Generating synthetic mixed-type longitudinal electronic health records for artificial intelligent applications

The recent availability of electronic health records (EHRs) have provided enormous opportunities to develop artificial intelligence (AI) algorithms. However, patient privacy has become a major concern that limits data sharing across hospital settings and subsequently hinders the advances in AI. Synthetic data, which benefits from the development and proliferation of generative models, has served as a promising substitute for real patient EHR data. However, the current generative models are limited as they only generate single type of clinical data for a synthetic patient, i.e., either continuous-valued or discrete-valued. To mimic the nature of clinical decision-making which encompasses various data types/sources, in this study, we propose a generative adversarial network (GAN) entitled EHR-M-GAN that simultaneously synthesizes mixed-type timeseries EHR data. EHR-M-GAN is capable of capturing the multidimensional, heterogeneous, and correlated temporal dynamics in patient trajectories. We have validated EHR-M-GAN on three publicly-available intensive care unit databases with records from a total of 141,488 unique patients, and performed privacy risk evaluation of the proposed model. EHR-M-GAN has demonstrated its superiority over state-of-the-art benchmarks for synthesizing clinical timeseries with high fidelity, while addressing the limitations regarding data types and dimensionality in the current generative models. Notably, prediction models for outcomes of intensive care performed significantly better when training data was augmented with the addition of EHR-M-GAN-generated timeseries. EHR-M-GAN may have use in developing AI algorithms in resource-limited settings, lowering the barrier for data acquisition while preserving patient privacy

Novel bioresorbable textile composites for medical applications

Currently, phosphate glass fibre (PGF) reinforced composites are a potential solution for bone repairing due to sufficient mechanical properties and full bioresorbability. In this study, a small inkle-type loom for hand weaving facilitated the production of PGF in textile form. These PGF textiles, along with unidirectional (UD) fibre mats made from the same batch of yarns, were utilised to manufacture fully resorbable textile composites (T-C) and 0°/90° lay-up UD fibre reinforced composites (0/90-C). Retention of flexural properties and weight loss of the composites were evaluated during degradation in phosphate buffered saline (PBS) at 37°C for 28 days. The initial flexural strength values that were observed for the T-C and 0/90-C composites were ∼;176 MPa and ∼;137 MPa, whilst the modulus values were 8.6 GPa and 6.9 GPa, respectively. The higher flexural strength and modulus values for the T-C when compared to those of 0/90-C were attributed to the textile weaving manually, resulting in a biased fabric with a higher density of fibres in the warp direction. ∼;20% flexural strength and ∼;25% flexural modulus were maintained for all composites at the 28 day interval. For this study, the textile achievement will be the significant milestone on the research of bioresorbable PGFs reinforced composite in medical application, and important step on the industrial direction of bioresorbable medical device. © 2017 International Committee on Composite Materials. All rights reserved

The Interaction of TPH2 and 5-HT2A Polymorphisms on Major Depressive Disorder Susceptibility in a Chinese Han Population: A Case-Control Study

Purpose: TPH2 and 5-HT2A appear to play vital roles in the homeostatic regulation of serotonin levels in the brain, their genetic variations may lead to impaired homeostatic regulation of serotonin resulting in abnormal levels of serotonin in the brain, thus predisposing individuals to MDD. However, research studies have yet to confirm which gene-gene interaction effect between TPH2 and 5-HT2A polymorphisms results in increased susceptibility to MDD.Methods: A total of 565 participants, consisting of 278 MDD patients and 287 healthy controls from the Chinese Han population, were recruited for the present study. Six single nucleotide polymorphisms (SNPs) of TPH2/5-HT2A were selected to assess their interaction by use of a generalized multifactor dimensionality reduction method.Results: A-allele carriers of rs11178997 and rs120074175 were more likely to suffer from MDD than T-allele carriers of rs11178997, or G-allele carriers of rs120074175. The interaction between TPH2 (rs120074175, rs11178997) and 5-HT2A (rs7997012) was considered as the best multi-locus model upon the MDD susceptibility.Conclusions: Our data identified an important effect of TPH2 genetic variants (rs11178997 and rs120074175) upon the risk of MDD, and suggested that the interaction of TPH2/5-HT2A polymorphism variants confer a greater susceptibility to MDD in Chinese Han population

Structural, thermal, in vitro degradation and cytocompatibility properties of P2O5-B2O3-CaO-MgO-Na2O-Fe2O3 glasses

Borophosphate glasses with compositions of (48 − x)P2O5-(12 + x)B2O3-14CaO-20MgO-1Na2O-5Fe2O3 (where x = 0, 3, 8 mol%) were prepared via a melt-quenching process. The effects of replacing P2O5 with B2O3 on the structural, thermal, degradation properties and cytocompatibility were investigated. Fourier transform infrared (FTIR) spectroscopy analysis confirmed the existence of BO3 triangular units and BO4 tetrahedral units within all the glasses with an increase of B/P ratio from 0.25 to 0.5. The BO4 units within the glass structure were observed to cause an increase in density (ρ) as well as glass transition (Tg) temperature and to decrease the crystallisation temperature (Tc). A decrease in thermal stability which indicated by process window was also observed in the case of substitution of P2O5 with B2O3. Degradation analysis of the glasses indicated that the dissolution rate increased with the addition of B2O3. The decrease in the thermal stability and chemical durability were attributed to the increase of BO3 units, which could increase crystallisation tendency and be easily hydrolysed by solution. The effect of boron addition on the cytocompatibility of the glasses was analysed using Alamar Blue and alkaline phosphatase (ALP) assays and DNA quantification. MG63 osteosarcoma cells cultured in direct contact with the glass samples surface for 14 days showed better cytocompatibility, compared to the tissue culture plastic (TCP) control group. In summary, the glass formulation with 12 mol% B2O3 presented the best cytocompatibility and thermal stability, thus could be considered for continuous fibre fabrication in future research and downstream activities

Farnesol-Induced Apoptosis in Candida albicans Is Mediated by Cdr1-p Extrusion and Depletion of Intracellular Glutathione

Farnesol is a key derivative in the sterol biosynthesis pathway in eukaryotic cells previously identified as a quorum sensing molecule in the human fungal pathogen Candida albicans. Recently, we demonstrated that above threshold concentrations, farnesol is capable of triggering apoptosis in C. albicans. However, the exact mechanism of farnesol cytotoxicity is not fully elucidated. Lipophilic compounds such as farnesol are known to conjugate with glutathione, an antioxidant crucial for cellular detoxification against damaging compounds. Glutathione conjugates act as substrates for ATP-dependent ABC transporters and are extruded from the cell. To that end, this current study was undertaken to validate the hypothesis that farnesol conjugation with intracellular glutathione coupled with Cdr1p-mediated extrusion of glutathione conjugates, results in total glutathione depletion, oxidative stress and ultimately fungal cell death. The combined findings demonstrated a significant decrease in intracellular glutathione levels concomitant with up-regulation of CDR1 and decreased cell viability. However, addition of exogenous reduced glutathione maintained intracellular glutathione levels and enhanced viability. In contrast, farnesol toxicity was decreased in a mutant lacking CDR1, whereas it was increased in a CDR1-overexpressing strain. Further, gene expression studies demonstrated significant up-regulation of the SOD genes, primary enzymes responsible for defense against oxidative stress, with no changes in expression in CDR1. This is the first study describing the involvement of Cdr1p-mediated glutathione efflux as a mechanism preceding the farnesol-induced apoptotic process in C. albicans. Understanding of the mechanisms underlying farnesol-cytotoxicity in C. albicans may lead to the development of this redox-cycling agent as an alternative antifungal agent

Thermal analysis of a mine buried in sand

“The aim of this thesis is to study the thermal signature produced by a squirt of heated waterjet for humanitarian demining. Thermal simulation of the process was developed using I-DEAS and FLUENT. In the experiments, the thermal signature generated from a single squirt of a heated water jet was investigated. A heated waterjet, as it penetrates the ground, digs a hole through which the heat radiates out. The possibility of using the thermal profile induced by a heated waterjet when viewed directly into the hole created by the waterjet to define mine location was explored. The thermal profile was taken viewing directly in the hole. I-DEAS was used to simulate the heat transfer and radiation phenomena associated with demining related problems. First, a mine buried in sand and the high temperature cone shaped hole on top the mine produced by the squirt was studied. Second, the radiation difference for different lengths of hole was studied. Third, the heat radiate to the IR camera from a hole on top a mine created by the waterjet was simulated. In the simulation, the mine is assigned the properties of metal and wood, respectively. From the metal and wood mine calculation results, some of the experimental results were verified. FLUENT was used to simulate a stream of high speed waterjet hitting the ground. From pressure and velocity distribution calculation, when water impinges on the ground, it will produce a cone shaped pressure zone which is the reason for the formation of a cone shaped hole on top of the mine”--Abstract, page iii

Error Analysis on ESA's Envisat ASAR Wave Mode Significant Wave Height Retrievals Using Triple Collocation Model

Nowadays, spaceborne Synthetic Aperture Radar (SAR) has become a powerful tool for providing significant wave height (SWH). Traditionally, validation of SAR derived SWH has been carried out against buoy measurements or model outputs, which only yield an inter-comparison, but not an "absolute" validation. In this study, the triple collocation error model has been introduced in the validation of Envisat ASAR derived SWH products. SWH retrievals from ASAR wave mode using ESA's algorithm are validated against in situ buoy data, and wave model hindcast results from WaveWatch III wave model, covering a period of six years. From the triple collocation validation analysis, the impacts of the collocation distance and water depth on the error of ASAR SWH are discussed. It is found that the error of Envisat ASAR SWH product is linear to the collocation distance, and decrease with the decreasing collocation distance. Using the linear regression fit method, the absolute error of Envisat ASAR SWH was obtained with zero collocation distance. The absolute Envisat ASAR wave height error of 0.49 m is presented in deep and open ocean from this triple collocation validation work, in contrast to a larger error of 0.56 m in coastal and shallow waters. One of the reasons for the larger Envisat ASAR SWH errors in the coastal waters may be the inaccurate Modulation Transfer Function (MTF) adopted in the Envisat ASAR wave retrieval algorithm