564 research outputs found

    Mapping Informative Clusters in a Hierarchial Framework of fMRI Multivariate Analysis

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    Pattern recognition methods have become increasingly popular in fMRI data analysis, which are powerful in discriminating between multi-voxel patterns of brain activities associated with different mental states. However, when they are used in functional brain mapping, the location of discriminative voxels varies significantly, raising difficulties in interpreting the locus of the effect. Here we proposed a hierarchical framework of multivariate approach that maps informative clusters rather than voxels to achieve reliable functional brain mapping without compromising the discriminative power. In particular, we first searched for local homogeneous clusters that consisted of voxels with similar response profiles. Then, a multi-voxel classifier was built for each cluster to extract discriminative information from the multi-voxel patterns. Finally, through multivariate ranking, outputs from the classifiers were served as a multi-cluster pattern to identify informative clusters by examining interactions among clusters. Results from both simulated and real fMRI data demonstrated that this hierarchical approach showed better performance in the robustness of functional brain mapping than traditional voxel-based multivariate methods. In addition, the mapped clusters were highly overlapped for two perceptually equivalent object categories, further confirming the validity of our approach. In short, the hierarchical framework of multivariate approach is suitable for both pattern classification and brain mapping in fMRI studies

    Dynamic Disorder in Quasi-Equilibrium Enzymatic Systems

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    Conformations and catalytic rates of enzymes fluctuate over a wide range of timescales. Despite these fluctuations, there exist some limiting cases in which the enzymatic catalytic rate follows the macroscopic rate equation such as the Michaelis-Menten law. In this paper we investigate the applicability of macroscopic rate laws for fluctuating enzyme systems in which catalytic transitions are slower than ligand binding-dissociation reactions. In this quasi-equilibrium limit, for an arbitrary reaction scheme we show that the catalytic rate has the same dependence on ligand concentrations as obtained from mass-action kinetics even in the presence of slow conformational fluctuations. These results indicate that the timescale of conformational dynamics – no matter how slow – will not affect the enzymatic rate in quasi-equilibrium limit. Our numerical results for two enzyme-catalyzed reaction schemes involving multiple substrates and inhibitors further support our general theory

    A Retrospective Analysis of the Haemodynamic and Metabolic Effects of Fluid Resuscitation in Vietnamese Adults with Severe Falciparum Malaria

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    BACKGROUND: Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP) guided, crystalloid based, resuscitation in adults. METHODS: Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation. RESULTS: 43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m(2) (95% Confidence interval (CI): 0.41 to 1.1)), but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: -0.1 to 1.3). The CVP and PAoP (pulmonary artery occlusion pressure) were highly inter-correlated (r(s) = 0.7, p<0.0001), but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit) or respiratory status (PaO(2)/FiO(2) ratio). There was no correlation between the oxygen delivery (DO(2)) and base deficit at the 63 time-points where they were assessed simultaneously (r(s) = -0.09, p = 0.46). CONCLUSIONS: In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs

    Body mass index as a predictor of healthy and disease-free life expectancy between ages 50 and 75 : a multicohort study

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    BACKGROUND: While many studies have shown associations between obesity and increased risk of morbidity and mortality, little comparable information is available on how body mass index (BMI) impacts health expectancy. We examined associations of BMI with healthy and chronic disease-free life expectancy in four European cohort studies. METHODS: Data were drawn from repeated waves of cohort studies in England, Finland, France and Sweden. BMI was categorized into four groups from normal weight (18.5-24.9 kg m(-2)) to obesity class II (>= 35 kg m(-2)). Health expectancy was estimated with two health indicators: sub-optimal self-rated health and having a chronic disease (cardiovascular disease, cancer, respiratory disease and diabetes). Multistate life table models were used to estimate sex-specific healthy life expectancy and chronic disease-free life expectancy from ages 50 to 75 years for each BMI category. RESULTS: The proportion of life spent in good perceived health between ages 50 and 75 progressively decreased with increasing BMI from 81% in normal weight men and women to 53% in men and women with class II obesity which corresponds to an average 7-year difference in absolute terms. The proportion of life between ages 50 and 75 years without chronic diseases decreased from 62 and 65% in normal weight men and women and to 29 and 36% in men and women with class II obesity, respectively. This corresponds to an average 9 more years without chronic diseases in normal weight men and 7 more years in normal weight women between ages 50 and 75 years compared to class II obese men and women. No consistent differences were observed between cohorts. CONCLUSIONS: Excess BMI is associated with substantially shorter healthy and chronic disease-free life expectancy, suggesting that tackling obesity would increase years lived in good health in populations.Peer reviewe

    Genome Sequence Analysis of Dengue Virus 1 Isolated in Key West, Florida

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    Dengue virus (DENV) is transmitted to humans through the bite of mosquitoes. In November 2010, a dengue outbreak was reported in Monroe County in southern Florida (FL), including greater than 20 confirmed human cases. The virus collected from the human cases was verified as DENV serotype 1 (DENV-1) and one isolate was provided for sequence analysis. RNA was extracted from the DENV-1 isolate and was used in reverse transcription polymerase chain reaction (RT-PCR) to amplify PCR fragments to sequence. Nucleic acid primers were designed to generate overlapping PCR fragments that covered the entire genome. The DENV-1 isolate found in Key West (KW), FL was sequenced for whole genome characterization. Sequence assembly, Genbank searches, and recombination analyses were performed to verify the identity of the genome sequences and to determine percent similarity to known DENV-1 sequences. We show that the KW DENV-1 strain is 99% identical to Nicaraguan and Mexican DENV-1 strains. Phylogenetic and recombination analyses suggest that the DENV-1 isolated in KW originated from Nicaragua (NI) and the KW strain may circulate in KW. Also, recombination analysis results detected recombination events in the KW strain compared to DENV-1 strains from Puerto Rico. We evaluate the relative growth of KW strain of DENV-1 compared to other dengue viruses to determine whether the underlying genetics of the strain is associated with a replicative advantage, an important consideration since local transmission of DENV may result because domestic tourism can spread DENVs
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