Potential-resolved electrogenerated chemiluminescence for the selective detection of multiple luminophores

Electrogenerated chemiluminescence (ECL) is fundamentally dependent on the applied electrode potential, and measuring ECL intensity over a range of different potentials is commonly used to examine the underlying chemical reaction pathways responsible for the emission of light. Several research groups have now demonstrated that the applied potential can be exploited to selectively elicit ECL from: 1) multiple excited states within a single chemical species; 2) multiple emitters sharing a common co-reactant; or 3) distinct ECL systems. This new generation of multiplexed ECL processes has been facilitated by the extensive development of novel electrochemiluminophores and instrumental approaches such as the near-continuous collection of ECL spectra with CCD detectors during voltammetry or chronoamperometry experiments. New dimensions: In electrogenerated chemiluminescence experiments the applied potential can be exploited to selectively elicit light from: multiple excited states within a single chemical species, multiple emitters sharing a common co-reactant, and distinct electrogenerated chemiluminescence systems. These findings may be used to develop low-cost portable analytical devices.

Abnormal behavior detection for early warning of terrorist attack

Many terrorist attacks are accomplished by bringing explosive devices hidden in ordinary-looking objects to public places. In such case, it is almost impossible to distinguish a terrorist from ordinary people just from the isolated appearance. However, valuable clues might be discovered through analyzing a series of actions of the same person. Abnormal behaviors of object fetching, deposit, or exchange in public places might indicate potential attacks. Based on the widely equipped CCTV surveillance systems at the entrance of many public places, this paper proposes an algorithm to detect such abnormal behaviors for early warning of terrorist attack.

Improvements to separation and detection for forensic analysis of illicit substances

This article gives an overview of our recent research into separation and detection of analytes of forensic interest. This work has been carried out in collaboration with local forensic service providers and is based on our previous studies of chemiluminescence detection, flow analysis and capillary electrophoresis as applied to process analytical chemistry for the pharmaceutical industry. Chemiluminescence has the potential to provide low limits of detection in combination with high selectivity, while capillary electrophoresis allows for rapid, highly efficient separations. Examples of recent forensic applications are presented and future directions are discussed.

Options for change in the Australian cervical cancer screening program in context of HPV detection and vaccination

Introduction:
Cervical cancer screening has been implemented for over a decade in Australia and has significantly reduced the mortality and morbidity of the disease. The emergence of new technologies for cervical cancer, such as the Human Papillomavirus (HPV) vaccine and DNA testing has encouraged debate regarding the effective use of resources in cervical cancer prevention. The present study evaluates the cost-effectiveness, from a health sector perspective, of various screening strategies in the era of these new technologies.

Methods:
A stochastic epidemiological model using a discrete event and continuous algorithm was developed to describe the natural history of cervical cancer. By allowing one member of the cohort into the model at a time, this micro-simulation model encompasses the characteristics of heterogeneity and can track individual life histories. To evaluate the cost-effectiveness of the HPV vaccine a Markov model was built to simulate the effect on the incidence of HPV and subsequent cervical cancer. A number of proposed screening strategies were evaluated with the stochastic model for the application of HPV DNA testing, with changes in the screening interval and target population. Health outcomes were measured by Disability-Adjusted Life-Years (DALYs), adjusted for application within an evaluation setting (i.e. the mortality component of the DALY was adjusted by a disability weight when early mortality due to cervical cancer is avoided). Costs in complying with the Australian updated guidelines were assessed by pathway analysis to estimate the resources associated with cervical cancer and its pre-cancerous lesion treatment. Sensitivity analyses were performed to investigate the key parameters that influenced the cost-effectiveness results.

Results:
Current practice has already brought huge health gain by preventing more than 4,000 deaths and saving more than 86,000 life-years in a cohort of a million women. Any of the alternative screening strategies alter the total amount of health gain by a small margin compared to current practice. The results of incremental analyses of the alternative screening strategies compared to current practice suggest the adoption of the HPV DNA test as a primary screening tool every 3 years commencing at age 18, or the combined pap smear/HPV test every 3 years commencing at age 25, are more costly than current practice but with reasonable ICERs (AUD$1,810 per DALY and AUD$18,600 per DALY respectively). Delaying commencement of Pap test screening to age 25 is less costly than current practice, but involves considerable health loss. The sensitivity analysis shows, however, that the screening test accuracy has a significant impact on these conclusions. Threshold analysis indicates that a sensitivity ranging from 0.80 to 0.86 for the combined test in women younger than 30 is required to produce an acceptable incremental cost-effectiveness ratio.

Conclusions:
The adoption of HPV and combined test with an extended screening interval is more costly but affordable, resulting in reasonable ICERs. They appear good value for money for the Australian health care system, but need more information on test accuracy to make an informed decision. Potential screening policy change under current Australian HPV Vaccination Program is current work in progress. A Markov model is built to simulate the effect on the incidence of HPV and subsequent cervical cancer. Adoption of HPV DNA test as a primary screening tool in the context of HPV vaccination is under evaluation.

Chaos theory based detection against network mimicking DDoS attacks

DDoS attack traffic is difficult to differentiate from legitimate network traffic during transit from the attacker, or zombies, to the victim. In this paper, we use the theory of network self-similarity to differentiate DDoS flooding attack traffic from legitimate self-similar traffic in the network. We observed that DDoS traffic causes a strange attractor to develop in the pattern of network traffic. From this observation, we developed a neural network detector trained by our DDoS prediction algorithm. Our preliminary experiments and analysis indicate that our proposed chaotic model can accurately and effectively detect DDoS attack traffic. Our approach has the potential to not only detect attack traffic during transit, but to also filter it.

Detection of endocrine disrupting chemicals in aerial invertebrates at sewage treatment works

Endocrine disrupting chemicals (EDCs) constitute a diverse group of chemical compounds which can alter endocrine function in exposed animals. Whilst most studies have focussed on exposure of wildlife to EDCs via aquatic routes, there is the potential for transfer into the terrestrial food chain through consumption of contaminated prey items developing in sewage sludge and waste water at sewage treatment works. In this study, we determine levels of EDCs in aerial insects whose larval stages develop on percolating filter beds at sewage treatment works. We compare absolute concentrations of known EDCs with those collected from aquatic environments not exposed to sewage effluent outflow. Our findings document for the first time that aerial invertebrates developing on sewage filter beds take up a range of chemicals thought to be incorporated from the sewage effluent, which act as endocrine disruptors. For two synthetic chemicals (17α-ethinylestradiol and butylated hydroxy aniline), concentrations were significantly higher in insects captured around percolating filter beds than sites over 2 km from the nearest sewage works. A number of species of insectivorous bats and birds, some of which are declining or threatened, use sewage works as principle foraging sites. We calculate approximate exposure levels for a species of bat known to forage within sewage works and suggest that further research is warranted to assess the ecological implications of consuming contaminated invertebrate prey

The analysis of café espresso using two-dimensional reversed phase–reversed phase high performance liquid chromatography with UV-absorbance and chemiluminescence detection

In this study, an activity based screening technique combining two-dimensional liquid chromatography (2DHPLC) with UV-absorbance and chemiluminescence detection was applied to study “Ristretto”, "Decaffeinatto” and “Volluto” espresso coffees. This technique, which coupled the separation power of 2DHPLC with the sensitivity and selectivity of the chemiluminescence detection, offers great potential for screening complex samples for antioxidant compounds. Detailed information regarding the complexity of the sample, and the variation between these three coffees could be obtained using this multidimensional-hyphenated method of analysis.

Selective excitation of concomitant electrochemiluminophores : tuning emission color by electrode potential

ECL in 3D: Selective electrogenerated chemiluminescence (ECL) of several ruthenium and iridium complexes simultaneously in solution can be controlled by electrode potential (see picture; λem=emission wavelength). These luminescent redox systems create a range of new possibilities for multi-analyte ECL detection, assessment of interdependent electrochemical/spectroscopic properties, and color tuning in light-emitting devices.

Wireless instantaneous neurotransmitter concentration system-based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring - laboratory investigation

Object  In a companion study, the authors describe the development of a new instrument named the Wireless Instantaneous Neurotransmitter Concentration System (WINCS), which couples digital telemetry with fast-scan cyclic voltammetry (FSCV) to measure extracellular concentrations of dopamine. In the present study, the authors describe the extended capability of the WINCS to use fixed potential amperometry (FPA) to measure extracellular concentrations of dopamine, as well as glutamate and adenosine. Compared with other electrochemical techniques such as FSCV or high-speed chronoamperometry, FPA offers superior temporal resolution and, in combination with enzyme-linked biosensors, the potential to monitor nonelectroactive analytes in real time.

Methods  The WINCS design incorporated a transimpedance amplifier with associated analog circuitry for FPA; a microprocessor; a Bluetooth transceiver; and a single, battery-powered, multilayer, printed circuit board. The WINCS was tested with 3 distinct recording electrodes: 1) a carbon-fiber microelectrode (CFM) to measure dopamine; 2) a glutamate oxidase enzyme–linked electrode to measure glutamate; and 3) a multiple enzyme–linked electrode (adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase) to measure adenosine. Proof-of-principle analyses included noise assessments and in vitro and in vivo measurements that were compared with similar analyses by using a commercial hardwired electrochemical system (EA161 Picostat, eDAQ; Pty Ltd). In urethane-anesthetized rats, dopamine release was monitored in the striatum following deep brain stimulation (DBS) of ascending dopaminergic fibers in the medial forebrain bundle (MFB). In separate rat experiments, DBS-evoked adenosine release was monitored in the ventrolateral thalamus. To test the WINCS in an operating room setting resembling human neurosurgery, cortical glutamate release in response to motor cortex stimulation (MCS) was monitored using a large-mammal animal model, the pig.

Results   The WINCS, which is designed in compliance with FDA-recognized consensus standards for medical electrical device safety, successfully measured dopamine, glutamate, and adenosine, both in vitro and in vivo. The WINCS detected striatal dopamine release at the implanted CFM during DBS of the MFB. The DBS-evoked adenosine release in the rat thalamus and MCS-evoked glutamate release in the pig cortex were also successfully measured. Overall, in vitro and in vivo testing demonstrated signals comparable to a commercial hardwired electrochemical system for FPA.

Conclusions  By incorporating FPA, the chemical repertoire of WINCS-measurable neurotransmitters is expanded to include glutamate and other nonelectroactive species for which the evolving field of enzyme-linked biosensors exists. Because many neurotransmitters are not electrochemically active, FPA in combination with enzyme-linked microelectrodes represents a powerful intraoperative tool for rapid and selective neurochemical sampling in important anatomical targets during functional neurosurgery.

Application of an adaptive neural network with symbolic rule extraction to fault detection and diagnosis in a power generation plant

Artificial neural networks have a good potential to be employed for fault diagnosis and condition monitoring problems in complex processes. In this paper, the applicability of the fuzzy ARTMAP (FAM) neural network as an intelligent learning system for fault detection and diagnosis in a power generation plant is described. The process under scrutiny is the circulating water (CW) system, with specific attention to the conditions of heat transfer and tube blockage in the CW system. A series of experiments has been conducted systematically to investigate the effectiveness of FAM in fault detection and diagnosis tasks. In addition, a set of domain rules has been extracted from the trained FAM network so that its predictions can be explained and justified. The outcomes demonstrate the benefits of employing FAM as an intelligent fault detection and diagnosis tool with an explanatory capability for monitoring and diagnosing complex processes in power generation plants.

Towards automated detection of depression from brain structural magnetic resonance images

Introduction : Depression is a major issue worldwide and is seen as a significant health problem. Stigma and patient denial, clinical experience, time limitations, and reliability of psychometrics are barriers to the clinical diagnoses of depression. Thus, the establishment of an automated system that could detect such abnormalities would assist medical experts in their decision-making process. This paper reviews existing methods for the automated detection of depression from brain structural magnetic resonance images (sMRI).Methods : Relevant sources were identified from various databases and online sites using a combination of keywords and terms including depression, major depressive disorder, detection, classification, and MRI databases. Reference lists of chosen articles were further reviewed for associated publications.Results : The paper introduces a generic structure for representing and describing the methods developed for the detection of depression from sMRI of the brain. It consists of a number of components including acquisition and preprocessing, feature extraction, feature selection, and classification.Conclusion : Automated sMRI-based detection methods have the potential to provide an objective measure of depression, hence improving the confidence level in the diagnosis and prognosis of depression.

Unsupervised DRG upcoding detection in healthcare databases

Diagnosis Related Group (DRG) upcoding is an anomaly in healthcare data that costs hundreds of millions of dollars in many developed countries. DRG upcoding is typically detected through resource intensive auditing. As supervised modeling of DRG upcoding is severely constrained by scope and timeliness of past audit data, we propose in this paper an unsupervised algorithm to filter data for potential identification of DRG upcoding. The algorithm has been applied to a hip replacement/revision dataset and a heart-attack dataset. The results are consistent with the assumptions held by domain experts.

Functionality of fatty acid chemoreception : a potential factor in the development of obesity?

Excess dietary fat consumption is recognized as a strong contributing factor in the development of overweight and obesity. Understanding why some individuals are better than others at regulating fat intake will become increasingly important and emerging associative evidence implicates attenuated fatty acid sensing in both the oral cavity and gastrointestinal (GI) tract in the development of obesity. Functional implications of impaired fatty acid chemoreception include diminished activation of the gustatory system, the cephalic response and satiety. This review will focus on knowledge from animal and human studies supporting the existence of oral fatty acid chemoreception including putative oral detection mechanisms, and how sensitivity to fatty acids is associated with fat consumption and fatty food preference.

The use of sensitive chemical antibodies for diagnosis: detection of low levels of Epcam in breast cancer

EpCAM is expressed at low levels in a variety of normal human epithelial tissues, but is overexpressed in 70–90% of carcinomas. From a clinico-pathological point of view, this has both prognostic and therapeutic significance. EpCAM was first suggested as a therapeutic target for the treatment of epithelial cancers in the 1990s. However, following several immunotherapy trials, the results have been mixed. It has been suggested that this is due, at least in part, to an unknown level of EpCAM expression in the tumors being targeted. Thus, selection of patients who would benefit from EpCAM immunotherapy by determining EpCAM status in the tumor biopsies is currently undergoing vigorous evaluation. However, current EpCAM antibodies are not robust enough to be able to detect EpCAM expression in all pathological tissues.

Here we report a newly developed EpCAM RNA aptamer, also known as a chemical antibody, which is not only specific but also more sensitive than current antibodies for the detection of EpCAM in formalin-fixed paraffin-embedded primary breast cancers. This new aptamer, together with our previously described aptamer, showed no non- specific staining or cross-reactivity with tissues that do not express EpCAM. They were able to reliably detect target proteins in breast cancer xenograft where an anti-EpCAM antibody (323/A3) showed limited or no reactivity. Our results demonstrated a more robust detection of EpCAM using RNA aptamers over antibodies in clinical samples with chromogenic staining. This shows the potential of aptamers in the future of histopathological diagnosis and as a tool to guide targeted immunotherapy.