Faculty Bibliography

Nucleic acid testing (NAT) for HIV, HBV and HCV shortens the time between infection and detection by available testing. A group of experts was selected to develop recommendations for the use of NAT in the HIV/HBV/HCV screening of potential organ donors. The rapid turnaround times needed for donor testing and the risk of death while awaiting transplantation make organ donor screening different from screening blood-or tissue donors. In donors with no identified risk factors, there is insufficient evidence to recommend routine NAT, as the benefits of NAT may not outweigh the disadvantages of NAT especially when false-positive results can lead to loss of donor organs. For donors with identified behavioral risk factors, NAT should be considered to reduce the risk of transmission and increase organ utilization. Informed consent balancing the risks of donor-derived infection against the risk of remaining on the waiting list should be obtained at the time of candidate listing and again at the time of organ offer. In conclusion, there is insufficient evidence to recommend universal prospective screening of organ donors for HIV, HCV and HBV using current NAT platforms. Further study of viral screening modalities may reduce disease transmission risk without excessive donor loss.

Sensory processing is often regarded as a passive process in which biological receptors like photoreceptors and mechanoreceptors transduce physical energy into a neural code. Recent findings, however, suggest that: first, most sensory processing is active, and largely determined by motor/attentional sampling routines; second, owing to rhythmicity in the motor routine, as well as to its entrainment of ambient rhythms in sensory regions, sensory inflow tends to be rhythmic; third, attentional manipulation of rhythms in sensory pathways is instrumental to perceptual selection. These observations outline the essentials of an Active Sensing paradigm, and argue for increased emphasis on the study of sensory processes as specific to the dynamic motor/attentional context in which inputs are acquired

Early intervention approaches have rarely been implemented for the prevention of attention deficit/hyperactivity disorder (ADHD). In this paper we explore whether such an approach may represent an important new direction for therapeutic innovation. We propose that such an approach is most likely to be of value when grounded in and informed by developmental models of the dynamic, complex and heterogeneous nature of the condition. First, we set out a rationale for early intervention grounded in the science of ADHD viewed through developmental models. Second, we re-examine the concept of disorder-onset from the perspective of developmental trajectories and phenotypes. Third, we examine potential causal pathways to ADHD with regard to originating risk, pathophysiological mediators, environmental moderators and developmental continuities. Finally, we explore the potential value of strategies for identifying young children at risk for ADHD, and implementing interventions in ways that can target these underlying pathogenic processes. The utility of such an approach represents an important area for future research but still requires 'proof of concept'. Therefore prior to widespread clinical implementation, far greater knowledge is required of (i) developmental pathways into ADHD, (ii) the value of identifying neuropsychological mediators of these pathways, and (iii) the extent to which targeting mediating mechanisms will improve treatment outcomes for children with ADHD

In this study, we attempted to clarify whether distractibility in ADHD might arise from increased sensory-driven interference or from inefficient top-down control. We employed an attentional filtering paradigm in which discrimination difficulty and distractor salience (amount of image "graying") were parametrically manipulated. Increased discrimination difficulty should add to the load of top-down processes, whereas increased distractor salience should produce stronger sensory interference. We found an unexpected interaction of discrimination difficulty and distractor salience. For difficult discriminations, ADHD children filtered distractors as efficiently as healthy children and adults; as expected, all three groups were slower to respond with high vs. low salience distractors. In contrast, for easy discriminations, robust between-group differences emerged: ADHD children were much slower and made more errors than either healthy children or adults. For easy discriminations, healthy children and adults filtered out high salience distractors as easily as low salience distractors, but ADHD children were slower to respond on trials with low salience distractors than they did on trials with high salience distractors. These initial results from a small sample of ADHD children have implications for models of attentional control, and ways in which it can malfunction. The fact that ADHD children exhibited efficient attentional filtering when task demands were high, but showed deficient and atypical distractor filtering under low task demands suggests that attention deficits in ADHD may stem from a failure to efficiently engage top-down control rather than an inability to implement filtering in sensory processing regions.

One goal of statistical shape analysis is the discrimination between two populations of objects. Whereas traditional shape analysis was mostly concerned with single objects, analysis of multi-object complexes presents new challenges related to alignment and pose. In this paper, we present a methodology for discriminant analysis of multiple objects represented by sampled medial manifolds. Non-euclidean metrics that describe geodesic distances between sets of sampled representations are used for alignment and discrimination. Our choice of discriminant method is the distance-weighted discriminant because of its generalization ability in high-dimensional, low sample size settings. Using an unbiased, soft discrimination score, we associate a statistical hypothesis test with the discrimination results. We explore the effectiveness of different choices of features as input to the discriminant analysis, using measures like volume, pose, shape, and the combination of pose and shape. Our method is applied to a longitudinal pediatric autism study with 10 subcortical brain structures in a population of 70 subjects. It is shown that the choices of type of global alignment and of intrinsic versus extrinsic shape features, the latter being sensitive to relative pose, are crucial factors for group discrimination and also for explaining the nature of shape change in terms of the application domain.

OBJECTIVE: The dual pathway model explains neuro-psychological heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) in terms of dissociable cognitive and motivational deficits each affecting some but not other patients. We explore whether deficits in temporal processing might constitute a third dissociable neuropsychological component of ADHD. METHOD: Nine tasks designed to tap three domains (inhibitory control, delay aversion and temporal processing) were administered to ADHD probands (n=71; ages 6 to 17 years), their siblings (n=71; 65 unaffected by ADHD) and a group of non-ADHD controls (n=50). IQ and working memory were measured. RESULTS: Temporal processing, inhibitory control and delay-related deficits represented independent neuropsychological components. ADHD children differed from controls on all factors. For ADHD patients, the co-occurrence of inhibitory, temporal processing and delay-related deficits was no greater than expected by chance with substantial groups of patients showing only one problem. Domain-specific patterns of familial co-segregation provided evidence for the validity of neuropsychological subgroupings. CONCLUSION: The current results illustrate the neuropsychological heterogeneity in ADHD and initial support for a triple pathway model. The findings need to be replicated in larger samples

BACKGROUND: Oxytocin is a neuropeptide that is associated with increased trust. Perceptions of trustworthiness are associated with detection of positive facial affect, which suggests that oxytocin may enhance the recognition of positive facial affect. The present study tests this hypothesis. METHODS: A double-blind, between-groups design was used, with 50 volunteers randomly assigned to receive intranasally administered oxytocin or placebo. Thirty-five minutes following the administration of oxytocin or placebo, participants identified anger, disgust, fear, happiness, sadness, and surprise expressions that were morphed with neutral faces such that they varied from 10% to 100% intensity. RESULTS: Oxytocin significantly and specifically improved the recognition of happy facial expressions; no significant differences in recognition of other expression were found. The improvement was not associated with gender, response biases, or changes in mood, and it was most pronounced for subtle expressions. CONCLUSIONS: Acute oxytocin administration enhances healthy adults' ability to accurately identify positive emotional facial expressions. These findings reinforce oxytocin's role in facilitating affiliative interactions and have implications for the treatment of conditions that are marked by social affiliation deficits.