FUNCTIONAL MR OF BRAIN ACTIVITY AND PERFUSION IN PATIENTS WITH CHRONIC CORTICAL STROKE

PURPOSE: (1) To determine whether functional MR can reliably map functional deficits in patients with stroke in the primary visual cortex; (2) to determine whether functional MR can reliably map perfusion deficits; and (3) to determine whether functional MR can give any additional diagnostic information beyond conventional MR. METHODS: Seven patients who had had a stroke in their primary visual system were examined using two functional MR techniques: (1) dynamic susceptibility contrast imaging, and (2) cortical activation mapping during full-field visual stimulation. Maps of relative cerebral blood volume and activation were created and compared with visual field examinations and conventional T2-weighted images on a quadrant-by-quadrant basis in five of these patients. RESULTS: Visual field mapping matched with both T2-weighted conventional images and activation mapping of 16 of 18 quadrants. In two quadrants, the activation maps detected abnormalities that were present on the visual field examination but not present on the T2-weighted images nor on the relative cerebral blood volume maps, which may indicate abnormal function without frank infarction. In addition, the activation maps demonstrated decreased activation in extrastriate cortex and had normal T2 signal and relative cerebral blood volume but was adjacent to infarcted primary cortex, mapping in vivo how stroke in one location can affect the function of distant tissue. CONCLUSION: Functional MR techniques can accurately map functional and perfusion deficits and thereby provide additional clinically useful information. Additional studies will be needed to determine the prognostic utility of functional MR in stroke patients

Enhanced refrigerant capacity in Gd-Al-Co microwires with a biphase nanocrystalline/amorphous structure

"A class of biphase nanocrystalline/amorphous Gd(50+5x)Al(30-5x)Co20 (x = 0, 1, 2) microwires fabricated directly by melt-extraction is reported. High resolution transmission electron microscopy and Fourier function transform based analysis indicate the presence of a volume fraction (similar to 20%) of similar to 10nm sized nanocrystallities uniformly embedded in an amorphous matrix. The microwires possess excellent magnetocaloric properties, with large values of the isothermal entropy change (-Delta S-M similar to 9.7 J kg(-1) K-1), the adiabatic temperature change (Delta T-ad similar to 5.2K), and the refrigerant capacity (RC similar to 654 J kg(-1)) for a field change of 5 T. The addition of Gd significantly alters T-C while preserving large values of the Delta S-M and RC. The nanocrystallites allow for enhanced RC as well as a broader operating temperature span of a magnetic bed for energy-efficient magnetic refrigeration.

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Sensitivity of MEG and EEG to Source Orientation

An important difference between magnetoencephalography (MEG) and electroencephalography (EEG) is that MEG is insensitive to radially oriented sources. We quantified computationally the dependency of MEG and EEG on the source orientation using a forward model with realistic tissue boundaries. Similar to the simpler case of a spherical head model, in which MEG cannot see radial sources at all, for most cortical locations there was a source orientation to which MEG was insensitive. The median value for the ratio of the signal magnitude for the source orientation of the lowest and the highest sensitivity was 0.06 for MEG and 0.63 for EEG. The difference in the sensitivity to the source orientation is expected to contribute to systematic differences in the signal-to-noise ratio between MEG and EEG.National Institutes of Health (U.S.) (Grant NS057500)National Institutes of Health (U.S.) (Grant NS037462)National Institutes of Health (U.S.) (Grant HD040712)National Center for Research Resources (U.S.) (P41RR14075)Mind Research Networ

Upwelling on the continental slope of the Alaskan Beaufort Sea : storms, ice, and oceanographic response

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C00A13, doi:10.1029/2008JC005009.The characteristics of Pacific-born storms that cause upwelling along the Beaufort Sea continental slope, the oceanographic response, and the modulation of the response due to sea ice are investigated. In fall 2002 a mooring array located near 152°W measured 11 significant upwelling events that brought warm and salty Atlantic water to shallow depths. When comparing the storms that caused these events to other Aleutian lows that did not induce upwelling, interesting trends emerged. Upwelling occurred most frequently when storms were located in a region near the eastern end of the Aleutian Island Arc and Alaskan Peninsula. Not only were these storms deep but they generally had northward-tending trajectories. While the steering flow aloft aided this northward progression, the occurrence of lee cyclogenesis due to the orography of Alaska seems to play a role as well in expanding the meridional influence of the storms. In late fall and early winter both the intensity and frequency of the upwelling diminished significantly at the array site. It is argued that the reduction in amplitude was due to the onset of heavy pack ice, while the decreased frequency was due to two different upper-level atmospheric blocking patterns inhibiting the far field influence of the storms.The following grants provided support for this study: National Science Foundation grants OPP-0731928 (R.S.P.) and OPP-0713250 (R.S.P. and P.S.F.), Office of Naval Research grant N00014-07-1-1040 (D.J.T. and R.A.G.), Natural Sciences and Engineering Research Council of Canada (G.W.K.M.), Woods Hole Oceanographic Institution Arctic Initiative (J.Y.)

MetaboHunter: an automatic approach for identification of metabolites from 1H-NMR spectra of complex mixtures

<p>Abstract</p> <p>Background</p> <p>One-dimensional ¹H-NMR spectroscopy is widely used for high-throughput characterization of metabolites in complex biological mixtures. However, the accurate identification of individual compounds is still a challenging task, particularly in spectral regions with higher peak densities. The need for automatic tools to facilitate and further improve the accuracy of such tasks, while using increasingly larger reference spectral libraries becomes a priority of current metabolomics research.</p> <p>Results</p> <p>We introduce a web server application, called MetaboHunter, which can be used for automatic assignment of ¹H-NMR spectra of metabolites. MetaboHunter provides methods for automatic metabolite identification based on spectra or peak lists with three different search methods and with possibility for peak drift in a user defined spectral range. The assignment is performed using as reference libraries manually curated data from two major publicly available databases of NMR metabolite standard measurements (HMDB and MMCD). Tests using a variety of synthetic and experimental spectra of single and multi metabolite mixtures show that MetaboHunter is able to identify, in average, more than 80% of detectable metabolites from spectra of synthetic mixtures and more than 50% from spectra corresponding to experimental mixtures. This work also suggests that better scoring functions improve by more than 30% the performance of MetaboHunter's metabolite identification methods.</p> <p>Conclusions</p> <p>MetaboHunter is a freely accessible, easy to use and user friendly ¹H-NMR-based web server application that provides efficient data input and pre-processing, flexible parameter settings, fast and automatic metabolite fingerprinting and results visualization via intuitive plotting and compound peak hit maps. Compared to other published and freely accessible metabolomics tools, MetaboHunter implements three efficient methods to search for metabolites in manually curated data from two reference libraries.</p> <p>Availability</p> <p><url>http://www.nrcbioinformatics.ca/metabohunter/</url></p

Say on Pay: A wolf in sheep’s clothing?

This paper debates whether Say on Pay can fix executive pay. We argue that Say on Pay benefits executive pay when shareholders’ voice offsets CEO power and mitigates directors’ information deficiencies. We admonish however that Say on Pay may raise novel problems. The pay resulting from Say on Pay can harm stakeholders whose interests differ from those of shareholders influential in pay- setting. Moreover, boards may resist shareholders’ intervention in pay-setting and, accordingly, manage compensation disclosures to ensure a passing shareholder vote. Consequently, Say on Pay may not only fail to remedy suboptimal pay but also legitimize it

Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders

Dissociable Influences of Auditory Object vs. Spatial Attention on Visual System Oscillatory Activity

Given that both auditory and visual systems have anatomically separate object identification (“what”) and spatial (“where”) pathways, it is of interest whether attention-driven cross-sensory modulations occur separately within these feature domains. Here, we investigated how auditory “what” vs. “where” attention tasks modulate activity in visual pathways using cortically constrained source estimates of magnetoencephalograpic (MEG) oscillatory activity. In the absence of visual stimuli or tasks, subjects were presented with a sequence of auditory-stimulus pairs and instructed to selectively attend to phonetic (“what”) vs. spatial (“where”) aspects of these sounds, or to listen passively. To investigate sustained modulatory effects, oscillatory power was estimated from time periods between sound-pair presentations. In comparison to attention to sound locations, phonetic auditory attention was associated with stronger alpha (7–13 Hz) power in several visual areas (primary visual cortex; lingual, fusiform, and inferior temporal gyri, lateral occipital cortex), as well as in higher-order visual/multisensory areas including lateral/medial parietal and retrosplenial cortices. Region-of-interest (ROI) analyses of dynamic changes, from which the sustained effects had been removed, suggested further power increases during Attend Phoneme vs. Location centered at the alpha range 400–600 ms after the onset of second sound of each stimulus pair. These results suggest distinct modulations of visual system oscillatory activity during auditory attention to sound object identity (“what”) vs. sound location (“where”). The alpha modulations could be interpreted to reflect enhanced crossmodal inhibition of feature-specific visual pathways and adjacent audiovisual association areas during “what” vs. “where” auditory attention