Aversive Stimuli and Functional Networks of Fear Learning in PTSD : 734

Background: One characteristic of post traumatic stress disorder is an inability to adapt to a safe environment i.e. to change behavior when predictions of adverse outcomes are not met. Recent studies have also indicated that PTSD patients have altered pain processing, with hyperactivation of the putamen and insula to aversive stimuli (Geuze et al, 2007). The present study examined neuronal responses to aversive and predicted aversive events. Methods: Twenty-four trauma exposed non-PTSD controls and nineteen subjects with PTSD underwent fMRI imaging during a partial reinforcement fear conditioning paradigm, with a mild electric shock as the unconditioned stimuli (UCS). Three conditions were analyzed: actual presentations of the UCS, events when a UCS was expected, but omitted (CS+), and events when the UCS was neither expected nor delivered (CS-). Results: The UCS evoked significant alterations in the pain matrix consisting of the brainstem, the midbrain, the thalamus, the insula, the anterior and middle cingulate and the contralateral somatosensory cortex. PTSD subjects displayed bilaterally elevated putamen activity to the electric shock, as compared to controls. In trials when USC was expected, but omitted, significant activations were observed in the brainstem, the midbrain, the anterior insula and the anterior cingulate. PTSD subjects displayed similar activations, but also elevated activations in the amygdala and the posterior insula. Conclusions: These results indicate altered fear and safety learning in PTSD, and neuronal activations are further explored in terms of functional connectivity using psychophysiological interaction analyses.

Object-oriented Bayesian networks for evaluating DIP-STR profiling results from unbalanced DNA mixtures.

The genetic characterization of unbalanced mixed stains remains an important area where improvement is imperative. In fact, with current methods for DNA analysis (Polymerase Chain Reaction with the SGM Plus™ multiplex kit), it is generally not possible to obtain a conventional autosomal DNA profile of the minor contributor if the ratio between the two contributors in a mixture is smaller than 1:10. This is a consequence of the fact that the major contributor's profile 'masks' that of the minor contributor. Besides known remedies to this problem, such as Y-STR analysis, a new compound genetic marker that consists of a Deletion/Insertion Polymorphism (DIP), linked to a Short Tandem Repeat (STR) polymorphism, has recently been developed and proposed elsewhere in literature [1]. The present paper reports on the derivation of an approach for the probabilistic evaluation of DIP-STR profiling results obtained from unbalanced DNA mixtures. The procedure is based on object-oriented Bayesian networks (OOBNs) and uses the likelihood ratio as an expression of the probative value. OOBNs are retained in this paper because they allow one to provide a clear description of the genotypic configuration observed for the mixed stain as well as for the various potential contributors (e.g., victim and suspect). These models also allow one to depict the assumed relevance relationships and perform the necessary probabilistic computations.

Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.

PURPOSE: Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS: A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS: Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION: Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.

Musical training intensity yields opposite effects on grey matter density in cognitive versus sensorimotor networks.

Using optimized voxel-based morphometry, we performed grey matter density analyses on 59 age-, sex- and intelligence-matched young adults with three distinct, progressive levels of musical training intensity or expertise. Structural brain adaptations in musicians have been repeatedly demonstrated in areas involved in auditory perception and motor skills. However, musical activities are not confined to auditory perception and motor performance, but are entangled with higher-order cognitive processes. In consequence, neuronal systems involved in such higher-order processing may also be shaped by experience-driven plasticity. We modelled expertise as a three-level regressor to study possible linear relationships of expertise with grey matter density. The key finding of this study resides in a functional dissimilarity between areas exhibiting increase versus decrease of grey matter as a function of musical expertise. Grey matter density increased with expertise in areas known for their involvement in higher-order cognitive processing: right fusiform gyrus (visual pattern recognition), right mid orbital gyrus (tonal sensitivity), left inferior frontal gyrus (syntactic processing, executive function, working memory), left intraparietal sulcus (visuo-motor coordination) and bilateral posterior cerebellar Crus II (executive function, working memory) and in auditory processing: left Heschl's gyrus. Conversely, grey matter density decreased with expertise in bilateral perirolandic and striatal areas that are related to sensorimotor function, possibly reflecting high automation of motor skills. Moreover, a multiple regression analysis evidenced that grey matter density in the right mid orbital area and the inferior frontal gyrus predicted accuracy in detecting fine-grained incongruities in tonal music.

Comparison of early cortical networks in efficient and inefficient visual search: an event-related potential study.

Functional magnetic resonance imaging studies have indicated that efficient feature search (FS) and inefficient conjunction search (CS) activate partially distinct frontoparietal cortical networks. However, it remains a matter of debate whether the differences in these networks reflect differences in the early processing during FS and CS. In addition, the relationship between the differences in the networks and spatial shifts of attention also remains unknown. We examined these issues by applying a spatio-temporal analysis method to high-resolution visual event-related potentials (ERPs) and investigated how spatio-temporal activation patterns differ for FS and CS tasks. Within the first 450 msec after stimulus onset, scalp potential distributions (ERP maps) revealed 7 different electric field configurations for each search task. Configuration changes occurred simultaneously in the two tasks, suggesting that contributing processes were not significantly delayed in one task compared to the other. Despite this high spatial and temporal correlation, two ERP maps (120-190 and 250-300 msec) differed between the FS and CS. Lateralized distributions were observed only in the ERP map at 250-300 msec for the FS. This distribution corresponds to that previously described as the N2pc component (a negativity in the time range of the N2 complex over posterior electrodes of the hemisphere contralateral to the target hemifield), which has been associated with the focusing of attention onto potential target items in the search display. Thus, our results indicate that the cortical networks involved in feature and conjunction searching partially differ as early as 120 msec after stimulus onset and that the differences between the networks employed during the early stages of FS and CS are not necessarily caused by spatial attention shifts.

Implementing statistical learning methods through Bayesian networks (Part 2): bayesian evaluations for results of black toner analyses in forensic document examination

This paper presents and discusses the use of Bayesian procedures - introduced through the use of Bayesian networks in Part I of this series of papers - for 'learning' probabilities from data. The discussion will relate to a set of real data on characteristics of black toners commonly used in printing and copying devices. Particular attention is drawn to the incorporation of the proposed procedures as an integral part in probabilistic inference schemes (notably in the form of Bayesian networks) that are intended to address uncertainties related to particular propositions of interest (e.g., whether or not a sample originates from a particular source). The conceptual tenets of the proposed methodologies are presented along with aspects of their practical implementation using currently available Bayesian network software.

Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.

BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

Constructing brain functional networks from EEG: partial and unpartial correlations.

We consider electroencephalograms (EEGs) of healthy individuals and compare the properties of the brain functional networks found through two methods: unpartialized and partialized cross-correlations. The networks obtained by partial correlations are fundamentally different from those constructed through unpartial correlations in terms of graph metrics. In particular, they have completely different connection efficiency, clustering coefficient, assortativity, degree variability, and synchronization properties. Unpartial correlations are simple to compute and they can be easily applied to large-scale systems, yet they cannot prevent the prediction of non-direct edges. In contrast, partial correlations, which are often expensive to compute, reduce predicting such edges. We suggest combining these alternative methods in order to have complementary information on brain functional networks.

Connectivity differences in brain networks.

The scenario considered here is one where brain connectivity is represented as a network and an experimenter wishes to assess the evidence for an experimental effect at each of the typically thousands of connections comprising the network. To do this, a univariate model is independently fitted to each connection. It would be unwise to declare significance based on an uncorrected threshold of α=0.05, since the expected number of false positives for a network comprising N=90 nodes and N(N-1)/2=4005 connections would be 200. Control of Type I errors over all connections is therefore necessary. The network-based statistic (NBS) and spatial pairwise clustering (SPC) are two distinct methods that have been used to control family-wise errors when assessing the evidence for an experimental effect with mass univariate testing. The basic principle of the NBS and SPC is the same as supra-threshold voxel clustering. Unlike voxel clustering, where the definition of a voxel cluster is unambiguous, 'clusters' formed among supra-threshold connections can be defined in different ways. The NBS defines clusters using the graph theoretical concept of connected components. SPC on the other hand uses a more stringent pairwise clustering concept. The purpose of this article is to compare the pros and cons of the NBS and SPC, provide some guidelines on their practical use and demonstrate their utility using a case study involving neuroimaging data.

Monitoring of illicit pill distribution networks using an image collection exploration framework

This paper proposes a novel approach for the analysis of illicit tablets based on their visual characteristics. In particular, the paper concentrates on the problem of ecstasy pill seizure profiling and monitoring. The presented method extracts the visual information from pill images and builds a representation of it, i.e. it builds a pill profile based on the pill visual appearance. Different visual features are used to build different image similarity measures, which are the basis for a pill monitoring strategy based on both discriminative and clustering models. The discriminative model permits to infer whether two pills come from the same seizure, while the clustering models groups of pills that share similar visual characteristics. The resulting clustering structure allows to perform a visual identification of the relationships between different seizures. The proposed approach was evaluated using a data set of 621 Ecstasy pill pictures. The results demonstrate that this is a feasible and cost effective method for performing pill profiling and monitoring.