Dopamine-related deficit in reward learning after catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa

Disturbances in reward processing have been implicated in bulimia nervosa (BN). Abnormalities in processing reward-related stimuli might be linked to dysfunctions of the catecholaminergic neurotransmitter system, but findings have been inconclusive. A powerful way to investigate the relationship between catecholaminergic function and behavior is to examine behavioral changes in response to experimental catecholamine depletion (CD). The purpose of this study was to uncover putative catecholaminergic dysfunction in remitted subjects with BN who performed a reinforcement-learning task after CD. CD was achieved by oral alpha-methyl-para-tyrosine (AMPT) in 19 unmedicated female subjects with remitted BN (rBN) and 28 demographically matched healthy female controls (HC). Sham depletion administered identical capsules containing diphenhydramine. The study design consisted of a randomized, double-blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were reward learning in a probabilistic reward task analyzed using signal-detection theory. Secondary outcome measures included self-report assessments, including the Eating Disorder Examination-Questionnaire. Relative to healthy controls, rBN subjects were characterized by blunted reward learning in the AMPT-but not in placebo-condition. Highlighting the specificity of these findings, groups did not differ in their ability to perceptually distinguish between stimuli. Increased CD-induced anhedonic (but not eating disorder) symptoms were associated with a reduced response bias toward a more frequently rewarded stimulus. In conclusion, under CD, rBN subjects showed reduced reward learning compared with healthy control subjects. These deficits uncover disturbance of the central reward processing systems in rBN related to altered brain catecholamine levels, which might reflect a trait-like deficit increasing vulnerability to BN.

Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages

There is increasing evidence that strain variation in Mycobacterium tuberculosis complex (MTBC) might influence the outcome of tuberculosis infection and disease. To assess genotype-phenotype associations, phylogenetically robust molecular markers and appropriate genotyping tools are required. Most current genotyping methods for MTBC are based on mobile or repetitive DNA elements. Because these elements are prone to convergent evolution, the corresponding genotyping techniques are suboptimal for phylogenetic studies and strain classification. By contrast, single nucleotide polymorphisms (SNP) are ideal markers for classifying MTBC into phylogenetic lineages, as they exhibit very low degrees of homoplasy. In this study, we developed two complementary SNP-based genotyping methods to classify strains into the six main human-associated lineages of MTBC, the "Beijing" sublineage, and the clade comprising Mycobacterium bovis and Mycobacterium caprae. Phylogenetically informative SNPs were obtained from 22 MTBC whole-genome sequences. The first assay, referred to as MOL-PCR, is a ligation-dependent PCR with signal detection by fluorescent microspheres and a Luminex flow cytometer, which simultaneously interrogates eight SNPs. The second assay is based on six individual TaqMan real-time PCR assays for singleplex SNP-typing. We compared MOL-PCR and TaqMan results in two panels of clinical MTBC isolates. Both methods agreed fully when assigning 36 well-characterized strains into the main phylogenetic lineages. The sensitivity in allele-calling was 98.6% and 98.8% for MOL-PCR and TaqMan, respectively. Typing of an additional panel of 78 unknown clinical isolates revealed 99.2% and 100% sensitivity in allele-calling, respectively, and 100% agreement in lineage assignment between both methods. While MOL-PCR and TaqMan are both highly sensitive and specific, MOL-PCR is ideal for classification of isolates with no previous information, whereas TaqMan is faster for confirmation. Furthermore, both methods are rapid, flexible and comparably inexpensive.

Associative processing and paranormal belief

In the present study we introduce a novel task for the quantitative assessment of both originality and speed of individual associations. This 'BAG' (Bridge-the-Associative-Gap) task was used to investigate the relationships between creativity and paranormal belief. Twelve strong 'believers' and 12 strong 'skeptics' in paranormal phenomena were selected from a large student population (n > 350). Subjects were asked to produce single-word associations to word pairs. In 40 trials the two stimulus words were semantically indirectly related and in 40 other trials the words were semantically unrelated. Separately for these two stimulus types, response commonalities and association latencies were calculated. The main finding was that for unrelated stimuli, believers produced associations that were more original (had a lower frequency of occurrence in the group as a whole) than those of the skeptics. For the interpretation of the result we propose a model of association behavior that captures both 'positive' psychological aspects (i.e., verbal creativity) and 'negative' aspects (susceptibility to unfounded inferences), and outline its relevance for psychiatry. This model suggests that believers adopt a looser response criterion than skeptics when confronted with 'semantic noise'. Such a signal detection view of the presence/absence of judgments for loose semantic relations may help to elucidate the commonalities between creative thinking, paranormal belief and delusional ideation.

School-age children show a bias toward fantasy classifications after playing a platform game

We investigated the influence of playing a video game on children’s ability to distinguish between fantasy and reality. School-age children played a platform game for 15 min and then performed a fantasy/reality distinction task in which they were to judge whether images (from the platform game and from other games) were fantasy images or reality images. Unlike those in the control group (who played a memory game), the children in the experimental group showed a response bias toward mistakenly classifying reality images from the video game as fantasy images (as determined by means of an analysis based on signal detection theory). We conclude that playing the video game exerted a short-term influence on children’s ability to distinguish between fantasy and reality.

Head to head comparison of optical coherence tomography, intravascular ultrasound echogenicity and virtual histology for the detection of changes in polymeric struts over time: insights from the ABSORB trial

To analyse and to compare the changes in the various optical coherence tomography (OCT), echogenicity and intravascular ultrasound virtual histology (VH) of the everolimus-eluting bioresorbable scaffold (ABSORB) degradation parameters during the first 12 months after ABSORB implantation. In the ABSORB study, changes in the appearance of the ABSORB scaffold were monitored over time using various intracoronary imaging modalities. The scaffold struts exhibited a progressive change in their black core area by OCT, in their ultrasound derived grey level intensity quantified by echogenicity, and in their backscattering ultrasound signal, identified as "pseudo dense-calcium" (DC) by VH.

Influence of the condition of the adjacent tooth surface on fluorescence measurements for the detection of approximal caries

The aim of this study was to test whether the status of the adjacent tooth surface has an influence on the signal of a new laser fluorescence (LF) device for the detection of approximal caries. Seventy-eight teeth were selected from a pool of extracted permanent human molars, frozen at -20 degrees C until use. Before being measured the teeth were defrosted, cleaned, and any calculus removed. As a control, a defined approximal surface of each tooth was measured with the LF device holding the tip with the detecting- and the reverse-side on it, but without a neighboring tooth contacting the surface. The proximal site under examination was then placed adjacent to a tooth, which had deep dentinal caries, a composite restoration, a provisional ZnO-Eugenol restoration, or a ceramic restoration. The adjacent tooth with the ZnO-Eugenol restoration, the composite restoration, and the dentinal caries all demonstrated a statistically significant increase of LF readings on sound tooth surfaces. Teeth with enamel or dentinal caries were only slightly (and not statistically significantly) influenced by the different types of neighboring surfaces compared with the control LF readings. It can be concluded that caries detection of approximal tooth surfaces with the new LF system might be influenced by the condition of the adjacent tooth surface.

Dissociated lateralization of transient and sustained blood oxygen level-dependent signal components in human primary auditory cortex

Among other auditory operations, the analysis of different sound levels received at both ears is fundamental for the localization of a sound source. These so-called interaural level differences, in animals, are coded by excitatory-inhibitory neurons yielding asymmetric hemispheric activity patterns with acoustic stimuli having maximal interaural level differences. In human auditory cortex, the temporal blood oxygen level-dependent (BOLD) response to auditory inputs, as measured by functional magnetic resonance imaging (fMRI), consists of at least two independent components: an initial transient and a subsequent sustained signal, which, on a different time scale, are consistent with electrophysiological human and animal response patterns. However, their specific functional role remains unclear. Animal studies suggest these temporal components being based on different neural networks and having specific roles in representing the external acoustic environment. Here we hypothesized that the transient and sustained response constituents are differentially involved in coding interaural level differences and therefore play different roles in spatial information processing. Healthy subjects underwent monaural and binaural acoustic stimulation and BOLD responses were measured using high signal-to-noise-ratio fMRI. In the anatomically segmented Heschl's gyrus the transient response was bilaterally balanced, independent of the side of stimulation, while in opposite the sustained response was contralateralized. This dissociation suggests a differential role at these two independent temporal response components, with an initial bilateral transient signal subserving rapid sound detection and a subsequent lateralized sustained signal subserving detailed sound characterization.

BOLD correlates of edge detection in human auditory cortex

Edges are important cues defining coherent auditory objects. As a model of auditory edges, sound on- and offset are particularly suitable to study their neural underpinnings because they contrast a specific physical input against no physical input. Change from silence to sound, that is onset, has extensively been studied and elicits transient neural responses bilaterally in auditory cortex. However, neural activity associated with sound onset is not only related to edge detection but also to novel afferent inputs. Edges at the change from sound to silence, that is offset, are not confounded by novel physical input and thus allow to examine neural activity associated with sound edges per se. In the first experiment, we used silent acquisition functional magnetic resonance imaging and found that the offset of pulsed sound activates planum temporale, superior temporal sulcus and planum polare of the right hemisphere. In the planum temporale and the superior temporal sulcus, offset response amplitudes were related to the pulse repetition rate of the preceding stimulation. In the second experiment, we found that these offset-responsive regions were also activated by single sound pulses, onset of sound pulse sequences and single sound pulse omissions within sound pulse sequences. However, they were not active during sustained sound presentation. Thus, our data show that circumscribed areas in right temporal cortex are specifically involved in identifying auditory edges. This operation is crucial for translating acoustic signal time series into coherent auditory objects.

Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor

Convulxin, a powerful platelet activator, was isolated from Crotalus durissus terrificus venom, and 20 amino acid N-terminal sequences of both subunits were determined. These indicated that convulxin belongs to the heterodimeric C-type lectin family. Neither antibodies against GPIb nor echicetin had any effect on convulxin-induced platelet aggregation showing that, in contrast to other venom C-type lectins acting on platelets, GPIb is not involved in convulxin-induced platelet activation. In addition, partially reduced/denatured convulxin only affects collagen-induced platelet aggregation. The mechanism of convulxin-induced platelet activation was examined by platelet aggregation, detection of time-dependent tyrosine phosphorylation of platelet proteins, and binding studies with 125I-convulxin. Convulxin induces signal transduction in part like collagen, involving the time-dependent tyrosine phosphorylation of Fc receptor gamma chain, phospholipase Cgamma2, p72(SYK), c-Cbl, and p36-38. However, unlike collagen, pp125(FAK) and some other bands are not tyrosine-phosphorylated. Convulxin binds to a glycosylated 62-kDa membrane component in platelet lysate and to p62/GPVI immunoprecipitated by human anti-p62/GPVI antibodies. Convulxin subunits inhibit both aggregation and tyrosine phosphorylation in response to collagen. Piceatannol, a tyrosine kinase inhibitor with some specificity for p72(SYK), showed differential effects on collagen and convulxin-stimulated signaling. These results suggest that convulxin uses the p62/GPVI but not the alpha2beta1 part of the collagen signaling pathways to activate platelets. Occupation and clustering of p62/GPVI may activate Src family kinases phosphorylating Fc receptor gamma chain and, by a mechanism previously described in T- and B-cells, activate p72(SYK) that is critical for downstream activation of platelets.

Distributed sensor failure detection in sensor networks

We investigate the problem of distributed sensors' failure detection in networks with a small number of defective sensors, whose measurements differ significantly from the neighbor measurements. We build on the sparse nature of the binary sensor failure signals to propose a novel distributed detection algorithm based on gossip mechanisms and on Group Testing (GT), where the latter has been used so far in centralized detection problems. The new distributed GT algorithm estimates the set of scattered defective sensors with a low complexity distance decoder from a small number of linearly independent binary messages exchanged by the sensors. We first consider networks with one defective sensor and determine the minimal number of linearly independent messages needed for its detection with high probability. We then extend our study to the multiple defective sensors detection by modifying appropriately the message exchange protocol and the decoding procedure. We show that, for small and medium sized networks, the number of messages required for successful detection is actually smaller than the minimal number computed theoretically. Finally, simulations demonstrate that the proposed method outperforms methods based on random walks in terms of both detection performance and convergence rate.

Evidence of direct detection of interstellar deuterium in the local interstellar medium by IBEX

We report the first in situ measurements of neutral deuterium originating in the local interstellar medium (LISM) in Earth’s orbit. These measurements were performed with the IBEX-Lo camera on NASA’s interstellar boundary explorer (IBEX) satellite. All data from the spring observation periods of 2009 through 2011 have been analysed. In the three years of the IBEX mission time, the observation geometry and orbit allowed for a total observation time of 115.3 days for the LISM. However, the effects of the spinning spacecraft and the stepping through 8 energy channels mean that we are only observing the interstellar wind for a total time of 1.44 days, in which 2 counts for interstellar deuterium were collected. We report here a conservative number, because a possibility of systematic error or additional noise, though eliminated in our analysis to the best of our knowledge, only supports detection at a 1-sigma level. From these observations, we derive a ratio D/H = (5.8 ± 4.4) × 10-4 at 1 AU. After modelling the transport and loss of D and H from the termination shock to Earth’s orbit, we find that our result of D/HLISM = (1.6 ± 1.2) × 10-5 agrees with D/HLIC = (1.6 ± 0.4) × 10-5 for the local interstellar cloud. This weak interstellar signal is extracted from a strong terrestrial background signal consisting of sputter products from the sensor’s conversion surface. As reference, we accurately measure the terrestrial D/H ratio in these sputtered products and then discriminate this terrestrial background source. Because of the diminishing D and H signal at Earth’s orbit during the rising solar activity due to photoionisation losses and increased photon pressure, our result demonstrates that in situ measurements of interstellar deuterium in the inner heliosphere are only possible during solar minimum conditions.

A robust reference signal generator for synchronized ventricular assist devices

Ventricular assist devices (VADs) are blood pumps that offer an option to support the circulation of patients with severe heart failure. Since a failing heart has a remaining pump function, its interaction with the VAD influences the hemodynamics. Ideally, the heart's action is taken into account for actuating the device such that the device is synchronized to the natural cardiac cycle. To realize this in practice, a reliable real-time algorithm for the automatic synchronization of the VAD to the heart rate is required. This paper defines the tasks such an algorithm needs to fulfill: the automatic detection of irregular heart beats and the feedback control of the phase shift between the systolic phases of the heart and the assist device. We demonstrate a possible solution to these problems and analyze its performance in two steps. First, the algorithm is tested using the MIT-BIH arrhythmia database. Second, the algorithm is implemented in a controller for a pulsatile and a continuous-flow VAD. These devices are connected to a hybrid mock circulation where three test scenarios are evaluated. The proposed algorithm ensures a reliable synchronization of the VAD to the heart cycle, while being insensitive to irregularities in the heart rate.

Localization of Epileptogenic Zone on Pre-surgical Intracranial EEG Recordings: Toward a Validation of Quantitative Signal Analysis Approaches

In patients diagnosed with pharmaco-resistant epilepsy, cerebral areas responsible for seizure generation can be defined by performing implantation of intracranial electrodes. The identification of the epileptogenic zone (EZ) is based on visual inspection of the intracranial electroencephalogram (IEEG) performed by highly qualified neurophysiologists. New computer-based quantitative EEG analyses have been developed in collaboration with the signal analysis community to expedite EZ detection. The aim of the present report is to compare different signal analysis approaches developed in four different European laboratories working in close collaboration with four European Epilepsy Centers. Computer-based signal analysis methods were retrospectively applied to IEEG recordings performed in four patients undergoing pre-surgical exploration of pharmaco-resistant epilepsy. The four methods elaborated by the different teams to identify the EZ are based either on frequency analysis, on nonlinear signal analysis, on connectivity measures or on statistical parametric mapping of epileptogenicity indices. All methods converge on the identification of EZ in patients that present with fast activity at seizure onset. When traditional visual inspection was not successful in detecting EZ on IEEG, the different signal analysis methods produced highly discordant results. Quantitative analysis of IEEG recordings complement clinical evaluation by contributing to the study of epileptogenic networks during seizures. We demonstrate that the degree of sensitivity of different computer-based methods to detect the EZ in respect to visual EEG inspection depends on the specific seizure pattern.

Metastases in normal-sized pelvic lymph nodes: detection with diffusion-weighted MR imaging

PURPOSE To prospectively assess the diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging in the detection of pelvic lymph node metastases in patients with prostate and/or bladder cancer staged as N0 with preoperative cross-sectional imaging. MATERIALS AND METHODS This study was approved by an independent ethics committee. Written informed consent was obtained from all patients. Patients with no enlarged lymph nodes on preoperative cross-sectional images who were scheduled for radical resection of the primary tumor and extended pelvic lymph node dissection were enrolled. All patients were examined with a 3-T MR unit, and examinations included conventional and DW MR imaging of the entire pelvis. Image analysis was performed by three independent readers blinded to any clinical information. Metastases were diagnosed on the basis of high signal intensity on high b value DW MR images and morphologic features (shape, border). Histopathologic examination served as the standard of reference. Sensitivity and specificity were calculated, and bias-corrected 95% confidence intervals (CIs) were obtained with the bootstrap method. The Fleiss and Cohen κ and median test were applied for statistical analyses. RESULTS A total of 4846 lymph nodes were resected in 120 patients. Eighty-eight lymph node metastases were found in 33 of 120 patients (27.5%). Short-axis diameter of these metastases was less than or equal to 3 mm in 68, more than 3 mm to 5 mm in 13, more than 5 mm to 8 mm in five; and more than 8 mm in two. On a per-patient level, the three readers correctly detected metastases in 26 (79%; 95% CI: 64%, 91%), 21 (64%; 95% CI: 45%, 79%), and 25 (76%; 95% CI: 60%, 90%) of the 33 patients with metastases, with respective specificities of 85% (95% CI: 78%, 92%), 79% (95% CI: 70%, 88%), and 84% (95% CI: 76%, 92%). Analyzed according to hemipelvis, lymph node metastases were detected with histopathologic examination in 44 of 240 pelvic sides (18%); the three readers correctly detected these on DW MR images in 26 (59%; 95% CI: 45%, 73%), 19 (43%; 95% CI: 27%, 57%), and 28 (64%; 95% CI: 47%, 78%) of the 44 cases. CONCLUSION DW MR imaging enables noninvasive detection of small lymph node metastases in normal-sized nodes in a substantial percentage of patients with prostate and bladder cancer diagnosed as N0 with conventional cross-sectional imaging techniques.