University of Ioannina

About: University of Ioannina is a education organization based out in Ioannina, Greece. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 7654 authors who have published 20594 publications receiving 671560 citations. The organization is also known as: Panepistimio Ioanninon.

Contradicted and Initially Stronger Effects in Highly Cited Clinical Research

Abstract: Context Controversy and uncertainty ensue when the results of clinical research on the effectiveness of interventions are subsequently contradicted. Controversies are most prominent when high-impact research is involved. Objectives To understand how frequently highly cited studies are contradicted or find effects that are stronger than in other similar studies and to discern whether spe- cific characteristics are associated with such refutation over time. Design All original clinical research studies published in 3 major general clinical jour- nals or high-impact-factor specialty journals in 1990-2003 and cited more than 1000 times in the literature were examined. Main Outcome Measure The results of highly cited articles were compared against subsequent studies of comparable or larger sample size and similar or better con- trolled designs. The same analysis was also performed comparatively for matched stud- ies that were not so highly cited. Results Of 49 highly cited original clinical research studies, 45 claimed that the inter- vention was effective. Of these, 7 (16%) were contradicted by subsequent studies, 7 oth- ers (16%) had found effects that were stronger than those of subsequent studies, 20 (44%) were replicated, and 11 (24%) remained largely unchallenged. Five of 6 highly- cited nonrandomized studies had been contradicted or had found stronger effects vs 9 of 39 randomized controlled trials (P=.008). Among randomized trials, studies with con- tradicted or stronger effects were smaller (P=.009) than replicated or unchallenged stud- ies although there was no statistically significant difference in their early or overall cita- tion impact. Matched control studies did not have a significantly different share of refuted results than highly cited studies, but they included more studies with "negative" results. Conclusions Contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes. The extent to which high citations may provoke contradictions and vice versa needs more study. Controversies are most common with highly cited nonrandomized studies, but even the most highly cited randomized trials may be challenged and refuted over time, especially small ones.

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Why most discovered true associations are inflated.

Abstract: Newly discovered true (non-null) associations often have inflated effects compared with the true effect sizes. I discuss here the main reasons for this inflation. First, theoretical considerations prove that when true discovery is claimed based on crossing a threshold of statistical significance and the discovery study is underpowered, the observed effects are expected to be inflated. This has been demonstrated in various fields ranging from early stopped clinical trials to genome-wide associations. Second, flexible analyses coupled with selective reporting may inflate the published discovered effects. The vibration ratio (the ratio of the largest vs. smallest effect on the same association approached with different analytic choices) can be very large. Third, effects may be inflated at the stage of interpretation due to diverse conflicts of interest. Discovered effects are not always inflated, and under some circumstances may be deflated-for example, in the setting of late discovery of associations in sequentially accumulated overpowered evidence, in some types of misclassification from measurement error, and in conflicts causing reverse biases. Finally, I discuss potential approaches to this problem. These include being cautious about newly discovered effect sizes, considering some rational down-adjustment, using analytical methods that correct for the anticipated inflation, ignoring the magnitude of the effect (if not necessary), conducting large studies in the discovery phase, using strict protocols for analyses, pursuing complete and transparent reporting of all results, placing emphasis on replication, and being fair with interpretation of results.

Graphite Oxide: Chemical Reduction to Graphite and Surface Modification with Primary Aliphatic Amines and Amino Acids

Abstract: The chemical reduction of graphite oxide (GO) to graphite by either NaBH4 or hydroquinone and also its surface modification with neutral, primary aliphatic amines and amino acids are described. Treatment of GO with NaBH4 leads to turbostatic graphite that upon calcination under an inert atmosphere is transformed to highly ordered graphitic carbon, while the reduction with hydroquinone yields directly crystalline graphite under soft thermal conditions. On account of the surface-exposed epoxy groups present in the GO solid, its surface modification with neutral, primary aliphatic amines or amine-containing molecules (amino acids and aminosiloxanes) takes place easily through the corresponding nucleophilic substitution reactions. In this way, valuable GO derivatives can be obtained, like molecular pillared GO, organically modified GO affording in organic solvents stable organosols or hydrophilic GO affording in water stable hydrosols and possessing direct cation exchange sites. The potential combination of s...

EEA1 links PI(3)K function to Rab5 regulation of endosome fusion

Abstract: GTPases and lipid kinases regulate membrane traffic along the endocytic pathway by mechanisms that are not completely understood. Fusion between early endosomes requires phosphatidylinositol-3-OH kinase (PI(3)K) activity as well as the small GTPase Rab5. Excess Rab5-GTP complex restores endosome fusion when PI(3)K is inhibited. Here we identify the early-endosomal autoantigen EEA1 which binds the PI(3)K product phosphatidylinositol-3-phosphate, as a new Rab5 effector that is required for endosome fusion. The association of EEA1 with the endosomal membrane requires Rab5-GTP and PI(3)K activity, and excess Rab5-GTP stabilizes the membrane association of EEA1 even when PI(3)K is inhibited. The identification of EEA1 as a direct Rab5 effector provides a molecular link between PI(3)K and Rab5, and its restricted distribution to early endosomes indicates that EEA1 may confer directionality to Rab5-dependent endocytic transport.