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Challenges and limitations in the interpretation of systematic reviews : making sense of clopidogrel and CYP2C19 pharmacogenetics
No full textFrom 2010 to 2012, nine systematic reviews reported highly variable conclusions regarding the association between carriage of a cytochrome P450 2C19 loss-of-function allele and the risk of adverse cardiovascular (CV) events in individuals using clopidogrel. Possible contributors to the variable findings include differences in patient populations, CV end points, and statistical models utilized by the systematic reviews, as well as unexplained heterogeneity, inconsistent/incomplete reporting, and risk of publication bias with respect to the primary studies.
Amyloid beta1–42 (Aβ42) up-regulates the expression of sortilin via the p75NTR/RhoA signaling pathway
No full textSortilin is the co-receptor of p75NTR which signals the cell death induced by Aβ and proneurotrophins. We found that sortilin is increased in the AD brain and up-regulated by Aβ and pro-brain-derived neurotrophic factor (proBDNF). Aβ-induced upregulation of sortilin is mediated by p75NTR and the down-streaming RhoA-ROCK signaling pathway. The Aβ/Sortilinp/75NTR signaling may play a role in the pathogenesis of AD.
Evaluation of the salt removal efficiency of capacitive deionisation: Kinetics, isotherms and thermodynamics
No full textRecruiting young adults to child maltreatment research through Facebook: A feasibility study
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On the effects of atmospheric-pressure microplasma array treatment on polymer and biological materials
No full textThis paper reports the first systematic investigation on the effects of atmospheric-pressure helium microplasma array treatment on the surface chemistries of model organic materials and a biological coating. These materials include polystyrene (PS), low-density polyethylene (LDPE) and ethylene tetrafluoroethylene (ETFE), and bovine serum albumin (BSA). The plasma treatment introduced a range of oxygen functionalities into the surface of the polymers, with oxygen incorporation reaching “saturation” after relatively short treatment times. PS and LDPE surfaces were more readily oxidised and to a greater depth compared to ETFE. The polymer surfaces became smoother at short plasma treatment times due to removal of adventitious hydrocarbon, but became rougher at longer treatment times as a result of etching of low molecular weight, volatile material from the surface. Atmospheric-pressure helium microplasma array treatment of a BSA layer resulted in the majority of the protein being removed from the underlying (PS) surface. The plasma treatment reduced the surface roughness of the BSA coating at short treatment times, but at longer treatment times, the surface roughness increased and the surfaces exhibited granular structures. All of the hydrophobic polymers became hydrophilic after the plasma treatment. The hydrophilicity of the surfaces decreased upon storage (hydrophobic recovery) and none of the polymers reverted to their original hydrophobic state, even after 500 h of storage. The knowledge presented in this paper may be useful in the development of new manufacturing processes based on atmospheric-pressure plasma and in the field of plasma medicine, particularly with respect to cleaning and sterilisation methods. In addition, it provides a foundation for future efforts to establish the mechanisms behind interactions of atmospheric-pressure plasmas with materials.
Exploring the mesenchymal stem cell niche using high throughput screening
No full textIn the field of stem cell technology, future advancements rely on the effective isolation, scale-up and maintenance of specific stem cell populations and robust procedures for their directed differentiation. The stem cell microenvironment – or niche – encompasses signal inputs from stem cells, supporting cells and from the extracellular matrix. In this context, the contribution of physicochemical surface variables is being increasingly recognised. This paradigm can be exploited to exert control over cellular behaviour. However, the number of parameters at play, and their complex interactions, presents a formidable challenge in delineating how the decisions of cell fate are orchestrated within the niche. Additionally, in the case of mesenchymal stem cells (MSC), more than one type of stem cell niche has been identified. By employing high throughput screening (HTS) strategies, common and specific attributes of each MSC niche can be probed. Here, we explore biological, chemical and physical parameters that are known to influence MSC self-renewal and differentiation. We then review techniques and strategies that allow the HTS of surface properties for conditions that direct stem cell fate, using MSC as a case study. Finally, challenges in recapturing the niche, particularly its three dimensional nature, in surface-based HTS formats are discussed.
Interaction of antibiotics with lipid vesicles on thin film porous silicon using reflectance interferometric fourier transform spectroscopy
No full textThe ability to observe interactions of drugs with cell membranes is an important area in pharmaceutical research. However, these processes are often difficult to understand due to the dynamic nature of cell membranes. Therefore, artificial systems composed of lipids have been used to study membrane properties and their interaction with drugs. Here, lipid vesicle adsorption, rupture, and formation of planar lipid bilayers induced by various antibiotics (surfactin, azithromycin, gramicidin, melittin and ciprofloxacin) and the detergent dodecyl-b-d-thiomaltoside (DOTM) was studied using reflective interferometric Fourier transform spectroscopy (RIFTS) on an oxidized porous silicon (pSi) surface as a transducer. The pSi transducer surfaces are prepared as thin films of 3 μm thickness with pore dimensions of a few nanometers in diameter by electrochemical etching of crystalline silicon followed by passivation with a thermal oxide layer. Furthermore, the sensitivity of RIFTS was investigated using three different concentrations of surfactin. Complementary techniques including atomic force microscopy, fluorescence recovery after photobleaching, and fluorescence microscopy were used to validate the RIFTS-based method and confirm adsorption and consequent rupture of vesicles to form a phospholipid bilayer upon the addition of antibiotics. The method provides a sensitive and real-time approach to monitor the antibiotic-induced transition of lipid vesicles to phospholipid bilayers.
Do clusters of test anxiety and academic buoyancy differentially predict academic performance?
No full textIn this study we adopted a person-centred approach to examine whether students could be identified in distinct clusters on the basis of their test anxiety and academic buoyancy scores, andwhether students' academic performance differed accordingly. We performed a cluster analysis on a sample of 469 secondary school students preparing for high-stakes examinations and we identified five empirically-distinct clusters. Three corresponded to a continuum of high test anxiety/low academic buoyancy, mid test anxiety/mid academic buoyancy and low test anxiety/high academic buoyancy. Two clusters corresponded to students with mid-high test anxiety and mid-high academic buoyancy. Academic performance was highest for students in clusters of low test anxiety/ high academic buoyancy or mid test anxiety/ high academic buoyancy. Performance was lowest for students in clusters of high test anxiety/ low academic buoyancy. These findings show how academic buoyancy may lower threat appraisal in some students and show a performance protective role in others.
Effective pruning for the discovery of conditional functional dependencies
No full textConditional functional dependencies (CFDs) have been proposed as a new type of semantic rules extended from traditional functional dependencies. They have shown great potential for detecting and repairing inconsistent data. Constant CFDs are 100% confidence association rules. The theoretical search space for the minimal set of CFDs is the set of minimal generators and their closures in data. This search space has been used in the currently most efficient constant CFD discovery algorithm. In this paper, we propose pruning criteria to further prune the theoretic search space, and design a fast algorithm for constant CFD discovery. We evaluate the proposed algorithm on a number of media to large real-world data sets. The proposed algorithm is faster than the currently most efficient constant CFD discovery algorithm, and has linear time performance in the size of a data set.