| 1. |
- Karaiskos, Ilias, et al.
(författare)
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Colistin Population Pharmacokinetics after Application of a Loading Dose of 9 MU Colistin Methanesulfonate in Critically Ill Patients
- 2015
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 59:12, s. 7240-7248
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Tidskriftsartikel (refereegranskat)abstract
- Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430-3436, 2009, http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241-4249, 2012, http://dx.doi.org/10.1128/AAC.06426-11; S.M. Garonzik, J. Li, V. Thamlikitkul, D.L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284-3294, 2011, http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (similar to 270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was 20%.
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| 2. |
- Angelopoulou, Michailia, et al.
(författare)
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Directly immersible silicon photonic probes : Application to rapid SARS-CoV-2 serological testing br
- 2022
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 215
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Tidskriftsartikel (refereegranskat)abstract
- Silicon photonic probes based on broad-band Mach-Zehnder interferometry are explored for the first time as directly immersible immunosensors alleviating the need for microfluidics and pumps. Each probe includes two U- shaped waveguides allowing light in- and out-coupling from the same chip side through a bifurcated fiber and a mechanical coupler. At the opposite chip side, two Mach-Zehnder interferometers (MZI) are located enabling real-time monitoring of binding reactions by immersion of this chip side into a sample. The sensing arm windows of the two MZIs have different length resulting in two distinct peaks in the Fourier domain, the phase shift of which can be monitored independently through Fast Fourier Transform of the output spectrum. The photonic probes analytical potential was demonstrated through detection of antibodies against SARS-CoV-2 in human serum samples. For this, one MZI was functionalized with the Receptor Binding Domain (RBD) of SARS-CoV-2 Spike 1 protein, and the other with bovine serum albumin to serve as reference. The biofunctionalized probes were immersed for 10 min in human serum sample and then for 5 min in goat anti-human IgG Fc specific antibody solution. Using a humanized rat antibody against SARS-CoV-2 RBD, a detection limit of 20 ng/mL was determined. Analysis of human serum samples indicated that the proposed sensor discriminated completely non- infected/non-vaccinated from vaccinated individuals, and the antibodies levels determined correlated well with those determined in the same samples by ELISA. These results demonstrated the potential of the proposed sensor to serve as an efficient tool for expeditious point-of-care testing
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| 3. |
- Brütt, Katharina, et al.
(författare)
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Competition and moral behavior: A meta-analysis of forty-five crowd-sourced experimental designs
- 2023
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Ingår i: Proceedings of the National Academy of Sciences - PNAS. - : National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 120:23
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Tidskriftsartikel (refereegranskat)abstract
- Does competition affect moral behavior? This fundamental question has been debated among leading scholars for centuries, and more recently, it has been tested in experimental studies yielding a body of rather inconclusive empirical evidence. A potential source of ambivalent empirical results on the same hypothesis is design heterogeneity-variation in true effect sizes across various reasonable experimental research protocols. To provide further evidence on whether competition affects moral behavior and to examine whether the generalizability of a single experimental study is jeopardized by design heterogeneity, we invited independent research teams to contribute experimental designs to a crowd-sourced project. In a large-scale online data collection, 18,123 experimental participants were randomly allocated to 45 randomly selected experimental designs out of 95 submitted designs. We find a small adverse effect of competition on moral behavior in a meta-analysis of the pooled data. The crowd-sourced design of our study allows for a clean identification and estimation of the variation in effect sizes above and beyond what could be expected due to sampling variance. We find substantial design heterogeneity-estimated to be about 1.6 times as large as the average standard error of effect size estimates of the 45 research designs-indicating that the informativeness and generalizability of results based on a single experimental design are limited. Drawing strong conclusions about the underlying hypotheses in the presence of substantive design heterogeneity requires moving toward much larger data collections on various experimental designs testing the same hypothesis.
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| 4. |
- Evangelou, Evangelos, et al.
(författare)
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A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:12, s. 2130-2136
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
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| 5. |
- Ioannidis, Konstantinos, 1976-
(författare)
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Designing the Edge : An Inquiry into the Psychospatial Nature of Meaning in the Architecture of the Urban Waterfront
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The initial goal of this effort is to develop a discussion on urban design process and thinking that acknowledges the needs of places with meaning in the design of the urban waterfront. The thesis addresses the fact that the problematic of the coastal formulation is intricate, comprising not only aspects related to the spatial organization and design of its domain but also shared properties originated by the presence and movement of the perceiving subject in the area. In this framework, the research attempts to provide an understanding of the main relationships that the subject cultivates inside the coastal space and to offer a broader spatial reading of its narrative function. On the hypothesis that this function is susceptible of interpretation, the thesis develops an interest in examining the effects of the psychospatial nature of meaning on the design and experience of the urban edge, for to interpret a narrative spatial construct is to specify its meaning. To explore the issue of waterfront places that speak of the subject, the research conceives the coastal space as a field of mediated parameters that pertain to three crucial operational premises: the symbolic function of the urban space near the water, the meaning behind the coastal form, and the engagement of the perceiving subject in the conscious or reflexive appropriation of the waterfront setting. These premises, traced as psychophysiological spaces, determine the intermediary, the integrative, and the expressive discourses for the development of places with meaning near the water. Through them, the thesis attempts a reading of the coastal domain based upon the material interpretation of the meanings and messages associated with the immediate experience of the onset of water‐born notions, concepts, and images. Writing about the dialectics between the psychospatial inquiry and the spatial experience of the edge, this thesis suggests that, contrary to the established preconception, the psychology of human‐edge relations submits the perceiving subject to the conception of the coastal form and shape.
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| 6. |
- Karaiskos, Ilias, et al.
(författare)
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Challenge for higher colistin dosage in critically ill patients receiving continuous venovenous haemodiafiltration
- 2016
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 48:3, s. 337-341
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Tidskriftsartikel (refereegranskat)abstract
- Traditionally, reduced daily doses of colistin methanesulphonate (CMS) in critically ill patients receiving continuous venovenous haemodiafiltration (CVVHDF) have resulted in suboptimal colistin concentrations. The necessity of a loading dose (LD) at treatment initiation has been proposed. A LD of 9 million IU (MU) [ca. 270 mg of colistin base activity (CBA)] was administrated with a maintenance dose of 4.5 MU (ca. 140 mg CBA) every 12 h (q12h) to eight critically ill patients receiving renal replacement therapy. Blood samples were collected immediately before and at different time intervals after the LD and the fourth dose, whilst pre-filter and post-filter blood samples were also collected. CMS and colistin concentrations were determined using an LC-MS/MS assay. Median maximum observed concentrations after the LD were 22.1 mg/L for CMS and 1.55 mg/L for colistin, whereas during maintenance dosing the corresponding values were 12.6 mg/L and 1.72 mg/L, respectively. CVVHDF clearance was determined as 2.98 L/h for colistin, equivalent to 62% of total apparent colistin clearance in CVVHDF patients. Both CMS and colistin were cleared by CVVHDF. Application of a LD of 9 MU CMS resulted in more rapid achievement of the target colistin concentration. Following implementation of a predicted pharmacokinetic model on plasma CMS/colistin concentrations, a LD of 12 MU CMS appears more appropriate, whilst a CMS maintenance dosage of at least 6.5-7.5 MU q12h is suggested in patients undergoing CVVHDF. However, further clinical studies are warranted to assess the safety of a LD of 12 MU CMS in patients receiving CVVHDF.
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| 7. |
- Rousopoulou, Vaia, et al.
(författare)
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Cognitive analytics platform with AI solutions for anomaly detection
- 2022
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Ingår i: Computers in industry (Print). - : Elsevier BV. - 0166-3615 .- 1872-6194. ; 134, s. 103555-103555
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a cognitive analytics platform for anomaly detection which is capable to handle, analyze and exploit resourcefully machine data from a shop-floor of factory, so as to support the emerging and growing needs of manufacturing industry. The introduced system contributes to industrial digitization and creation of smart factories by providing a generic platform which is a complete solution supporting standards-based factory connectivity, data management, various AI models training and comparisons, live predictions and real-time visualizations. The proposed system is built on a micro-service architecture, in order to be extendable and adaptive over time, and contains three core modules, the Data Acquisition, the Knowledge Management and the Predictive maintenance, which contribute to machine failure prediction and activate predictive maintenance procedures, to efficient production schemes and decision making, to monitor anomalies and handle unforeseen conditions, to predict future behaviours on time series etc. The proposed platform utilizes continuous re-training mechanisms enabling a self learning approach for the delivery of AI solutions, usable also for various production data, guaranteeing the quality of results without continuous monitoring and human-resources allocation for AI models’ retraining. This cognitive platform is supported by machine learning techniques and deep learning architectures in order to achieve the desired performance in the management of factory processes and needs. All the information generated by the proposed platform is provided to the end user through a user interface that utilizes advanced visualization techniques.
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| 8. |
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