30,764 research outputs found

    Altered functional and structural brain network organization in autism.

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    Structural and functional underconnectivity have been reported for multiple brain regions, functional systems, and white matter tracts in individuals with autism spectrum disorders (ASD). Although recent developments in complex network analysis have established that the brain is a modular network exhibiting small-world properties, network level organization has not been carefully examined in ASD. Here we used resting-state functional MRI (n = 42 ASD, n = 37 typically developing; TD) to show that children and adolescents with ASD display reduced short and long-range connectivity within functional systems (i.e., reduced functional integration) and stronger connectivity between functional systems (i.e., reduced functional segregation), particularly in default and higher-order visual regions. Using graph theoretical methods, we show that pairwise group differences in functional connectivity are reflected in network level reductions in modularity and clustering (local efficiency), but shorter characteristic path lengths (higher global efficiency). Structural networks, generated from diffusion tensor MRI derived fiber tracts (n = 51 ASD, n = 43 TD), displayed lower levels of white matter integrity yet higher numbers of fibers. TD and ASD individuals exhibited similar levels of correlation between raw measures of structural and functional connectivity (n = 35 ASD, n = 35 TD). However, a principal component analysis combining structural and functional network properties revealed that the balance of local and global efficiency between structural and functional networks was reduced in ASD, positively correlated with age, and inversely correlated with ASD symptom severity. Overall, our findings suggest that modeling the brain as a complex network will be highly informative in unraveling the biological basis of ASD and other neuropsychiatric disorders

    Role of eslicarbazepine in the treatment of epilepsy in adult patients with partial-onset seizures

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    Eslicarbazepine is a new dibenzazepine antiepileptic agent. It is a high affinity antagonist of the voltage-gated sodium channel. It is closely related to both carbamazepine and oxcarbazepine. Eslicarbazepine has similar affinity to inactivated sodium channels (channels in just activated neurons) as carbamazepine, and greater efficacy in animal models of seizure than oxcarbazepine. In human placebo-controlled trials of a single daily dose of eslicarbazepine added to other anti-epileptic agents, significant seizure reductions occurred with 800 and 1200 mg daily, with nearly half of the patients experiencing a greater than 50% reduction in seizure frequency. Adverse events (AEs) occurred in over 50% of patients receiving therapeutic doses of eslicarbazepine (compared to 31.4%–44.7% of placebo-treated subjects), but were generally mild or moderate. Eight to 19.6% of eslicarbazepine treated patients discontinued due to AEs (compared to 3.9%–8.5% of placebo-treated subjects). In these patients receiving combination anticonvulsant therapy, the most common AEs were dizziness, nausea and vomiting, somnolence, and diplopia. Eslicarbazepine is an effective and reasonably well-tolerated adjunct in patients with suboptimal control of their partial seizures

    DNA methylation profiling to assess pathogenicity of BRCA1 unclassified variants in breast cancer

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    Germline pathogenic mutations in BRCA1 increase risk of developing breast cancer. Screening for mutations in BRCA1 frequently identifies sequence variants of unknown pathogenicity and recent work has aimed to develop methods for determining pathogenicity. We previously observed that tumor DNA methylation can differentiate BRCA1-mutated from BRCA1-wild type tumors. We hypothesized that we could predict pathogenicity of variants based on DNA methylation profiles of tumors that had arisen in carriers of unclassified variants. We selected 150 FFPE breast tumor DNA samples [47 BRCA1 pathogenic mutation carriers, 65 BRCAx (BRCA1-wild type), 38 BRCA1 test variants] and analyzed a subset (n=54) using the Illumina 450K methylation platform, using the remaining samples for bisulphite pyrosequencing validation. Three validated markers (BACH2, C8orf31, and LOC654342) were combined with sequence bioinformatics in a model to predict pathogenicity of 27 variants (independent test set). Predictions were compared with standard multifactorial likelihood analysis. Prediction was consistent for c.5194-12G>A (IVS 19-12 G>A) (P>0.99); 13 variants were considered not pathogenic or likely not pathogenic using both approaches. We conclude that tumor DNA methylation data alone has potential to be used in prediction of BRCA1 variant pathogenicity but is not independent of estrogen receptor status and grade, which are used in current multifactorial models to predict pathogenicity

    Dizajniranje i sinteza novih derivata tiofenkarbohidrazida, tienopirazola i tienopirimidina s antioksidativnim i antitumorskim djelovanjem

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    2-Amino-5-acetyl-4-methyl-thiophene-3-carboxylic acid ethyl ester (1) and 5-acetyl-2-amino-4-methylthiophene-3-carbohydrazide (2) were synthesized and used as starting materials for the synthesis of new series of 1-(5-amino-4-(3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3a), 1-(5-amino-4-(4-chloro-3,5-dimethyl-1H-pyrazole-1-carbonyl)-3-methylthiophen-2-yl) ethanone (3b), 1-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) pyrazolidine-3,5-dione (4), (Z)-N\u27-(4-methyl-2-amino-5-acetylthiophene-3-carbonyl) formohydrazonic acid (5a), (Z)-ethyl-N\u27-(4-methyl-2-amino-5-acetylthiophene-3-carbonylformo hydrazonate (5b), 6-acetyl-3-amino-2,5-dimethylthieno2,3-dpyrimidin-4(3H)-one (8), 5-methyl-3-amino-2-mercapto-6-acetylthieno2,3-dpyrimidin-4(3H)-one (10) and 5-methyl-6-acetyl-2-thioxo-2,3-dihydrothieno2,3-dpyrimidin-4(1H)-one (12) as potential antioxidant and antitumor agents. Pharmacological results showed that compounds 6a, 6b, 8, 10 and 12 exhibited promising antitumor and antioxidant activity.Etilni ester 2-amino-5-acetil-4-metil-tiofen-3-karboksilne kiseline (1) i 5-acetil-2-amino-4-metiltiofen-3-karbohidrazid (2) sintetizirani su i upotrebljeni kao reaktanti u sintezi novih spojeva 1-(5-amino-4-(3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3a), 1-(5-amino-4-(4-klor-3,5-dimetil-1H-pirazol-1-karbonil)-3-metiltiofen-2-il) etanona (3b), 1-(4-metil-2-amino-5-acetiltiofen-3-karbonil) pirazolidin-3,5-diona (4), (Z)-N\u27-(4-metil-2-amino-5-acetiltiofen-3-karbonil) formohidrazonske kiseline (5a), (Z)-etil-N\u27-(4-metil-2-amino-5-acetiltiofen-3-karbonilformo hidrazonata (5b), 6-acetil-3-amino-2,5-dimetiltieno2,3-dpirimidin-4(3H)-one (8), 5-metil-3-amino-2-merkapto-6-acetiltieno2,3-dpirimidin-4(3H)-ona (10) i 5-metil-6-acetil-2-tiokso-2,3-dihidrotieno2,3-dpirimidin-4(1H)-ona (12) kao potencijalnih antioksidansa i citostatika. Farmakološka ispitivanja ukazuju na to da spojevi 6a, 6b, 8, 10 i 12 imaju značajno antitumorsko i antioksidativno djelovanje

    The scalar and tensor glueballs in the valence approximation

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    We evaluate the infinite volume, continuum limit of 0++0^{++} and 2++2^{++} glueball masses in the valence approximation. We find m0++=1740±71m_{0^{++}} = 1740 \pm 71 ~MeV and m2++=2359±128m_{2^{++}} = 2359 \pm 128 ~MeV, consistent with the interpretation of f0(1710)f_0 ( 1710 ) as the lightest scalar glueball.Comment: (talk presented by A. Vaccarino at Lattice 93) 3 pages of PostScript in uufiles compressed form. IBM-HET-94-

    World caf\ue9 method to engage smart energy-district project partners in assessing urban co-benefits

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    Urban energy-district projects introduce outstanding technological innovation in buildings and energy systems increasing sustainability in city neighborhoods. Such projects generate additional co-benefits for the city beyond changes in physical elements and development of social and institutional relationships (e.g. local employment, environmental quality, public health, property values, innovation attitude, etc.). Since exceeding main declared goals or not always clearly foreseen in the early project phase, these co-benefits are often not properly understood and considered. However, only their explicit recognition will make possible their inclusion in the assessment of the whole project\u2019s performance. From these considerations, this study faces the issue of engaging project partners in assessing co-benefits in order to consider a broad spectrum of relevant, positive effects in the evaluation process. Group knowledge and group thinking of this complex topic are investigated through the world caf\ue9 method, providing an atmosphere of trust and open discussions among participants. This empirical work lays the foundations to go beyond the mere economic measure as the sole criterion for assessing project effects, also including changes in end-user behavior and intangible asset
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