In JoVE (1)

Other Publications (57)

Articles by Ian Munro in JoVE

 JoVE Biology

Open Source High Content Analysis Utilizing Automated Fluorescence Lifetime Imaging Microscopy

1Photonics Group, Department of Physics, Imperial College London, 2Institute for Chemical Biology, Department of Chemistry, Imperial College London, 3MRC Clinical Sciences Centre, Hammersmith Hospital, 4Chemical Biology Section, Department of Chemistry, Imperial College London, 5Retroscreen Virology Ltd, 6Pfizer Global Research and Development, Pfizer Limited, Sandwich, Kent, UK, 7Centre for Histopathology, Imperial College London


JoVE 55119

Other articles by Ian Munro on PubMed

Carcinogenicity Bioassay of Bisphenol A

Toxicological Sciences : an Official Journal of the Society of Toxicology. Apr, 2002  |  Pubmed ID: 11896303

An Evaluation of the Possible Carcinogenicity of Bisphenol A to Humans

Regulatory Toxicology and Pharmacology : RTP. Apr, 2002  |  Pubmed ID: 12052008

Bisphenol A (BPA) is a monomer component of polycarbonate plastics and epoxy resins. These resins are used in numerous consumer products, including food-contact plastics. There has been considerable scientific debate about the relevance to humans of reported estrogenic actions of BPA. Much less attention has been focused on the carcinogenic potential of BPA. The carcinogenic potential of BPA was assessed through a review of metabolic data, genetic toxicity studies, long-term toxicity/carcinogenicity studies, and estimates of consumer exposure. Following a weight-of-evidence approach as recommended by IARC and U.S. EPA, it was concluded that BPA is not likely to be carcinogenic to humans. The bases for this conclusion included: (a) the results of an NTP study which provided no substantive evidence to indicate that BPA is carcinogenic to rodents; (b) the lack of activity of BPA, at noncytotoxic concentrations, in standard in vitro genetic toxicity tests; (c) the lack of genotoxic activity of BPA in a GLP-compliant in vivo mouse micronucleus assay; and (d) the results of metabolism studies showing BPA is rapidly glucuronidated without evidence of formation of potentially reactive intermediates, except possibly at high doses that could saturate detoxication pathways. In addition, exposure assessment reveals that current use of BPA would result in only a trivial human exposure.

Aspartame: Review of Safety

Regulatory Toxicology and Pharmacology : RTP. Apr, 2002  |  Pubmed ID: 12180494

Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and flavor enhancer. The safety of aspartame and its metabolic constituents was established through extensive toxicology studies in laboratory animals, using much greater doses than people could possibly consume. Its safety was further confirmed through studies in several human subpopulations, including healthy infants, children, adolescents, and adults; obese individuals; diabetics; lactating women; and individuals heterozygous (PKUH) for the genetic disease phenylketonuria (PKU) who have a decreased ability to metabolize the essential amino acid, phenylalanine. Several scientific issues continued to be raised after approval, largely as a concern for theoretical toxicity from its metabolic components--the amino acids, aspartate and phenylalanine, and methanol--even though dietary exposure to these components is much greater than from aspartame. Nonetheless, additional research, including evaluations of possible associations between aspartame and headaches, seizures, behavior, cognition, and mood as well as allergic-type reactions and use by potentially sensitive subpopulations, has continued after approval. These findings are reviewed here. The safety testing of aspartame has gone well beyond that required to evaluate the safety of a food additive. When all the research on aspartame, including evaluations in both the premarketing and postmarketing periods, is examined as a whole, it is clear that aspartame is safe, and there are no unresolved questions regarding its safety under conditions of intended use.

Regulation of Foods with Health Claims: a Proposal

Canadian Journal of Public Health = Revue Canadienne De Sante Publique. Sep-Oct, 2002  |  Pubmed ID: 12353449

Health claims linking foods and food components to disease are prohibited in Canada because of limitations of the Food and Drugs Act. Changes to the Act to permit such claims would require a Bill to Parliament, a lengthy and impractical solution. In this paper, an alternative approach is proposed, that is, to regulate "Foods with Health Claims" under a subsection of the Drug Regulations. Generic claims would be regulated in a similar manner to Class IV or minimum risk drugs, whereby monographs would be created for constituents for which claims are proposed. Product-specific claims would be individually evaluated. Each food bearing a claim would carry a Food Identification Number (FIN), provided by Health Canada through application. Details of procedures and conditions for the FIN process are suggested. The FIN plan would provide an expedient, balanced and accountable approach to allow health claims on food products in Canada.

Soy Isoflavones: a Safety Review

Nutrition Reviews. Jan, 2003  |  Pubmed ID: 12638461

Soy isoflavones have been a component of the diet of certain populations for centuries. The consumption of soy generally has been considered beneficial, with a potentially protective effect against a number of chronic diseases; because of their estrogenic activity, however, negative effects of isoflavones have been postulated. This review examines the literature associated with the safety of soy isoflavones, including dietary soy isoflavone exposure data of populations with high soy intakes, human studies in which soy protein or isoflavones were provided, and toxicologic studies investigating the potential genotoxicity, carcinogenicity, and reproductive and developmental toxicity of soy isoflavones. Whereas results in some studies are limited or conflicting, when viewed in its entirety, the current literature supports the safety of isoflavones as typically consumed in diets based on soy or containing soy products.

Benefit of Higher Closed-loop Bandwidths in Ocular Adaptive Optics

Optics Express. Oct, 2003  |  Pubmed ID: 19471373

We present an ocular adaptive optics system with a wavefront sampling rate of 240 Hz and maximum recorded closed-loop bandwidth close to 25 Hz, but with typical performances around 10 Hz. The measured bandwidth depended on the specific system configuration and the particular subject tested. An analysis of the system performance as a function of achieved bandwidth showed consistently higher Strehl ratios for higher closed-loop bandwidths. This may be attributed to a combination of limitations on the available technology and the dynamics of ocular aberrations. We observed dynamic behaviour with a maximum frequency content around 30 Hz.

The FEMA GRAS Assessment of Cinnamyl Derivatives Used As Flavor Ingredients

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Feb, 2004  |  Pubmed ID: 14667463

This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of cinnamyl derivatives as flavoring ingredients is evaluated.

Time-domain Fluorescence Lifetime Imaging Applied to Biological Tissue

Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology. Aug, 2004  |  Pubmed ID: 15295637

Fluorescence lifetime imaging (FLIM) is a functional imaging methodology that can provide information, not only concerning the localisation of specific fluorophores, but also about the local fluorophore environment. It may be implemented in scanning confocal or multi-photon microscopes, or in wide-field microscopes and endoscopes. When applied to tissue autofluorescence, it reveals intrinsic excellent contrast between different types and states of tissue. This article aims to review our recent progress in developing time-domain FLIM technology for microscopy and endoscopy and applying it to biological tissue.

Replacing the Prolapsed Bovine Uterus

The Veterinary Record. Sep, 2004  |  Pubmed ID: 15470977

Criteria for the Safety Evaluation of Flavoring Substances. The Expert Panel of the Flavor and Extract Manufacturers Association

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Aug, 2005  |  Pubmed ID: 15950813

The current status of the GRAS evaluation program of flavoring substances operated by the Expert Panel of FEMA is discussed. The Panel maintains a rigorous rotating 10-year program of continuous review of scientific data related to the safety evaluation of flavoring substances. The Panel concluded a comprehensive review of the GRAS (GRASa) status of flavors in 1985 and began a second comprehensive review of the same substances and any recently GRAS materials in 1994. This second re-evaluation program of chemical groups of flavor ingredients, recognized as the GRAS reaffirmation (GRASr) program, is scheduled to be completed in 2005. The evaluation criteria used by the Panel during the GRASr program reflects the significant impact of advances in biochemistry, molecular biology and toxicology that have allowed for a more complete understanding of the molecular events associated with toxicity. The interpretation of novel data on the relationship of dose to metabolic fate, formation of protein and DNA adducts, enzyme induction, and the cascade of cellular events leading to toxicity provides a more comprehensive basis upon which to evaluate the safety of the intake of flavor ingredients under conditions of intended use. The interpretation of genotoxicity data is evaluated in the context of other data such as in vivo animal metabolism and lifetime animal feeding studies that are more closely related to actual human experience. Data are not viewed in isolation, but comprise one component that is factored into the Panel's overall safety assessment. The convergence of different methodologies that assess intake of flavoring substances provides a greater degree of confidence in the estimated intake of flavor ingredients. When these intakes are compared to dose levels that in some cases result in related chemical and biological effects and the subsequent toxicity, it is clear that exposure to these substances through flavor use presents no significant human health risk.

Weak Correlation Between the Aberration Dynamics of the Human Eye and the Cardiopulmonary System

Journal of the Optical Society of America. A, Optics, Image Science, and Vision. Jul, 2005  |  Pubmed ID: 16053145

It is fairly well established that the higher-order aberrations of the eye fluctuate over relatively short time periods, but as yet there is no conclusive evidence regarding the origin of these fluctuations. We measured the aberrations and the pulse pressure wave simultaneously for five subjects. The aberrations were measured by using a Shack-Hartmann sensor sampling at 21.2 Hz. We decomposed the aberration data into Zernike coefficients up to and including fifth order and also calculated the rms wave-front error. From the pulse data the heart rate variability signal was also derived. Coherence function analysis showed that for all subjects there was a weak correlation between many of the aberrations and the pulse and the derived heart rate variability. The pulse and the heart rate variability can account for only 11% +/- 2% and 20% +/- 2%, respectively, of the aberration dynamics.

Nutritional and Safety Assessments of Foods and Feeds Nutritionally Improved Through Biotechnology

Food and Nutrition Bulletin. Dec, 2005  |  Pubmed ID: 16465993

Time-resolved Fluorescence Imaging of Solvent Interactions in Microfluidic Devices

Optics Express. Aug, 2005  |  Pubmed ID: 19498640

We present the application of wide-field time-resolved fluorescence imaging methods for the study of solvent interactions and mixing in microfluidic devices. Time-resolved imaging of fluorescence polarization anisotropy allows us to image the local viscosity of fluorescence in three dimensions in order to directly monitor solvent mixing within a microfluidic channel. This provides a viscosity image acquisition time of the order of minutes, and has been applied to a steady-state laminar flow configuration. To image dynamic fluid mixing in real-time, we demonstrate high-speed fluorescence lifetime imaging at 12.3 Hz applied to DASPI, which directly exhibits a solvent viscosity-dependant fluorescence lifetime. These two methods facilitate a high degree of quantification of microfluidic flow in 3-D and/or at high speed, providing a tool for studying fluid dynamics and for developing enhanced microfluidic assays.

Setting Tolerable Upper Intake Levels for Nutrients

The Journal of Nutrition. Feb, 2006  |  Pubmed ID: 16424133

This paper is intended to present the background and general principles embodied in the model for the risk assessment of nutrients of the Food and Nutrition Board (FNB) of the Institute of Medicine, National Academies. Because no one had previously developed a comprehensive approach to the risk assessment of nutrients, the FNB Subcommittee on Upper Reference Levels of Nutrients first looked at various options that could be used to accomplish this task. During initial meetings, the committee considered a variety of options for setting tolerable upper intake levels and settled on the risk assessment approach described in this paper.

Fluorescence Lifetime Imaging Provides Enhanced Contrast when Imaging the Phase-sensitive Dye Di-4-ANEPPDHQ in Model Membranes and Live Cells

Biophysical Journal. Jun, 2006  |  Pubmed ID: 16617080

We apply fluorescence lifetime imaging to the membrane phase-sensing dye di-4-ANEPPDHQ in model membranes and live cells. We show that the 1700 ps lifetime shift between liquid-disordered and liquid-ordered phases offers greater contrast than the 60 nm spectral shift previously reported. Detection of cholesterol-rich membrane microdomains is confirmed by observation of the temperature dependence of membrane order and by cholesterol depletion using methyl-beta-cyclodextrin.

The 5th Workshop on the Assessment of Adequate Intake of Dietary Amino Acids: General Discussion 2

The Journal of Nutrition. Jun, 2006  |  Pubmed ID: 16702351

Microclusters of Inhibitory Killer Immunoglobulin-like Receptor Signaling at Natural Killer Cell Immunological Synapses

The Journal of Cell Biology. Jul, 2006  |  Pubmed ID: 16801390

We report the supramolecular organization of killer Ig-like receptor (KIR) phosphorylation using a technique applicable to imaging phosphorylation of any green fluorescent protein-tagged receptor at an intercellular contact or immune synapse. Specifically, we use fluorescence lifetime imaging (FLIM) to report Förster resonance energy transfer (FRET) between GFP-tagged KIR2DL1 and a Cy3-tagged generic anti-phosphotyrosine monoclonal antibody. Visualization of KIR phosphorylation in natural killer (NK) cells contacting target cells expressing cognate major histocompatibility complex class I proteins revealed that inhibitory signaling is spatially restricted to the immune synapse. This explains how NK cells respond appropriately when simultaneously surveying susceptible and resistant target cells. More surprising, phosphorylated KIR was confined to microclusters within the aggregate of KIR, contrary to an expected homogeneous distribution of KIR signaling across the immune synapse. Also, yellow fluorescent protein-tagged Lck, a kinase important for KIR phosphorylation, accumulated in a multifocal distribution at inhibitory synapses. Spatial confinement of receptor phosphorylation within the immune synapse may be critical to how activating and inhibitory signals are integrated in NK cells.

Use of Hydrogen Peroxide-based Tooth Whitening Products and Its Relationship to Oral Cancer

Journal of Esthetic and Restorative Dentistry : Official Publication of the American Academy of Esthetic Dentistry ... [et Al.]. 2006  |  Pubmed ID: 16831183

Tooth whitening products containing hydrogen peroxide or carbamide peroxide were evaluated in this review for potential oral cancer risk from their use. Hydrogen peroxide is genotoxic in vitro, but not in vivo. Hydrogen peroxide was not considered to pose a genotoxic risk to humans. The animal toxicology data relevant to the assessment of the carcinogenicity of hydrogen peroxide do not indicate that it has significant carcinogenic activity at any site, including the oral cavity. Hydrogen peroxide was found to enhance the carcinogenic effects of potent DNA reactive carcinogens in experimental animals. However, these experimental conditions are artificial as they are related to high exposures and are of no relevance to potential human exposures to low quantities of hydrogen peroxide from the use of tooth whitening products. Clinical data on hydrogen peroxide-containing tooth whitening products show no evidence for the development of preneoplastic or neoplastic oral lesions. Exposures to hydrogen peroxide received by the oral cavity are exceedingly low, of short duration (30-60 minutes), and could not plausibly enhance any carcinogenic risk associated with exposure of the oral cavity to chemicals in cigarette smoke or to alcohol, both known risk factors for the development of oral cancer.

An Evaluation of the Maximized Survey-derived Daily Intake (MSDI) As a Practical Method to Estimate Intake of Flavouring Substances

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. Nov, 2006  |  Pubmed ID: 16905233

Realistic estimates of intake are essential for risk assessments of flavouring agents, since substantial over or underestimations introduce inaccuracies into such evaluations. The objectives of this study were to examine the relationship between intakes estimated using methods based on the reported volume of production [e.g., maximized survey-derived daily intake (MSDI)] versus use-level data [e.g., possible average daily intake (PADI) and modified theoretical added maximum daily intake (mTAMDI)]. The impact of volatility, self-limiting organoleptic properties and whether 10% of the population are eaters, an assumption in the MSDI calculation, on intake estimates were investigated. Analyses on 221 flavouring substances showed that intake estimates derived from MSDI correlated with values determined from detailed 14-day menu-census data, PADI, and mTAMDI. Comparisons of menu-census intake data adjusted to account for factors such as volatile losses showed that MSDI estimates are realistic and sufficiently conservative, whereas mTAMDI results in substantial overestimates of intake. Very few flavours have less than 10% eaters, and in the worst case, this assumption underestimates percent eaters by a factor of about 4. This investigation supports the use of MSDI as a conservative yet practical method to estimate intake of flavouring substances.

The Safety of Whey Protein Concentrate Derived from the Milk of Cows Immunized Against Clostridium Difficile

Regulatory Toxicology and Pharmacology : RTP. Apr, 2007  |  Pubmed ID: 17293018

A whey protein concentrate prepared from the milk of cows that have been immunized against Clostridium difficile (C. difficile) and its toxins, toxin A and toxin B, is produced for use as a medical food for the dietary management of patients with C. difficile-associated diarrhea (CDAD) to prevent a relapse of the infection. The safety of anti-C. difficile whey protein concentrate (anti-CD WPC) is supported by analytical data comparing the composition of raw milk from immunized cows versus that from non-immunized cows, and the composition of anti-CD WPC versus that of regular whey protein concentrate. Additionally, a prospective clinical study was conducted in 77 patients with CDAD to demonstrate the safety of consuming anti-CD WPC to prevent relapse of the infection. This study, which included adverse event monitoring, physical examinations, and extensive hematological and biochemical assessments, showed that anti-CD WPC is safe to consume by patients with CDAD. The available analytical and clinical evidence demonstrate that anti-CD WPC is safe for use by individuals with CDAD, under the described conditions of use.

The Nature and Impact of Incontinence in Men Who Have Undergone Prostate Surgery and Implications for Nursing Practice

Contemporary Nurse. Feb, 2007  |  Pubmed ID: 17348784

The aim of this study was to increase knowledge and understanding of the nature and experiences of incontinence in men one or more years post prostate surgery.

Rapid Hyperspectral Fluorescence Lifetime Imaging

Microscopy Research and Technique. May, 2007  |  Pubmed ID: 17366615

We report a rapid hyperspectral fluorescence lifetime imaging (FLIM) instrument that exploits high-speed FLIM technology in a line-scanning microscope. We demonstrate the acquisition of whole-field optically sectioned hyperspectral fluorescence lifetime image stacks (with 32 spectral bins) in less than 40 s and illustrate its application to unstained biological tissue.

Fluorescence-lifetime Imaging of DNA-dye Interactions Within Continuous-flow Microfluidic Systems

Angewandte Chemie (International Ed. in English). 2007  |  Pubmed ID: 17436333

The Lived Experience of Gay Men Caring for Others with HIV/AIDS: Resilient Coping Skills

International Journal of Nursing Practice. Apr, 2008  |  Pubmed ID: 18315825

There is a dearth of research conducted on the relationship aspect of gay men caring for gay men. This Australian research conducted in 2002 investigated the emotional effects of HIV/AIDS on the gay male carers of gay men with the disease. This study was phenomenological inquiry and employed van Manen's approach to content analysis. Twelve participants for the study were recruited. The results produced emergent themes relating to coping with HIV/AIDS, living day-to-day with HIV/AIDS, coping with the last phase of AIDS towards death, saying goodbye and remembrance. This research highlights the resilient coping style of carers of persons living with HIV/AIDS. The research also gives rise to recommendations for practice and educational contexts in terms of the support and care considerations for persons living with HIV/AIDS and their carers.

Mental Illness and Substance Use: an Australian Perspective

International Journal of Mental Health Nursing. Aug, 2008  |  Pubmed ID: 18666908

This paper presents a review of the literature of service trends and practice recommendations for management of those with the dual diagnosis of mental illness and substance abuse. The method for the review was to search bibliographical data bases and hand held literature published in English between 1990 and 2007. Using the search terms dual diagnosis, and co-morbidity and mental illness, 93 abstracts were selected and reviewed. The authors concluded that a collaborative approach to care with better integration of drug and alcohol services within mental health would benefit clients with a dual diagnosis. Improved education to enhance the assessment and diagnosis of this client group is also considered essential for clinicians in both mental health and alcohol and drugs services.

Three-dimensional Molecular Mapping in a Microfluidic Mixing Device Using Fluorescence Lifetime Imaging

Optics Letters. Aug, 2008  |  Pubmed ID: 18709122

Fluorescence lifetime imaging (FLIM) is used to quantitatively map the concentration of a small molecule in three dimensions in a microfluidic mixing device. The resulting experimental data are compared with computational fluid-dynamics (CFD) simulations. A line-scanning semiconfocal FLIM microscope allows the full mixing profile to be imaged in a single scan with submicrometer resolution over an arbitrary channel length from the point of confluence. Following experimental and CFD optimization, mixing times down to 1.3+/-0.4 ms were achieved with the single-layer microfluidic device.

Multiplexed FRET to Image Multiple Signaling Events in Live Cells

Biophysical Journal. Nov, 2008  |  Pubmed ID: 18757561

We report what to our knowledge is a novel approach for simultaneous imaging of two different Förster resonance energy transfer (FRET) sensors in the same cell with minimal spectral cross talk. Previous methods based on spectral ratiometric imaging of the two FRET sensors have been limited by the availability of suitably bright acceptors for the second FRET pair and the spectral cross talk incurred when measuring in four spectral windows. In contrast to spectral ratiometric imaging, fluorescence lifetime imaging (FLIM) requires measurement of the donor fluorescence only and is independent of emission from the acceptor. By combining FLIM-FRET of the novel red-shifted TagRFP/mPlum FRET pair with spectral ratiometric imaging of an ECFP/Venus pair we were thus able to maximize the spectral separation between our chosen fluorophores while at the same time overcoming the low quantum yield of the far red acceptor mPlum. Using this technique, we could read out a TagRFP/mPlum intermolecular FRET sensor for reporting on small Ras GTP-ase activation in live cells after epidermal growth factor stimulation and an ECFP/Venus Cameleon FRET sensor for monitoring calcium transients within the same cells. The combination of spectral ratiometric imaging of ECFP/Venus and high-speed FLIM-FRET of TagRFP/mPlum can thus increase the spectral bandwidth available and provide robust imaging of multiple FRET sensors within the same cell. Furthermore, since FLIM does not require equal stoichiometries of donor and acceptor, this approach can be used to report on both unimolecular FRET biosensors and protein-protein interactions with the same cell.

High Speed Unsupervised Fluorescence Lifetime Imaging Confocal Multiwell Plate Reader for High Content Analysis

Journal of Biophotonics. Dec, 2008  |  Pubmed ID: 19343677

We report an automated optically sectioning fluorescence lifetime imaging (FLIM) multiwell plate reader for high content analysis (HCA) in drug discovery and accelerated research in cell biology. The system utilizes a Nipkow disc confocal microscope and performs unsupervised FLIM with autofocus, automatic setting of acquisition parameters and automated localisation of cells in the field of view. We demonstrate its applications to test dye solutions, fixed and live cells and FLIM-FRET.

Nursing Considerations for Dual Diagnosis in Mental Health

International Journal of Nursing Practice. Apr, 2009  |  Pubmed ID: 19335524

It is the intention of this literature review to present suggestions for nursing practice with reference to the care of the dually diagnosed. Nursing care of the dually diagnosed client is complex. Clinicians from both drug and alcohol services and mental health services have long recognized that neither service area provides adequate clinical care to those clients who have a dual diagnosis of substance abuse and mental illness. It is now > 10 years since a ground-breaking Australian study recognized this. To ascertain whether there has been improvement in the service management of clients who have a dual diagnosis, and to determine the best practice interventions in the area of mental health nursing, we undertook a review of the literature. The databases CINAHL, MEDLINE, PsycARTICLES and PsychINFO were searched and 185 articles met the inclusion criteria. From this review, it seems that gaps still remain in the provision of services and that mental health nurses might be best placed to provide integrated care to those clients who have a dual diagnosis and present to mental health services. This requires mental health nurses to have skills in substance use detection and knowledge of potential care implications for the client in the context of their substance use.

Stevioside and Related Compounds: Therapeutic Benefits Beyond Sweetness

Pharmacology & Therapeutics. Jun, 2009  |  Pubmed ID: 19344740

An Overview of the Safety of Sucralose

Regulatory Toxicology and Pharmacology : RTP. Oct, 2009  |  Pubmed ID: 19464334

Sucralose is a non-nutritive sweetener used in a broad range of foods and beverages and is the non-nutritive sweetener in retail SPLENDA Sweetening Products, composed of sucralose and common food ingredients. A review of the extensive body of evidence that supports the safety of sucralose is provided. The results of an independent review of a new study investigating the safety of a sucralose-mixture retail product, Granulated SPLENDA No Calorie Sweetener, are also discussed. The collective evidence supports the conclusion that the ingredient, sucralose, is safe for use in food and that the sucralose-mixture product, Granulated SPLENDA No Calorie Sweetener, is also safe for its intended use.

The Blame Game

Nursing Standard (Royal College of Nursing (Great Britain) : 1987). Jun 10-16, 2009  |  Pubmed ID: 19579371

Application of a Key Events Dose-response Analysis to Nutrients: a Case Study with Vitamin A (retinol)

Critical Reviews in Food Science and Nutrition. Sep, 2009  |  Pubmed ID: 19690996

The methodology used to establish tolerable upper intake levels (UL) for nutrients borrows heavily from risk assessment methods used by toxicologists. Empirical data are used to identify intake levels associated with adverse effects, and Uncertainty Factors (UF) are applied to establish ULs, which in turn inform public health decisions and standards. Use of UFs reflects lack of knowledge regarding the biological events that underlie response to the intake of a given nutrient, and also regarding the sources of variability in that response. In this paper, the Key Events Dose-Response Framework (KEDRF) is used to systematically consider the major biological steps that lead from the intake of the preformed vitamin A to excess systemic levels, and subsequently to increased risk of adverse effects. Each step is examined with regard to factors that influence whether there is progression toward the adverse effect of concern. The role of homeostatic mechanisms is discussed, along with the types of research needed to improve understanding of dose-response for vitamin A. This initial analysis illustrates the potential of the KEDRF as a useful analytical tool for integrating current knowledge regarding dose-response, generating questions that will focus future research efforts, and clarifying how improved knowledge and data could be used to reduce reliance on UFs.

Technological Challenges of Addressing New and More Complex Migrating Products from Novel Food Packaging Materials

Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment. Dec, 2009  |  Pubmed ID: 19938328

The risk assessment of migration products resulting from packaging material has and continues to pose a difficult challenge. In most jurisdictions, there are regulatory requirements for the approval or notification of food contact substances that will be used in packaging. These processes generally require risk assessment to ensure safety concerns are addressed. The science of assessing food contact materials was instrumental in the development of the concept of Threshold of Regulation and the Threshold of Toxicological Concern procedures. While the risk assessment process is in place, the technology of food packaging continues to evolve to include new initiatives, such as the inclusion of antimicrobial substances or enzyme systems to prevent spoilage, use of plastic packaging intended to remain on foods as they are being cooked, to the introduction of more rigid, stable and reusable materials, and active packaging to extend the shelf-life of food. Each new technology brings with it the potential for exposure to new and possibly novel substances as a result of migration, interaction with other chemical packaging components, or, in the case of plastics now used in direct cooking of products, degradation products formed during heating. Furthermore, the presence of trace levels of certain chemicals from packaging that were once accepted as being of low risk based on traditional toxicology studies are being challenged on the basis of reports of adverse effects, particularly with respect to endocrine disruption, alleged to occur at very low doses. A recent example is the case of bisphenol A. The way forward to assess new packaging technologies and reports of very low dose effects in non-standard studies of food contact substances is likely to remain controversial. However, the risk assessment paradigm is sufficiently robust and flexible to be adapted to meet these challenges. The use of the Threshold of Regulation and the Threshold of Toxicological Concern concepts may play a critical role in the risk assessment of new food packaging technologies in the future.

The Nuclear Threat: when It Hurts to Think. 1985

Medicine, Conflict, and Survival. Oct-Dec, 2009  |  Pubmed ID: 20178193

The Burden of Care of Gay Male Carers Caring for Men Living with HIV/AIDS

American Journal of Men's Health. Dec, 2010  |  Pubmed ID: 20031938

The notion of caregiver 'burden' has been used as a term that refers to the financial, physical and emotional effects of caring. This Australian 2002 research investigated the caregiver burden of HIV/AIDS on the gay male carers of gay men with the disease.

Nursing Care of Clients Treated with Atypical Antipsychotics Who Have a Risk of Developing Metabolic Instability And/or Type 2 Diabetes

Archives of Psychiatric Nursing. Feb, 2010  |  Pubmed ID: 20117688

The aim of this article is to present a current discussion related to the nursing care of clients treated with atypical antipsychotic medicines and who have a risk of developing metabolic instability and/or Type 2 diabetes. The importance of such a discussion is to provide both the novice and the experienced nurse with additional knowledge of this current health issue with which to inform their nursing practice.

Australians Living with and Managing Hepatitis C

Issues in Mental Health Nursing. Aug, 2010  |  Pubmed ID: 20624020

This paper discusses the psychosocial impact of being diagnosed with hepatitis C virus (HCV). The paper clarifies some of the key misconceptions about the virus, especially the impact HCV has on people who have been recently diagnosed. An individual's reaction to the HCV diagnosis and the subsequent lifestyle challenges to maintain health, well-being, family, and social networks are discussed, particularly the issues surrounding mental health in respect to a recent chronic illness diagnosis and how to manage the trajectory of the illness in the community and individually. HCV disclosure and its effect on intimacy are also detailed. For people living with both a diagnosed mental illness and HCV, managing the illness can be complicated. Not only are these individuals concerned about their mental illness, its treatment, and the social stigma and discrimination associated with it, they also may be alarmed over their future physical health. The paper is preliminary to research using the psychotherapeutic approach of Cognitive Behavioural Therapy (CBT) in groups of persons with a dual diagnosis of mental illness and HCV.

Wide-field Fluorescence Lifetime Imaging of Cancer

Biomedical Optics Express. Aug, 2010  |  Pubmed ID: 21258496

Optical imaging of tissue autofluorescence has the potential to provide rapid label-free screening and detection of surface tumors for clinical applications, including when combined with endoscopy. Quantitative imaging of intensity-based contrast is notoriously difficult and spectrally resolved imaging does not always provide sufficient contrast. We demonstrate that fluorescence lifetime imaging (FLIM) applied to intrinsic tissue autofluorescence can directly contrast a range of surface tissue tumors, including in gastrointestinal tissues, using compact, clinically deployable instrumentation achieving wide-field fluorescence lifetime images of unprecedented clarity. Statistically significant contrast is observed between cancerous and healthy colon tissue for FLIM with excitation at 355 nm. To illustrate the clinical potential, wide-field fluorescence lifetime images of unstained ex vivo tissue have been acquired at near video rate, which is an important step towards real-time FLIM for diagnostic and interoperative imaging, including for screening and image-guided biopsy applications.

FLIM FRET Technology for Drug Discovery: Automated Multiwell-plate High-content Analysis, Multiplexed Readouts and Application in Situ

Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry. Feb, 2011  |  Pubmed ID: 21337485

A fluorescence lifetime imaging (FLIM) technology platform intended to read out changes in Förster resonance energy transfer (FRET) efficiency is presented for the study of protein interactions across the drug-discovery pipeline. FLIM provides a robust, inherently ratiometric imaging modality for drug discovery that could allow the same sensor constructs to be translated from automated cell-based assays through small transparent organisms such as zebrafish to mammals. To this end, an automated FLIM multiwell-plate reader is described for high content analysis of fixed and live cells, tomographic FLIM in zebrafish and FLIM FRET of live cells via confocal endomicroscopy. For cell-based assays, an exemplar application reading out protein aggregation using FLIM FRET is presented, and the potential for multiple simultaneous FLIM (FRET) readouts in microscopy is illustrated.

Vitamin D Mushrooms: Comparison of the Composition of Button Mushrooms (Agaricus Bisporus) Treated Postharvest with UVB Light or Sunlight

Journal of Agricultural and Food Chemistry. Aug, 2011  |  Pubmed ID: 21736377

This study compared the compositional changes in mushrooms exposed to sunlight with those occurring after commercial ultraviolet (UV) light processing. Button mushrooms (75 kg) were processed in the presence or absence of UVB light; a third group was exposed to direct sunlight. Mushroom composition was evaluated using chemical analyses. Vitamin D concentrations were 5, 410, and 374 μg/100 g (dw) in control, UVB, and sunlight groups, respectively. On a dry weight basis, no significant changes in vitamin C, folate, vitamins B(6), vitamin B(5), riboflavin, niacin, amino acids, fatty acids, ergosterol, or agaritine were observed following UVB processing. Sunlight exposure resulted in a 26% loss of riboflavin, evidence of folate oxidation, and unexplained increases in ergosterol (9.5%). It was concluded that compositional effects of UVB light are limited to changes in vitamin D and show no detrimental changes relative to natural sunlight exposure and, therefore, provide important information relevant to the suitability and safety of UVB light technology for vitamin D enhanced mushrooms.

Application of Ultrafast Gold Luminescence to Measuring the Instrument Response Function for Multispectral Multiphoton Fluorescence Lifetime Imaging

Optics Express. Jul, 2011  |  Pubmed ID: 21934746

When performing multiphoton fluorescence lifetime imaging in multiple spectral emission channels, an instrument response function must be acquired in each channel if accurate measurements of complex fluorescence decays are to be performed. Although this can be achieved using the reference reconvolution technique, it is difficult to identify suitable fluorophores with a mono-exponential fluorescence decay across a broad emission spectrum. We present a solution to this problem by measuring the IRF using the ultrafast luminescence from gold nanorods. We show that ultrafast gold nanorod luminescence allows the IRF to be directly obtained in multiple spectral channels simultaneously across a wide spectral range. We validate this approach by presenting an analysis of multispectral autofluorescence FLIM data obtained from human skin ex vivo.

Quantification of Cellular Autofluorescence of Human Skin Using Multiphoton Tomography and Fluorescence Lifetime Imaging in Two Spectral Detection Channels

Biomedical Optics Express. Dec, 2011  |  Pubmed ID: 22162820

We explore the diagnostic potential of imaging endogenous fluorophores using two photon microscopy and fluorescence lifetime imaging (FLIM) in human skin with two spectral detection channels. Freshly excised benign dysplastic nevi (DN) and malignant nodular Basal Cell Carcinomas (nBCCs) were excited at 760 nm. The resulting fluorescence signal was binned manually on a cell by cell basis. This improved the reliability of fitting using a double exponential decay model and allowed the fluorescence signatures from different cell populations within the tissue to be identified and studied. We also performed a direct comparison between different diagnostic groups. A statistically significant difference between the median mean fluorescence lifetime of 2.79 ns versus 2.52 ns (blue channel, 300-500 nm) and 2.08 ns versus 1.33 ns (green channel, 500-640 nm) was found between nBCCs and DN respectively, using the Mann-Whitney U test (p < 0.01). Further differences in the distribution of fluorescence lifetime parameters and inter-patient variability are also discussed.

Managing People with Mental Health Presentations in Emergency Departments--a Service Exploration of the Issues Surrounding Responsiveness from a Mental Health Care Consumer and Carer Perspective

Australasian Emergency Nursing Journal : AENJ. Aug, 2012  |  Pubmed ID: 22947687

Mainstreaming of mental health services (MHS) within the Australian medical system has generated a fundamental transformation in the way consumers and carers access emergency MHS. People present to the Emergency Department (ED) with many health issues which can often include the management of their mental illness, physical co morbidity, or substance use. This paper discusses the issues surrounding access to EDs for clients, families and staff in the context of presentations for mental health problems at a southern metropolitan hospital in Victoria. The pilot project utilised focus groups with mental health care consumers and carers to collaboratively focus on and document the mental health client's 'journey of care' in the ED. There is evidence to suggest from this project that the ED mental health client journey needs continuous improvement and evaluation.

Multiphoton Multispectral Fluorescence Lifetime Tomography for the Evaluation of Basal Cell Carcinomas

PloS One. 2012  |  Pubmed ID: 22984428

We present the first detailed study using multispectral multiphoton fluorescence lifetime imaging to differentiate basal cell carcinoma cells (BCCs) from normal keratinocytes. Images were acquired from 19 freshly excised BCCs and 27 samples of normal skin (in & ex vivo). Features from fluorescence lifetime images were used to discriminate BCCs with a sensitivity/specificity of 79%/93% respectively. A mosaic of BCC fluorescence lifetime images covering >1 mm(2) is also presented, demonstrating the potential for tumour margin delineation. Using 10,462 manually segmented cells from the image data, we quantify the cellular morphology and spectroscopic differences between BCCs and normal skin for the first time. Statistically significant increases were found in the fluorescence lifetimes of cells from BCCs in all spectral channels, ranging from 19.9% (425-515 nm spectral emission) to 39.8% (620-655 nm emission). A discriminant analysis based diagnostic algorithm allowed the fraction of cells classified as malignant to be calculated for each patient. This yielded a receiver operator characteristic area under the curve for the detection of BCC of 0.83. We have used both morphological and spectroscopic parameters to discriminate BCC from normal skin, and provide a comprehensive base for how this technique could be used for BCC assessment in clinical practice.

The Environment of Inpatient Healthcare Delivery and Its Influence on the Outcome of Care

HERD. 2012  |  Pubmed ID: 23224845

This paper addresses issues arising in the literature regarding the environmental design of inpatient healthcare settings and their impact on care.

The Acceptability and Efficacy of a Group Cognitive Behavioural Therapy Programme in a Community Mental Health Setting

Community Mental Health Journal. Jun, 2013  |  Pubmed ID: 22294509

This paper presents data on a patient evaluation of a group cognitive behavioural therapy programme in an applied setting and its efficacy for reducing generalised anxiety and or depression, and distress. Patients (n=14) participated in one of two 8-week group cognitive behavioural therapy programmes for generalised anxiety or depression, within a mental health service. Patients’ perceptions of the programme were collected via an evaluation questionnaire, and data on clinical outcomes were sourced from patients’ case notes. Most patients who were invited to participate in the programme (n=14 of 17), and their evaluations were generally favourable. Almost all participants (93%) indicated that the programme either met or exceeded their expectations. The clinical outcomes of the intervention were similar to those found in efficacy studies reported in the published literature (approximately half to threequarters of one standard deviation improvement in anxiety, depression, and distress scores).

Review of the Regulation and Safety Assessment of Food Substances in Various Countries and Jurisdictions

Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment. 2013  |  Pubmed ID: 23781843

This review compares the regulations, definitions and approval processes for substances intentionally added to or unintentionally present in human food in the following specific countries/jurisdictions: Argentina, Australia, Brazil, Canada, China, the European Union, Japan, Mexico, New Zealand, and the United States. This includes direct food additives, food ingredients, flavouring agents, food enzymes and/or processing aids, food contact materials, novel foods, and nanoscale materials for food applications. The regulatory authority of each target jurisdiction/country uses its own regulatory framework and although the definitions, regulations and approval processes may vary among all target countries, in general there are many similarities. In all cases, the main purpose of each authority is to establish a regulatory framework and maintain/enforce regulations to ensure that food consumed and sold within its respective countries is safe. There is a move towards harmonisation of food regulations, as illustrated by Australia and New Zealand and by Mercosur. The European Union has also established regulations, which are applicable for all member states, to establish a common authorisation procedure for direct food additives, flavourings and enzymes. Although the path for approval of different categories of food additives varies from jurisdiction to jurisdiction, there are many commonalities in terms of the data requirements and considerations for assessment of the safety of use of food additives, including the use of positive lists of approved substances, pre-market approval, and a separation between science and policy decisions. The principles applied are largely reflective of the early work by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) committees and JECFA assessments of the safety of food additives for human and animal foods.

Rapid Global Fitting of Large Fluorescence Lifetime Imaging Microscopy Datasets

PloS One. 2013  |  Pubmed ID: 23940626

Fluorescence lifetime imaging (FLIM) is widely applied to obtain quantitative information from fluorescence signals, particularly using Förster Resonant Energy Transfer (FRET) measurements to map, for example, protein-protein interactions. Extracting FRET efficiencies or population fractions typically entails fitting data to complex fluorescence decay models but such experiments are frequently photon constrained, particularly for live cell or in vivo imaging, and this leads to unacceptable errors when analysing data on a pixel-wise basis. Lifetimes and population fractions may, however, be more robustly extracted using global analysis to simultaneously fit the fluorescence decay data of all pixels in an image or dataset to a multi-exponential model under the assumption that the lifetime components are invariant across the image (dataset). This approach is often considered to be prohibitively slow and/or computationally expensive but we present here a computationally efficient global analysis algorithm for the analysis of time-correlated single photon counting (TCSPC) or time-gated FLIM data based on variable projection. It makes efficient use of both computer processor and memory resources, requiring less than a minute to analyse time series and multiwell plate datasets with hundreds of FLIM images on standard personal computers. This lifetime analysis takes account of repetitive excitation, including fluorescence photons excited by earlier pulses contributing to the fit, and is able to accommodate time-varying backgrounds and instrument response functions. We demonstrate that this global approach allows us to readily fit time-resolved fluorescence data to complex models including a four-exponential model of a FRET system, for which the FRET efficiencies of the two species of a bi-exponential donor are linked, and polarisation-resolved lifetime data, where a fluorescence intensity and bi-exponential anisotropy decay model is applied to the analysis of live cell homo-FRET data. A software package implementing this algorithm, FLIMfit, is available under an open source licence through the Open Microscopy Environment.

Caring for the Mental Illness Patient in Emergency Departments--an Exploration of the Issues from a Healthcare Provider Perspective

Journal of Clinical Nursing. Jul, 2014  |  Pubmed ID: 24313388

To identify issues, from the emergency department clinicians' viewpoint, with the management of patients presenting to the emergency department with a mental illness.

Mental Health Recovery: Lived Experience of Consumers, Carers and Nurses

Contemporary Nurse. Sep, 2014  |  Pubmed ID: 25196697

Abstract Background Mental health recovery is a prominent topic of discussion in the global mental health settings. The concept of mental health recovery brought about a major shift in the traditional philosophical views of many mental health systems. Aim The purpose of this article is to outline the results of a qualitative study on mental health recovery, which involved mental health consumers, carers and mental health nurses from an Area Mental Health Service in Victoria, Australia. This paper is part one of the results that explored the meaning of recovery. Methods The study used van Manen's hermeneutic phenomenology to analyse the data. Findings Themes suggested that the cohort had varying views on recovery that were similar and dissimilar. The similar views were categorised under two processes involving the self, an internal process and an external process. These two processes involved reclaiming various aspects of oneself, living life, cure or absence of symptoms and contribution to community. The dissimilar views involved returning to pre-illness state and recovery was impossible. Conclusion This study highlights the need for placing importance to the person's sense of self in the recovery process.

Mental Health Recovery: Lived Experience of Consumers, Carers and Nurses

Contemporary Nurse. 2015  |  Pubmed ID: 26041103

Background Mental health recovery is a prominent topic of discussion in the global mental health settings. The concept of mental health recovery brought about a major shift in the traditional philosophical views of many mental health systems. Aim The purpose of this article is to outline the results of a qualitative study on mental health recovery, which involved mental health consumers, carers and mental health nurses from an Area Mental Health Service in Victoria, Australia. This paper is Part One of the results that explored the meaning of recovery. Methods The study used van Manen's hermeneutic phenomenology to analyse the data. Findings Themes suggested that the cohort had varying views on recovery that were similar and dissimilar. The similar views were categorised under two processes involving the self, an internal process and an external process. These two processes involved reclaiming various aspects of oneself, living life, cure or absence of symptoms and contribution to community. The dissimilar views involved returning to pre-illness state and recovery was impossible. Conclusion This study highlights the need for placing importance on the person's sense of self in the recovery process.

Men's Mental Health

Australian Nursing & Midwifery Journal. Nov, 2015  |  Pubmed ID: 26749891

Electromagnetic Stirring in a Microbioreactor with Non-conventional Chamber Morphology and Implementation of Multiplexed Mixing

Journal of Chemical Technology and Biotechnology (Oxford, Oxfordshire : 1986). Oct, 2015  |  Pubmed ID: 27546945

Microbioreactors have emerged as novel tools for early bioprocess development. Mixing lies at the heart of bioreactor operation (at all scales). The successful implementation of micro-stirring methods is thus central to the further advancement of microbioreactor technology. The aim of this study was to develop a micro-stirring method that aids robust microbioreactor operation and facilitates cost-effective parallelization.

MANAGING DIABETES AND MENTAL ILLNESS

Australian Nursing & Midwifery Journal. Apr, 2016  |  Pubmed ID: 27254993

The Enigma of Neurogenic Thoracic Outlet Syndrome Following Motor Vehicle Collisions

Canadian Journal of Surgery. Journal Canadien De Chirurgie. Aug, 2016  |  Pubmed ID: 27454840

The concept of neurogenic thoracic outlet syndrome (N-TOS) including upper and lower plexus syndromes secondary to soft tissue neck injury after motor vehicle collisions (MVCs) has been contentious. We considered that analysis of objective data from this group of patients could provide insight into this controversial type of N-TOS.

EasySTORM: a Robust, Lower-cost Approach to Localisation and TIRF Microscopy

Journal of Biophotonics. Sep, 2016  |  Pubmed ID: 27592533

TIRF and STORM microscopy are super-resolving fluorescence imaging modalities for which current implementations on standard microscopes can present significant complexity and cost. We present a straightforward and low-cost approach to implement STORM and TIRF taking advantage of multimode optical fibres and multimode diode lasers to provide the required excitation light. Combined with open source software and relatively simple protocols to prepare samples for STORM, including the use of Vectashield for non-TIRF imaging, this approach enables TIRF and STORM imaging of cells labelled with appropriate dyes or expressing suitable fluorescent proteins to become widely accessible at low cost.

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