Learning an atlas of a cognitive process in its functional geometry

Proceedings of the 22nd International Conference, IPMI 2011, Kloster Irsee, Germany, July 3-8, 2011.In this paper we construct an atlas that captures functional characteristics of a cognitive process from a population of individuals. The functional connectivity is encoded in a low-dimensional embedding space derived from a diffusion process on a graph that represents correlations of fMRI time courses. The atlas is represented by a common prior distribution for the embedded fMRI signals of all subjects. The atlas is not directly coupled to the anatomical space, and can represent functional networks that are variable in their spatial distribution. We derive an algorithm for fitting this generative model to the observed data in a population. Our results in a language fMRI study demonstrate that the method identifies coherent and functionally equivalent regions across subjects.National Science Foundation (U.S.) (IIS/CRCNS 0904625)National Science Foundation (U.S.) (CAREER grant 0642971)National Institutes of Health (U.S.) (NCRR NAC P41- RR13218)National Institute of Biomedical Imaging and Bioengineering (U.S.) (U54-EB005149)National Institutes of Health (U.S.) (U41RR019703)National Institutes of Health (U.S.) (P01CA067165)Seventh Framework Programme (European Commission) (n◦257528 (KHRESMOI)

Carbon and nitrogen turnover in the Arctic deep sea: in situ benthic community response to diatom and coccolithophorid phytodetritus

In the Arctic Ocean, increased sea surface temperature and sea ice retreat have triggered shifts in phytoplankton communities. In Fram Strait, coccolithophorids have been occasionally observed to replace diatoms as the dominating taxon of spring blooms. Deep-sea benthic communities depend strongly on such blooms, but with a change in quality and quantity of primarily produced organic matter (OM) input, this may likely have implications for deep-sea life. We compared the in situ responses of Arctic deep-sea benthos to input of phytodetritus from a diatom (Thalassiosira sp.) and a coccolithophorid (Emiliania huxleyi) species. We traced the fate of 13C- and 15N-labelled phytodetritus into respiration, assimilation by bacteria and infauna in a 4-day and 14-day experiment. Bacteria were key assimilators in the Thalassiosira OM degradation, whereas Foraminifera and other infauna were at least as important as bacteria in the Emiliania OM assimilation. After 14 days, 5 times less carbon and 3.8 times less nitrogen of the Emiliania detritus was recycled compared to Thalassiosira detritus. This implies that the utilization of Emiliania OM may be less efficient than for Thalassiosira OM. Our results indicate that a shift from diatom-dominated input to a coccolithophorid-dominated pulse could entail a delay in OM cycling, which may affect benthopelagic coupling.</p

Phase I/randomized phase II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma: North Central Cancer Treatment Group N1174 (Alliance)

Background Patients with glioblastoma (GBM) have a poor prognosis and limited effective treatment options. Bevacizumab has been approved for treatment of recurrent GBM, but there is questionable survival benefit. Based on preclinical and early clinical data indicating that CD105 upregulation may represent a mechanism of resistance to bevacizumab, we hypothesized that combining bevacizumab with the anti-CD105 antibody TRC105 may improve efficacy in recurrent GBM.Methods Phase I dose-escalation/comparative randomized phase II trial in patients with GBM. During phase I, the maximum tolerated dose (MTD) of TRC105 in combination with bevacizumab was determined. In phase II, patients were randomized 1:1 to TRC105 and bevacizumab or bevacizumab monotherapy. Patients receivedTRC105 (10 mg/kg) weekly and bevacizumab (10 mg/kg) every 2 weeks. Efficacy, as assessed by progression-free survival (PFS), was the primary endpoint; safety, quality of life, and correlative outcomes were also evaluated.Results In total, 15 patients were enrolled in phase I and 101 in phase II; 52 patients were randomized to TRC105 with bevacizumab and 49 to bevacizumab monotherapy. The MTD was determined to be 10 mg/kg TRC105 weekly plus bevacizumab 10 mg/kg every 2 weeks. An increased occurrence of grade &gt;= 3 adverse events was seen in the combination arm, including higher incidences of anemia. Median PFS was similar in both treatment arms: 2.9 months for combination versus 3.2 months for bevacizumab monotherapy (HR = 1.16, 95% CI = 0.75-1.78, P = .51). Quality of life scores were similar for both treatment arms.Conclusions TRC105 in combination with bevacizumab was well tolerated in patients with recurrent GBM, but no difference in efficacy was observed compared to bevacizumab monotherapy

Fast network centrality analysis using GPUs

<p>Abstract</p> <p>Background</p> <p>With the exploding volume of data generated by continuously evolving high-throughput technologies, biological network analysis problems are growing larger in scale and craving for more computational power. General Purpose computation on Graphics Processing Units (GPGPU) provides a cost-effective technology for the study of large-scale biological networks. Designing algorithms that maximize data parallelism is the key in leveraging the power of GPUs.</p> <p>Results</p> <p>We proposed an efficient data parallel formulation of the All-Pairs Shortest Path problem, which is the key component for shortest path-based centrality computation. A betweenness centrality algorithm built upon this formulation was developed and benchmarked against the most recent GPU-based algorithm. Speedup between 11 to 19% was observed in various simulated scale-free networks. We further designed three algorithms based on this core component to compute closeness centrality, eccentricity centrality and stress centrality. To make all these algorithms available to the research community, we developed a software package <it>gpu</it>-<it>fan </it>(GPU-based Fast Analysis of Networks) for CUDA enabled GPUs. Speedup of 10-50× compared with CPU implementations was observed for simulated scale-free networks and real world biological networks.</p> <p>Conclusions</p> <p><it>gpu</it>-<it>fan </it>provides a significant performance improvement for centrality computation in large-scale networks. Source code is available under the GNU Public License (GPL) at <url>http://bioinfo.vanderbilt.edu/gpu-fan/</url>.</p

The association of Social Anxiety Disorder, Alcohol Use Disorder and reproduction: Results from four nationally representative samples of adults in the USA.

Social Anxiety Disorder (SAD) and Alcohol Use Disorder (AUD) are highly prevalent and frequently co-occur. The results of population studies suggest that SAD tends to precede AUD, and the results of laboratory studies suggest that alcohol use facilitates social behaviors in socially anxious individuals. Therefore, we posited that, in a modern context, a tendency to consume alcohol may be positively selected for among socially anxious individuals by its effect on the likelihood of finding a partner and reproducing. We tested the hypothesis that a higher proportion of individuals with a lifetime diagnosis of SAD and AUD reproduce (i.e., have at least one child) relative to individuals with SAD absent AUD in an individual participant meta-analysis based on over 65,000 adults derived from four nationally representative cross-sectional samples. We then cross-validated these findings against the results of a 10-year follow up of one of these surveys. Lifetime history of SAD was not associated with reproduction whereas lifetime history of AUD was positively associated with reproduction. There was no statistically detectable difference in the proportion of individuals with a lifetime history of SAD with or without AUD who reproduced. There was considerable heterogeneity in all of the analyses involving SAD, suggesting that there are likely to be other pertinent variables relating to SAD and reproduction that should be delineated

Natural Products Chemistry and Taxonomy of the Marine Cyanobacterium Blennothrix cantharidosmum

A Papua New Guinea field collection of the marine cyanobacterium Blennothrix cantharidosmum was investigated for its cytotoxic constituents. Bioassay-guided isolation defined the cytotoxic components as the known compounds lyngbyastatins 1 and 3. However, six new acyl proline derivatives, tumonoic acids D−I, plus the known tumonoic acid A were also isolated. Their planar structures were defined from NMR and MS data, while their stereostructures followed from a series of chiral chromatographies, degradation sequences, and synthetic approaches. The new compounds were tested in an array of assays, but showed only modest antimalarial and inhibition of quorum sensing activities. Nevertheless, these are the first natural products to be reported from this genus, and this inspired a detailed morphologic and 16S rDNA-based phylogenetic analysis of the producing organism

Familial hypercholesterolaemia: identification and management. Evidence reviews for case-finding, diagnosis and statin monotherapy

This guideline covers identifying and managing familial hypercholesterolaemia (FH), a specific type of high cholesterol that runs in the family, in children, young people and adults. It aims to help identify people at increased risk of coronary heart disease as a result of having FH. In November 2017, we reviewed the evidence for case finding and diagnosis, identification using cascade testing, and management using statins. We amended recommendations in sections 1.1, 1.2 and 1.3

“Thinking about Not-Thinking”: Neural Correlates of Conceptual Processing during Zen Meditation

Recent neuroimaging studies have identified a set of brain regions that are metabolically active during wakeful rest and consistently deactivate in a variety the performance of demanding tasks. This “default network” has been functionally linked to the stream of thoughts occurring automatically in the absence of goal-directed activity and which constitutes an aspect of mental behavior specifically addressed by many meditative practices. Zen meditation, in particular, is traditionally associated with a mental state of full awareness but reduced conceptual content, to be attained via a disciplined regulation of attention and bodily posture. Using fMRI and a simplified meditative condition interspersed with a lexical decision task, we investigated the neural correlates of conceptual processing during meditation in regular Zen practitioners and matched control subjects. While behavioral performance did not differ between groups, Zen practitioners displayed a reduced duration of the neural response linked to conceptual processing in regions of the default network, suggesting that meditative training may foster the ability to control the automatic cascade of semantic associations triggered by a stimulus and, by extension, to voluntarily regulate the flow of spontaneous mentation

Imaging of Functional Connectivity in the Mouse Brain

Functional neuroimaging (e.g., with fMRI) has been difficult to perform in mice, making it challenging to translate between human fMRI studies and molecular and genetic mechanisms. A method to easily perform large-scale functional neuroimaging in mice would enable the discovery of functional correlates of genetic manipulations and bridge with mouse models of disease. To satisfy this need, we combined resting-state functional connectivity mapping with optical intrinsic signal imaging (fcOIS). We demonstrate functional connectivity in mice through highly detailed fcOIS mapping of resting-state networks across most of the cerebral cortex. Synthesis of multiple network connectivity patterns through iterative parcellation and clustering provides a comprehensive map of the functional neuroarchitecture and demonstrates identification of the major functional regions of the mouse cerebral cortex. The method relies on simple and relatively inexpensive camera-based equipment, does not require exogenous contrast agents and involves only reflection of the scalp (the skull remains intact) making it minimally invasive. In principle, fcOIS allows new paradigms linking human neuroscience with the power of molecular/genetic manipulations in mouse models