167 research outputs found
Long-range interactions in Monte Carlo simulation of confined water
We investigate methods for the treatment of long-range interactions in the context of grand canonical Monte Carlo (GCMC) simulations of water adsorption in slit-shaped activated carbon pores. Several approaches, ranging from the simple minimum image convention to the more complex two-dimensional Ewald summations, are implemented and compared with respect to accuracy and speed of computation. The performance of some of these methods in GCMC is found to be significantly different from that in molecular dynamics applications. Of all the methods studied, one proposed by Heyes and van Swol was the most promising, providing the best balance between accuracy and speed. In our application, it was shown to be about 2 times faster than the fastest of the two-dimensional Ewald methods. We expect this conclusion to apply in general to systems that are periodic in two dimensions and finite in the third
Reasoning with Non-Numeric Linguistic Variables
Where decisions are based on imprecise numeric data and linguistic variables, the development of automated decision aids presents particular difficulties. In such applications, linguistic variables often take their values from a pre-ordered set of vaguely defined linguistic terms. The mathematical structures that arise from the assumption that sets of linguistic terms are pair-wise tolerant are considered. A homomorphism between tolerance spaces, filter bases and fuzzy numbers is shown. A proposal for modeling linguistic terms with an ordered set of fuzzy numbers is introduced. A procedure for structured knowledge acquisition based on the topology of the term sets and the cognitive theory of prototypes is shown to give rise to sparse rule bases. Similarity as a function of ādistanceā between fuzzy numbers treated as tolerance mappings is used as an inference mechanism in sparse rule bases to give linguistically valued outputs. Measuring the ādistanceā between fuzzy sets to correspond to intuitive notions of nearness is not straightforward, since the usual metric axioms are not adequate. An alternative way of measuring ādistanceā between fuzzy numbers is introduced, which reduces to the usual one when applied to crisp numbers
Effect of human rotavirus vaccine on severe diarrhea in African infants.
BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. METHODS: We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. RESULTS: A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. CONCLUSIONS: Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.
Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancerārelated mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we identified a LOX/hypoxia signature associated with poor patient survival in resectable patients. We found that LOX expression is upregulated in metastatic tumors from Pdx1āCre KrasG12D/+ Trp53R172H/+ (KPC) mice and that inhibition of LOX in these mice suppressed metastasis. Mechanistically, LOX inhibition suppressed both migration and invasion of KPC cells. LOX inhibition also synergized with gemcitabine to kill tumors and significantly prolonged tumorāfree survival in KPC mice with earlyāstage tumors. This was associated with stromal alterations, including increased vasculature and decreased fibrillar collagen, and increased infiltration of macrophages and neutrophils into tumors. Therefore, LOX inhibition is able to reverse many of the features that make PDAC inherently refractory to conventional therapies and targeting LOX could improve outcome in surgically resectable disease
Research Article (New England Journal of Medicine) Effect of human rotavirus vaccine on severe diarrhea in African infants
Background: Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children.Methods: We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine ā the pooled vaccine group ā or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale.Results: A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirusĀ gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirusĀ gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group.Conclusions: Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.
The integrin Ī±vĪ²6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy
Pancreatic ductal adenocarcinoma (PDAC) has a fiveāyear survival rate of <4% and desperately needs novel effective therapeutics. Integrin Ī±vĪ²6 has been linked with poor prognosis in cancer but its potential as a target in PDAC remains unclear. We report that transcriptional expression analysis revealed high levels of Ī²6 mRNA correlated strongly with significantly poorer survival (n=491 cases, p= 3.17x10ā8). In two separate cohorts we showed that over 80% of PDAC expressed Ī±vĪ²6 protein and that paired metastases retained Ī±vĪ²6 expression. In vitro, integrin Ī±vĪ²6 promoted PDAC cell growth, survival, migration and invasion. Treatment of both Ī±vĪ²6āpositive human PDAC xenografts and transgenic mice bearing Ī±vĪ²6āpositive PDAC with the Ī±vĪ²6 blocking antibody 264RAD, combined with gemcitabine, significantly reduced tumour growth (p<0.0001) and increased survival (Logārank test, p<0.05). Antibody therapy was associated with suppression of both tumour cell activity (suppression of pErk growth signals, increased apoptosis seen as activated Caspase 3) and suppression of the proātumourigenic microenvironment (suppression of TGFĪ² signalling, fewer Ī±SMAāpositive myofibroblasts, decreased blood vessel density). These data show that Ī±vĪ²6 promotes PDAC growth through both tumour cell and tumour microenvironment mechanisms and represents a valuable target for PDAC therapy
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Spatial patterns of the tau pathology in progressive supranuclear palsy
Progressive supranuclear palsy (PSP) is characterized neuropathologically by neuronal loss, gliosis, and the presence of tau-immunoreactive neuronal and glial cell inclusions affecting subcortical and some cortical regions. The objectives of this study were to determine (1) the spatial patterns of the tau-immunoreactive pathology, viz., neurofibrillary tangles (NFT), oligodendroglial inclusions (GI), tufted astrocytes (TA), and Alzheimer's disease-type neuritic plaques (NP) in PSP and (2) to investigate the spatial correlations between the histological features. Post-mortem material of cortical and subcortical regions of eight PSP cases was studied. Spatial pattern analysis was applied to the NFT, GI, TA, NP, abnormally enlarged neurons (EN), surviving neurons, and glial cells. NFT, GI, and TA were distributed either at random or in regularly distributed clusters. The EN and NP were mainly randomly distributed. Clustering of NFT and EN was more frequent in the cortex and subcortical regions, respectively. Variations in NFT density were not spatially correlated with the densities of either GI or TA, but were positively correlated with the densities of EN and surviving neurons in some regions. (1) NFT were the most widespread tau-immunoreactive pathology in PSP being distributed randomly in subcortical regions and in regular clusters in cortical regions, (2) GI and TA were more localized and exhibited a regular pattern of clustering in subcortical regions, and (3) neuronal and glial cell pathologies were not spatially correlated. Ā© 2012 Springer-Verlag
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