SBT can be characterized as a perturbation of heart rate dynamics. A non-equilibrium, but steady-state FDT allows us to predict the heart rate recovery after the SBT stress. We show that the responses of groups of similar patients to the spontaneous breathing trial can be predicted by this approach. This mathematical framework may serve as part of the basis for personalized critical care.

  10. Prediction of metabolic and cardiopulmonary responses to maximum cycle ergometry: a randomised study.

    Science.gov (United States)

    Neder, J A; Nery, L E; Castelo, A; Andreoni, S; Lerario, M C; Sachs, A; Silva, A C; Whipp, B J

    1999-12-01

    All of the most widely-cited studies for the prediction of maximum exercise responses have utilized either volunteers or referred subjects. Therefore, selection bias, with overestimation of the reference values, is a likely consequence. In order to establish a set of predictive equations for the gas exchange, ventilatory and cardiovascular responses to maximum ramp-incremental cycle ergometry, this study prospectively evaluated 120 sedentary individuals (60 males, 60 females, aged 20-80), randomly-selected from >8,000 subjects. Regular physical activity pattern by questionnaire, body composition by anthropometry and dual energy X-ray absorptiometry (n = 75) and knee strength by isokinetic dynamometry were also assessed. Previously reported equations typically overestimated the subjects' peak oxygen uptake (p<0.05). Prediction linear equations for the main variables of clinical interest were established by backward stepwise regression analysis including: sex, age, knee extensor peak torque, bone-free lean leg mass, total and lean body mass, height, and physical activity scores. Reference intervals (95% confidence limits) were calculated: some of these values differed markedly from those formerly recommended. The results therefore might provide a more appropriate frame of reference for interpretation of the responses to symptom-limited ramp incremental cycle ergometry in sedentary subjects; i.e. those usually referred for clinical cardiopulmonary exercise tests.

  11. Algorithms to Improve the Prediction of Postprandial Insulinaemia in Response to Common Foods

    Directory of Open Access Journals (Sweden)

    Kirstine J. Bell

    2016-04-01

    Full Text Available Dietary patterns that induce excessive insulin secretion may contribute to worsening insulin resistance and beta-cell dysfunction. Our aim was to generate mathematical algorithms to improve the prediction of postprandial glycaemia and insulinaemia for foods of known nutrient composition, glycemic index (GI and glycemic load (GL. We used an expanded database of food insulin index (FII values generated by testing 1000 kJ portions of 147 common foods relative to a reference food in lean, young, healthy volunteers. Simple and multiple linear regression analyses were applied to validate previously generated equations for predicting insulinaemia, and develop improved predictive models. Large differences in insulinaemic responses within and between food groups were evident. GL, GI and available carbohydrate content were the strongest predictors of the FII, explaining 55%, 51% and 47% of variation respectively. Fat, protein and sugar were significant but relatively weak predictors, accounting for only 31%, 7% and 13% of the variation respectively. Nutritional composition alone explained only 50% of variability. The best algorithm included a measure of glycemic response, sugar and protein content and explained 78% of variation. Knowledge of the GI or glycaemic response to 1000 kJ portions together with nutrient composition therefore provides a good approximation for ranking of foods according to their “insulin demand”.

  12. 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

    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...

  13. Predicting placebo response in adolescents with major depressive disorder: The Adolescent Placebo Impact Composite Score (APICS).

    Science.gov (United States)

    Nakonezny, Paul A; Mayes, Taryn L; Byerly, Matthew J; Emslie, Graham J

    2015-09-01

    The aim of this study was to construct a composite scoring system to predict the probability of placebo response in adolescents with Major Depressive Disorder (MDD). Participants of the current study were 151 adolescents (aged 12-17 years) who were randomized to the placebo arm (placebo transdermal patches) of a randomized controlled trial (RCT) comparing the selegiline transdermal patch with placebo (DelBello et al., 2014). The primary outcome of response was defined as a CGI-I score of 1 or 2 (very much or much improved) at week 12 (study-end) or exit. As a first step, a multiple logistic mixed model was used to estimate the odds of placebo response from each predictor in the model, including age, CDRS-R total at baseline (depressive symptom severity), history of recurrent depression (yes vs. no), sex (female vs. male), and race (non-Caucasian vs. Caucasian). On the basis of the initial logistic mixed model analysis, we then constructed an Adolescent Placebo Impact Composite Score (APICS) that became the sole predictor in a re-specified Bayesian logistic regression model to estimate the probability of placebo response. Finally, the AUC for the APICS was tested against a nominal area of 0.50 to evaluate how well the APICS discriminated placebo response status. Among the 151 adolescents, with a mean age of 14.6 years (SD = 1.6) and a mean baseline CDRS-R total of 60.6 (SD = 12.1), 68.2% were females, 50.3% was Caucasian, and 39.7% had a history of recurrent depression. Placebo response rate was 58.3%. Based on the logistic mixed model, the re-specified equation with the highest discriminatory ability to estimate the probability of placebo response was APICS = age + (0.32 × CDRS-R Total at baseline) + (-2.85 × if female) + (-5.50 × if history of recurrent depression) + (-5.85 × if non-Caucasian). The AUC for this model was 0.59 (p = .049). Within a Bayesian decision-theoretic framework, in 95.5% of the time, the 10,000 posterior Monte Carlo samples suggested

  14. 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.

  15. 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. (c) 2016 APA, all rights reserved).

  16. Predicting in vivo responses to biomaterials via combined in vitro and in silico analysis.

    Science.gov (United States)

    Wolf, Matthew T; Vodovotz, Yoram; Tottey, Stephen; Brown, Bryan N; Badylak, Stephen F

    2015-02-01

    The host response to both synthetic and biologically derived biomaterials is a temporally regulated, complex process that involves multiple interacting cell types. This complexity has classically limited the efficacy of in vitro assays for predicting the in vivo outcome, necessitating the use of costly animal models for biomaterial development. The present study addressed these challenges by developing an in vitro assay that characterized the dynamic inflammatory response of human monocyte-derived-macrophages to biomaterials, coupled with quasi-mechanistic analysis in silico analysis: principal component analysis (PCA) and dynamic network analysis (DyNA). Synthetic and extracellular matrix (ECM)-derived materials were evaluated using this method, and were then associated with the in vivo remodeling and macrophage polarization response in a rodent skeletal muscle injury model. PCA and DyNA revealed a distinct in vitro macrophage response to ECM materials that corresponded to constructive remodeling and an increased M2 macrophage presence in vivo. In contrast, PCA and DyNA suggested a response to crosslinked ECM and synthetic materials characteristic of a foreign body reaction and dominant M1 macrophage response. These results suggest that in silico analysis of an in vitro macrophage assay may be useful as a predictor for determining the in vivo host response to implanted biomaterials.

  17. Personalized medicine in psoriasis: developing a genomic classifier to predict histological response to Alefacept

    Directory of Open Access Journals (Sweden)

    Haider Asifa S

    2010-02-01

    Full Text Available Abstract Background Alefacept treatment is highly effective in a select group patients with moderate-to-severe psoriasis, and is an ideal candidate to develop systems to predict who will respond to therapy. A clinical trial of 22 patients with moderate to severe psoriasis treated with alefacept was conducted in 2002-2003, as a mechanism of action study. Patients were classified as responders or non-responders to alefacept based on histological criteria. Results of the original mechanism of action study have been published. Peripheral blood was collected at the start of this clinical trial, and a prior analysis demonstrated that gene expression in PBMCs differed between responders and non-responders, however, the analysis performed could not be used to predict response. Methods Microarray data from PBMCs of 16 of these patients was analyzed to generate a treatment response classifier. We used a discriminant analysis method that performs sample classification from gene expression data, via "nearest shrunken centroid method". Centroids are the average gene expression for each gene in each class divided by the within-class standard deviation for that gene. Results A disease response classifier using 23 genes was created to accurately predict response to alefacept (12.3% error rate. While the genes in this classifier should be considered as a group, some of the individual genes are of great interest, for example, cAMP response element modulator (CREM, v-MAF avian musculoaponeurotic fibrosarcoma oncogene family (MAFF, chloride intracellular channel protein 1 (CLIC1, also called NCC27, NLR family, pyrin domain-containing 1 (NLRP1, and CCL5 (chemokine, cc motif, ligand 5, also called regulated upon activation, normally T expressed, and presumably secreted/RANTES. Conclusions Although this study is small, and based on analysis of existing microarray data, we demonstrate that a treatment response classifier for alefacept can be created using gene

  18. Quantitative CD3 PET Imaging Predicts Tumor Growth Response to Anti-CTLA-4 Therapy.

    Science.gov (United States)

    Larimer, Benjamin M; Wehrenberg-Klee, Eric; Caraballo, Alexander; Mahmood, Umar

    2016-10-01

    Immune checkpoint inhibitors have made rapid advances, resulting in multiple Food and Drug Administration-approved therapeutics that have markedly improved survival. However, these benefits are limited to a minority subpopulation that achieves a response. Predicting which patients are most likely to benefit would be valuable for individual therapy optimization. T-cell markers such as CD3-by examining active recruitment of the T cells responsible for cancer-cell death-represent a more direct approach to monitoring tumor immune response than pretreatment biopsy or genetic screening. This approach could be especially effective as numerous different therapeutic strategies emerge, decreasing the need for drug-specific biomarkers and instead focusing on T-cell infiltration, which has been previously correlated with treatment response. A CD3 PET imaging agent targeting T cells was synthesized to test the role of such imaging as a predictive marker. The (89)Zr-p-isothiocyanatobenzyl-deferoxamine-CD3 PET probe was assessed in a murine tumor xenograft model of anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) immunotherapy of colon cancer. Imaging on day 14 revealed 2 distinct groups of mice stratified by PET signal intensity. Although there was no significant difference in tumor volume on the day of imaging, in the high-uptake group subsequent measurements revealed significantly smaller tumors than in either the low-uptake group or the untreated controls. In contrast, there was no significant difference in the size of tumors between the low-uptake and untreated control mice. These findings indicate that high CD3 PET uptake in the anti-CTLA-4-treated mice correlated with subsequent reduced tumor volume and was a predictive biomarker of response. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  19. Alkaline phosphatase predicts response in polycystic liver disease during somatostatin analogue therapy: a pooled analysis.

    Science.gov (United States)

    Gevers, Tom J G; Nevens, Frederik; Torres, Vicente E; Hogan, Marie C; Drenth, Joost P H

    2016-04-01

    Somatostatin analogues reduce liver volumes in polycystic liver disease. However, patients show considerable variability in treatment responses. Our aim was to identify specific patient, disease or treatment characteristics that predict response in polycystic liver disease during somatostatin analogue therapy. We pooled the individual patient data of four trials that evaluated long-acting somatostatin analogues (120 mg lanreotide or 40 mg octreotide) for 6-12 months in polycystic liver disease patients. We performed uni- and multivariate linear regression analysis with preselected patient, disease and drug variables to identify independent predictors of response, defined as per cent change in liver or kidney volume (in ADPKD subgroup). All analyses were adjusted for baseline liver volume and centre. We included 153 polycystic liver disease patients (86% female, median liver volume 4974 ml) from three international centres, all treated with octreotide (n = 70) or lanreotide (n = 83). Mean reduction in liver volume was 4.4% (range -31.6 to +9.4%). Multivariate linear regression revealed that elevated baseline alkaline phosphatase was associated with increased liver volume reduction during therapy (-2.7%, 95% CI -5.1 to -0.2%, P = 0.04), independently of baseline liver volume. Somatostatin analogue type, underlying diagnosis and eGFR did not affect response. In our ADPKD subpopulation (n = 100), elevated alkaline phosphatase predicted liver volume reduction (-3.2%, P = 0.03) but did not predict kidney volume reduction (+0.1%, P = 0.97). Total gastro-intestinal symptom severity decreased with therapy in a subgroup analysis (n = 95; P Alkaline phosphatase is a liver-specific, independent predictor of response in polycystic liver disease during somatostatin analogue therapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Prediction of response to neoadjuvant chemotherapy in breast cancer: a radiomic study

    Science.gov (United States)

    Wu, Guolin; Fan, Ming; Zhang, Juan; Zheng, Bin; Li, Lihua

    2017-03-01

    Breast cancer is one of the most malignancies among women in worldwide. Neoadjuvant Chemotherapy (NACT) has gained interest and is increasingly used in treatment of breast cancer in recent years. Therefore, it is necessary to find a reliable non-invasive assessment and prediction method which can evaluate and predict the response of NACT. Recent studies have highlighted the use of MRI for predicting response to NACT. In addition, molecular subtype could also effectively identify patients who are likely have better prognosis in breast cancer. In this study, a radiomic analysis were performed, by extracting features from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and immunohistochemistry (IHC) to determine subtypes. A dataset with fifty-seven breast cancer patients were included, all of them received preoperative MRI examination. Among them, 47 patients had complete response (CR) or partial response (PR) and 10 had stable disease (SD) to chemotherapy based on the RECIST criterion. A total of 216 imaging features including statistical characteristics, morphology, texture and dynamic enhancement were extracted from DCE-MRI. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.923 (P = 0.0002) in leave-one-out crossvalidation. The performance of the classifier increased to 0.960, 0.950 and 0.936 when status of HER2, Luminal A and Luminal B subtypes were added into the statistic model, respectively. The results of this study demonstrated that IHC determined molecular status combined with radiomic features from DCE-MRI could be used as clinical marker that is associated with response to NACT.

  1. Predicting ecological responses in a changing ocean: the effects of future climate uncertainty.

    Science.gov (United States)

    Freer, Jennifer J; Partridge, Julian C; Tarling, Geraint A; Collins, Martin A; Genner, Martin J

    2018-01-01

    Predicting how species will respond to climate change is a growing field in marine ecology, yet knowledge of how to incorporate the uncertainty from future climate data into these predictions remains a significant challenge. To help overcome it, this review separates climate uncertainty into its three components (scenario uncertainty, model uncertainty, and internal model variability) and identifies four criteria that constitute a thorough interpretation of an ecological response to climate change in relation to these parts (awareness, access, incorporation, communication). Through a literature review, the extent to which the marine ecology community has addressed these criteria in their predictions was assessed. Despite a high awareness of climate uncertainty, articles favoured the most severe emission scenario, and only a subset of climate models were used as input into ecological analyses. In the case of sea surface temperature, these models can have projections unrepresentative against a larger ensemble mean. Moreover, 91% of studies failed to incorporate the internal variability of a climate model into results. We explored the influence that the choice of emission scenario, climate model, and model realisation can have when predicting the future distribution of the pelagic fish, Electrona antarctica. Future distributions were highly influenced by the choice of climate model, and in some cases, internal variability was important in determining the direction and severity of the distribution change. Increased clarity and availability of processed climate data would facilitate more comprehensive explorations of climate uncertainty, and increase in the quality and standard of marine prediction studies.

  2. Predicting photosynthesis and transpiration responses to ozone: decoupling modeled photosynthesis and stomatal conductance

    Directory of Open Access Journals (Sweden)

    D. Lombardozzi

    2012-08-01

    Full Text Available Plants exchange greenhouse gases carbon dioxide and water with the atmosphere through the processes of photosynthesis and transpiration, making them essential in climate regulation. Carbon dioxide and water exchange are typically coupled through the control of stomatal conductance, and the parameterization in many models often predict conductance based on photosynthesis values. Some environmental conditions, like exposure to high ozone (O3 concentrations, alter photosynthesis independent of stomatal conductance, so models that couple these processes cannot accurately predict both. The goals of this study were to test direct and indirect photosynthesis and stomatal conductance modifications based on O3 damage to tulip poplar (Liriodendron tulipifera in a coupled Farquhar/Ball-Berry model. The same modifications were then tested in the Community Land Model (CLM to determine the impacts on gross primary productivity (GPP and transpiration at a constant O3 concentration of 100 parts per billion (ppb. Modifying the Vcmax parameter and directly modifying stomatal conductance best predicts photosynthesis and stomatal conductance responses to chronic O3 over a range of environmental conditions. On a global scale, directly modifying conductance reduces the effect of O3 on both transpiration and GPP compared to indirectly modifying conductance, particularly in the tropics. The results of this study suggest that independently modifying stomatal conductance can improve the ability of models to predict hydrologic cycling, and therefore improve future climate predictions.

  3. Coupling of EIT with computational lung modeling for predicting patient-specific ventilatory responses.

    Science.gov (United States)

    Roth, Christian J; Becher, Tobias; Frerichs, Inéz; Weiler, Norbert; Wall, Wolfgang A

    2017-04-01

    Providing optimal personalized mechanical ventilation for patients with acute or chronic respiratory failure is still a challenge within a clinical setting for each case anew. In this article, we integrate electrical impedance tomography (EIT) monitoring into a powerful patient-specific computational lung model to create an approach for personalizing protective ventilatory treatment. The underlying computational lung model is based on a single computed tomography scan and able to predict global airflow quantities, as well as local tissue aeration and strains for any ventilation maneuver. For validation, a novel "virtual EIT" module is added to our computational lung model, allowing to simulate EIT images based on the patient's thorax geometry and the results of our numerically predicted tissue aeration. Clinically measured EIT images are not used to calibrate the computational model. Thus they provide an independent method to validate the computational predictions at high temporal resolution. The performance of this coupling approach has been tested in an example patient with acute respiratory distress syndrome. The method shows good agreement between computationally predicted and clinically measured airflow data and EIT images. These results imply that the proposed framework can be used for numerical prediction of patient-specific responses to certain therapeutic measures before applying them to an actual patient. In the long run, definition of patient-specific optimal ventilation protocols might be assisted by computational modeling.NEW & NOTEWORTHY In this work, we present a patient-specific computational lung model that is able to predict global and local ventilatory quantities for a given patient and any selected ventilation protocol. For the first time, such a predictive lung model is equipped with a virtual electrical impedance tomography module allowing real-time validation of the computed results with the patient measurements. First promising results

  4. Authoritarian parenting predicts reduced electrocortical response to observed adolescent offspring rewards.

    Science.gov (United States)

    Levinson, Amanda R; Speed, Brittany C; Nelson, Brady; Bress, Jennifer N; Hajcak, Greg

    2017-03-01

    Parenting styles are robust predictors of offspring outcomes, yet little is known about their neural underpinnings. In this study, 44 parent-adolescent dyads (Mage of adolescent = 12.9) completed a laboratory guessing task while EEG was continuously recorded. In the task, each pair member received feedback about their own monetary wins and losses and also observed the monetary wins and losses of the other member of the pair. We examined the association between self-reported parenting style and parents' electrophysiological responses to watching their adolescent winning and losing money, dubbed the observational Reward Positivity (RewP) and observational feedback negativity (FN), respectively. Self-reported authoritarian parenting predicted reductions in parents' observational RewP but not FN. This predictive relationship remained after adjusting for sex of both participants, parents' responsiveness to their own wins, and parental psychopathology. 'Exploratory analyses found that permissive parenting was associated with a blunting of the adolescents' response to their parents' losses'. These findings suggest that parents' rapid neural responses to their child's successes may relate to the harsh parenting behaviors associated with authoritarian parenting. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  5. Early prediction of long-term response to cabergoline in patients with macroprolactinomas.

    Science.gov (United States)

    Lee, Youngki; Ku, Cheol Ryong; Kim, Eui-Hyun; Hong, Jae Won; Lee, Eun Jig; Kim, Sun Ho

    2014-09-01

    Cabergoline 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. We 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. Forty 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 cabergoline (β=-1.181 mg/week), and two of four patients who underwent surgery were able to discontinue cabergoline. Determining cabergoline response using TVR and NP 3 months after treatment is useful for predicting later outcomes. However, further cabergoline administration should be considered for 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.

  6. 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.

  7. Autonomy support and responsibility-sharing predict blood glucose monitoring frequency among youth with diabetes.

    Science.gov (United States)

    Wu, Yelena P; Rausch, Joseph; Rohan, Jennifer M; Hood, Korey K; Pendley, Jennifer S; Delamater, Alan; Drotar, Dennis

    2014-10-01

    Adolescence poses a number of special challenges for youth and their families managing the Type 1 diabetes medical regimen. Little is known on how family and youth factors and management of the regimen change over the course of early adolescence and predict adherence to the regimen during this developmental period. Youth with Type 1 diabetes (n = 239) and their maternal caregivers completed measures of diabetes-specific autonomy support, diabetes-related family conflict, regimen responsibility, and blood glucose monitoring frequency (BGMF) at 4 timepoints over a 3-year period. Autonomy support and BGMF significantly decreased over time and responsibility for the diabetes regimen shifted from the caregiver toward youth over time. Significant changes in perceived family conflict over time differed depending on the reporter. Baseline BGMF, changes in caregiver autonomy support, and changes in responsibility for the regimen significantly predicted changes in BGMF over time. This study documents changes in autonomy support, youth responsibility for the diabetes regimen, and BGMF during the transition into early adolescence. Higher levels of caregiver autonomy support preserve BGMF during a developmental period in which BGMF typically deteriorates.

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

    Science.gov (United States)

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

    2010-01-01

    AIM: To investigate whether intra-procedural diffusion-weighted magnetic resonance imaging can predict response of hepatocellular carcinoma (HCC) during transcatheter 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. Anatomical imaging and diffusion-weighted imaging (b = 0, 500 s/mm2) were performed on a 1.5-T unit. Tumor enhancement and apparent diffusion coefficient (ADC, mm2/s) values were assessed immediately before and at 1 and 3 mo after TACE. We calculated the percent change (PC) in ADC values at all time points. We compared follow-up ADC values to baseline values using a paired t test (α = 0.05). RESULTS: The intra-procedural sensitivity, specificity, and positive and negative predictive values (%) for detecting a complete or partial 1-mo tumor response using ADC PC thresholds of ±5%, ±10%, and ±15% were 77, 67, 91, and 40; 54, 67, 88, and 25; and 46, 100, 100, and 30, respectively. There was no clear predictive value for the 3-mo follow-up. Compared to baseline, the immediate post-procedure and 1-mo mean ADC values both increased; the latter obtaining statistical significance (1.48 ± 0.29 mm2/s vs 1.65 ± 0.35 × 10-3 mm2/s, P 15% predicted 1-mo anatomical HCC response with the greatest accuracy, and can provide valuable feedback at the time of TACE. PMID:20593501

  9. 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.

  10. 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.

  11. Species' traits help predict small mammal responses to habitat homogenization by an invasive grass.

    Science.gov (United States)

    Ceradini, Joseph P; Chalfoun, Anna D

    2017-07-01

    Invasive plants can negatively affect native species, however, the strength, direction, and shape of responses may vary depending on the type of habitat alteration and the natural history of native species. To prioritize conservation of vulnerable species, it is therefore critical to effectively predict species' responses to invasive plants, which may be facilitated by a framework based on species' traits. We studied the population and community responses of small mammals and changes in habitat heterogeneity across a gradient of cheatgrass (Bromus tectorum) cover, a widespread invasive plant in North America. We live-trapped small mammals over two summers and assessed the effect of cheatgrass on native small mammal abundance, richness, and species-specific and trait-based occupancy, while accounting for detection probability and other key habitat elements. Abundance was only estimated for the most common species, deer mice (Peromyscus maniculatus). All species were pooled for the trait-based occupancy analysis to quantify the ability of small mammal traits (habitat association, mode of locomotion, and diet) to predict responses to cheatgrass invasion. Habitat heterogeneity decreased with cheatgrass cover. Deer mouse abundance increased marginally with cheatgrass. Species richness did not vary with cheatgrass, however, pocket mouse (Perognathus spp.) and harvest mouse (Reithrodontomys spp.) occupancy tended to decrease and increase, respectively, with cheatgrass cover, suggesting a shift in community composition. Cheatgrass had little effect on occupancy for deer mice, 13-lined ground squirrels (Spermophilus tridecemlineatus), and Ord's kangaroo rat (Dipodomys ordii). Species' responses to cheatgrass primarily corresponded with our a priori predictions based on species' traits. The probability of occupancy varied significantly with a species' habitat association but not with diet or mode of locomotion. When considered within the context of a rapid habitat change

  12. Species’ traits help predict small mammal responses to habitat homogenization by an invasive grass

    Science.gov (United States)

    Ceradini, Joseph P.; Chalfoun, Anna

    2017-01-01

    Invasive plants can negatively affect native species, however, the strength, direction, and shape of responses may vary depending on the type of habitat alteration and the natural history of native species. To prioritize conservation of vulnerable species, it is therefore critical to effectively predict species’ responses to invasive plants, which may be facilitated by a framework based on species’ traits. We studied the population and community responses of small mammals and changes in habitat heterogeneity across a gradient of cheatgrass (Bromus tectorum) cover, a widespread invasive plant in North America. We live-trapped small mammals over two summers and assessed the effect of cheatgrass on native small mammal abundance, richness, and species-specific and trait-based occupancy, while accounting for detection probability and other key habitat elements. Abundance was only estimated for the most common species, deer mice (Peromyscus maniculatus). All species were pooled for the trait-based occupancy analysis to quantify the ability of small mammal traits (habitat association, mode of locomotion, and diet) to predict responses to cheatgrass invasion. Habitat heterogeneity decreased with cheatgrass cover. Deer mouse abundance increased marginally with cheatgrass. Species richness did not vary with cheatgrass, however, pocket mouse (Perognathus spp.) and harvest mouse (Reithrodontomys spp.) occupancy tended to decrease and increase, respectively, with cheatgrass cover, suggesting a shift in community composition. Cheatgrass had little effect on occupancy for deer mice, 13-lined ground squirrels (Spermophilus tridecemlineatus), and Ord's kangaroo rat (Dipodomys ordii). Species’ responses to cheatgrass primarily corresponded with our a priori predictions based on species’ traits. The probability of occupancy varied significantly with a species’ habitat association but not with diet or mode of locomotion. When considered within the context of a rapid

  13. Predicting Mountainous Watershed Biogeochemical Dynamics, Including Response to Droughts and Early Snowmelt

    Science.gov (United States)

    Hubbard, S. S.; Williams, K. H.; Long, P.; Agarwal, D.; Banfield, J. F.; Beller, H. R.; Bouskill, N.; Brodie, E.; Maxwell, R. M.; Nico, P. S.; Steefel, C. I.; Steltzer, H.; Tokunaga, T. K.; Wainwright, H. M.

    2016-12-01

    Climate change, extreme weather, land-use change, and other perturbations are significantly reshaping interactions with in watersheds throughout the world. While mountainous watersheds are recognized as the water towers for the world, hydrological processes in watersheds also mediate biogeochemical processes that support all terrestrial life. Developing predictive understanding of watershed hydrological and biogeochemical functioning is challenging, as complex interactions occurring within a heterogeneous watershed can lead to a cascade of effects on downstream water availability and quality. Although these interactions can have significant implications for energy production, agriculture, water quality, and other benefits valued by society, uncertainty associated with predicting watershed function is high. The Watershed Function project aims to substantially reduce this uncertainty through developing a predictive understanding of how mountainous watersheds retain and release downgradient water, nutrients, carbon, and metals. In particular, the project is exploring how early snowmelt, drought, and other disturbances will influence mountainous watershed dynamics at seasonal to decadal timescales. The Watershed Function project is being carried out in a headwater mountainous catchment of the Upper Colorado River Basin, within a watershed characterized by significant gradients in elevation, vegetation and hydrogeology. A system-within system project perspective posits that the integrated watershed response to disturbances can be adequately predicted through consideration of interactions and feedbacks occurring within a limited number of subsystems, each having distinct vegetation-subsurface biogeochemical-hydrological characteristics. A key technological goal is the development of scale-adaptive simulation capabilities that can incorporate genomic information where and when it is useful for predicting the overall watershed response to disturbance. Through developing

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

    Science.gov (United States)

    2010-01-01

    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 anxiety and a high TAS score, predict a good response to hypnotherapy. PMID:21138549

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

    Science.gov (United States)

    Carruthers, Helen R; Morris, Julie; Tarrier, Nicholas; Whorwell, Peter J

    2010-12-07

    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. 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. 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 anxiety and a high TAS score, predict a good response to hypnotherapy.

  16. 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.

  17. Clinical Examination Does Not Predict Response to Albuterol in Ventilated Infants With Bronchiolitis.

    Science.gov (United States)

    Schramm, Craig M; Sala, Kathleen A; Carroll, Christopher L

    2017-01-01

    Bronchiolitis is a common respiratory infection in infants that is sometimes treated with albuterol. Response to albuterol is determined by clinical assessment, but this subjective determination is potentially unreliable. In this study, we compared providers' clinical assessment of response to albuterol with the measurement of response by pulmonary mechanics in intubated, sedated, and ventilated infants. Before and 20 minutes following racemic albuterol therapy, a nurse, respiratory therapist, and physician performed simultaneous examinations and assessed response to albuterol in a population of intubated infants with bronchiolitis. Measurements of ventilator-derived pulmonary mechanics were obtained at these same times. This study was conducted in a PICU of a children's hospital. Seventy-five paired clinical assessments were made in 25 infants who were intubated and mechanically ventilated for severe bronchiolitis. Pulmonary function measurements and clinical assessments before and after administration of albuterol. Response to albuterol was defined using a threshold of improvement in respiratory system resistance from baseline. Nine children (36%) had greater than 20% change and were deemed responders. Providers' discrimination of response was poor. The positive predictive values of nurses, respiratory therapists, and physicians were 38%, 25%, and 25%, respectively, and the negative predictive values were 67%, 54%, and 59%, respectively. Overall accuracy was 44% for nurses, 40% for respiratory therapists, and 48% for physicians. When comparing separate assessments of wheezing, aeration, and expiratory time, there was poor agreement between groups of providers in all variables (κ bronchiolitis. Without assessment of pulmonary mechanics, caution should be used in classifying children with bronchiolitis as responders to albuterol.

  18. 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.

  19. Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times.

    Science.gov (United States)

    Memon, Khairuddin; Kulik, Laura; Lewandowski, Robert J; Wang, Edward; Riaz, Ahsun; Ryu, Robert K; Sato, Kent T; Marshall, Karen; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Senthilnathan, Seanthan; Baker, Talia; Gates, Vanessa L; Abecassis, Michael; Benson, Al B; Mulcahy, Mary F; Omary, Reed A; Salem, Riad

    2011-08-01

    It is not clear whether survival times of patients with hepatocellular carcinoma (HCC) are associated with their response to therapy. We analyzed the association between tumor response and survival times of patients with HCC who were treated with locoregional therapies (LRTs) (chemoembolization and radioembolization). Patients received LRTs over a 9-year period (n = 463). Patients with metastases, portal venous thrombosis, or who had received transplants were excluded; 159 patients with Child-Pugh B7 or lower were analyzed. Response (based on European Association for the Study of the Liver [EASL] and World Health Organization [WHO] criteria) was associated with survival times using the landmark, risk-of-death, and Mantel-Byar methodologies. In a subanalysis, survival times of responders were compared with those of patients with stable disease and progressive disease. Based on 6-month data, in landmark analysis, responders survived longer than nonresponders (based on EASL but not WHO criteria: P = .002 and .0694). The risk of death was also lower for responders (based on EASL but not WHO criteria: P = .0463 and .707). Landmark analysis of 12-month data showed that responders survived longer than nonresponders (P < .0001 and .004, based on EASL and WHO criteria, respectively). The risk of death was lower for responders (P = .0132 and .010, based on EASL and WHO criteria, respectively). By the Mantel-Byar method, responders had longer survival than nonresponders, based on EASL criteria (P < .0001; P = .596 with WHO criteria). In the subanalysis, responders lived longer than patients with stable disease or progressive disease. Radiographic response to LRTs predicts survival time. EASL criteria for response more consistently predicted survival times than WHO criteria. The goal of LRT should be to achieve a radiologic response, rather than to stabilize disease. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. Neoadjuvant palbociclib on ER+ breast cancer (N007): clinical response and EndoPredict value.

    Science.gov (United States)

    Chow, Louis Wc; Morita, Satoshi; Chow, Christopher Yc; Ng, Wai Kuen; Toi, Masakazu

    2017-11-20

    To test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2-ve invasive breast cancer, 2cm or greater, were enrolled in an open-label, single arm study. Twenty eligible patients were given letrozole 2.5mg per day together with palbociclib 125mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery. The primary end-points were clinical response rates (cRR) and preoperative endocrine prognostic index (PEPI). The secondary end-points were pathologic response and gene expression testing with EP test on collected tumor samples. 17 patients showed a clinical response of 50% or more, including 8 complete response and 9 partial response. There was significant reduction in area (Ppalbociclib treatment. 6 patients with intermediate and three patients with high PEPI risk scores were found to have low EPclin scores. All patients with high PEPI relapse risk score had high EPclin score. Effective clinical response was demonstrated by neoadjuvant letrozole in combination with palbociclib. Compared with PEPI, EPclin might be a better parameter to estimate prognosis after neoadjuvant therapy.

  1. 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).

  2. 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

  3. Lack of Furosemide Responsiveness Predicts Acute Kidney Injury in Infants After Cardiac Surgery.

    Science.gov (United States)

    Kakajiwala, Aadil; Kim, Ji Young; Hughes, John Z; Costarino, Andrew; Ferguson, John; Gaynor, J William; Furth, Susan L; Blinder, Joshua J

    2017-10-01

    This was a retrospective study to determine whether lack of furosemide responsiveness (LFR) predicts acute kidney injury (AKI) after cardiopulmonary bypass surgery in infants. Infants (less than 1 year of age) undergoing cardiopulmonary bypass surgery, receiving routine postoperative furosemide (0.8 to 1.2 mg/kg per dose between 8 and 24 hours after surgery) were included. Urine output was measured 2 and 6 hours after furosemide dose. Lack of furosemide responsiveness was defined a priori as urine output less than 1 mL · kg -1 · h -1 after furosemide. Serum creatinine was corrected for fluid balance. Acute kidney injury was determined using changes in uncorrected and corrected serum creatinine. The predictive utility of LFR was assessed using receiver-operating characteristics curve analysis. We analyzed 568 infants who underwent cardiopulmonary bypass. Eighty-one (14.3%) had AKI using uncorrected serum creatinine; AKI occurred in 41 (7.2%) after correcting for fluid overload. Patients with AKI had a lower response to furosemide (median urine output 2 hours: 1.2 versus 3.4 mL · kg -1 · h -1 , p = 0.01; median urine output 6 hours: 1.3 versus 2.9 mL · kg -1 · h -1 , p = 0.01). After creatinine correction, LFR predicts AKI development (area under receiver-operating characteristics curve of 0.74 at 2 hours and 0.77 at 6 hours). After adjusting for surgical complexity using The Society of Thoracic Surgeons/European Association for Cardiothoracic Surgery mortality categories, the area under the receiver-operating characteristics curve was 0.74 at 2 hours and 0.81 at 6 hours. Patients with urine output greater than 1 mL · kg -1 · h -1 were unlikely to have AKI (negative predictive value, 97%). After correcting serum creatinine for fluid balance and adjusting for surgical complexity, LFR performs fairly at 2 hours, whereas at 6 hours, LFR is a good AKI predictor. Prospective studies are needed to validate whether diuretic responsiveness predicts AKI. Copyright

  4. Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.

    Science.gov (United States)

    Pompas-Veganzones, N; Sandonis, V; Perez-Lanzac, Alberto; Beltran, M; Beardo, P; Juárez, A; Vazquez, F; Cozar, J M; Alvarez-Ossorio, J L; Sanchez-Carbayo, Marta

    2016-10-01

    Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed

  5. Cone-beam computed tomography in lung stereotactic ablative radiation therapy: predictive parameters of early response.

    Science.gov (United States)

    Mazzola, Rosario; Fiorentino, Alba; Ricchetti, Francesco; Giaj Levra, Niccolò; Fersino, Sergio; Di Paola, Gioacchino; Lo Casto, Antonio; Ruggieri, Ruggero; Alongi, Filippo

    2016-06-20

    To analyze lung lesion volume variations by contouring on cone-beam CT (CBCT) images to evaluate the early predictive parameters of stereotactic ablative radiation therapy (SABR) treatment response. The prescribed dose of SABR was varied according to the tumour site (central or peripheral) and maximum diameter of the lesions by using a strategy of risk-adapted dose prescription with a dose range between 48 and 70 Gy in 3-10 consecutive fractions. For the purpose of the analysis, the gross tumour volume (GTV) was recontoured for each patient at first and last CBCT using two lung levels/windows: (a) -600/1000 HU and (b) -1000/250 HU. Univariate analysis was performed to evaluate a correlation between lung lesion variations on CBCT using the two levels/windows and treatment response 6 months after SABR. Independent variables were the number of fractions, time between initial and final fraction, biologically effective dose and pre-SABR GTV. Cut points of lesion volume reduction were evaluated to determine the correlation with complete response 6 months after SABR. 41 lung lesions were evaluated. 82 lung lesions were recontoured for each CBCT level/window. A lung lesion shrinkage of at least 20% was revealed to be statistically related to complete response 6 months after SABR for both the CBCT levels/windows used. The probability of complete response ranged between six and eight times higher in respect to CBCT levels/windows -600/1000 HU and -1000/250 HU, respectively, compared with patients without a lesion shrinkage of 20% at the last session of SABR. According to current findings, a lung lesion shrinkage of at least 20% at the last session of SABR could be predictable of complete response 6 months thereafter. Further investigations about this topic are needed. Prediction of the early tumour response could be useful to personalize imaging restaging after the completion of SABR or to incorporate additional therapies in case of poor responders to improve

  6. A dynamic eco-evolutionary model predicts slow response of alpine plants to climate warming.

    Science.gov (United States)

    Cotto, Olivier; Wessely, Johannes; Georges, Damien; Klonner, Günther; Schmid, Max; Dullinger, Stefan; Thuiller, Wilfried; Guillaume, Frédéric

    2017-05-05

    Withstanding extinction while facing rapid climate change depends on a species' ability to track its ecological niche or to evolve a new one. Current methods that predict climate-driven species' range shifts use ecological modelling without eco-evolutionary dynamics. Here we present an eco-evolutionary forecasting framework that combines niche modelling with individual-based demographic and genetic simulations. Applying our approach to four endemic perennial plant species of the Austrian Alps, we show that accounting for eco-evolutionary dynamics when predicting species' responses to climate change is crucial. Perennial species persist in unsuitable habitats longer than predicted by niche modelling, causing delayed range losses; however, their evolutionary responses are constrained because long-lived adults produce increasingly maladapted offspring. Decreasing population size due to maladaptation occurs faster than the contraction of the species range, especially for the most abundant species. Monitoring of species' local abundance rather than their range may likely better inform on species' extinction risks under climate change.

  7. Prediction of Vertical-Plane Wave Loading and Ship Responses in High Seas

    DEFF Research Database (Denmark)

    Wang, Zhaohui; Xia, Jinzhu; Jensen, Jørgen Juncher

    2000-01-01

    The non-linearities in wave- and slamming-induced rigid-body motions and structural responses of ships such as heave, pitch and vertical bending moments are consistently investigated based on a rational time-domain strip method. A hydrodynamic model for predicting sectional green water force is a...... for a VLCC. The non-linearities in motions and structural loads of conventional monohull ships seem well predicted by the present non-linear strip theory.......The non-linearities in wave- and slamming-induced rigid-body motions and structural responses of ships such as heave, pitch and vertical bending moments are consistently investigated based on a rational time-domain strip method. A hydrodynamic model for predicting sectional green water force...... is also outlined for the investigation of the effect of green watrer oads on the globalhull girder bending moment. The computational results based on the non-linear time-domain strip theory are compared with those based on the fully non-linear 3-D panel method SWAN-DNW and other published results...

  8. 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

  9. Predictive Computational Modeling of the Mucosal Immune Responses during Helicobacter pylori Infection

    Science.gov (United States)

    Carbo, Adria; Bassaganya-Riera, Josep; Pedragosa, Mireia; Viladomiu, Monica; Marathe, Madhav; Eubank, Stephen; Wendelsdorf, Katherine; Bisset, Keith; Hoops, Stefan; Deng, Xinwei; Alam, Maksudul; Kronsteiner, Barbara; Mei, Yongguo; Hontecillas, Raquel

    2013-01-01

    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 characterized the

  10. Combining Prognostic and Predictive Enrichment Strategies to Identify Children With Septic Shock Responsive to Corticosteroids.

    Science.gov (United States)

    Wong, Hector R; Atkinson, Sarah J; Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie C; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Raj, Shekhar S; Gertz, Shira; Lindsell, Christopher J

    2016-10-01

    Prognostic and predictive enrichment strategies are fundamental tools of precision medicine. Identifying children with septic shock who may benefit from corticosteroids remains a challenge. We combined prognostic and predictive strategies to identify a pediatric septic shock subgroup responsive to corticosteroids. We conducted a secondary analysis of 288 previously published pediatric subjects with septic shock. For prognostic enrichment, each study subject was assigned a baseline mortality probability using the pediatric sepsis biomarker risk model. For predictive enrichment, each study subject was allocated to one of two septic shock endotypes, based on a 100-gene signature reflecting adaptive immunity and glucocorticoid receptor signaling. The primary study endpoint was complicated course, defined as the persistence of two or more organ failures at day 7 of septic shock or 28-day mortality. We used logistic regression to test for an association between corticosteroids and complicated course within endotype. Among endotype B subjects at intermediate to high pediatric sepsis biomarker risk model-based risk of mortality, corticosteroids were independently associated with more than a 10-fold reduction in the risk of a complicated course (relative risk, 0.09; 95% CI, 0.01-0.54; p = 0.007). A combination of prognostic and predictive strategies based on serum protein and messenger RNA biomarkers can identify a subgroup of children with septic shock who may be more likely to benefit from corticosteroids. Prospective validation of these strategies and the existence of this subgroup are warranted.

  11. 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.

  12. Does stress reactivity or response to amphetamine predict smoking progression in young adults? A preliminary study.

    Science.gov (United States)

    de Wit, Harriet; Vicini, Lisa; Childs, Emma; Sayla, Maliha A; Terner, Jolan

    2007-02-01

    Recent studies with laboratory animals indicate that a constellation of behavioral factors predict progression to self-administer drugs. Relatively little is known about behavioral or biological factors that predict the progression in drug use from initial experimentation to regular use in human drug users. The present exploratory study examined reactivity to an acute stressor and reactivity to a single dose of a dopaminergic drug as predictors in progression to heavier smoking in young cigarette smokers over a 6-month period. Forty-four college students who were light to moderate smokers participated in three laboratory sessions, followed by a follow-up interview 6 months later to determine smoking level. On one of the laboratory sessions subjects underwent the Trier Social Stress Test, and on the others they ingested capsules containing placebo or 20 mg D-amphetamine. Outcome measures included subjective ratings of mood and measures of heart rate and salivary cortisol. We found modest positive relationships between stress reactivity and certain responses to amphetamine. Further, stress-induced increases in cortisol were positively related to increases in cigarette smoking in the 31 subjects who we were able to contact at 6 months. Although these results are highly preliminary, they resemble the relationships previously reported in laboratory animals, suggesting that some of the same factors that predict drug-self-administration in rodents predict progression in drug use among young adults.

  13. Types of parent verbal responsiveness that predict language in young children with autism spectrum disorder.

    Science.gov (United States)

    McDuffie, Andrea; Yoder, Paul

    2010-08-01

    This study examined short-term predictive associations between 5 different types of parent verbal responsiveness and later spoken vocabulary for 32 young children with a confirmed diagnosis of autism spectrum disorder (ASD). Parent verbal utterances were coded from videotapes of naturalistic parent-child play sessions using interval and event-based coding. A vocabulary difference score, calculated using the MacArthur Communicative Development Inventories (L. Fenson et al., 1993), was used as the outcome measure of spoken vocabulary 6 months later. Parent follow-in comments and follow-in directives predicted spoken vocabulary after controlling for child engagement. Parent expansions of child verbal utterances predicted spoken vocabulary after controlling for child talkativeness. When entered together into a regression analysis, metrics that represented (a) the number of parent utterances following into the child's focus of attention and (b) the number of parent utterances responding to child verbal communication acts both accounted for unique variance in predicting change in spoken vocabulary from Time 1 to Time 2. Parent verbal utterances that follow into the child's current focus of attention or respond to child verbal communication acts may facilitate the process of early vocabulary acquisition by mitigating the need for children with ASD to use attention-following as a word-learning strategy.

  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. Prediction of Acoustically Induced Random Vibration Response of Satellite Equipments with Proposed Asymptotic Apparent Mass

    Science.gov (United States)

    Ando, Shigemasa; Shi, Qinzhong

    Acoustically induced random vibration of satellite equipment mounted on honeycomb panels is a critical design consideration in satellite equipment development. Prediction of this random vibration is performed in the early stage of satellite design to specify the design limit value of random vibration excitation for satellite equipment. Various prediction methods for response prediction using Statistical Energy Analysis (SEA) have been developed: (i) NASA Lewis method, (ii) point-mass impedance method, and (iii) area-coupling impedance method. However, the first method has limited accuracy for heavy and concentrated equipment, the second one often overestimates, and the third one requires a detailed parameter. A new method combining the asymptotic apparent mass of specific equipment with NASA Lewis method is proposed herein. This proposed method takes the elastic behavior of satellite equipment rather than a rigid mass. The acoustic excitation experiments for nine real satellites (404 equipments in all) were conducted to compare existing methods to the proposed method statistically. Results show that the proposed method provides the most accurate prediction in the important frequency range.

  16. 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.

  17. Observed parent-child relationship quality predicts antibody response to vaccination in children.

    Science.gov (United States)

    O'Connor, Thomas G; Wang, Hongyue; Moynihan, Jan A; Wyman, Peter A; Carnahan, Jennifer; Lofthus, Gerry; Quataert, Sally A; Bowman, Melissa; Burke, Anne S; Caserta, Mary T

    2015-08-01

    Quality of the parent-child relationship is a robust predictor of behavioral and emotional health for children and adolescents; the application to physical health is less clear. We investigated the links between observed parent-child relationship quality in an interaction task and antibody response to meningococcal conjugate vaccine in a longitudinal study of 164 ambulatory 10-11 year-old children; additional analyses examine associations with cortisol reactivity, BMI, and somatic illness. Observed Negative/Conflict behavior in the interaction task predicted a less robust antibody response to meningococcal serotype C vaccine in the child over a 6 month-period, after controlling for socio-economic and other covariates. Observer rated interaction conflict also predicted increased cortisol reactivity following the interaction task and higher BMI, but these factors did not account for the link between relationship quality and antibody response. The results begin to document the degree to which a major source of child stress exposure, parent-child relationship conflict, is associated with altered immune system development in children, and may constitute an important public health consideration. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Working memory load-dependent brain response predicts behavioral training gains in older adults.

    Science.gov (United States)

    Heinzel, Stephan; Lorenz, Robert C; Brockhaus, Wolf-Rüdiger; Wüstenberg, Torsten; Kathmann, Norbert; Heinz, Andreas; Rapp, Michael A

    2014-01-22

    In the domain of working memory (WM), a sigmoid-shaped relationship between WM load and brain activation patterns has been demonstrated in younger adults. It has been suggested that age-related alterations of this pattern are associated with changes in neural efficiency and capacity. At the same time, WM training studies have shown that some older adults are able to increase their WM performance through training. In this study, functional magnetic resonance imaging during an n-back WM task at different WM load levels was applied to compare blood oxygen level-dependent (BOLD) responses between younger and older participants and to predict gains in WM performance after a subsequent 12-session WM training procedure in older adults. We show that increased neural efficiency and capacity, as reflected by more "youth-like" brain response patterns in regions of interest of the frontoparietal WM network, were associated with better behavioral training outcome beyond the effects of age, sex, education, gray matter volume, and baseline WM performance. Furthermore, at low difficulty levels, decreases in BOLD response were found after WM training. Results indicate that both neural efficiency (i.e., decreased activation at comparable performance levels) and capacity (i.e., increasing activation with increasing WM load) of a WM-related network predict plasticity of the WM system, whereas WM training may specifically increase neural efficiency in older adults.

  19. Prediction of Breeding Values and Selection Responses With Genetic Heterogeneity of Environmental Variance

    Science.gov (United States)

    Mulder, H. A.; Bijma, P.; Hill, W. G.

    2007-01-01

    There is empirical evidence that genotypes differ not only in mean, but also in environmental variance of the traits they affect. Genetic heterogeneity of environmental variance may indicate genetic differences in environmental sensitivity. The aim of this study was to develop a general framework for prediction of breeding values and selection responses in mean and environmental variance with genetic heterogeneity of environmental variance. Both means and environmental variances were treated as heritable traits. Breeding values and selection responses were predicted with little bias using linear, quadratic, and cubic regression on individual phenotype or using linear regression on the mean and within-family variance of a group of relatives. A measure of heritability was proposed for environmental variance to standardize results in the literature and to facilitate comparisons to “conventional” traits. Genetic heterogeneity of environmental variance can be considered as a trait with a low heritability. Although a large amount of information is necessary to accurately estimate breeding values for environmental variance, response in environmental variance can be substantial, even with mass selection. The methods developed allow use of the well-known selection index framework to evaluate breeding strategies and effects of natural selection that simultaneously change the mean and the variance. PMID:17277375

  20. 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. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  1. 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.

  2. Citric Acid Metabolism in Resistant Hypertension: Underlying Mechanisms and Metabolic Prediction of Treatment Response.

    Science.gov (United States)

    Martin-Lorenzo, Marta; Martinez, Paula J; Baldan-Martin, Montserrat; Ruiz-Hurtado, Gema; Prado, Jose Carlos; Segura, Julian; de la Cuesta, Fernando; Barderas, Maria G; Vivanco, Fernando; Ruilope, Luis Miguel; Alvarez-Llamas, Gloria

    2017-11-01

    Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered (Pcitric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. © 2017 American Heart Association, Inc.

  3. Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis.

    Science.gov (United States)

    Valenzuela, R M; Kaufman, M; Balashov, K E; Ito, K; Buyske, S; Dhib-Jalbut, S

    2016-11-15

    A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS) treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3months, the change in IL-4 from baseline to 6months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6months had an area under the curve (AUC) of 0.80. A high IL-18 level at baseline and a reduction of TNF-alpha over time are associated with a response to GA. Although the study identified predictive biomarkers of clinical response to GA, the results will need to be validated in other data sets. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Proteomic-Based Biosignatures in Breast Cancer Classification and Prediction of Therapeutic Response

    Science.gov (United States)

    He, Jianbo; Whelan, Stephen A.; Lu, Ming; Shen, Dejun; Chung, Debra U.; Saxton, Romaine E.; Faull, Kym F.; Whitelegge, Julian P.; Chang, Helena R.

    2011-01-01

    Protein-based markers that classify tumor subtypes and predict therapeutic response would be clinically useful in guiding patient treatment. We investigated the LC-MS/MS-identified protein biosignatures in 39 baseline breast cancer specimens including 28 HER2-positive and 11 triple-negative (TNBC) tumors. Twenty proteins were found to correctly classify all HER2 positive and 7 of the 11 TNBC tumors. Among them, galectin-3-binding protein and ALDH1A1 were found preferentially elevated in TNBC, whereas CK19, transferrin, transketolase, and thymosin β4 and β10 were elevated in HER2-positive cancers. In addition, several proteins such as enolase, vimentin, peroxiredoxin 5, Hsp 70, periostin precursor, RhoA, cathepsin D preproprotein, and annexin 1 were found to be associated with the tumor responses to treatment within each subtype. The MS-based proteomic findings appear promising in guiding tumor classification and predicting response. When sufficiently validated, some of these candidate protein markers could have great potential in improving breast cancer treatment. PMID:22110952

  5. The potential use of expression profiling: implications for predicting treatment response in rheumatoid arthritis.

    Science.gov (United States)

    Smith, Samantha Louise; Plant, Darren; Eyre, Stephen; Barton, Anne

    2013-07-01

    Whole genome expression profiling, or transcriptomics, is a high throughput technology with the potential for major impacts in both clinical settings and drug discovery and diagnostics. In particular, there is much interest in this technique as a mechanism for predicting treatment response. Gene expression profiling entails the quantitative measurement of messenger RNA levels for thousands of genes simultaneously with the inherent possibility of identifying biomarkers of response to a particular therapy or by singling out those at risk of serious adverse events. This technology should contribute to the era of stratified medicine, in which patient specific populations are matched to potentially beneficial drugs via clinical tests. Indeed, in the oncology field, gene expression testing is already recommended to allow rational use of therapies to treat breast cancer. However, there are still many issues surrounding the use of the various testing platforms available and the statistical analysis associated with the interpretation of results generated. This review will discuss the implications this promising technology has in predicting treatment response and outline the various advantages and pitfalls associated with its use.

  6. Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

    Science.gov (United States)

    Lövdahl, Jenny; Ringström, Gisela; Agerforz, Pia; Törnblom, Hans; Simrén, Magnus

    2015-07-01

    Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.

  7. Does salivary gland scintigraphy predict response to pilocarpine in patients with post-radiotherapy xerostomia?

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, R.A.; Cowan, R.A.; Slevin, N.J.; Allan, E.; Gupta, N.K. [Department of Clinical Oncology, Christie Hospital, Manchester (United Kingdom); Owens, S.E.; Jeans, S.P.; Roberts, J.K.; Hillel, P.G. [North Western Medical Physics, Christie Hospital, Manchester (United Kingdom); Collins, C.D. [Department of Radiology, Christie Hospital, Manchester (United Kingdom)

    1999-03-01

    This study was undertaken to determine whether standard salivary gland scintigraphy may be used for the objective assessment of salivary gland sialogogues, in particular oral pilocarpine, in the treatment of post-radiotherapy xerostomia. Nine patients, with xerostomia following radiotherapy to the head and neck region underwent salivary gland scintigraphy with technetium-99m pertechnetate (40 MBq) both before and following 1 month of oral pilocarpine (5 mg tds). For each scan, the percentage uptake in the first 14 min, the peak uptake, time to peak uptake and the percentage of activity excreted following lemon juice stimulation were calculated. The results were correlated with the subjective response as assessed by questionnaire and visual analogue scale. We found no correlation between subjective response and any of the four scan parameters analysed. We could not identify any parameter that predicted those patients who would respond to pilocarpine. In addition, only one parameter, the percentage of activity excreted following stimulation, correlated with previous dose of radiotherapy to the gland. In conclusion, in this study salivary gland scintigraphy did not appear to correlate with or predict response to oral pilocarpine. However, future studies might consider performing salivary gland scintigraphy prior to radiotherapy as well as at differing time points following the commencement of pilocarpine. (orig.) With 6 figs., 1 tab., 20 refs.

  8. Agitation predicts response of depression to botulinum toxin treatment in a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Marc Axel Wollmer

    2014-03-01

    Full Text Available In a randomized, controlled trial (n=30 we showed that botulinum toxin injection to the glabellar region produces a marked improvement in the symptoms of major depression. We hypothesized that the mood-lifting effect was mediated by facial feedback mechanisms. Here we assessed if agitation, which may be associated with increased dynamic psychomotor activity of the facial musculature, can predict response to the treatment. To test this hypothesis we re-analyzed the data of the scales from our previous study on a single item basis and compared the baseline scores in the agitation item (item 9 of the Hamilton Depression Rating Scale (HAM-D between responders (n=9 and participants who did not attain response (n=6 among the recipients of onabotulinumtoxinA (n=15. Results: Responders had significantly higher item 9 scores at baseline (1.56+0.88 vs. 0.33+0.52, t(13=3.04, d=1.7, p=0.01, while no other single item of the HAM-D or the Beck Depression Inventory was associated with treatment response. The agitation score had an overall precision of 78% in predicting response in a receiver operating characteristic (ROC analysis (area under the curve, AUC=0.87. These data provide a link between response to botulinum toxin treatment with a psychomotor manifestation of depression and thereby indirect support of the proposed facial feedback mechanism of action. Moreover, it suggests that patients with agitated depression may particularly benefit from botulinum toxin treatment.

  9. fMRI Response to Alcohol Pictures Predicts Subsequent Transition to Heavy Drinking in College Students

    Science.gov (United States)

    Dager, Alecia D.; Anderson, Beth M.; Rosen, Rivkah; Khadka, Sabin; Sawyer, Broderick; Jiantonio-Kelly, Rachel E.; Austad, Carol S.; Raskin, Sarah A.; Tennen, Howard; Wood, Rebecca M.; Fallahi, Carolyn R.; Pearlson, Godfrey D.

    2014-01-01

    Background and Aims Young adults show the highest rates of escalating drinking, yet the neural risk mechanisms remain unclear. Heavy drinkers show variant functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to alcohol cues, which may presage increasing drinking. In this longitudinal study, we ascertained whether BOLD response to alcohol pictures predicted subsequent heavy drinking among college students. Methods Participants were forty-three 18- to 21-year-olds in the United States who underwent BOLD scanning and completed monthly substance use surveys over the following year. Participants were categorized according to baseline and follow-up drinking into 13 continuously moderate drinkers, 16 continuously heavy drinkers, and 14 transitioners who drank moderately at baseline but heavily by follow-up. During fMRI scanning at baseline, participants viewed alcohol and matched non-alcohol beverage images. Results We observed group differences in alcohol cue-elicited BOLD response in bilateral caudate, orbitofrontal cortex, medial frontal cortex/anterior cingulate and left insula (clusters>2619ml, voxel-wise F(2,40)>3.23, palcoholism family history, impulsivity), BOLD response best predicted escalating drinking amount and alcohol-related problems. Conclusions Neural response to pictures of alcohol is substantially enhanced among United States college students who subsequently escalate drinking. Greater cue-reactivity is associated with larger increases in drinking and alcohol-related problems, regardless of other baseline factors. Thus, neural cue-reactivity could uniquely facilitate identifying individuals at greatest risk for future problematic drinking. PMID:24304235

  10. Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

    Science.gov (United States)

    Zlobec, Inti; Molinari, Francesca; Martin, Vittoria; Mazzucchelli, Luca; Saletti, Piercarlo; Trezzi, Rosangela; De Dosso, Sara; Vlajnic, Tatjana; Frattini, Milo; Lugli, Alessandro

    2010-01-01

    AIM: To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS: Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and “high-grade” tumor budding was defined as 15 buds/high-power field. RESULTS: Tumor buds and K-RAS mutation both correctly classified 68% of patients. All patients with K-RAS mutation (n = 7) or high-grade tumor budding (n = 11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P = 0.008)]. CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting. PMID:20939111

  11. Predictive value of androgens and multivariate model for poor ovarian response.

    Science.gov (United States)

    Guo, Jing; Zhang, Qingxue; Li, Yu; Huang, Jia; Wang, Wenjun; Huang, Lili; Zhao, Xiaomiao; Yang, Dongzi

    2014-06-01

    No single or multivariate model is effective for predicting poor ovarian response (POR) with satisfactory sensitivity and specificity. This study investigated whether dehydroepiandrosterone sulphate (DHEAS) or basal testosterone concentrations could be effective predictors of POR defined by the Bologna criteria. This retrospective study included 79 poor responders and 128 normal responders. Serum FSH, LH, oestradiol, DHEAS and testosterone concentrations on day 3 of the menstrual cycle before the treatment cycle were measured. All patients received standard ovarian stimulation with FSH under pituitary suppression with gonadotrophin-releasing hormone agonist. DHEAS concentration was not significantly different between poor and normal responders or between pregnant and nonpregnant women. Basal testosterone, unlike DHEAS concentration, was predictive, but with limited ability as a single predictor, for POR. The multivariate model composed of age, AFC, FSH, FSH/LH and testosterone was reliably predictive for POR (ROC(AUC) = 0.976, cut-off point >0.51, sensitivity 88.6%, specificity 98.3%) and clinical pregnancy (ROC(AUC) = 0.716, cut-off point ⩽-0.22, sensitivity 75%, specificity 62.5%) and was better than antral follicle count for predicting both POR and clinical pregnancy. This multivariate model might be useful for identifying patients at risk of poor response in order to optimize the stimulation regimens. No single or multivariate model is effective for predicting poor ovarian response (POR) with satisfactory sensitivity and specificity. It has been suggested that androgens stimulate folliculogenesis and their concentrations might be correlated with oocyte yield after ovulation induction. We investigated whether dehydroepiandrosterone sulphate (DHEAS) or basal testosterone concentrations could be effective predictors for POR defined by the Bologna criteria. This is a retrospective study with 79 poor responders and 128 normal responders. Serum FSH, LH, oestradiol

  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...... scenarios, the EBV approach was as effective as or slightly better than the DYD approach at predicting breeding value, dependent on simulated scenarios and statistical models. Applying a Bayesian common prior model (the same prior distribution of marker effect variance) and a linear mixed model (GBLUP......), 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. Seismic Response Prediction of Buildings with Base Isolation Using Advanced Soft Computing Approaches

    Directory of Open Access Journals (Sweden)

    Mosbeh R. Kaloop

    2017-01-01

    Full Text Available Modeling response of structures under seismic loads is an important factor in Civil Engineering as it crucially affects the design and management of structures, especially for the high-risk areas. In this study, novel applications of advanced soft computing techniques are utilized for predicting the behavior of centrically braced frame (CBF buildings with lead-rubber bearing (LRB isolation system under ground motion effects. These techniques include least square support vector machine (LSSVM, wavelet neural networks (WNN, and adaptive neurofuzzy inference system (ANFIS along with wavelet denoising. The simulation of a 2D frame model and eight ground motions are considered in this study to evaluate the prediction models. The comparison results indicate that the least square support vector machine is superior to other techniques in estimating the behavior of smart structures.

  14. 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.)

  15. 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.

  16. 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

    2015-01-01

    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. PMID:25083933

  17. Hypo-collagenesis in photoaged skin predicts response to anti-aging cosmeceuticals.

    Science.gov (United States)

    Sachs, Dana L; Rittié, Laure; Chubb, Heather A; Orringer, Jeffrey; Fisher, Gary; Voorhees, John J

    2013-06-01

    Chronic sun exposure causes photoaging, the appearance of prematurely aged skin. This phenomenon is characterized by progressive alteration of the dermal extracellular matrix, including elastin and collagen fibers. While many cosmeceuticals claim to improve the appearance of photoaged skin, data are lacking regarding their ability to induce molecular responses associated with wrinkle effacement, particularly increased collagen production. To conduct a meta-analysis to determine whether there was a factor(s) that could predict response to various cosmeceuticals. Hundred subjects enrolled in five separate studies of cosmeceuticals containing: L-ascorbic acid, pentapeptide, α-lipoic acid, yeast extract, or 1% idebenone. Five groups consisting of 16-20 volunteers applied one cosmeceutical to their photodamaged forearms for several weeks. Punch biopsies were obtained pretreatment and post-treatment and analyzed for type I procollagen by ELISA. Analysis of basal collagenesis reinforced the notion that hypo-collagenesis is associated with photoaging severity, independent of age or gender. Treatment outcome varied greatly among subjects, ranging from no improvement to a 7-fold increase in collagenesis. Retrospective statistical meta-analysis was conducted to determine whether age, gender, type of cosmeceutical, or evidence of hypo-collagenesis in untreated skin could predict responsiveness to cosmeceuticals. Our analysis revealed that subjects with hypo-collagenesis responded 6.4 times more often than subjects with normo-collagenesis. Hypo-collagenesis was the only factor that influenced treatment outcome. This study therefore identifies hypo-collagenesis as the unique parameter predicting anti-aging cosmeceutical treatment outcome. These findings provide a basis for future cosmetic testing and the potential development of custom formula skin care. © 2013 Wiley Periodicals, Inc.

  18. Role of genomic factors beyond thymidylate synthase in the prediction of response to 5-fluorouracil.

    Science.gov (United States)

    Peters, Godefridus J; Smid, K; Meijer, E; van Groeningen, C J; Leon, L G

    2016-12-01

    5-Fluorouracil (5FU) is still a major drug in combinations regimens for the treatment of colorectal cancer (CRC) both in the adjuvant and palliative setting. 5FU or its oral prodrug capecitabine is usually combined with irinotecan/oxaliplatin and the novel agents bevacizumab/cetuximab. Although this improved the outcome, the overall prognosis in patients with metastasized disease is still relatively poor. Although the target for 5FU, thymidylate synthase was shown to have a predictive value, this could only predict response in a subset of patients. Given the heterogeneous and complex nature of CRC, it is likely that other aberrations can affect therapeutic response. As an alternative, we investigated Copy number alterations using oligonucleotide-based high-throughput array-comparative-genomic-hybridization (aCGH) to obtain an unbiased screening of the whole genetic spectrum. Chromosomal aberrations have been identified in 85% of CRC patients and include genomic regions harboring copy number alterations in the DNA. These alterations may change the expression of many genes and might explain the differential response to therapy as shown in recent studies with several 5FU combinations. In order to clarify new predictive parameters for 5FU, we used aCGH in a historical cohort of patients, which received treatment with single agent 5FU, and an unsupervised clustering analysis showed a statistical (p < 0.05) difference between responding and nonresponding patients. We also find that several regions showed differences between responders/non-responders, such as losses in 12p12.3-12q15 and in 18p (where TS is located) in responding patients. Genome-wide analysis may provide an additional tool to discriminate between responders and nonresponders.

  19. Individual differences in cortisol stress response predict increases in voice pitch during exam stress.

    Science.gov (United States)

    Pisanski, Katarzyna; Nowak, Judyta; Sorokowski, Piotr

    2016-09-01

    Despite a long history of empirical research, the potential vocal markers of stress remain unclear. Previous studies examining speech under stress most consistently report an increase in voice pitch (the acoustic correlate of fundamental frequency, F0), however numerous studies have failed to replicate this finding. In the present study we tested the prediction that these inconsistencies are tied to variation in the severity of the stress response, wherein voice changes may be observed predominantly among individuals who show a cortisol stress response (i.e., an increase in free cortisol levels) above a critical threshold. Voice recordings and saliva samples were collected from university psychology students at baseline and again immediately prior to an oral examination. Voice recordings included both read and spontaneous speech, from which we measured mean, minimum, maximum, and the standard deviation in F0. We observed an increase in mean and minimum F0 under stress in both read and spontaneous speech, whereas maximum F0 and its standard deviation showed no systematic changes under stress. Our results confirmed that free cortisol levels increased by an average of 74% (ranging from 0 to 270%) under stress. Critically, increases in cortisol concentrations significantly predicted increases in mean F0 under stress for both speech types, but did not predict variation in F0 at baseline. On average, stress-induced increases in voice pitch occurred only when free cortisol levels more than doubled their baseline concentrations. Our results suggest that researchers examining speech under stress should control for individual differences in the magnitude of the stress response. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Ryohei Miyazaki

    Full Text Available Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs and anaplastic lymphoma kinase (ALK inhibitors have dramatically changed the strategy of medical treatment of lung cancer. Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4-ALK fusion gene prior to chemotherapy to predict their clinical response. The succinate dehydrogenase inhibition (SDI test and collagen gel droplet embedded culture drug sensitivity test (CD-DST are established in vitro drug sensitivity tests, which may predict the sensitivity of patients to cytotoxic anticancer drugs. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs.The growth inhibitory effects of erlotinib and crizotinib were confirmed for lung cancer cell lines using SDI and CD-DST. The sensitivity of 35 cases of surgically resected lung cancer to erlotinib was examined using SDI or CD-DST, and compared with EGFR mutation status.HCC827 (Exon19: E746-A750 del and H3122 (EML4-ALK cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M cells were. The viability of the surgically resected lung cancer was 60.0 ± 9.8 and 86.8 ± 13.9% in EGFR-mutants vs. wild types in the SDI (p = 0.0003. The cell viability was 33.5 ± 21.2 and 79.0 ± 18.6% in EGFR mutants vs. wild-type cases (p = 0.026 in CD-DST.In vitro drug sensitivity evaluated by either SDI or CD-DST correlated with EGFR gene status. Therefore, SDI and CD-DST may be useful predictors of potential clinical responses to the molecular anticancer drugs, cyclopedically.

  1. Prediction of resistance development against drug combinations by collateral responses to component drugs

    DEFF Research Database (Denmark)

    Munck, Christian; Gumpert, Heidi; Nilsson Wallin, Annika

    2014-01-01

    to do so. Thus, predictive models are needed to rationally design resistance-limiting therapeutic regimens. Using adaptive evolution, we studied the resistance response of the common pathogen Escherichia coli to 5 different single antibiotics and all 10 different antibiotic drug pairs. By analyzing...... adaptation to the component drugs. Then, using engineered E. coli strains, we confirmed that drug resistance mutations that imposed collateral sensitivity were suppressed in a drug pair growth environment. These results provide a framework for rationally selecting drug combinations that limit resistance...

  2. When Winners Become Losers: Predicted Nonlinear Responses of Arctic Birds to Increasing Woody Vegetation.

    Directory of Open Access Journals (Sweden)

    Sarah J Thompson

    Full Text Available Climate change is facilitating rapid changes in the composition and distribution of vegetation at northern latitudes, raising questions about the responses of wildlife that rely on arctic ecosystems. One widely observed change occurring in arctic tundra ecosystems is an increasing dominance of deciduous shrub vegetation. Our goals were to examine the tolerance of arctic-nesting bird species to existing gradients of vegetation along the boreal forest-tundra ecotone, to predict the abundance of species across different heights and densities of shrubs, and to identify species that will be most or least responsive to ongoing expansion of shrubs in tundra ecosystems. We conducted 1,208 point counts on 12 study blocks from 2012-2014 in northwestern Alaska, using repeated surveys to account for imperfect detection of birds. We considered the importance of shrub height, density of low and tall shrubs (i.e. shrubs >0.5 m tall, percent of ground cover attributed to shrubs (including dwarf shrubs <0.5 m tall, and percent of herbaceous plant cover in predicting bird abundance. Among 17 species considered, only gray-cheeked thrush (Catharus minimus abundance was associated with the highest values of all shrub metrics in its top predictive model. All other species either declined in abundance in response to one or more shrub metrics or reached a threshold where further increases in shrubs did not contribute to greater abundance. In many instances the relationship between avian abundance and shrubs was nonlinear, with predicted abundance peaking at moderate values of the covariate, then declining at high values. In particular, a large number of species were responsive to increasing values of average shrub height with six species having highest abundance at near-zero values of shrub height and abundance of four other species decreasing once heights reached moderate values (≤ 33 cm. Our findings suggest that increases in shrub cover and density will negatively

  3. Predicting the crack response for a pipe with a complex crack

    Science.gov (United States)

    Lukes, Robert G.

    Traditional flaw evaluation in the nuclear field uses conservative methods to predict maximum load carrying capacity for flaws in a given pipe. There is a need in the nuclear industry for more accurate estimates of the load carrying capacity of nuclear piping such that probabilistic tools can be used to predict the time to failure for various types of cracks. These more accurate estimates will allow the nuclear industry to repair flaws at a more appropriate time considering external factors such as costs and man-rem planning along with the flaw repair. Analysis of the maximum load carrying capacity of a pipe with a complex crack (CC) has gained increased importance due to the recent identification of long CC's that have appeared in dissimilar metal (DM) welds thought to be caused by primary water stress corrosion cracking (PWSCC). A coded solution for a single material with a weld was developed that gives an accurate maximum load and crack driving force prediction for a pipe with a through wall crack (TWC), called LBBEng. To support the analysis of a CC, traditionally, an assumption is used that the CC performs similar to that of a TWC of a reduced thickness (TWCr). This modification gives a conservative prediction of the maximum load carrying capacity for a CC in a single material but was never verified for a CC in a DM weld. From the evaluation of the DM weld test data, along with finite element analysis, it can be demonstrated that the crack response of a CC can be predicted by a TWC model when modifications are made to the reduced thickness method.

  4. 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...

  5. The modelling of avian visual perception predicts behavioural rejection responses to foreign egg colours.

    Science.gov (United States)

    Cassey, Phillip; Honza, Marcel; Grim, Tomas; Hauber, Mark E

    2008-10-23

    How do birds tell the colours of their own and foreign eggs apart? We demonstrate that perceptual modelling of avian visual discrimination can predict behavioural rejection responses to foreign eggs in the nest of wild birds. We use a photoreceptor noise-limited colour opponent model of visual perception to evaluate its accuracy as a predictor of behavioural rates of experimental egg discrimination in the song thrush Turdus philomelos. The visual modelling of experimental and natural eggshell colours suggests that photon capture from the ultraviolet and short wavelength-sensitive cones elicits egg rejection decisions in song thrushes, while inter-clutch variation of egg coloration provides sufficient contrasts for detecting conspecific parasitism in this species. Biologically realistic sensory models provide an important tool for relating variability of behavioural responses to perceived phenotypic variation.

  6. Using physiology to predict the responses of ants to climatic warming.

    Science.gov (United States)

    Diamond, Sarah E; Penick, Clint A; Pelini, Shannon L; Ellison, Aaron M; Gotelli, Nicholas J; Sanders, Nathan J; Dunn, Robert R

    2013-12-01

    Physiological intolerance of high temperatures places limits on organismal responses to the temperature increases associated with global climatic change. Because ants are geographically widespread, ecologically diverse, and thermophilic, they are an ideal system for exploring the extent to which physiological tolerance can predict responses to environmental change. Here, we expand on simple models that use thermal tolerance to predict the responses of ants to climatic warming. We investigated the degree to which changes in the abundance of ants under warming reflect reductions in the thermal niche space for their foraging. In an eastern deciduous forest system in the United States with approximately 40 ant species, we found that for some species, the loss of thermal niche space for foraging was related to decreases in abundance with increasing experimental climatic warming. However, many ant species exhibited no loss of thermal niche space. For one well-studied species, Temnothorax curvispinosus, we examined both survival of workers and growth of colonies (a correlate of reproductive output) as functions of temperature in the laboratory, and found that the range of thermal tolerances for colony growth was much narrower than for survival of workers. We evaluated these functions in the context of experimental climatic warming and found that the difference in the responses of these two attributes to temperature generates differences in the means and especially the variances of expected fitness under warming. The expected mean growth of colonies was optimized at intermediate levels of warming (2-4°C above ambient); yet, the expected variance monotonically increased with warming. In contrast, the expected mean and variance of the survival of workers decreased when warming exceeded 4°C above ambient. Together, these results for T. curvispinosus emphasize the importance of measuring reproduction (colony growth) in the context of climatic change: indeed, our examination

  7. 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. 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.

  9. Predicting post-traumatic stress disorder treatment response in refugees: Multilevel analysis.

    Science.gov (United States)

    Haagen, Joris F G; Ter Heide, F Jackie June; Mooren, Trudy M; Knipscheer, Jeroen W; Kleber, Rolf J

    2017-03-01

    Given the recent peak in refugee numbers and refugees' high odds of developing post-traumatic stress disorder (PTSD), finding ways to alleviate PTSD in refugees is of vital importance. However, there are major differences in PTSD treatment response between refugees, the determinants of which are largely unknown. This study aimed at improving PTSD treatment for adult refugees by identifying PTSD treatment response predictors. A prospective longitudinal multilevel modelling design was used to predict PTSD severity scores over time. We analysed data from a randomized controlled trial with pre-, post-, and follow-up measurements of the safety and efficacy of eye movement desensitization and reprocessing and stabilization in asylum seekers and refugees suffering from PTSD. Lack of refugee status, comorbid depression, demographic, trauma-related and treatment-related variables were analysed as potential predictors of PTSD treatment outcome. Treatment outcome data from 72 participants were used. The presence (B = 6.5, p = .03) and severity (B = 6.3, p Refugee patients who suffer from PTSD and severe comorbid depression benefit less from treatment aimed at alleviating PTSD. Results highlight the need for treatment adaptations for PTSD and comorbid severe depression in traumatized refugees, including testing whether initial targeting of severe depressive symptoms increases PTSD treatment effectiveness. There are differences in post-traumatic stress disorder (PTSD) treatment response between traumatized refugees. Comorbid depressive disorder and depression severity predict poor PTSD response. Refugees with PTSD and severe depression may not benefit from PTSD treatment. Targeting comorbid severe depression before PTSD treatment is warranted. This study did not correct for multiple hypothesis testing. Comorbid depression may differentially impact alternative PTSD treatments. © 2016 The British Psychological Society.

  10. 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. Copyright © 2015 the authors 0270-6474/15/3510503-07$15.00/0.

  11. Exposure to Violence Predicting Cortisol Response During Adolescence and Early Adulthood: Understanding Moderating Factors

    Science.gov (United States)

    Heinze, Justin E.; Miller, Alison L.; Stoddard, Sarah A.; Zimmerman, Marc A.

    2014-01-01

    Previous research on the association between violence and biological stress regulation has been largely cross-sectional, and has also focused on childhood. Using longitudinal data from a low-income, high-risk, predominantly African-American sample (n = 266; 57 % female), we tested hypotheses about the influence of cumulative exposure to violence during adolescence and early adulthood on cortisol responses in early adulthood. We found that cumulative exposure to violence predicted an attenuated cortisol response. Further, we tested whether sex, mothers’ support, or fathers’ support moderated the effect of exposure to violence on cortisol responses. We found that the effect of cumulative exposure to violence on cortisol was modified by sex; specifically, males exposed to violence exhibited a more attenuated response pattern. In addition, the effect of cumulative exposure to violence on cortisol was moderated by the presence of fathers’ support during adolescence. The findings contribute to a better understanding of how cumulative exposure to violence influences biological outcomes, emphasizing the need to understand sex and parental support as moderators of risk. PMID:24458765

  12. 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. © 2014 John Wiley & Sons Ltd.

  13. Telomere length and procedural justice predict stress reactivity responses to unfair outcomes in African Americans.

    Science.gov (United States)

    Lucas, Todd; Pierce, Jennifer; Lumley, Mark A; Granger, Douglas A; Lin, Jue; Epel, Elissa S

    2017-09-07

    This experiment demonstrates that chromosomal telomere length (TL) moderates response to injustice among African Americans. Based on worldview verification theory - an emerging psychosocial framework for understanding stress - we predicted that acute stress responses would be most pronounced when individual-level expectancies for justice were discordant with justice experiences. Healthy African Americans (N=118; 30% male; M age=31.63years) provided dried blood spot samples that were assayed for TL, and completed a social-evaluative stressor task during which high versus low levels of distributive (outcome) and procedural (decision process) justice were simultaneously manipulated. African Americans with longer telomeres appeared more resilient (in emotional and neuroendocrine response-higher DHEAs:cortisol) to receiving an unfair outcome when a fair decision process was used, whereas African Americans with shorter telomeres appeared more resilient when an unfair decision process was used. TL may indicate personal histories of adversity and associated stress-related expectancies that influence responses to injustice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Novel transformation-based response prediction of shear building using interval neural network

    Science.gov (United States)

    Chakraverty, S.; Sahoo, Deepti Moyi

    2017-04-01

    Present paper uses powerful technique of interval neural network (INN) to simulate and estimate structural response of multi-storey shear buildings subject to earthquake motion. The INN is first trained for a real earthquake data, viz., the ground acceleration as input and the numerically generated responses of different floors of multi-storey buildings as output. Till date, no model exists to handle positive and negative data in the INN. As such here, the bipolar data in [ -1, 1] are converted first to unipolar form, i.e., to [0, 1] by means of a novel transformation for the first time to handle the above training patterns in normalized form. Once the training is done, again the unipolar data are converted back to its bipolar form by using the inverse transformation. The trained INN architecture is then used to simulate and test the structural response of different floors for various intensity earthquake data and it is found that the predicted responses given by INN model are good for practical purposes.

  15. 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.

  16. Predicting the effective response of bulk polycrystalline ferroelectric ceramics via improved spectral phase field methods

    Science.gov (United States)

    Vidyasagar, A.; Tan, W. L.; Kochmann, D. M.

    2017-09-01

    Understanding the electromechanical response of bulk polycrystalline ferroelectric ceramics requires scale-bridging approaches. Recent advances in fast numerical methods to compute the homogenized mechanical response of materials with heterogeneous microstructure have enabled the solution of hitherto intractable systems. In particular, the use of a Fourier-based spectral method as opposed to the traditional finite element method has gained significant interest in the homogenization of periodic microstructures. Here, we solve the periodic, electro-mechanically-coupled boundary value problem at the mesoscale of polycrystalline ferroelectrics in order to extract the effective response of barium titanate (BaTiO3) and lead zirconate titanate (PZT) under applied electric fields. Results include the effective electric hysteresis and the associated butterfly curve of strain vs. electric field for mean stress-free electric loading. Computational predictions of the 3D polycrystalline response show convincing agreement with our experimental electric cycling and strain hysteresis data for PZT-5A. In addition to microstructure-dependent effective physics, we also show how finite-difference-based approximations in the spectral solution scheme significantly reduce instability and ringing phenomena associated with spectral techniques and lead to spatial convergence with h-refinement, which have been major challenges when modeling high-contrast systems such as polycrystals.

  17. 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.

  18. Neutrophil-to-Lymphocyte Ratio for Predicting Loss of Response to Infliximab in Ulcerative Colitis.

    Science.gov (United States)

    Nishida, Yu; Hosomi, Shuhei; 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

    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. 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. 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). 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.

  19. Experience with decision support system and comfort with topic predict clinicians' responses to alerts and reminders.

    Science.gov (United States)

    Bauer, Nerissa S; Carroll, Aaron E; Saha, Chandan; Downs, Stephen M

    2016-04-01

    Clinicians at our institution typically respond to about half of the prompts they are given by the clinic's computer decision support system (CDSS). We sought to examine factors associated with clinician response to CDSS prompts as part of a larger, ongoing quality improvement effort to optimize CDSS use. We examined patient, prompt, and clinician characteristics associated with clinician response to decision support prompts from the Child Health Improvement through Computer Automation (CHICA) system. We asked pediatricians who were nonusers of CHICA to rate decision support topics as "easy" or "not easy" to discuss with patients and their guardians. We analyzed these ratings and data, from July 1, 2009 to January 29, 2013, utilizing a hierarchical regression model, to determine whether factors such as comfort with the prompt topic and the length of the user's experience with CHICA contribute to user response rates. We examined 414 653 prompts from 22 260 patients. The length of time a clinician had been using CHICA was associated with an increase in their prompt response rate. Clinicians were more likely to respond to topics rated as "easy" to discuss. The position of the prompt on the page, clinician gender, and the patient's age, race/ethnicity, and preferred language were also predictive of prompt response rate. This study highlights several factors associated with clinician prompt response rates that could be generalized to other health information technology applications, including the clinician's length of exposure to the CDSS, the prompt's position on the page, and the clinician's comfort with the prompt topic. Incorporating continuous quality improvement efforts when designing and implementing health information technology may ensure that its use is optimized. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. QRS frequency characteristics help predict response to cardiac resynchronization in left bundle branch block less than 150 milliseconds.

    Science.gov (United States)

    Niebauer, Mark J; Rickard, John; Polakof, Landon; Tchou, Patrick J; Varma, Niraj

    2014-12-01

    Baseline QRS duration (QRSd) ≥150 ms is a recognized predictor of clinical improvement by cardiac resynchronization therapy (CRT), particularly for those with left bundle branch (LBBB). Patients with QRSd 52% below 10 Hz was especially predictive of response in those with QRSd <150 ms. In these patients, this power threshold was highly predictive of CRT response (positive predictive value 85.7%, negative predictive value 71.4%). In this group of CRT recipients with LBBB, retrospective analysis of QRS frequency content below 10 Hz had greater predictive value for CRT response than baseline QRSd, particularly in those with QRSd <150 ms. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  1. A combination of baseline plasma immune markers can predict therapeutic response in multidrug resistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Selena Ferrian

    Full Text Available To identify plasma markers predictive of therapeutic response in patients with multidrug resistant tuberculosis (MDR-TB.Fifty HIV-negative patients with active pulmonary MDR-TB were analysed for six soluble analytes in plasma at the time of initiating treatment (baseline and over six months thereafter. Patients were identified as sputum culture positive or negative at baseline. Culture positive patients were further stratified by the median time to sputum culture conversion (SCC as fast responders (< 76 days or slow responders (≥ 76 days. Chest X-ray scores, body mass index, and sputum smear microscopy results were obtained at baseline.Unsupervised hierarchical clustering revealed that baseline plasma levels of IP-10/CXCL10, VEGF-A, SAA and CRP could distinguish sputum culture and cavitation status of patients. Among patients who were culture positive at baseline, there were significant positive correlations between plasma levels of CRP, SAA, VEGF-A, sIL-2Rα/CD40, and IP-10 and delayed SCC. Using linear discriminant analysis (LDA and Receiver Operating Curves (ROC, we showed that a combination of MCP-1/CCL2, IP-10, sIL-2Rα, SAA, CRP and AFB smear could distinguish fast from slow responders and were predictive of delayed SCC with high sensitivity and specificity.Plasma levels of specific chemokines and inflammatory markers measured before MDR-TB treatment are candidate predictive markers of delayed SCC. These findings require validation in a larger study.

  2. Life-history traits and landscape characteristics predict macro-moth responses to forest fragmentation.

    Science.gov (United States)

    Slade, Eleanor M; Merckx, Thomas; Riutta, Terhi; Bebber, Daniel P; Redhead, David; Riordan, Philip; Macdonald, David W

    2013-07-01

    How best to manage forest patches, mitigate the consequences of forest fragmentation, and enable landscape permeability are key questions facing conservation scientists and managers. Many temperate forests have become increasingly fragmented, resulting in reduced interior forest habitat, increased edge habitats, and reduced connectivity. Using a citizen science landscape-scale mark-release-recapture study on 87 macro-moth species, we investigated how both life-history traits and landscape characteristics predicted macro-moth responses to forest fragmentation. Wingspan, wing shape, adult feeding, and larval feeding guild predicted macro-moth mobility, although the predictive power of wingspan and wing shape depended on the species' affinity to the forest. Solitary trees and small fragments functioned as "stepping stones," especially when their landscape connectivity was increased, by being positioned within hedgerows or within a favorable matrix. Mobile forest specialists were most affected by forest fragmentation: despite their high intrinsic dispersal capability, these species were confined mostly to the largest of the forest patches due to their strong affinity for the forest habitat, and were also heavily dependent on forest connectivity in order to cross the agricultural matrix. Forest fragments need to be larger than five hectares and to have interior forest more than 100 m from the edge in order to sustain populations of forest specialists. Our study provides new insights into the movement patterns of a functionally important insect group, with implications for the landscape-scale management of forest patches within agricultural landscapes.

  3. Response-predictive gene expression profiling of glioma progenitor cells in vitro.

    Directory of Open Access Journals (Sweden)

    Sylvia Moeckel

    Full Text Available 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.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.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.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.

  4. 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. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  5. Defining and Predicting Patterns of Early Response in a Web-Based Intervention for Depression.

    Science.gov (United States)

    Lutz, Wolfgang; Arndt, Alice; Rubel, Julian; Berger, Thomas; Schröder, Johanna; Späth, Christina; Meyer, Björn; Greiner, Wolfgang; Gräfe, Viola; Hautzinger, Martin; Fuhr, Kristina; Rose, Matthias; Nolte, Sandra; Löwe, Bernd; Hohagen, Fritz; Klein, Jan Philipp; Moritz, Steffen

    2017-06-09

    Web-based interventions for individuals with depressive disorders have been a recent focus of research and may be an effective adjunct to face-to-face psychotherapy or pharmacological treatment. The aim of our study was to examine the early change patterns in Web-based interventions to identify differential effects. We applied piecewise growth mixture modeling (PGMM) to identify different latent classes of early change in individuals with mild-to-moderate depression (n=409) who underwent a CBT-based web intervention for depression. Overall, three latent classes were identified (N=409): Two early response classes (n=158, n=185) and one early deterioration class (n=66). Latent classes differed in terms of outcome (PClass membership significantly improved outcome prediction by 24.8% over patient intake characteristics (P<.001) and significantly added to the prediction of adherence (P=.04). These findings suggest that in Web-based interventions outcome and adherence can be predicted by patterns of early change, which can inform treatment decisions and potentially help optimize the allocation of scarce clinical resources.

  6. Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism

    Science.gov (United States)

    Watanabe, Takamitsu; Otowa, Takeshi; Abe, Osamu; Kuwabara, Hitoshi; Aoki, Yuta; Natsubori, Tatsunobu; Takao, Hidemasa; Kakiuchi, Chihiro; Kondo, Kenji; Ikeda, Masashi; Iwata, Nakao; Kasai, Kiyoto; Sasaki, Tsukasa

    2017-01-01

    Abstract Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin’s effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs—including rs53576 and rs2254298—were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD. PMID:27798253

  7. Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

    Science.gov (United States)

    Toss, Angela; Venturelli, Marta; Peterle, Chiara; Piacentini, Federico; Cascinu, Stefano; Cortesi, Laura

    2017-01-04

    In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc.) significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

  8. A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina.

    Science.gov (United States)

    Maturana, Matias I; Apollo, Nicholas V; Hadjinicolaou, Alex E; Garrett, David J; Cloherty, Shaun L; Kameneva, Tatiana; Grayden, David B; Ibbotson, Michael R; Meffin, Hamish

    2016-04-01

    Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants). Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time) despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs) stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron's electrical receptive field (ERF), i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy.

  9. A Simple and Accurate Model to Predict Responses to Multi-electrode Stimulation in the Retina.

    Directory of Open Access Journals (Sweden)

    Matias I Maturana

    2016-04-01

    Full Text Available Implantable electrode arrays are widely used in therapeutic stimulation of the nervous system (e.g. cochlear, retinal, and cortical implants. Currently, most neural prostheses use serial stimulation (i.e. one electrode at a time despite this severely limiting the repertoire of stimuli that can be applied. Methods to reliably predict the outcome of multi-electrode stimulation have not been available. Here, we demonstrate that a linear-nonlinear model accurately predicts neural responses to arbitrary patterns of stimulation using in vitro recordings from single retinal ganglion cells (RGCs stimulated with a subretinal multi-electrode array. In the model, the stimulus is projected onto a low-dimensional subspace and then undergoes a nonlinear transformation to produce an estimate of spiking probability. The low-dimensional subspace is estimated using principal components analysis, which gives the neuron's electrical receptive field (ERF, i.e. the electrodes to which the neuron is most sensitive. Our model suggests that stimulation proportional to the ERF yields a higher efficacy given a fixed amount of power when compared to equal amplitude stimulation on up to three electrodes. We find that the model captures the responses of all the cells recorded in the study, suggesting that it will generalize to most cell types in the retina. The model is computationally efficient to evaluate and, therefore, appropriate for future real-time applications including stimulation strategies that make use of recorded neural activity to improve the stimulation strategy.

  10. Functional brain network modularity predicts response to cognitive training after brain injury.

    Science.gov (United States)

    Arnemann, Katelyn L; Chen, Anthony J-W; Novakovic-Agopian, Tatjana; Gratton, Caterina; Nomura, Emi M; D'Esposito, Mark

    2015-04-14

    We tested the value of measuring modularity, a graph theory metric indexing the relative extent of integration and segregation of distributed functional brain networks, for predicting individual differences in response to cognitive training in patients with brain injury. Patients with acquired brain injury (n = 11) participated in 5 weeks of cognitive training and a comparison condition (brief education) in a crossover intervention study design. We quantified the measure of functional brain network organization, modularity, from functional connectivity networks during a state of tonic attention regulation measured during fMRI scanning before the intervention conditions. We examined the relationship of baseline modularity with pre- to posttraining changes in neuropsychological measures of attention and executive control. The modularity of brain network organization at baseline predicted improvement in attention and executive function after cognitive training, but not after the comparison intervention. Individuals with higher baseline modularity exhibited greater improvements with cognitive training, suggesting that a more modular baseline network state may contribute to greater adaptation in response to cognitive training. Brain network properties such as modularity provide valuable information for understanding mechanisms that influence rehabilitation of cognitive function after brain injury, and may contribute to the discovery of clinically relevant biomarkers that could guide rehabilitation efforts. © 2015 American Academy of Neurology.

  11. 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.

  12. Predictive Factors of the Response of Rectal Cancer to Neoadjuvant Radiochemotherapy

    Directory of Open Access Journals (Sweden)

    Anita De Rossi

    2011-04-01

    Full Text Available Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy (pRCT, but the response is not uniform. Identification of patients with higher likelihood of responding to pRCT is clinically relevant, as patients with resistant tumors could be spared exposure to radiation or DNA-damaging drugs that are associated with adverse side effects. To highlight predictive biomarkers of response to pRCT, a systematic search of PubMed was conducted with a combination of the following terms: “rectal”, “predictive”, “radiochemotherapy”, “neoadjuvant”, “response” and “biomarkers”. Genetic polymorphisms in epithelial growth factor receptor (EGFR and thymidylate synthase (TS genes, the expression of several markers, such as EGFR, bcl-2/bax and cyclooxygenase (COX-2, and circulating biomarkers, such as serum carcinoembryonic antigen (CEA level, are promising as predictor markers, but need to be further evaluated. The majority of the studies did not support the predictive value of p53, while the values of Ki-67, TS and p21 is still controversial. Gene expression profiles of thousands of genes using microarrays, microRNA studies and the search for new circulating molecules, such as human telomerase reverse transcriptase mRNA and cell-free DNA, are providing interesting results that might lead to the identification of new useful biomarkers. Evaluation of biomarkers in larger, prospective trials are required to guide therapeutic strategies.

  13. Predictive Factors of the Response of Rectal Cancer to Neoadjuvant Radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Spolverato, Gaya; Pucciarelli, Salvatore [Department of Oncology and Surgical Sciences, Section of Surgery, University of Padova, Padova 35128 (Italy); Bertorelle, Roberta [Istituto Oncologico Veneto-IRCCS, Padova 35128 (Italy); De Rossi, Anita, E-mail: anita.derossi@unipd.it [Istituto Oncologico Veneto-IRCCS, Padova 35128 (Italy); Department of Oncology and Surgical Sciences, Section of Oncology, University of Padova, Padova 35128 (Italy); Nitti, Donato [Department of Oncology and Surgical Sciences, Section of Surgery, University of Padova, Padova 35128 (Italy)

    2011-04-26

    Locally advanced rectal cancer is currently treated with pre-operative radiochemotherapy (pRCT), but the response is not uniform. Identification of patients with higher likelihood of responding to pRCT is clinically relevant, as patients with resistant tumors could be spared exposure to radiation or DNA-damaging drugs that are associated with adverse side effects. To highlight predictive biomarkers of response to pRCT, a systematic search of PubMed was conducted with a combination of the following terms: “rectal”, “predictive”, “radiochemotherapy”, “neoadjuvant”, “response” and “biomarkers”. Genetic polymorphisms in epithelial growth factor receptor (EGFR) and thymidylate synthase (TS) genes, the expression of several markers, such as EGFR, bcl-2/bax and cyclooxygenase (COX)-2, and circulating biomarkers, such as serum carcinoembryonic antigen (CEA) level, are promising as predictor markers, but need to be further evaluated. The majority of the studies did not support the predictive value of p53, while the values of Ki-67, TS and p21 is still controversial. Gene expression profiles of thousands of genes using microarrays, microRNA studies and the search for new circulating molecules, such as human telomerase reverse transcriptase mRNA and cell-free DNA, are providing interesting results that might lead to the identification of new useful biomarkers. Evaluation of biomarkers in larger, prospective trials are required to guide therapeutic strategies.

  14. Frontal and limbic activation during inhibitory control predicts treatment response in major depressive disorder.

    Science.gov (United States)

    Langenecker, Scott A; Kennedy, Susan E; Guidotti, Leslie M; Briceno, Emily M; Own, Lawrence S; Hooven, Thomas; Young, Elizabeth A; Akil, Huda; Noll, Douglas C; Zubieta, Jon-Kar

    2007-12-01

    Inhibitory control or regulatory difficulties have been explored in major depressive disorder (MDD) but typically in the context of affectively salient information. Inhibitory control is addressed specifically by using a task devoid of affectively-laden stimuli, to disentangle the effects of altered affect and altered inhibitory processes in MDD. Twenty MDD and 22 control volunteer participants matched by age and gender completed a contextual inhibitory control task, the Parametric Go/No-go (PGNG) task during functional magnetic resonance imaging. The PGNG includes three levels of difficulty, a typical continuous performance task and two progressively more difficult versions including Go/No-go hit and rejection trials. After this test, 15 of 20 MDD patients completed a full 10-week treatment with s-citalopram. There was a significant interaction among response time (control subjects better), hits (control subjects better), and rejections (patients better). The MDD participants had greater activation compared with the control group in frontal and anterior temporal areas during correct rejections (inhibition). Activation during successful inhibitory events in bilateral inferior frontal and left amygdala, insula, and nucleus accumbens and during unsuccessful inhibition (commission errors) in rostral anterior cingulate predicted post-treatment improvement in depression symptoms. The imaging findings suggest that in MDD subjects, greater neural activation in frontal, limbic, and temporal regions during correct rejection of lures is necessary to achieve behavioral performance equivalent to control subjects. Greater activation in similar regions was further predictive of better treatment response in MDD.

  15. 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.

  16. 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.

  17. Predicting behavioural responses to novel organisms: state-dependent detection theory.

    Science.gov (United States)

    Trimmer, Pete C; Ehlman, Sean M; Sih, Andrew

    2017-01-25

    Human activity alters natural habitats for many species. Understanding variation in animals' behavioural responses to these changing environments is critical. We show how signal detection theory can be used within a wider framework of state-dependent modelling to predict behavioural responses to a major environmental change: novel, exotic species. We allow thresholds for action to be a function of reserves, and demonstrate how optimal thresholds can be calculated. We term this framework 'state-dependent detection theory' (SDDT). We focus on behavioural and fitness outcomes when animals continue to use formerly adaptive thresholds following environmental change. In a simple example, we show that exposure to novel animals which appear dangerous-but are actually safe-(e.g. ecotourists) can have catastrophic consequences for 'prey' (organisms that respond as if the new organisms are predators), significantly increasing mortality even when the novel species is not predatory. SDDT also reveals that the effect on reproduction can be greater than the effect on lifespan. We investigate factors that influence the effect of novel organisms, and address the potential for behavioural adjustments (via evolution or learning) to recover otherwise reduced fitness. Although effects of environmental change are often difficult to predict, we suggest that SDDT provides a useful route ahead. © 2017 The Author(s).

  18. Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

    Directory of Open Access Journals (Sweden)

    Angela Toss

    2017-01-01

    Full Text Available In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc. significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

  19. 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.

  20. A framework for prediction of response to HCV therapy using different data mining techniques.

    Science.gov (United States)

    El Houby, Enas M F

    2014-01-01

    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.

  1. Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy.

    Directory of Open Access Journals (Sweden)

    Ahmed A Alkhateeb

    Full Text Available Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml or CRP (>7.25 mg/l was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.

  2. Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism.

    Science.gov (United States)

    Watanabe, Takamitsu; Otowa, Takeshi; Abe, Osamu; Kuwabara, Hitoshi; Aoki, Yuta; Natsubori, Tatsunobu; Takao, Hidemasa; Kakiuchi, Chihiro; Kondo, Kenji; Ikeda, Masashi; Iwata, Nakao; Kasai, Kiyoto; Sasaki, Tsukasa; Yamasue, Hidenori

    2017-03-01

    Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin's effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs-including rs53576 and rs2254298-were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  3. Analysis of predictive factors for rapid virologic response in treating patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    ZHANG Dandan

    2014-12-01

    Full Text Available ObjectiveTo analyze the predictive factors for rapid virologic response (RVR in patients with chronic hepatitis C (CHC who received combination therapy with pegylated interferon (PEG-IFN and ribavirin. MethodsA total of 127 CHC patients who were admitted to our department from 2010 to 2012 and received PEG-IFN combined with ribavirin were enrolled in this retrospective cohort study. The patients were divided into RVR group and non-RVR (NRVR group according to their virologic responses after 4 weeks of antiviral therapy. Demographic characteristics and the clinical features prior to treatment were compared between the two groups, and the potential factors that contributed to the acquisition of RVR were analyzed. Comparison of categorical data between groups was made by chi-square test, predictive factors were analyzed by nonparametric test for two independent samples (Mann-Whitney U test, independent predictive factors were tested by univariate and multivariate logistic regression analyses, and the continuous variables of predictive factors were analyzed using receiver operating characteristic curves. ResultsOf the 127 CHC patients, 86 were males and 41 females. There were 11 confirmed cases of liver cirrhosis. There were 100 patients (78.74% who achieved an RVR, and 27 (21.26% with NRVR. Nonparametric analysis showed that eight factors, which were age, time of infection, level of pre-treatment alanine aminotransferase, level of pre-treatment hyaluronic acid, development of hypertension, type of interferon, pathway of infection, and hepatitis C virus (HCV genotype, were significantly different between the RVR and NRVR groups (P<0.05. The logistic regression analysis identified the following factors as independent predictive factors for RVR: non-genotype 1 (OR: 0.203, 95%CI: 0.051-0.802, P<0.05, time of infection (OR: 0.925, 95%CI: 0.868-0.987, P<0.05, and absence of hypertension (OR: 0.129, 95%CI: 0.032-0.521, P<0.05. Conclusion

  4. 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.

  5. 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.

  6. A predictive model for residual disease after (chemo radiotherapy in oropharyngeal carcinoma: Combined radiological and clinical evaluation of tumor response

    Directory of Open Access Journals (Sweden)

    Zeno A.R. Gouw

    2017-10-01

    Conclusion: For response evaluation in OPC, the combination of CS and Ojiri-score improved the predictive accuracy by reducing false positives compared to them individually. FDG-PET/CT is promising to further reduce false positives.

  7. Predicting species distribution and abundance responses to climate change: why it is essential to include biotic interactions across trophic levels

    NARCIS (Netherlands)

    Van der Putten, W.H.; Macel, M.; Visser, M.E.

    2010-01-01

    Current predictions on species responses to climate change strongly rely on projecting altered environmental conditions on species distributions. However, it is increasingly acknowledged that climate change also influences species interactions. We review and synthesize literature information on

  8. Time-based prediction in motor control: evidence from grip force response to external load perturbations.

    Science.gov (United States)

    Kwok, Hoi Fei; Wing, Alan M

    2006-10-01

    An object held in precision grip creates predictable load forces on the hand during voluntary hand movement and these are associated with anticipatory modulation of grip force. Conflicting results have been obtained over whether predictable external load perturbations result in anticipatory grip force responses (e.g. Blakemore et al. in J Neurosci 18(18):7511-7518, 1998; Weeks et al. in Exp Brain Res 132:404-410, 2000). This paper investigated whether the discrepancies reflect differences in the methods used in estimating the time delay. Subjects held a manipulandum that delivered load force perturbations in the form of pulses of variable duration and interval or periodic 0.5 and 1 Hz square waves or sinusoids. The grip forces exerted by the subjects were measured. Two methods were used to assess the time delay of the grip force in relation to the load force: (1) cross-spectral analysis, (2) a single threshold method applied on time-locked averaged data. Despite a phase lag shown by the cross-spectral analysis, the threshold method revealed grip force increased 264.8+/-40.2 ms before the onset of the load force when 0.5 Hz square waves were used as the load force perturbation and 70.2+/-17.0 ms before the load force when 1 Hz square waves were used. Computer simulations indicated that the single threshold method gives a more sensitive estimate of the onset time than the cross-spectral analysis. We conclude that discrepancies in previous studies reflect differences in the methods used to assess the time-delay and that there is an anticipatory component in the grip force response to predictable external load perturbation.

  9. Is electromyography a predictive test of patient response to biofeedback in the treatment of fecal incontinence?

    Science.gov (United States)

    Lacima, Gloria; Pera, Miguel; González-Argenté, Xavier; Torrents, Abiguei; Valls-Solé, Josep; Espuña-Pons, Montserrat

    2016-03-01

    Biofeedback is effective in more than 70% of patients with fecal incontinence. However, reliable predictors of successful treatment have not been identified. The aim was to identify clinical variables and diagnostic tests, particularly electromyography, that could predict a successful outcome. We included 135 consecutive women with fecal incontinence treated with biofeedback. Clinical evaluation, manometry, ultrasonography, electromyography, and pudendal nerve terminal motor latency were performed before therapy. Treatment outcome was assessed using a symptoms diary, Wexner incontinence score and the patient's subjective perception. According to the symptoms diaries, 106 (78.5%) women had a good clinical result and 29 (21.5%) had a poor result. There were no differences in age, severity and type of fecal incontinence. Maximum resting pressure (39.3 ± 19.1 mmHg vs. 33.7 ± 20.2 mmHg; P = 0.156) and maximum squeeze pressure (91.8 ± 33.2 mmHg vs. 79.8 ± 31.2 mmHg; P = 0.127) were higher in patients having good clinical outcome although the difference was not significant. There were no differences in the presence of sphincter defects or abnormalities in electromyographic recordings. Logistic regression analysis found no independent predictive factor for good clinical outcome. Biofeedback is effective in more than 75% of patients with fecal incontinence. Clinical characteristics of patients and results of baseline tests have no predictive value of response to therapy. Specifically, we found no association between severity of electromyographic deficit and clinical response. © 2015 Wiley Periodicals, Inc.

  10. 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

  11. Validation of an individualised model of human thermoregulation for predicting responses to cold air

    Science.gov (United States)

    van Marken Lichtenbelt, Wouter D.; Frijns, Arjan J. H.; van Ooijen, Marieke J.; Fiala, Dusan; Kester, Arnold M.; van Steenhoven, Anton A.

    2007-01-01

    Most computer models of human thermoregulation are population based. Here, we individualised the Fiala model [Fiala et al. (2001) Int J Biometeorol 45:143 159] with respect to anthropometrics, body fat, and metabolic rate. The predictions of the adapted multisegmental thermoregulatory model were compared with measured skin temperatures of individuals. Data from two experiments, in which reclining subjects were suddenly exposed to mild to moderate cold environmental conditions, were used to study the effect on dynamic skin temperature responses. Body fat was measured by the three-compartment method combining underwater weighing and deuterium dilution. Metabolic rate was determined by indirect calorimetry. In experiment 1, the bias (mean difference) between predicted and measured mean skin temperature decreased from 1.8°C to -0.15°C during cold exposure. The standard deviation of the mean difference remained of the same magnitude (from 0.7°C to 0.9°C). In experiment 2 the bias of the skin temperature changed from 2.0±1.09°C using the standard model to 1.3±0.93°C using individual characteristics in the model. The inclusion of individual characteristics thus improved the predictions for an individual and led to a significantly smaller systematic error. However, a large part of the discrepancies in individual response to cold remained unexplained. Possible further improvements to the model accomplished by inclusion of more subject characteristics (i.e. body fat distribution, body shape) and model refinements on the level of (skin) blood perfusion, and control functions, are discussed.

  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.

    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

  14. Cardiac filling volumes versus pressures for predicting fluid responsiveness after cardiovascular surgery: the role of systolic cardiac function

    NARCIS (Netherlands)

    Trof, Ronald J.; Danad, Ibrahim; Reilingh, Mikel W. L.; Breukers, Rose-Marieke Bge; Groeneveld, Ab Johan

    2011-01-01

    ABSTRACT: INTRODUCTION: Static cardiac filling volumes have been suggested to better predict fluid responsiveness than filling pressures, but this may not apply to hearts with systolic dysfunction and dilatation. We evaluated the relative value of cardiac filling volume and pressures for predicting

  15. 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.

  16. Alcohol challenge responses predict future alcohol use disorder symptoms: a 6-year prospective study.

    Science.gov (United States)

    King, Andrea C; McNamara, Patrick J; Hasin, Deborah S; Cao, Dingcai

    2014-05-15

    Propensity for alcohol misuse may be linked to an individuals' response to alcohol. This study examined the role of alcohol response phenotypes to future drinking problems. One hundred four young heavy social drinkers participated in a within-subject, double-blind, placebo-controlled laboratory alcohol challenge study with 6-year follow-up. Participants were examined for subjective responses before and after receiving an intoxicating dose of alcohol (.8 g/kg) or a placebo beverage, given in random order. Follow-up was conducted in 5 waves over 6 years after the sessions to assess drinking behaviors and alcohol use disorder (AUD) symptoms. Retention was high with 98% (509 of 520) of possible follow-ups completed. Greater sensitivity to alcohol, in terms of stimulation and rewarding effects (like, want more) and lower sensitivity to alcohol sedation predicted greater number of AUD symptoms through 6 years of follow-up. Cluster analyses revealed that for half the sample, increasing levels of stimulation and liking were predictors of more AUD symptoms with the other half divided between those showing like and want more and want more alone as significant predictors. The findings extend previous findings and offer new empirical insights into the propensity for excessive drinking and alcohol problems. Heightened alcohol stimulation and reward sensitivity robustly predicted more alcohol use disorder symptoms over time associated with greater binge-drinking frequency. These drinking problems were maintained and progressed as these participants were entering their third decade of life, a developmental interval when continued alcohol misuse becomes more deviant. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. Predicting future forests: Understanding diverse phenological responses within a community and functional trait framework

    Science.gov (United States)

    Wolkovich, E. M.; Flynn, D. F. B.

    2016-12-01

    In recent years increasing attention has focused on plant phenology as an important indicator of the biological impacts of climate change, as many plants have shifted their leafing and flowering earlier with increasing temperatures. As data have accumulated, researchers have found a link between phenological responses to warming and plant performance and invasions. Such work suggests phenology may not only be a major impact of warming, but a critical predictor of future plant performance. Yet alongside this increasing interest in phenology, important issues remain unanswered: responses to warming for species at the same site or in the same genus vary often by weeks or more and the explanatory power of phenology for performance and invasions when analyzed across diverse datasets remains low. We propose progress can come from explicitly considering phenology within a community context and as a critical plant trait correlated with other major plant functional traits. Here, we lay out a framework for our proposal: specifically we review how we expect phenology and phenological cues of different species within a community to vary and what other functional traits are predicted to co-vary with phenological traits. Much research currently suggests phenology is a critical functional trait that is shaped strongly by the environment. Plants are expected to adjust their phenologies to avoid periods of high abiotic risk and/or high competition. Thus we may expect phenology to correlate strongly to other traits involved in mitigating risk and high competition. Results from recent meta-analyses as well as experimental and observational research from 28 species in northeastern North American temperate forests suggest that species within a community show the predicted diversified set of phenological cues. We review early work on links to other functional traits and in closing review how these correlations may in turn determine the diversity of phenological responses observed for

  18. Can volumetric ADC measurement help predict response to Y90 radioembolization in HCC?

    Science.gov (United States)

    Vouche, Michael; Salem, Riad; Lewandowski, Robert J; Miller, Frank H

    2015-08-01

    To compare changes in RECIST, anatomical volume, mRECIST, and volumetric diffusion-weighted Imaging parameters (3D apparent diffusion coefficient (ADC) measurements), with pathological analysis of hepatocellular carcinoma (HCC) treated by (90)Yttrium radioembolization (Y90). 21 patients were treated by Y90 as a sole treatment modality for solitary, >2 cm HCC that underwent liver transplantation. MRI at baseline, 1 and 3 months post-Y90, and tumor pathological findings on explants were reviewed in all patients. Compared to baseline (RECIST/volume: 3.6 cm/17.7 cm(3)), RECIST and volume were not modified after Y90 (1 month, p = 0.28/0.09 RECIST/tumor volume; 3 months, p = 0.28/0.54). In contrast, mRECIST (3.3-1.4 cm, p < 0.001), mean ADC (0.185-1.093 mm(2)/s × 10(-3), p = 0.04), and ADC standard deviation (STD) (0.041-0.201 mm(2)/s × 10(-3), p = 0.0496) changed as earlier as 1 month post-Y90. ADC STD % change was higher in ADC responding lesions than non-responding lesions at 1 month (p = 0.002) and 3 months (p = 0.008). All lesions exhibited necrosis on pathological analysis (11 partially viable, 10 complete pathological necrosis (CPN)) but no imaging criterion was able to predict CPN. mRECIST (±ADC) at 1 (κ ± ADC = 0.08/0.06) or 3 months (κ = -0.06/-0.06) were poor predictors of pathological response. As soon as 1 month post-treatment, mRECIST and volumetric ADC performed better than traditional size RECIST or volumetric parameters in detecting imaging response to Y90; however, CPN cannot be predicted by any criteria. Improvements in methodologies to assess response and identification of better surrogates are awaited.

  19. Patient SWAP-200 Personality Dimensions and FFM Traits: Do They Predict Therapist Responses?

    Science.gov (United States)

    Tanzilli, Annalisa; Lingiardi, Vittorio; Hilsenroth, Mark

    2017-08-24

    The main aim of this study was to examine the relationship between therapists' emotional responses and patients' personality evaluated by 3 dimensional diagnostic approaches empirically derived from the Shedler-Westen Assessment Procedure-200 (SWAP-200; Westen & Shedler, 1999a, 1999b): Two of these rely on the 5-factor model (FFM) domains, that were assessed with different SWAP-200 FFM versions developed by Shedler and Westen (SW-FFM scales; 2004) and McCrae, Löckenhoff, and Costa (MLC-FFM scales; 2005); the third approach is based on a multifaceted model of personality syndromes (SWAP personality dimension scales; see Shedler & Westen, 2004). A national sample of psychiatrists and psychologists (N = 166) of various theoretical orientations completed the Therapist Response Questionnaire (TRQ; Zittel Conklin & Westen, 2003) to identify patterns of therapist response, and the SWAP-200 to assess personality regarding a patient currently in their care. The findings showed good levels of construct validity between the SW-FFM and MLC-FFM scales, with the exception of the Openness trait. Moreover, specific SW-FFM and MLC-FFM scales were significantly associated with distinct SWAP personality dimension scales according in a conceptually meaningful nomological network. Although there were significant, theoretically coherent, and systematic relationships between therapists' responses and patients' personality features, overall the contribution of the SW-FFM and MLC-FFM traits in predicting therapists' responses was less sizable than the SWAP personality dimensions. These results seem to confirm the diagnostic and therapeutic value of countertransference as an essential tool in understanding psychological traits/dimensions that underlie the patients' psychopathology, both from within and outside of the FFM. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Intravoxel incoherent motion (IVIM histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Gene Y. Cho

    Full Text Available Objective: To examine the prognostic capabilities of intravoxel incoherent motion (IVIM metrics and their ability to predict response to neoadjuvant treatment (NAT. Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. Methods: This IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions. Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12–14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT, excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. Results: Average, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased (∼70% and VTT% values generally decreased (∼20% post-treatment. Conclusion: Dp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT. Keywords: Breast cancer, Diffusion weighted MRI, Intravoxel incoherent motion, Neoadjuvant treatment, Response evaluation criteria in solid tumors

  1. Day differences in the cortisol awakening response predict day differences in synaptic plasticity in the brain.

    Science.gov (United States)

    Clow, Angela; Law, Robin; Evans, Phil; Vallence, Ann-Maree; Hodyl, Nicolette A; Goldsworthy, Mitchell R; Rothwell, John R; Ridding, Michael C

    2014-05-01

    The cortisol awakening response (CAR) is the most prominent, dynamic and variable part of the circadian pattern of cortisol secretion. Despite this, its precise purpose is unknown. Aberrant patterns of the CAR are associated with impaired physical and mental health and reduced cognitive function, suggesting that it may have a pervasive role or roles. It has been suggested that the CAR primes the brain for the expected demands of the day but the mechanisms underlying this process are unknown. We examined temporal covariation of the CAR and rapid transcranial magnetic stimulation (rTMS)-induced long term depression (LTD)-like responses in the motor cortex. Plasticity was evaluated across 180 measures from five time points on four sessions across nine healthy researcher participants, mean age 25 ± 2.5 years. Plasticity estimates were obtained in the afternoon after measurement of the CAR on 4 days, at least 3 days apart. As both CAR magnitude and rTMS-induced responses are variable across days, we hypothesized that days with larger than individual average CARs would be associated with a greater than individual average plasticity response. This was confirmed by mixed regression modelling where variation in the CAR predicted variation in rTMS-induced responses (df: 1, 148.24; F: 10.41; p = 0.002). As the magnitude of the CAR is regulated by the "master" circadian CLOCK, and synaptic plasticity is known to be modulated by peripheral "slave" CLOCK genes, we suggest that the CAR may be a mediator between the master and peripheral circadian systems to entrain daily levels of synaptic plasticity.

  2. 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.

  3. Diagnostic Value of Electrocardiogram in Predicting Exaggerated Blood Pressure Response to Exercise Stress Testing.

    Science.gov (United States)

    Eshraghi, Ali; Ebdali, Reyhaneh Takalloo; Sajjadi, Seyed Sajed; Golnezhad, Reza

    2016-08-01

    It is believed that an exaggerated blood pressure response (EBPR) to exercise stress test is associated with a higher risk of cardiovascular events. It is also assumed that QT dispersion (QT-d), which was originally proposed to measure the spatial dispersion of ventricular recovery times, may have a relationship to cardiovascular events. The objective of this study was to examine the difference of changes in QT-d, Maxi-QT, Mini-QT, and QT-c (corrected QT interval) of the electrocardiogram in two groups of patients with exaggerated blood pressure responses (EBPR group) and normal responses (control group) to exercise testing. Also, the diagnostic value of each of these criteria in the prediction of EBPR was studied. This cross-sectional study was conducted from May 2015 to February 2016 on patients suspected of coronary artery disease (CAD) undergoing exercise testing who had been referred to Ghaem and Imam Reza hospitals in Mashhad (Iran). All patients underwent a treadmill exercise test with the 12-lead ECG, which was optically scanned and digitized for analysis of QT-d, QT max, and QT min. Patients were divided into two groups of normal and EBPR to exercise testing. QT changes of ECG were compared between the two groups, and the diagnostic accuracy of QT variables for prediction of EBPR to exercise testing was studied. A multiple linear regression analysis (MLR), Pearson Chi-qquare, independent samples t-test, and receiver operating characteristic (ROC) curve were used as statistical methods in IBM SPSS version 19. Sixty patients (55% male) with a mean age of 50.48 ± 10.89 years were studied in two groups of normal (n=30) and exaggerated blood pressure response (n=30) to exercise testing. Maximum QT and QT dispersion were statistically different in individuals' exaggerated blood pressure response to exercise stress test (p exercise testing. Also, a significant difference in maxi-QT and QT-d was observed between two groups of patients with normal and EBPR during

  4. Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

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    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).

  5. The evolving landscape of Title IX: Predicting mandatory reporters' responses to sexual assault disclosures.

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    Holland, Kathryn J; Cortina, Lilia M

    2017-10-01

    Approximately 1 in 4 women is sexually assaulted in college, a problem that federal law has attempted to address with recent changes. Under the evolving landscape of Title IX, and related law, universities nationwide have overhauled their sexual assault policies, procedures, and resources. Many of the new policies designate undergraduate resident assistants (RAs) as Responsible Employees-requiring them to provide assistance and report to the university if a fellow student discloses sexual assault. We investigated factors that predict the likelihood of RAs enacting their policy mandate, that is, reporting sexual assault disclosures to university authorities and referring survivors to sexual assault resources. Based on data from 305 Responsible Employee RAs, we found that likelihood to report and refer varied, depending on RAs' knowledge of reporting procedures and resources, trust in these supports, and perceptions of mandatory reporting policy. Understanding mandatory reporter behavior is crucial, because help-providers' responses can have serious implications for the recovery of sexual assault survivors. Our findings elucidate some effects of changes in the interpretation and implementation of Title IX, with potential to inform the development of more theoretically and empirically informed policies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. 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.

  7. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa

    Directory of Open Access Journals (Sweden)

    Ma Weimin

    2011-01-01

    Full Text Available Abstract In order to examine whether variation in interleukin-10 promoter polymorphism would predict the likelihood of sustain response of chronic hepatitis B to treatment with interferon alfa (IFN-α, the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with 52 chronic hepatitis B were determined by polymerase chain reaction (PCR-bared techniques, restriction enzyme digestion or direct sequencing. The relationship to the outcome of antiviral therapy for chronic HBV infection was studied in 24 patients who had a virologically sustained response(SR and in 28 non-responder(NR to interferon alfa-2b and several IL-10 variants were more frequent among SR compared with NR. Carriage of the -592A allele, -592A/A genotype and -1082/-1819/-592 ATA haplotype was associated with SR. Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis B to IFN-α therapy.

  8. Prevalence of Ventilatory Conditions for Dynamic Fluid Responsiveness Prediction in 2 Tertiary Intensive Care Units.

    Science.gov (United States)

    Mendes, Pedro V; Rodrigues, Bruno N; Miranda, Leandro C; Zampieri, Fernando G; Queiroz, Eduardo L; Schettino, Guilherme; Azevedo, Luciano C; Park, Marcelo; Taniguchi, Leandro U

    2016-05-01

    Dynamic parameters for fluid responsiveness obtained from heart-lung interaction during invasive mechanical ventilation require specific conditions not always present in intensive care unit (ICU) patients. The aim of this study was to examine the prevalence of these conditions in critically ill patients. We conducted a prospective observational study in 2 medical-surgical ICUs. We evaluated whether it would be possible to measure dynamic indices of fluid responsiveness when fluid expansion was administered. We recorded whether the patients were in controlled invasive mechanical ventilation with tidal volume >8 mL/kg and without arrhythmias. The proportion of patients who fulfilled these conditions was recorded. A post hoc subgroup analyses by terciles of Simplified Acute Physiology Score 3 (SAPS3) were performed. A total of 826 fluid challenges were undertaken in 424 patients during the study. The use of controlled mechanical ventilation with tidal volume > 8 mL/kg and without arrhythmias occurred in only 2.9% of the patients at the time of fluid challenge episodes. There was an increase in the prevalence of these conditions as the severity of the patients also increased: lower tercile of SAPS3 (0%), intermediate tercile (2%), and higher tercile (6.9%; P parameters for predicting fluid responsiveness in ICU may have restricted applicability in daily practice, even in more severe patients, due to low prevalence of required conditions. © The Author(s) 2014.

  9. A general method to predict unbalance responses of geared rotor systems

    Science.gov (United States)

    Yang, Yi; Wang, Jiaying; Wang, Xurong; Dai, Yiping

    2016-10-01

    This paper concerns a general method to predict unbalance responses for a geared rotor system, which contains n shafts and at least n-1 spur and/or helical gear meshes. Finite element models of spur gear pairs and helical gear pairs are developed with arbitrary orientation angles, respectively. Then, a general method with a strict mathematical proof is proposed to calculate maximum axis radii of the unbalance response orbit for a geared rotor system. The proposed method is validated through three applications, i.e, a spur geared two-shaft rotor system, a spur geared multi-shaft rotor system and a helical geared multi-shaft rotor system. A classical modal synthesis is also employed as a comparison. Results show that proposed analytical solutions are consistent with the numerical results and have advantages over the modal synthesis. In addition, plenty of computer processing time can be saved with the proposed method. The method reported here may be of interest to engineers and educators attempting to handle the unbalance response analysis effectively and easily.

  10. 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.

  11. 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.

  12. 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. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  13. Novelty response and 50 kHz ultrasonic vocalizations: Differential prediction of locomotor and affective response to amphetamine in Sprague-Dawley rats.

    Science.gov (United States)

    Garcia, Erik J; Cain, Mary E

    2016-02-01

    Novelty and sensation seeking (NSS) predisposes humans and rats to experiment with psychostimulants. In animal models, different tests of NSS predict different phases of drug dependence. Ultrasonic vocalizations (USVs) are evoked by psychomotor stimulants and measure the affective/motivation response to stimuli, yet the role NSS has on USVs in response to amphetamine is not determined. The aim of the present study was to determine if individual differences in NSS and USVs can predict locomotor and USV response to amphetamine (0.0, 0.3, and 1.0 mg/kg) after acute and chronic exposure. Thirty male rats were tested for their response to novelty (IEN), choice to engage in novelty (NPP), and heterospecific play (H-USV). Rats were administered non-contingent amphetamine or saline for seven exposures, and USVs and locomotor activity were measured. After a 14-day rest, rats were administered a challenge dose of amphetamine. Regression analyses indicated that amphetamine dose-dependently increased locomotor activity and the NPP test negatively predicted treatment-induced locomotor activity. The H-USV test predicted treatment-induced frequency-modulated (FM) USVs, but the strength of prediction depended on IEN response. Results provide evidence that locomotor activity and FM USVs induced by amphetamine represent different behavioral responses. The prediction of amphetamine-induced FM USVs by the H-USV screen was changed by the novelty response, indicating that the affective value of amphetamine-measured by FM USVs-depends on novelty response. This provides evidence that higher novelty responders may develop a tolerance faster and may escalate intake faster.

  14. A method for predicting full scale buffet response with rigid wind tunnel model fluctuating pressure data. Volume 1: Prediction method development and assessment

    Science.gov (United States)

    Cunningham, A. M., Jr.; Benepe, D. B.; Watts, D.; Waner, P. G.

    1978-01-01

    The method requires unsteady aerodynamic forces, natural airplane modes, and the measured pressure data as input. A gust response computer program is used to calculate buffet response due to the forcing function posed by the measured pressure data. By calculating both symmetric and antisymmetric solutions, upper and lower bounds on full-scale buffet response are formed. Comparisons of predictions with flight test results are made and the effects of horizontal tail loads and static aeroelasticity are shown. Discussions are also presented on the effects of primary wing torsion modes, chordwise and spanwise phase angles, and altitude.

  15. Response time variability and response inhibition predict affective problems in adolescent girls, not in boys : the TRAILS study

    NARCIS (Netherlands)

    van Deurzen, Patricia A. M.; Buitelaar, Jan K.; Brunnekreef, J. Agnes; Ormel, Johan; Minderaa, Ruud B.; Hartman, Catharina A.; Huizink, Anja C.; Speckens, Anne E. M.; Oldehinkel, A. J.; Slaats-Willemse, Dorine I. E.

    The present study examines the relationship between neurocognitive functioning and affective problems through adolescence, in a cross-sectional and longitudinal perspective. Baseline response speed, response speed variability, response inhibition, attentional flexibility and working memory were

  16. Quitting smoking : The importance of non-smoker identity in predicting smoking behaviour and responses to a smoking ban

    NARCIS (Netherlands)

    Meijer, Eline; Gebhardt, Winifred A.; Dijkstra, Arie; Willemsen, Marc C.; Van Laar, Colette

    2015-01-01

    Objective: We examined how smoker' and non-smoker' self- and group-identities and socio-economic status (SES) may predict smoking behaviour and responses to antismoking measures (i.e. the Dutch smoking ban in hospitality venues). We validated a measure of responses to the smoking ban.Design:

  17. Examining the Predictive Validity of a Dynamic Assessment of Decoding to Forecast Response to Tier 2 Intervention

    Science.gov (United States)

    Cho, Eunsoo; Compton, Donald L.; Fuchs, Douglas; Fuchs, Lynn S.; Bouton, Bobette

    2014-01-01

    The purpose of this study was to examine the role of a dynamic assessment (DA) of decoding in predicting responsiveness to Tier 2 small-group tutoring in a response-to-intervention model. First grade students (n = 134) who did not show adequate progress in Tier 1 based on 6 weeks of progress monitoring received Tier 2 small-group tutoring in…

  18. Absolute lymphocyte count predicts the response to new H1N1 vaccination in pediatric cancer patients

    NARCIS (Netherlands)

    Mavinkurve-Groothuis, A.M.C.; Flier, M. van der; Stelma, F.F.; Leer-Buter, C.C. van; Preijers, F.W.M.B.; Hoogerbrugge, P.M.

    2013-01-01

    We measured the vaccination response to the new H1N1 in relation to lymphocyte count prior to vaccination in pediatric cancer patients. Absolute lymphocyte count above the lower normal limits (LNL) for age prior to vaccination predicts the response to influenza vaccination in pediatric cancer

  19. Short- and long-term effects of habitat fragmentation differ but are predicted by response to the matrix.

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    Evans, Maldwyn J; Banks, Sam C; Driscoll, Don A; Hicks, Andrew J; Melbourne, Brett A; Davies, Kendi F

    2017-03-01

    Habitat loss and fragmentation are major threats to biodiversity and ecosystem processes. Our current understanding of the impacts of habitat loss and fragmentation is based largely on studies that focus on either short-term or long-term responses. Short-term responses are often used to predict long-term responses and make management decisions. The lack of studies comparing short- and long-term responses to fragmentation means we do not adequately understand when and how well short-term responses can be extrapolated to predict long-term responses, and when or why they cannot. To address this gap, we used data from one of the world's longest-running fragmentation experiments, The Wog Wog Habitat Fragmentation Experiment. Using data for carabid beetles, we found that responses in the long term (more than 22 yr post-fragmentation ≈22 generations) often contrasted markedly with those in the short term (5 yr post-fragmentation). The total abundance of all carabids, species richness and the occurrence of six species declined in the short term in the fragments but increased over the long term. The occurrence of three species declined initially and continued to decline, whilst another species was positively affected initially but decreased in the long term. Species' responses to the matrix that surrounds the fragments strongly predicted both the direction (increase/decline in occurrence) and magnitude of their responses to fragmentation. Additionally, species' responses to the matrix were somewhat predicted by their preferences for different types of native habitat (open vs. shaded). Our study highlights the degree of the matrix's influence in fragmented landscapes, and how this influence can change over time. We urge caution in using short-term responses to forecast long-term responses in cases where the matrix (1) impacts species' responses to fragmentation (by isolating them, creating new habitat or altering fragment habitat) and (2) is likely to change through time

  20. 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...

  1. Early perception of medication benefit predicts subsequent antipsychotic response in schizophrenia: "the consumer has a point" revisited.

    Science.gov (United States)

    Ascher-Svanum, Haya; Weiden, Peter; Nyhuis, Allen W; Faries, Douglas E; Stauffer, Virginia; Kollack-Walker, Sara; Kinon, Bruce J

    2014-07-01

    An easy-to-administer tool for predicting response to antipsychotic treatment could improve the acute management of patients with schizophrenia. We assessed whether a patient's perception of medication benefit early in treatment could predict subsequent response or nonresponse to continued use of the same treatment. This post hoc analysis used data from a randomized, open-label trial of antipsychotics for treatment of schizophrenia in which attitudes about medication adherence were assessed after two weeks of antipsychotic treatment using the Rating of Medication Influences (ROMI) scale. The analysis included 439 patients who had Positive and Negative Syndrome Scale (PANSS) and ROMI scale data at Weeks 2 and 8. Scores on the ROMI subscale Perceived Medication Benefit factor were used to predict subsequent antipsychotic response at Week 8, defined as a .20% reduction from baseline on the PANSS. Logistic regression was used to identify a cut-off score for the Perceived Medication Benefit factor that could accurately identify antipsychotic responders vs. nonresponders at Wee