34 results on '"LUKE D"'
Search Results
2. Self-digitization chip for single-cell genotyping of cancer-related mutations.
- Author
-
Alison M Thompson, Jordan L Smith, Luke D Monroe, Jason E Kreutz, Thomas Schneider, Bryant S Fujimoto, Daniel T Chiu, Jerald P Radich, and Amy L Paguirigan
- Subjects
Medicine ,Science - Abstract
Cancer is a heterogeneous disease, and patient-level genetic assessments can guide therapy choice and impact prognosis. However, little is known about the impact of genetic variability within a tumor, intratumoral heterogeneity (ITH), on disease progression or outcome. Current approaches using bulk tumor specimens can suggest the presence of ITH, but only single-cell genetic methods have the resolution to describe the underlying clonal structures themselves. Current techniques tend to be labor and resource intensive and challenging to characterize with respect to sources of biological and technical variability. We have developed a platform using a microfluidic self-digitization chip to partition cells in stationary volumes for cell imaging and allele-specific PCR. Genotyping data from only confirmed single-cell volumes is obtained and subject to a variety of relevant quality control assessments such as allele dropout, false positive, and false negative rates. We demonstrate single-cell genotyping of the NPM1 type A mutation, an important prognostic indicator in acute myeloid leukemia, on single cells of the cell line OCI-AML3, describing a more complex zygosity distribution than would be predicted via bulk analysis.
- Published
- 2018
- Full Text
- View/download PDF
3. Occupancy and detectability modelling of vertebrates in northern Australia using multiple sampling methods.
- Author
-
Luke D Einoder, Darren M Southwell, José J Lahoz-Monfort, Graeme R Gillespie, Alaric Fisher, and Brendan A Wintle
- Subjects
Medicine ,Science - Abstract
Understanding where species occur and how difficult they are to detect during surveys is crucial for designing and evaluating monitoring programs, and has broader applications for conservation planning and management. In this study, we modelled occupancy and the effectiveness of six sampling methods at detecting vertebrates across the Top End of northern Australia. We fitted occupancy-detection models to 136 species (83 birds, 33 reptiles, 20 mammals) of 242 recorded during surveys of 333 sites in eight conservation reserves between 2011 and 2016. For modelled species, mean occupancy was highly variable: birds and reptiles ranged from 0.01-0.81 and 0.01-0.49, respectively, whereas mammal occupancy was lower, ranging from 0.02-0.30. Of the 11 environmental covariates considered as potential predictors of occupancy, topographic ruggedness, elevation, maximum temperature, and fire frequency were retained more readily in the top models. Using these models, we predicted species occupancy across the Top End of northern Australia (293,017 km2) and generated species richness maps for each species group. For mammals and reptiles, high richness was associated with rugged terrain, while bird richness was highest in coastal lowland woodlands. On average, detectability of diurnal birds was higher per day of surveys (0.33 ± 0.09) compared with nocturnal birds per night of spotlighting (0.13 ± 0.06). Detectability of reptiles was similar per day/night of pit trapping (0.30 ± 0.09) as per night of spotlighting (0.29 ± 0.11). On average, mammals were highly detectable using motion-sensor cameras for a week (0.36 ± 0.06), with exception of smaller-bodied species. One night of Elliott trapping (0.20 ± 0.06) and spotlighting (0.19 ± 0.06) was more effective at detecting mammals than cage (0.08 ± 0.03) and pit trapping (0.05 ± 0.04). Our estimates of species occupancy and detectability will help inform decisions about how best to redesign a long-running vertebrate monitoring program in the Top End of northern Australia.
- Published
- 2018
- Full Text
- View/download PDF
4. Optimization of fluorophores for chemical tagging and immunohistochemistry of Drosophila neurons.
- Author
-
Geoffrey W Meissner, Jonathan B Grimm, Rebecca M Johnston, Ben Sutcliffe, Julian Ng, Gregory S X E Jefferis, Sebastian Cachero, Luke D Lavis, and Oz Malkesman
- Subjects
Medicine ,Science - Abstract
The use of genetically encoded 'self-labeling tags' with chemical fluorophore ligands enables rapid labeling of specific cells in neural tissue. To improve the chemical tagging of neurons, we synthesized and evaluated new fluorophore ligands based on Cy, Janelia Fluor, Alexa Fluor, and ATTO dyes and tested these with recently improved Drosophila melanogaster transgenes. We found that tissue clearing and mounting in DPX substantially improves signal quality when combined with specific non-cyanine fluorophores. We compared and combined this labeling technique with standard immunohistochemistry in the Drosophila brain.
- Published
- 2018
- Full Text
- View/download PDF
5. A shift from motorised travel to active transport: What are the potential health gains for an Australian city?
- Author
-
Belen Zapata-Diomedi, Luke D Knibbs, Robert S Ware, Kristiann C Heesch, Marko Tainio, James Woodcock, and J Lennert Veerman
- Subjects
Medicine ,Science - Abstract
INTRODUCTION:An alarmingly high proportion of the Australian adult population does not meet national physical activity guidelines (57%). This is concerning because physical inactivity is a risk factor for several chronic diseases. In recent years, an increasing emphasis has been placed on the potential for transport and urban planning to contribute to increased physical activity via greater uptake of active transport (walking, cycling and public transport). In this study, we aimed to estimate the potential health gains and savings in health care costs of an Australian city achieving its stated travel targets for the use of active transport. METHODS:Additional active transport time was estimated for the hypothetical scenario of Brisbane (1.1 million population 2013) in Australia achieving specified travel targets. A multi-state life table model was used to estimate the number of health-adjusted life years, life-years, changes in the burden of diseases and injuries, and the health care costs associated with changes in physical activity, fine particle (
- Published
- 2017
- Full Text
- View/download PDF
6. A Novel Method and Its Application to Measuring Pathogen Decay in Bioaerosols from Patients with Respiratory Disease.
- Author
-
Graham R Johnson, Luke D Knibbs, Timothy J Kidd, Claire E Wainwright, Michelle E Wood, Kay A Ramsay, Scott C Bell, and Lidia Morawska
- Subjects
Medicine ,Science - Abstract
This work aimed to develop an in vivo approach for measuring the duration of human bioaerosol infectivity. To achieve this, techniques designed to target short-term and long-term bioaerosol aging, were combined in a tandem system and optimized for the collection of human respiratory bioaerosols, without contamination. To demonstrate the technique, cough aerosols were sampled from two persons with cystic fibrosis and chronic Pseudomonas aeruginosa infection. Measurements and cultures from aerosol ages of 10, 20, 40, 900 and 2700 seconds were used to determine the optimum droplet nucleus size for pathogen transport and the airborne bacterial biological decay. The droplet nuclei containing the greatest number of colony forming bacteria per unit volume of airborne sputum were between 1.5 and 2.6 μm. Larger nuclei of 3.9 μm, were more likely to produce a colony when impacted onto growth media, because the greater volume of sputum comprising the larger droplet nuclei, compensated for lower concentrations of bacteria within the sputum of larger nuclei. Although more likely to produce a colony, the larger droplet nuclei were small in number, and the greatest numbers of colonies were instead produced by nuclei from 1.5 to 5.7 μm. Very few colonies were produced by smaller droplet nuclei, despite their very large numbers. The concentration of viable bacteria within the dried sputum comprising the droplet nuclei exhibited an orderly dual decay over time with two distinct half-lives. Nuclei exhibiting a rapid biological decay process with a 10 second half-life were quickly exhausted, leaving only a subset characterized by a half-life of greater than 10 minutes. This finding implied that a subset of bacteria present in the aerosol was resistant to rapid biological decay and remained viable in room air long enough to represent an airborne infection risk.
- Published
- 2016
- Full Text
- View/download PDF
7. Trait Anticipatory Pleasure Predicts Effort Expenditure for Reward.
- Author
-
Joachim T Geaney, Michael T Treadway, and Luke D Smillie
- Subjects
Medicine ,Science - Abstract
Research in motivation and emotion has been increasingly influenced by the perspective that processes underpinning the motivated approach of rewarding goals are distinct from those underpinning enjoyment during reward consummation. This distinction recently inspired the construction of the Temporal Experience of Pleasure Scale (TEPS), a self-report measure that distinguishes trait anticipatory pleasure (pre-reward feelings of desire) from consummatory pleasure (feelings of enjoyment and gratification upon reward attainment). In a university community sample (N = 97), we examined the TEPS subscales as predictors of (1) the willingness to expend effort for monetary rewards, and (2) affective responses to a pleasant mood induction procedure. Results showed that both anticipatory pleasure and a well-known trait measure of reward motivation predicted effort-expenditure for rewards when the probability of being rewarded was relatively low. Against expectations, consummatory pleasure was unrelated to induced pleasant affect. Taken together, our findings provide support for the validity of the TEPS anticipatory pleasure scale, but not the consummatory pleasure scale.
- Published
- 2015
- Full Text
- View/download PDF
8. Regulation of Staphylococcus aureus MntC expression and its role in response to oxidative stress.
- Author
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Luke D Handke, Julio C Hawkins, Alita A Miller, Kathrin U Jansen, and Annaliesa S Anderson
- Subjects
Medicine ,Science - Abstract
Staphylococcus aureus is a successful human pathogen that has developed several approaches to evade the immune system, including resistance strategies to prevent oxidative killing by immune cells. One mechanism by which this evasion occurs is by production of superoxide dismutase enzymes, which require manganese as a cofactor. Manganese is acquired by the manganese transporter MntABC. One component of this operon, MntC, has been proposed as a potential vaccine candidate due to its early in vivo expression and its ability to provide protection in preclinical models of staphylococcal infection. In the current study, we interrogate the role of this protein in protecting S. aureus from oxidative stress. We demonstrate that mutation of mntC in a number of invasive S. aureus clinical isolates results in increased sensitivity to oxidative stress. In addition, we show that while downregulation of mntC transcription is triggered upon exposure to physiological concentrations of manganese, MntC protein is still present on the bacterial surface at these same concentrations. Taken together, these results provide insight into the role of this antigen for the pathogen.
- Published
- 2013
- Full Text
- View/download PDF
9. FGF2 delays tectal neurogenesis, increases tectal cell numbers, and alters tectal lamination in embryonic chicks.
- Author
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Luke D McGowan, Roula A Alaama, and Georg F Striedter
- Subjects
Medicine ,Science - Abstract
Intraventricular injections of the fibroblast growth factor 2 (FGF2) are known to increase the size of the optic tectum in embryonic chicks. Here we show that this increase in tectum size is due to a delay in tectal neurogenesis, which by definition extends the proliferation of tectal progenitors. Specifically, we use cumulative labeling with the thymidine analog EdU to demonstrate that FGF2 treatment on embryonic day 4 (ED4) reduces the proportion and absolute number of unlabeled cells in the rostroventral tectum when EdU infusions are begun on ED5, as one would expect if FGF2 retards tectal neurogenesis. We also examined FGF2's effect on neurogenesis in the caudodorsal tectum, which is born 2-3 days after the rostroventral tectum, by combining FGF2 treatment on ED4 with EDU infusions beginning on ED8. Again, FGF2 treatment reduced the proportion and number of EdU-negative (i.e., unlabeled) cells, consistent with a delay in neurogenesis. Collectively, these data indicate FGF2 in embryonic chicks delays neurogenesis throughout much of the tectum and continues to do so for several days after the FGF2 injection. One effect of this delay in neurogenesis is that tectal cell numbers more than double. In addition, tectal laminae that are born early in development become abnormally thin and cell-sparse after FGF2 treatment, whereas late-born layers remain unaffected. Combined with the results of prior work, these data indicate that FGF2 delays tectal neurogenesis and, thereby, triggers a cascade of changes in tectum size and morphology.
- Published
- 2013
- Full Text
- View/download PDF
10. Chronic exposure of corals to fine sediments: lethal and sub-lethal impacts.
- Author
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Florita Flores, Mia O Hoogenboom, Luke D Smith, Timothy F Cooper, David Abrego, and Andrew P Negri
- Subjects
Medicine ,Science - Abstract
Understanding the sedimentation and turbidity thresholds for corals is critical in assessing the potential impacts of dredging projects in tropical marine systems. In this study, we exposed two species of coral sampled from offshore locations to six levels of total suspended solids (TSS) for 16 weeks in the laboratory, including a 4 week recovery period. Dose-response relationships were developed to quantify the lethal and sub-lethal thresholds of sedimentation and turbidity for the corals. The sediment treatments affected the horizontal foliaceous species (Montipora aequituberculata) more than the upright branching species (Acropora millepora). The lowest sediment treatments that caused full colony mortality were 30 mg l(-1) TSS (25 mg cm(-2) day(-1)) for M. aequituberculata and 100 mg l(-1) TSS (83 mg cm(-2) day(-1)) for A. millepora after 12 weeks. Coral mortality generally took longer than 4 weeks and was closely related to sediment accumulation on the surface of the corals. While measurements of damage to photosystem II in the symbionts and reductions in lipid content and growth indicated sub-lethal responses in surviving corals, the most reliable predictor of coral mortality in this experiment was long-term sediment accumulation on coral tissue.
- Published
- 2012
- Full Text
- View/download PDF
11. FGF2 Delays Tectal Neurogenesis, Increases Tectal Cell Numbers, and Alters Tectal Lamination in Embryonic Chicks
- Author
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McGowan, Luke D, Alaama, Roula A, Striedter, Georg F, and Kihara, Alexandre Hiroaki
- Subjects
Fibroblast-Growth-Factor ,Brain Evolution ,Optic Tectum ,Cycle Exit ,Differentiation ,Progenitors ,Precursors ,Expansion ,Neurons ,Retina - Published
- 2013
12. Advancing statistical treatment of photolocomotor behavioral response study data
- Author
-
Natalie Mastin, Luke Durell, Bryan W. Brooks, and Amanda S. Hering
- Subjects
Medicine ,Science - Published
- 2024
13. Optimization of fluorophores for chemical tagging and immunohistochemistry of Drosophila neurons
- Author
-
Rebecca M. Johnston, Sebastian Cachero, Luke D. Lavis, Jonathan B. Grimm, Gregory S.X.E. Jefferis, Ben Sutcliffe, Geoffrey W. Meissner, Julian Ng, Oz Malkesman, Apollo-University Of Cambridge Repository, Jefferis, Gregory [0000-0002-0587-9355], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Neuropil ,lcsh:Medicine ,Animals, Genetically Modified ,chemistry.chemical_compound ,0302 clinical medicine ,Signal quality ,Animal Cells ,Medicine and Health Sciences ,lcsh:Science ,Cross Reactivity ,Neurons ,Liquid Chromatography ,Multidisciplinary ,Tissue clearing ,Microscopy, Confocal ,biology ,Molecular Structure ,Chemistry ,Drosophila Melanogaster ,Chromatographic Techniques ,Brain ,Eukaryota ,Esters ,General Medicine ,Animal Models ,Immunohistochemistry ,3. Good health ,Cell biology ,Insects ,Experimental Organism Systems ,Optical Equipment ,Physical Sciences ,Engineering and Technology ,Female ,Drosophila ,Drosophila melanogaster ,Cellular Types ,General Agricultural and Biological Sciences ,Research Article ,Fluorophore ,Arthropoda ,Transgene ,education ,Immunology ,Equipment ,Glial Cells ,Research and Analysis Methods ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Model Organisms ,Animals ,Drosophila (subgenus) ,Immunohistochemistry Techniques ,Alexa Fluor ,Fluorescent Dyes ,Staining and Labeling ,Lasers ,lcsh:R ,Organisms ,Chemical Compounds ,Biology and Life Sciences ,Cell Biology ,biology.organism_classification ,Invertebrates ,High Performance Liquid Chromatography ,Histochemistry and Cytochemistry Techniques ,030104 developmental biology ,Cellular Neuroscience ,Immunologic Techniques ,lcsh:Q ,030217 neurology & neurosurgery ,Neuroscience - Abstract
The use of genetically encoded ‘self-labeling tags’ with chemical fluorophore ligands enables rapid labeling of specific cells in neural tissue. To improve the chemical tagging of neurons, we synthesized and evaluated new fluorophore ligands based on Cy, Janelia Fluor, Alexa Fluor, and ATTO dyes and tested these with recently improved Drosophila melanogaster transgenes. We found that tissue clearing and mounting in DPX substantially improves signal quality when combined with specific non-cyanine fluorophores. We compared and combined this labeling technique with standard immunohistochemistry in the Drosophila brain.
- Published
- 2018
14. Occupancy and detectability modelling of vertebrates in northern Australia using multiple sampling methods
- Author
-
Brendan A. Wintle, Graeme R. Gillespie, Alaric Fisher, José J. Lahoz-Monfort, Luke D. Einoder, and Darren M. Southwell
- Subjects
0106 biological sciences ,Topography ,Occupancy ,Ecological Metrics ,Species distribution ,Oceania ,Biodiversity ,lcsh:Medicine ,Nocturnal ,Biology ,010603 evolutionary biology ,01 natural sciences ,Birds ,Geographical Locations ,Animals ,lcsh:Science ,Conservation Science ,Mammals ,Islands ,Landforms ,Multidisciplinary ,Ecology ,010604 marine biology & hydrobiology ,Spotlighting ,Ecology and Environmental Sciences ,lcsh:R ,Organisms ,Australia ,Species diversity ,Biology and Life Sciences ,Eukaryota ,Reptiles ,Species Diversity ,Geomorphology ,Monitoring program ,Vertebrates ,Amniotes ,People and Places ,Earth Sciences ,lcsh:Q ,Physical geography ,Species richness ,Research Article - Abstract
Understanding where species occur and how difficult they are to detect during surveys is crucial for designing and evaluating monitoring programs, and has broader applications for conservation planning and management. In this study, we modelled occupancy and the effectiveness of six sampling methods at detecting vertebrates across the Top End of northern Australia. We fitted occupancy-detection models to 136 species (83 birds, 33 reptiles, 20 mammals) of 242 recorded during surveys of 333 sites in eight conservation reserves between 2011 and 2016. For modelled species, mean occupancy was highly variable: birds and reptiles ranged from 0.01-0.81 and 0.01-0.49, respectively, whereas mammal occupancy was lower, ranging from 0.02-0.30. Of the 11 environmental covariates considered as potential predictors of occupancy, topographic ruggedness, elevation, maximum temperature, and fire frequency were retained more readily in the top models. Using these models, we predicted species occupancy across the Top End of northern Australia (293,017 km2) and generated species richness maps for each species group. For mammals and reptiles, high richness was associated with rugged terrain, while bird richness was highest in coastal lowland woodlands. On average, detectability of diurnal birds was higher per day of surveys (0.33 ± 0.09) compared with nocturnal birds per night of spotlighting (0.13 ± 0.06). Detectability of reptiles was similar per day/night of pit trapping (0.30 ± 0.09) as per night of spotlighting (0.29 ± 0.11). On average, mammals were highly detectable using motion-sensor cameras for a week (0.36 ± 0.06), with exception of smaller-bodied species. One night of Elliott trapping (0.20 ± 0.06) and spotlighting (0.19 ± 0.06) was more effective at detecting mammals than cage (0.08 ± 0.03) and pit trapping (0.05 ± 0.04). Our estimates of species occupancy and detectability will help inform decisions about how best to redesign a long-running vertebrate monitoring program in the Top End of northern Australia.
- Published
- 2018
15. Correction: Occupancy and detectability modelling of vertebrates in northern Australia using multiple sampling methods
- Author
-
Einoder, Luke D., primary, Southwell, Darren M., additional, Lahoz-Monfort, José J., additional, Gillespie, Graeme R., additional, Fisher, Alaric, additional, and Wintle, Brendan A., additional
- Published
- 2018
- Full Text
- View/download PDF
16. Occupancy and detectability modelling of vertebrates in northern Australia using multiple sampling methods
- Author
-
Einoder, Luke D., primary, Southwell, Darren M., additional, Lahoz-Monfort, José J., additional, Gillespie, Graeme R., additional, Fisher, Alaric, additional, and Wintle, Brendan A., additional
- Published
- 2018
- Full Text
- View/download PDF
17. Optimization of fluorophores for chemical tagging and immunohistochemistry of Drosophila neurons
- Author
-
Meissner, Geoffrey W., primary, Grimm, Jonathan B., additional, Johnston, Rebecca M., additional, Sutcliffe, Ben, additional, Ng, Julian, additional, Jefferis, Gregory S. X. E., additional, Cachero, Sebastian, additional, Lavis, Luke D., additional, and Malkesman, Oz, additional
- Published
- 2018
- Full Text
- View/download PDF
18. Self-digitization chip for single-cell genotyping of cancer-related mutations
- Author
-
Thompson, Alison M., primary, Smith, Jordan L., additional, Monroe, Luke D., additional, Kreutz, Jason E., additional, Schneider, Thomas, additional, Fujimoto, Bryant S., additional, Chiu, Daniel T., additional, Radich, Jerald P., additional, and Paguirigan, Amy L., additional
- Published
- 2018
- Full Text
- View/download PDF
19. A shift from motorised travel to active transport: What are the potential health gains for an Australian city?
- Author
-
Zapata-Diomedi, Belen, primary, Knibbs, Luke D., additional, Ware, Robert S., additional, Heesch, Kristiann C., additional, Tainio, Marko, additional, Woodcock, James, additional, and Veerman, J. Lennert, additional
- Published
- 2017
- Full Text
- View/download PDF
20. A Novel Method and Its Application to Measuring Pathogen Decay in Bioaerosols from Patients with Respiratory Disease
- Author
-
Luke D. Knibbs, Lidia Morawska, Scott C. Bell, Kay A. Ramsay, Michelle Wood, Claire E. Wainwright, Graham R. Johnson, and Timothy J. Kidd
- Subjects
0301 basic medicine ,Male ,Time Factors ,010504 meteorology & atmospheric sciences ,Pulmonology ,Cystic Fibrosis ,Physiology ,Evaporation ,Air Microbiology ,lcsh:Medicine ,Pathology and Laboratory Medicine ,01 natural sciences ,Coughing ,Medicine and Health Sciences ,lcsh:Science ,Inhalation exposure ,Infectivity ,Fluids ,Inhalation Exposure ,Multidisciplinary ,Radiochemistry ,Vaporization ,Physics ,Respiration ,Pseudomonas Aeruginosa ,Condensed Matter Physics ,Bacterial Pathogens ,Body Fluids ,Chemistry ,Medical Microbiology ,Physical Sciences ,Vapors ,medicine.symptom ,Pathogens ,Anatomy ,Phase Transitions ,Bioaerosol ,Research Article ,Nuclear Decay ,Adult ,States of Matter ,Materials by Structure ,030106 microbiology ,Indoor bioaerosol ,Materials Science ,Biology ,Microbiology ,03 medical and health sciences ,Young Adult ,Signs and Symptoms ,Diagnostic Medicine ,Pseudomonas ,medicine ,Humans ,Pseudomonas Infections ,Microbial Pathogens ,0105 earth and related environmental sciences ,Nuclear Physics ,Aerosols ,Bacteria ,lcsh:R ,Organisms ,Sputum ,Biology and Life Sciences ,Bacteria Present ,biology.organism_classification ,Respiration Disorders ,Aerosol ,Mucus ,Cough ,Mixtures ,Respiratory Infections ,lcsh:Q ,Physiological Processes - Abstract
This work aimed to develop an in vivo approach for measuring the duration of human bioaerosol infectivity. To achieve this, techniques designed to target short-term and long-term bioaerosol aging, were combined in a tandem system and optimized for the collection of human respiratory bioaerosols, without contamination. To demonstrate the technique, cough aerosols were sampled from two persons with cystic fibrosis and chronic Pseudomonas aeruginosa infection. Measurements and cultures from aerosol ages of 10, 20, 40, 900 and 2700 seconds were used to determine the optimum droplet nucleus size for pathogen transport and the airborne bacterial biological decay. The droplet nuclei containing the greatest number of colony forming bacteria per unit volume of airborne sputum were between 1.5 and 2.6 μm. Larger nuclei of 3.9 μm, were more likely to produce a colony when impacted onto growth media, because the greater volume of sputum comprising the larger droplet nuclei, compensated for lower concentrations of bacteria within the sputum of larger nuclei. Although more likely to produce a colony, the larger droplet nuclei were small in number, and the greatest numbers of colonies were instead produced by nuclei from 1.5 to 5.7 μm. Very few colonies were produced by smaller droplet nuclei, despite their very large numbers. The concentration of viable bacteria within the dried sputum comprising the droplet nuclei exhibited an orderly dual decay over time with two distinct half-lives. Nuclei exhibiting a rapid biological decay process with a 10 second half-life were quickly exhausted, leaving only a subset characterized by a half-life of greater than 10 minutes. This finding implied that a subset of bacteria present in the aerosol was resistant to rapid biological decay and remained viable in room air long enough to represent an airborne infection risk.
- Published
- 2016
21. Self-digitization chip for single-cell genotyping of cancer-related mutations
- Author
-
Daniel T. Chiu, Amy L. Paguirigan, Bryant S. Fujimoto, Thomas Schneider, Luke D. Monroe, Alison M. Thompson, Jerald P. Radich, Jordan L. Smith, and Jason E. Kreutz
- Subjects
0301 basic medicine ,Heredity ,Genotyping Techniques ,Surfactants ,lcsh:Medicine ,Artificial Gene Amplification and Extension ,Polymerase Chain Reaction ,Biochemistry ,Neoplasms ,lcsh:Science ,Oligonucleotide Array Sequence Analysis ,Staining ,Multidisciplinary ,Cell Staining ,Lipids ,3. Good health ,Genetic Mapping ,Physical Sciences ,Mutation (genetic algorithm) ,Research Article ,Genotyping ,NPM1 ,Materials Science ,Variant Genotypes ,Computational biology ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Genetics ,medicine ,Genetic variability ,Allele ,Molecular Biology Techniques ,Molecular Biology ,Alleles ,Materials by Attribute ,lcsh:R ,Biology and Life Sciences ,Cancer ,medicine.disease ,Zygosity ,Nuclear Staining ,030104 developmental biology ,Genetic Loci ,Specimen Preparation and Treatment ,Mutation ,lcsh:Q ,Oils - Abstract
Cancer is a heterogeneous disease, and patient-level genetic assessments can guide therapy choice and impact prognosis. However, little is known about the impact of genetic variability within a tumor, intratumoral heterogeneity (ITH), on disease progression or outcome. Current approaches using bulk tumor specimens can suggest the presence of ITH, but only single-cell genetic methods have the resolution to describe the underlying clonal structures themselves. Current techniques tend to be labor and resource intensive and challenging to characterize with respect to sources of biological and technical variability. We have developed a platform using a microfluidic self-digitization chip to partition cells in stationary volumes for cell imaging and allele-specific PCR. Genotyping data from only confirmed single-cell volumes is obtained and subject to a variety of relevant quality control assessments such as allele dropout, false positive, and false negative rates. We demonstrate single-cell genotyping of the NPM1 type A mutation, an important prognostic indicator in acute myeloid leukemia, on single cells of the cell line OCI-AML3, describing a more complex zygosity distribution than would be predicted via bulk analysis.
- Published
- 2018
22. Trait Anticipatory Pleasure Predicts Effort Expenditure for Reward
- Author
-
Michael T. Treadway, Joachim T. Geaney, and Luke D. Smillie
- Subjects
Adult ,Male ,Pleasure ,Adolescent ,media_common.quotation_subject ,lcsh:Medicine ,Affect (psychology) ,Reward ,Humans ,lcsh:Science ,media_common ,Motivation ,Multidisciplinary ,Gratification ,Perspective (graphical) ,lcsh:R ,Behavioral activation ,Anticipation, Psychological ,Anticipation ,Feeling ,Trait ,Female ,lcsh:Q ,Psychology ,Social psychology ,Research Article - Abstract
Research in motivation and emotion has been increasingly influenced by the perspective that processes underpinning the motivated approach of rewarding goals are distinct from those underpinning enjoyment during reward consummation. This distinction recently inspired the construction of the Temporal Experience of Pleasure Scale (TEPS), a self-report measure that distinguishes trait anticipatory pleasure (pre-reward feelings of desire) from consummatory pleasure (feelings of enjoyment and gratification upon reward attainment). In a university community sample (N = 97), we examined the TEPS subscales as predictors of (1) the willingness to expend effort for monetary rewards, and (2) affective responses to a pleasant mood induction procedure. Results showed that both anticipatory pleasure and a well-known trait measure of reward motivation predicted effort-expenditure for rewards when the probability of being rewarded was relatively low. Against expectations, consummatory pleasure was unrelated to induced pleasant affect. Taken together, our findings provide support for the validity of the TEPS anticipatory pleasure scale, but not the consummatory pleasure scale.
- Published
- 2015
23. A Novel Method and Its Application to Measuring Pathogen Decay in Bioaerosols from Patients with Respiratory Disease
- Author
-
Johnson, Graham R., primary, Knibbs, Luke D., additional, Kidd, Timothy J., additional, Wainwright, Claire E., additional, Wood, Michelle E., additional, Ramsay, Kay A., additional, Bell, Scott C., additional, and Morawska, Lidia, additional
- Published
- 2016
- Full Text
- View/download PDF
24. Trait Anticipatory Pleasure Predicts Effort Expenditure for Reward
- Author
-
Geaney, Joachim T., primary, Treadway, Michael T., additional, and Smillie, Luke D., additional
- Published
- 2015
- Full Text
- View/download PDF
25. Shearwater foraging in the Southern Ocean: the roles of prey availability and winds
- Author
-
Henri Weimerskirch, Mark A. Hindell, David R. Thompson, Eric J. Woehler, Adam N. H. Smith, Ben Raymond, Darren Scott, Luke D. Einoder, Serguei Sokolov, Matt H. Pinkerton, Graham W. Hosie, Paul M. Sagar, Daniel P. Costa, Scott A. Shaffer, Caitlin Vertigan, Antarctic Wildlife Research Unit, University of Tasmania [Hobart, Australia] (UTAS), Department of Zoology, University of Otago [Dunedin, Nouvelle-Zélande], Centre d'études biologiques de Chizé (CEBC), and Centre National de la Recherche Scientifique (CNRS)
- Subjects
0106 biological sciences ,Puffinus ,Science ,Oceans and Seas ,Foraging ,Marine Biology ,Wind ,Physical oceanography ,010603 evolutionary biology ,01 natural sciences ,Shearwater ,Ecology/Marine and Freshwater Ecology ,Birds ,Marine and Aquatic Sciences/Biological Oceanography ,Animals ,14. Life underwater ,Polar front ,Marine biology ,Marine and Aquatic Sciences/Ecology ,Multidisciplinary ,biology ,Ecology ,010604 marine biology & hydrobiology ,Pelagic zone ,Biodiversity ,15. Life on land ,biology.organism_classification ,13. Climate action ,Predatory Behavior ,[SDE]Environmental Sciences ,Upwelling ,Medicine ,Ecology/Ecosystem Ecology ,Marine and Aquatic Sciences/Physical Oceanography ,Research Article - Abstract
International audience; BACKGROUND: Sooty (Puffinus griseus) and short-tailed (P. tenuirostris) shearwaters are abundant seabirds that range widely across global oceans. Understanding the foraging ecology of these species in the Southern Ocean is important for monitoring and ecosystem conservation and management. METHODOLOGY/PRINCIPAL FINDINGS: Tracking data from sooty and short-tailed shearwaters from three regions of New Zealand and Australia were combined with at-sea observations of shearwaters in the Southern Ocean, physical oceanography, near-surface copepod distributions, pelagic trawl data, and synoptic near-surface winds. Shearwaters from all three regions foraged in the Polar Front zone, and showed particular overlap in the region around 140 degrees E. Short-tailed shearwaters from South Australia also foraged in Antarctic waters south of the Polar Front. The spatial distribution of shearwater foraging effort in the Polar Front zone was matched by patterns in large-scale upwelling, primary production, and abundances of copepods and myctophid fish. Oceanic winds were found to be broad determinants of foraging distribution, and of the flight paths taken by the birds on long foraging trips to Antarctic waters. CONCLUSIONS/SIGNIFICANCE: The shearwaters displayed foraging site fidelity and overlap of foraging habitat between species and populations that may enhance their utility as indicators of Southern Ocean ecosystems. The results highlight the importance of upwellings due to interactions of the Antarctic Circumpolar Current with large-scale bottom topography, and the corresponding localised increases in the productivity of the Polar Front ecosystem.
- Published
- 2010
26. A cross-sectional analysis of podiatrist-initiated review processes after issuing prescribed foot orthoses
- Author
-
Luke Donnan, Anna Horn, and Emma Baker
- Subjects
Medicine ,Science - Abstract
Background Foot orthoses are widely used in clinical practice to treat foot, lower limb and back pathology. As published information guiding the clinical use of foot orthoses is scarce, the aim of this study is to profile the review processes used by practicing podiatrists after issuing an orthotic device. Methods A cross-sectional observational study design formed the basis for a self-administered online questionnaire. The questionnaire was distributed through podiatry networks based in Australia. Results Two-hundred and thirty-eight practicing podiatrists participated in this study. Ninety-seven percent of respondents indicated that they would recommend a review appointment after the initial fitting of an orthotic device. Forty percent (n = 84) of respondents scheduled the first review appointment four weeks after the initial fitting, while 33% (n = 69) preferred a two-week review period. A second review consultation was standard practice for 32% (n = 68) or respondents, and were typically scheduled either two (23%, n = 12) or four (38%, n = 20) weeks after the initial review consultation. Annual review of orthotic devices was recommended by 64% (n = 123) of participants in the study, while 19% (n = 37) would suggest that yearly reviews were scheduled only if required. Conclusions Variation was identified in the orthotic review processes used by practicing podiatrists, although most respondents recommend a routine short-term review appointment for foot orthoses. It is not clear why practitioners adopt such varied approaches. In the absence of any clear evidence on this topic, it may be that the differing approaches to patient review reflect different philosophical perspectives regarding patient management.
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- 2022
27. Regulation of Staphylococcus aureus MntC Expression and Its Role in Response to Oxidative Stress
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Handke, Luke D., primary, Hawkins, Julio C., additional, Miller, Alita A., additional, Jansen, Kathrin U., additional, and Anderson, Annaliesa S., additional
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- 2013
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28. Chronic Exposure of Corals to Fine Sediments: Lethal and Sub-Lethal Impacts
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Flores, Florita, primary, Hoogenboom, Mia O., additional, Smith, Luke D., additional, Cooper, Timothy F., additional, Abrego, David, additional, and Negri, Andrew P., additional
- Published
- 2012
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29. Regulation of Staphylococcus aureus MntC Expression and Its Role in Response to Oxidative Stress.
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Handke, Luke D., Hawkins, Julio C., Miller, Alita A., Jansen, Kathrin U., and Anderson, Annaliesa S.
- Subjects
- *
STAPHYLOCOCCUS aureus , *GENETIC regulation , *OXIDATIVE stress , *PATHOGENIC bacteria , *BACTERIAL vaccines , *IMMUNE system , *DRUG resistance , *SENSITIVITY analysis , *BACTERIA - Abstract
Staphylococcus aureus is a successful human pathogen that has developed several approaches to evade the immune system, including resistance strategies to prevent oxidative killing by immune cells. One mechanism by which this evasion occurs is by production of superoxide dismutase enzymes, which require manganese as a cofactor. Manganese is acquired by the manganese transporter MntABC. One component of this operon, MntC, has been proposed as a potential vaccine candidate due to its early in vivo expression and its ability to provide protection in preclinical models of staphylococcal infection. In the current study, we interrogate the role of this protein in protecting S. aureus from oxidative stress. We demonstrate that mutation of mntC in a number of invasive S. aureus clinical isolates results in increased sensitivity to oxidative stress. In addition, we show that while downregulation of mntC transcription is triggered upon exposure to physiological concentrations of manganese, MntC protein is still present on the bacterial surface at these same concentrations. Taken together, these results provide insight into the role of this antigen for the pathogen. [ABSTRACT FROM AUTHOR]
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- 2013
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30. Evaluation of radiation treatment volumes for unknown primaries of the head and neck in the era of FDG PET.
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Alexis Platek, Michael Mix, Varun Chowdhry, Mark Farrugia, Michael A Lacombe, Jeffrey A Bogart, Luke Degraaf, Austin Iovoli, Hassan Arshad, Kimberly Wooten, Vishal Gupta, Wesley L Hicks, Mary E Platek, Seung S Hahn, and Anurag K Singh
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Medicine ,Science - Abstract
ObjectivesPositron-emission tomography (PET) has improved identification of the primary tumor as well as occult nodal burden in cancer of the head and neck. Nevertheless, there are still patients where the primary tumor cannot be located. In these situations, the standard of care is comprehensive head and neck radiation therapy however it is unclear whether this is necessary. This study examines the effects of radiation treatment volume on outcomes among using data from two cancer centers in unknown primary carcinoma of the head and neck.MethodsPatients received unilateral (n = 34), or bilateral radiation (n = 28). Patient factors such as age, gender, smoking history, and patterns of failure were compared using Mann Whitney U and Chi Square. Overall survival (OS) and disease free survival (DFS) trends were estimated using Kaplan-Meier survival curves. Effect of treatment volume on survival was examined using multivariate cox proportional hazard regression model.ResultsNo significant differences were observed in the frequency of local (p = 0.32), regional (p = 0.50), or distant (p = 0.76) failures between unilateral and bilateral radiation therapy. By Kaplan-Meier estimates, OS (3-year OS bilateral = 71.67%, unilateral = 77.90%, p = 0.50) and DFS (3-year DFS bilateral = 77.92%, unilateral = 69.43%, p = 0.63) were similar between the two treatment approaches. Lastly, multivariate analysis did not demonstrate any significant differences in outcome by treatment volumes (OS: HR = 0.74, 95% CI: 0.31, 1.81, p = 0.51; DFS: HR: 0.68, 95% CI: 0.24, 1.93, p = 0.47).ConclusionsUnilateral radiation therapy compared with bilateral produced similar survival.
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- 2020
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31. Use of Renal Replacement Therapy May Influence Graft Outcomes following Liver Transplantation for Acute Liver Failure: A Propensity-Score Matched Population-Based Retrospective Cohort Study.
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Stephen R Knight, Gabriel C Oniscu, Luke Devey, Kenneth J Simpson, Stephen J Wigmore, and Ewen M Harrison
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Medicine ,Science - Abstract
IntroductionAcute kidney injury is associated with a poor prognosis in acute liver failure but little is known of outcomes in patients undergoing transplantation for acute liver failure who require renal replacement therapy.MethodsA retrospective analysis of the United Kingdom Transplant Registry was performed (1 January 2001-31 December 2011) with patient and graft survival determined using Kaplan-Meier methods. Cox proportional hazards models were used together with propensity-score based full matching on renal replacement therapy use.ResultsThree-year patient and graft survival for patients receiving renal replacement therapy were 77.7% and 72.6% compared with 85.1% and 79.4% for those not requiring renal replacement therapy (PConclusionIn patients being transplanted for acute liver failure, use of renal replacement therapy is a strong predictor of patient death and graft loss. Those not receiving renal replacement therapy with an elevated serum creatinine may be at greater risk of early graft failure than those receiving renal replacement therapy. A low threshold for instituting renal replacement therapy may therefore be beneficial.
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- 2016
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32. Brief Glutamine Pretreatment Increases Alveolar Macrophage CD163/Heme Oxygenase-1/p38-MAPK Dephosphorylation Pathway and Decreases Capillary Damage but Not Neutrophil Recruitment in IL-1/LPS-Insufflated Rats.
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Ana Fernandez-Bustamante, Amanda Agazio, Paul Wilson, Nancy Elkins, Luke Domaleski, Qianbin He, Kaily A Baer, Angela F D Moss, Paul E Wischmeyer, and John E Repine
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Medicine ,Science - Abstract
Glutamine (GLN) attenuates acute lung injury (ALI) but its effect on alveolar macrophages is unknown. We hypothesized that GLN pretreatment would induce the anti-inflammatory CD163/heme oxygenase (HO)-1/p38-MAPK dephosphorylation pathway in alveolar macrophages and reduce ALI in rats insufflated with interleukin-1 (IL-1) and lipopolysaccharide (LPS).Male Sprague-Dawley rats were randomized to the following groups: GLN-IL-1/LPS-, GLN+IL-1/LPS-, GLN-IL-1/LPS+, and GLN+IL-1/LPS+. GLN pretreatment was given via gavage (1 g/kg L-alanyl-L-glutamine) daily for 2 days. ALI was subsequently induced by insufflating 50 ng IL-1 followed by 5mg/kg E.coli LPS. After 24h, bronchoalveolar lavage (BAL) protein, lactate dehydrogenase (LDH) and neutrophil concentrations were analyzed. BAL alveolar macrophage CD163+ expression, HO-1 and p38-MAPK concentrations were measured, as well as alveolar macrophage tumor necrosis factor (TNF)-α and interleukin (IL)-10 concentrations. Histology and immunofluorescence studies were also performed.Following IL-1/LPS insufflation, GLN pretreated rats had significantly decreased BAL protein and LDH concentrations, but not BAL neutrophil counts, compared to non-GLN pretreated rats. The number of alveolar macrophages and the number of CD163+ macrophages were significantly increased in GLN pretreated IL-1/LPS-insufflated rats compared to non-GLN pretreated, IL-1/LPS-insufflated rats. GLN pretreatment before IL-1/LPS also significantly increased HO-1 concentrations and dephosphorylated p38-MAPK levels but not cytokine levels in alveolar macrophages. Immunofluorescence localized CD163 and HO-1 in alveolar macrophages.Short-term GLN pretreatment activates the anti-inflammatory CD163/HO-1/p38-MAPK dephosphorylation pathway of alveolar macrophages and decreases capillary damage but not neutrophil recruitment in IL-1/LPS-insufflated rats.
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- 2015
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33. Study protocol for transforming health equity research in integrated primary care: Antiracism as a disruptive innovation.
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Naar S, Pettus C, Anderson N, Pooler-Burgess M, Ralston P, Flynn H, Combs T, Baquet C, Schatschneider C, and Luke D
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- Humans, Racism, Black or African American, Community-Based Participatory Research, Healthcare Disparities, Antiracism, Primary Health Care, Health Equity
- Abstract
Among the consequences of systemic racism in health care are significant health disparities among Black/African American individuals with comorbid physical and mental health conditions. Despite decades of studies acknowledging health disparities based on race, significant change has not occurred. There are shockingly few evidence-based antiracism interventions. New paradigms are needed to intervene on, and not just document, racism in health care systems. We are developing a transformative paradigm for new antiracism interventions for primary care settings that integrate mental and physical health care. The paradigm is the first of its kind to integrate community-based participatory research and systems science, within an established model of early phase translation to rigorously define new antiracism interventions. This protocol will use a novel application of systems sciences by combining the qualitative systems sciences methods (group model building; GMB) with quantitative methods (simulation modeling) to develop a comprehensive and community-engaged view of both the drivers of racism and the potential impact of antiracism interventions. Community participants from two integrated primary health care systems will engage in group GMB workshops with researchers to 1) Describe and map the complex dynamic systems driving racism in health care practices, 2) Identify leverage points for disruptive antiracism interventions, policies and practices, and 3) Review and prioritize a list of possible intervention strategies. Advisory committees will provide feedback on the design of GMB procedures, screen potential intervention components for impact, feasibility, and acceptability, and identify gaps for further exploration. Simulation models will be generated based on contextual factors and provider/patient characteristics. Using Item Response Theory, we will initiate the process of developing core measures for assessing the effectiveness of interventions at the organizational-systems and provider levels to be tested under a variety of conditions. While we focus on Black/African Americans, we hope that the resulting transformative paradigm can be applied to improve health equity among other marginalized groups., Competing Interests: The authors have no competing interests., (Copyright: © 2024 Naar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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34. Extended difficulties following the use of psychedelic drugs: A mixed methods study.
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Evans J, Robinson OC, Argyri EK, Suseelan S, Murphy-Beiner A, McAlpine R, Luke D, Michelle K, and Prideaux E
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- Humans, Emotions, Anxiety, Fear, Anxiety Disorders, Hallucinogens adverse effects
- Abstract
Long-term adverse experiences following psychedelic use can persist for weeks, months, or even years, and are relatively unexplored in psychedelic research. Our convergent mixed-method study gained quantitative and qualitative data from 608 participants who reported extended difficulties following psychedelic experiences. Data was gathered on the context of use, the nature and duration of the challenges they experienced (including a written description of these), plus a range of possible risk factors and perceived causes. The most common forms of extended difficulty were feelings of anxiety and fear, existential struggle, social disconnection, depersonalization and derealization. For approximately one-third of the participants, problems persisted for over a year, and for a sixth, they endured for more than three years. It was found that a shorter duration of difficulties was predicted by knowledge of dose, drug type and lower levels of difficulty reported during the psychoactive experience, while a narrower range of difficulties was predicted by taking the drug in a guided setting. Implications for psychedelic harm reduction are discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Evans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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