Advanced papillary serous carcinoma of the uterine cervix: a case with a remarkable response to paclitaxel and carboplatin combination chemotherapy

Papillary serous carcinoma of the uterine cervix (PSCC) is a very rare, recently described variant of cervical adenocarcinoma. This review, describes a case of stage IV PSCC whose main tumor existed in the uterine cervix and invaded one third of the inferior part of the anterior and posterior vaginal walls. Furthermore, it had metastasized from the para-aortic lymph nodes to bilateral neck lymph nodes. Immnoreactivity for CA125 was positive, whereas the staining for p53 and WT-1 were negative in both the original tumor and the metastatic lymph nodes. Six cycles of paclitaxel and carboplatin combination chemotherapy were administered and the PSCC dramatically decreased in size. The main tumor of the uterine cervix showed a complete response by magnetic resonance imaging (MRI), and on rebiopsy, more than 95% of the tumor cells in the cervix had microscopically disapperared. This is the first report of PSCC in which combination chemotherapy was used and showed a remarkable response

Temporal Integration of Movement: The Time-Course of Motion Streaks Revealed by Masking

Temporal integration in the visual system causes fast-moving objects to leave oriented ‘motion streaks’ in their wake, which could be used to facilitate motion direction perception. Temporal integration is thought to occur over 100 ms in early cortex, although this has never been tested for motion streaks. Here we compare the ability of fast-moving (‘streaky’) and slow-moving fields of dots to mask briefly flashed gratings either parallel or orthogonal to the motion trajectory. Gratings were presented at various asynchronies relative to motion onset (from to ms) to sample the time-course of the accumulating streaks. Predictions were that masking would be strongest for the fast parallel condition, and would be weak at early asynchronies and strengthen over time as integration rendered the translating dots more streaky and grating-like. The asynchrony where the masking function reached a plateau would correspond to the temporal integration period. As expected, fast-moving dots caused greater masking of parallel gratings than orthogonal gratings, and slow motion produced only modest masking of either grating orientation. Masking strength in the fast, parallel condition increased with time and reached a plateau after 77 ms, providing an estimate of the temporal integration period for mechanisms encoding motion streaks. Interestingly, the greater masking by fast motion of parallel compared with orthogonal gratings first reached significance at 48 ms before motion onset, indicating an effect of backward masking by motion streaks

Reading between Eye Saccades

Background: Skilled adult readers, in contrast to beginners, show no or little increase in reading latencies as a function of the number of letters in words up to seven letters. The information extraction strategy underlying such efficiency in word identification is still largely unknown, and methods that allow tracking of the letter information extraction through time between eye saccades are needed to fully address this question. Methodology/Principal Findings: The present study examined the use of letter information during reading, by means of the Bubbles technique. Ten participants each read 5,000 five-letter French words sampled in space-time within a 200 ms window. On the temporal dimension, our results show that two moments are especially important during the information extraction process. On the spatial dimension, we found a bias for the upper half of words. We also show for the first time that letter positions four, one, and three are particularly important for the identification of five-letter words. Conclusions/Significance: Our findings are consistent with either a partially parallel reading strategy or an optimal serial reading strategy. We show using computer simulations that this serial reading strategy predicts an absence of a wordlength effect for words from four- to seven letters in length. We believe that the Bubbles technique will play an importan

Optimality of Human Contour Integration

For processing and segmenting visual scenes, the brain is required to combine a multitude of features and sensory channels. It is neither known if these complex tasks involve optimal integration of information, nor according to which objectives computations might be performed. Here, we investigate if optimal inference can explain contour integration in human subjects. We performed experiments where observers detected contours of curvilinearly aligned edge configurations embedded into randomly oriented distractors. The key feature of our framework is to use a generative process for creating the contours, for which it is possible to derive a class of ideal detection models. This allowed us to compare human detection for contours with different statistical properties to the corresponding ideal detection models for the same stimuli. We then subjected the detection models to realistic constraints and required them to reproduce human decisions for every stimulus as well as possible. By independently varying the four model parameters, we identify a single detection model which quantitatively captures all correlations of human decision behaviour for more than 2000 stimuli from 42 contour ensembles with greatly varying statistical properties. This model reveals specific interactions between edges closely matching independent findings from physiology and psychophysics. These interactions imply a statistics of contours for which edge stimuli are indeed optimally integrated by the visual system, with the objective of inferring the presence of contours in cluttered scenes. The recurrent algorithm of our model makes testable predictions about the temporal dynamics of neuronal populations engaged in contour integration, and it suggests a strong directionality of the underlying functional anatomy

Heart rate variability and the relationship between trauma exposure age, and psychopathology in a post-conflict setting

BACKGROUND: Cumulative exposure to potentially traumatic events (PTEs) increases risk for mental distress in conflict-affected settings, but the psychophysiological mechanisms that mediate this dose-response relationship are unknown. We investigated diminished heart rate variability (HRV) - an index of vagus nerve function and a robust predictor of emotion regulation capacity - as a vulnerability marker that potentially mediates the association between PTE exposure, age and symptoms of posttraumatic stress disorder (PTSD), psychological distress and aggressive behavior, in a community sample from Timor-Leste - a post-conflict country with a history of mass violence. METHOD: Resting state heart rate data was recorded from 45 cases of PTSD, depression and intermittent explosive disorder (IED); and 29 non-case controls. RESULTS: Resting HRV was significantly reduced in the combined case group compared with non-cases (p = .021; Cohen's d = 0.5). A significant mediation effect was also observed, whereby a sequence of increased age, reduced HRV and elevated PTSD symptoms mediated the association between PTE exposure and distress (B = .06, SE = .05, 95% CI = [.00-.217]) and aggression (B = .02, SE = .02, 95% CI = [.0003-.069])). CONCLUSION: The findings demonstrate an association between diminished resting HRV and psychopathology. Moreover, age-related HRV reductions emerged as a potential psychophysiological mechanism that underlies enhanced vulnerability to distress and aggression following cumulative PTE exposure

Differential Expressions of Adhesive Molecules and Proteases Define Mechanisms of Ovarian Tumor Cell Matrix Penetration/Invasion

Epithelial ovarian cancer is an aggressive and deadly disease and understanding its invasion mechanisms is critical for its treatment. We sought to study the penetration/invasion of ovarian tumor cells into extracellular matrices (ECMs) using a fibroblast-derived three-dimensional (3D) culture model and time-lapse and confocal imaging. Twelve ovarian tumor cells were evaluated and classified into distinct groups based on their ECM remodeling phenotypes; those that degraded the ECM (represented by OVCAR5 cells) and those that did not (represented by OVCAR10 cells). Cells exhibiting a distinct ECM modifying behavior were also segregated by epithelial- or mesenchymal-like phenotypes and uPA or MMP-2/MMP-9 expression. The cells, which presented epithelial-like phenotypes, penetrated the ECM using proteases and maintained intact cell-cell interactions, while cells exhibiting mesenchymal phenotypes modified the matrices via Rho-associated serine/threonine kinase (ROCK) in the absence of apparent cell-cell interactions. Overall, this study demonstrates that different mechanisms of modifying matrices by ovarian tumor cells may reflect heterogeneity among tumors and emphasize the need to systematically assess these mechanisms to better design effective therapies

1/f2 Characteristics and Isotropy in the Fourier Power Spectra of Visual Art, Cartoons, Comics, Mangas, and Different Categories of Photographs

Art images and natural scenes have in common that their radially averaged (1D) Fourier spectral power falls according to a power-law with increasing spatial frequency (1/f2 characteristics), which implies that the power spectra have scale-invariant properties. In the present study, we show that other categories of man-made images, cartoons and graphic novels (comics and mangas), have similar properties. Further on, we extend our investigations to 2D power spectra. In order to determine whether the Fourier power spectra of man-made images differed from those of other categories of images (photographs of natural scenes, objects, faces and plants and scientific illustrations), we analyzed their 2D power spectra by principal component analysis. Results indicated that the first fifteen principal components allowed a partial separation of the different image categories. The differences between the image categories were studied in more detail by analyzing whether the mean power and the slope of the power gradients from low to high spatial frequencies varied across orientations in the power spectra. Mean power was generally higher in cardinal orientations both in real-world photographs and artworks, with no systematic difference between the two types of images. However, the slope of the power gradients showed a lower degree of mean variability across spectral orientations (i.e., more isotropy) in art images, cartoons and graphic novels than in photographs of comparable subject matters. Taken together, these results indicate that art images, cartoons and graphic novels possess relatively uniform 1/f2 characteristics across all orientations. In conclusion, the man-made stimuli studied, which were presumably produced to evoke pleasant and/or enjoyable visual perception in human observers, form a subset of all images and share statistical properties in their Fourier power spectra. Whether these properties are necessary or sufficient to induce aesthetic perception remains to be investigated

Expression and Function of Androgen Receptor Coactivator p44/Mep50/WDR77 in Ovarian Cancer

Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR) and estrogen receptor (ER) in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis

How Noisy Adaptation of Neurons Shapes Interspike Interval Histograms and Correlations

Channel noise is the dominant intrinsic noise source of neurons causing variability in the timing of action potentials and interspike intervals (ISI). Slow adaptation currents are observed in many cells and strongly shape response properties of neurons. These currents are mediated by finite populations of ionic channels and may thus carry a substantial noise component. Here we study the effect of such adaptation noise on the ISI statistics of an integrate-and-fire model neuron by means of analytical techniques and extensive numerical simulations. We contrast this stochastic adaptation with the commonly studied case of a fast fluctuating current noise and a deterministic adaptation current (corresponding to an infinite population of adaptation channels). We derive analytical approximations for the ISI density and ISI serial correlation coefficient for both cases. For fast fluctuations and deterministic adaptation, the ISI density is well approximated by an inverse Gaussian (IG) and the ISI correlations are negative. In marked contrast, for stochastic adaptation, the density is more peaked and has a heavier tail than an IG density and the serial correlations are positive. A numerical study of the mixed case where both fast fluctuations and adaptation channel noise are present reveals a smooth transition between the analytically tractable limiting cases. Our conclusions are furthermore supported by numerical simulations of a biophysically more realistic Hodgkin-Huxley type model. Our results could be used to infer the dominant source of noise in neurons from their ISI statistics

Model Cortical Association Fields Account for the Time Course and Dependence on Target Complexity of Human Contour Perception

Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas) distributed among groups of randomly rotated fragments (clutter). The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms), followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas