Lipid Metabolic Defects and Lipid-Dependent Gating of Voltage-Gated Ion Channels

Eukaryotic cells contain phospholipids and nonphospholipids. The latter lack phosphodiester groups in their head group regions. Lipid-dependent gating of voltage-gated ion channels represents a steady-state energetic effect of nonphospholipids in favoring the resting state of voltage-sensor domains (VSDs) of the channels. It suggests adaptation of ion channels to lipid compositions in their native niche and significant roles of low-to-intermediate affinity lipid-binding sites at the channels. The nonphospholipids include glycoglycerolipids, glycosphingolipids, ceramides, cholesterol or cholesterol esters, diacylglycerol (DAG), fatty acids, cation lipids, etc. Change in relative ratios of phospholipids to nonphospholipids can shift the energetic levels of the VSDs and the gating of these channels, which in turn may alter excitability in certain cells. It is expected that reduced relative abundance of nonphospholipids / phospholipids in plasma membranes may change resting transmembrane potential or gating transitions of voltage-gated Na or K channels. The net results will be a change in action potential firing at least in certain areas of an excitable cell. Such changes in the central nervous system (CNS) are anticipated to affect brain functions and contribute to early-onset neurological phenotypes observed in patients carrying lipid metabolic defects. We will describe the basics of lipid-dependent gating and review its projected links to phenotypes of monogenic lipid metabolic defects and related changes of lipid composition in cell membranes as well as altered neuronal excitability in CNS. However, lack of high-resolution techniques to measure lipid composition around individual channels in cell membranes has been limiting the studies of direct connections between lipid redistribution caused by metabolic defects and altered ion channel activities. Potential solutions will be described for future studies

What Influences Employees to Use Enterprise Social Networks? A Socio-Technical Perspective

The adoption of enterprise social network (ESN) for greater employee engagement and knowledge sharing practices within organisations is proliferating. However, ESN investments have thus far not resulted in expected gains in organisational benefits due to underutilisation by employees. Limited understanding of the implications of ESN use leads to a paucity of recommendations for effective use within an organisation. This research-in-progress paper seeks to determine the factors influencing the use of ESN among employees in a large Australian utility organisation, with the aim of contributing to a practical understanding of the key success factors of the use of this new workplace social platform. Our preliminary findings indicated that the employees’ ESN behaviour tends to be influenced by socio-technical factors, including technological (i.e. platform and content quality), organisational (i.e. top management support and ESN facilitating conditions), social (i.e. critical mass and communication climate), individual (i.e. perceived benefits, knowledge self-efficacy and time commitment) and task (i.e. task characteristics) factors. This paper concludes that a successful implementation of ESN in an organisation involves the nexus between these five factors and provides several recommendations about how ESN use can be enhanced

Identifying the underlying structure and dynamic interactions in a voting network

We analyse the structure and behaviour of a specific voting network using a dynamic structure-based methodology which draws on Q-Analysis and social network theory. Our empirical focus is on the Eurovision Song Contest over a period of 20 years. For a multicultural contest of this kind, one of the key questions is how the quality of a song is judged and how voting groups emerge. We investigate structures that may identify the winner based purely on the topology of the network. This provides a basic framework to identify what the characteristics associated with becoming a winner are, and may help to establish a homogenous criterion for subjective measures such as quality. Further, we measure the importance of voting cliques, and present a dynamic model based on a changing multidimensional measure of connectivity in order to reveal the formation of emerging community structure within the contest. Finally, we study the dynamic behaviour exhibited by the network in order to understand the clustering of voting preferences and the relationship between local and global properties.Comment: 20 pages, 10 figures, 3 tables, submitted to Physica

Improved identification of left atrial enlargement in patients with obesity

Accurate standardization of left atrium volume (LAV) in patients with obesity is challenging. The aim of this study was to investigate and to examine the relation between LAV indexed to height2 and left atrial function in patients with moderate to severe obesity. Echocardiograms of patients with moderate to severe obesity (body mass index (BMI) ≥ 35 kg/m2) without known cardiac disease were analyzed. LAV was indexed to body surface area (BSA) and height2, and patients were divided into those with or without left atrial enlargement (LAE) based on normalization using either BSA (LAEbsa) or height2 (LAEh2). Using speckle tracking echocardiography, LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were assessed as a measure of LA function. LA dysfunction was defined as LASct &lt; 14%. A total of 142 patients were included in the analysis of whom 54.2% had LAEh2 and 18.3% LAEBSA. The LAEh2 group had significantly lower LASct (12.2% ± 3.2% vs. 13.6% ± 4.5%, p = 0.019) as compared to the patients without LAEh2. Significantly more patients with LA dysfunction would be correctly identified by LAEh2 than by LAEBSA (41.5% vs. 15.0%, p &lt; 0.001). In patients with moderate to severe obesity, the use of LAEh2 identified significantly more patients with decreased LA function. LAVh2 should be preferred over LAVBSA in patients with moderate to severe obesity.</p

A general computational method for robustness analysis with applications to synthetic gene networks

Motivation: Robustness is the capacity of a system to maintain a function in the face of perturbations. It is essential for the correct functioning of natural and engineered biological systems. Robustness is generally defined in an ad hoc, problem-dependent manner, thus hampering the fruitful development of a theory of biological robustness, recently advocated by Kitano

Quantitative Analysis of Nucleic Acid Hybridization on Magnetic Particles and Quantum Dot-Based Probes

In the present study we describe sandwich design hybridization probes consisting of magnetic particles (MP) and quantum dots (QD) with target DNA, and their application in the detection of avian influenza virus (H5N1) sequences. Hybridization of 25-, 40-, and 100-mer target DNA with both probes was analyzed and quantified by flow cytometry and fluorescence microscopy on the scale of single particles. The following steps were used in the assay: (i) target selection by MP probes and (ii) target detection by QD probes. Hybridization efficiency between MP conjugated probes and target DNA hybrids was controlled by a fluorescent dye specific for nucleic acids. Fluorescence was detected by flow cytometry to distinguish differences in oligo sequences as short as 25-mer capturing in target DNA and by gel-electrophoresis in the case of QD probes. This report shows that effective manipulation and control of micro- and nanoparticles in hybridization assays is possible

Pilot Medical Certification Period Health State Forecasts

DTFAWA-10-C-00080The Federal Aviation Administration (FAA) Office of Aerospace Medicine supports research to use available healthcare data to inform policies regarding pilots' medical certifications. The MITRE Corporation's Center for Advanced System Development (MITRE CAASD) was asked to examine methods in advanced data analytics and machine learning (ML) to inform such risk-based decision-making. As an initial step in assessing the potential predictive value of commercially available healthcare data, the FAA provided MITRE CAASD the IBM MarketScan dataset\u2014a large set of commercial healthcare claims records. Using this dataset, we developed methods for identifying health status and changes in health status across conditions; for measuring changes in health status among enrollees with diabetes mellitus (DM); and for measuring the onset of new cases of DM, traumatic brain injury, sleep apnea, and chronic obstructive pulmonary disease. We developed a repeatable workflow and modeled these conditions using a wide range of ML methods. We conclude that ML-based predictive modeling of health conditions from IBM MarketScan data is feasible and informative. However, additional clinical information from commercially available electronic health records would likely improve accuracy and more closely align with future FAA needs

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Effects of Blood Products on Inflammatory Response in Endothelial Cells In Vitro

BACKGROUND: Transfusing blood products may induce inflammatory reactions within the vascular compartment potentially leading to a systemic inflammatory response. Experiments were designed to assess the inflammatory potential of different blood products in an endothelial cell-based in vitro model and to compare baseline levels of potentially activating substances in transfusion products. METHODS: The inflammatory response from pre-activated (endotoxin-stimulated) and non-activated endothelial cells as well as neutrophil endothelial transmigration in response to packed red blood cells (PRBC), platelet concentrates (PC) and fresh frozen plasma (FFP) was determined. Baseline inflammatory mediator and lipid concentrations in blood products were evaluated. RESULTS: Following incubation with all blood products, an increased inflammatory mediator release from endothelial cells was observed. Platelet concentrates, and to a lesser extent also FFP, caused the most pronounced response, which was accentuated in already pre-stimulated endothelial cells. Inflammatory response of endothelial cells as well as blood product-induced migration of neutrophils through the endothelium was in good agreement with the lipid content of the according blood product. CONCLUSION: Within the group of different blood transfusion products both PC and FFP have a high inflammatory potential with regard to activation of endothelial cells. Inflammation upon blood product exposure is strongly accentuated when endothelial cells are pre-injured. High lipid contents in the respective blood products goes along with an accentuated inflammatory reaction from endothelial cells

Supercontinuum applications in high resolution non invasive optical imaging

Progress will be presented in adapting supercontinuum sources to a variety of applications with emphasis on signal processing procedures. These are customised to alleviate noise and take full advantage of the large bandwidth and large power spectral density of modern supercontinuum sources