Eye movements and driving : insights into methodology, individual differences and training

Driving is a complex visuomotor task, and the study of eye movements can provide interesting and detailed insights into driving behaviour. The aim of this thesis was to understand (a) what methods are useful to assess driving behaviour, (b) the reasons we observe differences in eye movements when driving, and (c) offer a possible visual training method. The first experiment compared drivers’ eye movements and hazard perception performance in an active simulated driving task and a passive video driving task. A number of differences were found, including an extended horizontal and vertical visual search and faster response to the hazards in the video task. It was concluded that when measuring driving behaviour in an active task, vision, attention and action interact in a complex manner that is reflected in a specific pattern of eye movements that is different to when driving behaviour is measured using typical video paradigms. The second experiment investigated how cognitive functioning may influence eye movement behaviour when driving. It was found that those with better cognitive functioning exhibited more efficient eye movement behaviour than those with poorer cognitive functioning. The third experiment compared the eye movement and driving behaviour of an older adult population and a younger adult population. There were no differences in the eye movement behaviour. However, the older adults drove significantly slower, suggesting attentional compensation. The final experiment investigated the efficacy of using eye movement videos as a visual training tool for novice drivers. It was found that novice drivers improved their visual search strategy when driving after viewing videos of an expert driver’s eye movements. The results of this thesis helps to provide insights into how the visual system is used for a complex behaviour such as driving. It also furthers the understanding of what may contribute to, and what may prevent, road accidents

Quantitative prediction of in vivo inhibitory interactions involving glucuronidated drugs from in vitro data: the effect of fluconazole on zidovudine glucuronidation

Using the fluconazole–zidovudine (AZT) interaction as a model, to determine whether inhibition of UDP–glucuronosyltransferase (UGT) catalysed drug metabolism in vivo could be predicted quantitatively from in vitro kinetic data generated in the presence and absence bovine serum albumin (BSA). Methods Kinetic constants for AZT glucuronidation were generated using human liver microsomes (HLM) and recombinant UGT2B7, the principal enzyme responsible for AZT glucuronidation, as the enzyme sources with and without fluconazole. K i values were used to estimate the decrease in AZT clearance in vivo . Results Addition of BSA (2%) to incubations decreased the K m values for AZT glucuronidation by 85–90% for the HLM (923 ± 357 to 91 ± 9 µm) and UGT2B7 (478–70 µm) catalysed reactions, with little effect on V max . Fluconazole, which was shown to be a selective inhibitor of UGT2B7, competitively inhibited AZT glucuronidation by HLM and UGT2B7. Like the K m , BSA caused an 87% reduction in the K i for fluconazole inhibition of AZT glucuronidation by HLM (1133 ± 403 to 145 ± 36 µm) and UGT2B7 (529 to 73 µm). K i values determined for fluconazole using HLM and UGT2B7 in the presence (but not absence) of BSA predicted an interaction in vivo . The predicted magnitude of the interaction ranged from 41% to 217% of the reported AUC increase in patients, depending on the value of the in vivo fluconazole concentration employed in calculations. Conclusions K i values determined under certain experimental conditions may quantitatively predict inhibition of UGT catalysed drug glucuronidation in vivo .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72685/1/j.1365-2125.2006.02588.x.pd

Trophic interactions of megafauna in the Mariana and Kermadec trenches inferred from stable isotope analysis

Hadal trenches house distinct ecosystems but we know little about their sources of nutrition or trophic structures. We evaluated megafaunal food web structure and nutritional sources in the Kermadec and Mariana trenches using carbon and nitrogen stable isotope analysis (δ15N and δ13C values) of bulk tissues and proteinaceous individual amino acids (AAs). In the Kermadec Trench, bulk δ15N values ranged from 5.8‰ in trench sediment to 17.5‰ in tissues of the supergiant amphipod, Allicela gigantea. δ15N values of detritivores were much higher than those of sediments (by 7.5‰ more). The δ13C values ranged from −21.4‰ in sediments to −17.3‰ in the brittle star, Ophiolimna sp., and did not co-vary with δ15N values. In the Mariana Trench, only bait-attending fauna and surface sediments were available for analysis. Mariana Trench fishes, amphipods, and sediments had slightly lower δ15N values than those from the Kermadec Trench, possibly because the Mariana Trench lies under more oligotrophic surface waters. We found evidence for multiple food inputs to the system in each trench, namely substantially higher δ15N values in detritivores relative to sediment and high variability in δ13C values. Trophic levels determined from isotopic analysis of individual AAs in the Kermadec Trench ranged from three for detritivores to five for fishes. Source AA δ15N values were variable (range of ~7.0‰ in average δ15N source AA values), with much of this variation occurring in small amphipods. For the other fauna sampled, there was a significant increase in δ15N source AA values with increasing collection depth. This increase could reflect larger amounts of highly microbially reworked organic matter with increasing depth or sporadic input from turbidity flows. Although further sampling across a broader faunal diversity will be required to understand these food webs, our results provide new insights into hadal trophic interactions and suggest that trench food webs are very dynamic

Label-Free Density Measurements of Radial Peripapillary Capillaries in the Human Retina

Radial peripapillary capillaries (RPCs) comprise a unique network of capillary beds within the retinal nerve fibre layer (RNFL) and play a critical role in satisfying the nutritional requirements of retinal ganglion cell (RGC) axons. Understanding the topographical and morphological characteristics of these networks through in vivo techniques may improve our understanding about the role of RPCs in RGC axonal health and disease. This study utilizes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for quantitatively studying RPC networks in the human retina. Six different retinal eccentricities from 16 healthy eyes were imaged using svOCT. The same eccentricities were histologically imaged in 9 healthy donor eyes with a confocal scanning laser microscope. Donor eyes were subject to perfusion-based labeling techniques prior to retinal dissection, flat mounting and visualization with the microscope. Capillary density and diameter measurements from each eccentricity in svOCT and histological images were compared. Data from svOCT images were also analysed to determine if there was a correlation between RNFL thickness and RPC density. The results are as follows: (1) The morphological characteristics of RPC networks on svOCT images are comparable to histological images; (2) With the exception of the nasal peripapillary region, there were no significant differences in RPC density measurements between svOCT and histological images; (3) Capillary diameter measurements were significantly greater in svOCT images compared to histology; (4) There is a positive correlation between RPC density and RNFL thickness. The findings in this study suggest that svOCT is a reliable modality for analyzing RPC networks in the human retina. It may therefore be a valuable tool for aiding our understanding about vasculogenic mechanisms that are involved in RGC axonopathies. Further work is required to explore the reason for some of the quantitative differences between svOCT and histology

TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms

The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCβ3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCβ3 and the TRPV1 channel; 2) serotonin, or a selective agonist, α-methyl-serotonin (α-Me-5-HT), requires the presence of PLCβ3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCβ3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD^+ neurons that represent ≈90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1+ nociceptors led to a significant behavioral deficit for pruritogens, including α-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways

Iron homeostasis and post-hemorrhagic hydrocephalus: A review

Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain development, characterizes our understanding of iron transport in the developing brain, and describes potential mechanisms by which iron overload may cause PHH and brain injury. We also review novel preclinical treatments for IVH that specifically target iron. Understanding iron handling within the brain and central nervous system may provide a basis for preventative, targeted treatments for iron-mediated pathogenesis of GMH-IVH and PHH

Screening for coping style increases the power of gene expression studies

Background: Individuals of many vertebrate species show different stress coping styles and these have a striking influence on how gene expression shifts in response to a variety of challenges. Principal Findings: This is clearly illustrated by a study in which common carp displaying behavioural predictors of different coping styles (characterised by a proactive, adrenaline-based or a reactive, cortisol-based response) were subjected to inflammatory challenge and specific gene transcripts measured in individual brains. Proactive and reactive fish differed in baseline gene expression and also showed diametrically opposite responses to the challenge for 80% of the genes investigated. Significance: Incorporating coping style as an explanatory variable can account for some the unexplained variation that is common in gene expression studies, can uncover important effects that would otherwise have passed unnoticed and greatly enhances the interpretive value of gene expression data

Molecular Characterization of Host-Specific Biofilm Formation in a Vertebrate Gut Symbiont

Although vertebrates harbor bacterial communities in their gastrointestinal tract whose composition is host-specific, little is known about the mechanisms by which bacterial lineages become selected. The goal of this study was to characterize the ecological processes that mediate host-specificity of the vertebrate gut symbiont Lactobacillus reuteri, and to systematically identify the bacterial factors that are involved. Experiments with monoassociated mice revealed that the ability of L. reuteri to form epithelial biofilms in the mouse forestomach is strictly dependent on the strain’s host origin. To unravel the molecular basis for this host-specific biofilm formation, we applied a combination of transcriptome analysis and comparative genomics and identified eleven genes of L. reuteri 100-23 that were predicted to play a role. We then determined expression and importance of these genes during in vivo biofilm formation in monoassociated mice. This analysis revealed that six of the genes were upregulated in vivo, and that genes encoding for proteins involved in epithelial adherence, specialized protein transport, cell aggregation, environmental sensing, and cell lysis contributed to biofilm formation. Inactivation of a serine-rich surface adhesin with a devoted transport system (the SecA2-SecY2 pathway) completely abrogated biofilm formation, indicating that initial adhesion represented the most significant step in biofilm formation, likely conferring host specificity. In summary, this study established that the epithelial selection of bacterial symbionts in the vertebrate gut can be both specific and highly efficient, resulting in biofilms that are exclusively formed by the coevolved strains, and it allowed insight into the bacterial effectors of this process

Comparing airborne algorithms for greenhouse gas flux measurements over the Alberta oil sands

To combat global warming, Canada has committed to reducing greenhouse gases to be (GHGs) 40 %–45 % below 2005 emission levels by 2025. Monitoring emissions and deriving accurate inventories are essential to reaching these goals. Airborne methods can provide regional and area source measurements with small error if ideal conditions for sampling are met. In this study, two airborne mass-balance box-flight algorithms were compared to assess the extent of their agreement and their performance under various conditions. The Scientific Aviation’s (SciAv) Gaussian algorithm and the Environment and Climate Change Canada’s top-down emission rate retrieval algorithm (TERRA) were applied to data from five samples. Estimates were compared using standard procedures, by systematically testing other method fits, and by investigating the effects on the estimates when method assumptions were not met. Results indicate that in standard scenarios the SciAv and TERRA mass-balance box-flight methods produce similar estimates that agree (3%–25%) within algorithm uncertainties (4%– 34%). Implementing a sample-specific surface extrapolation procedure for the SciAv algorithm may improve emission estimation. Algorithms disagreed when non-ideal conditions occurred (i.e., under non-stationary atmospheric conditions). Overall, the results provide confidence in the box-flight methods and indicate that emissions estimates are not overly sensitive to the choice of algorithm but demonstrate that fundamental algorithm assumptions should be assessed for each flight. Using a different method, the Airborne Visible InfraRed Imaging Spectrometer – Next Generation (AVIRIS-NG) independently mapped individual plumes with emissions 5 times larger than the source SciAv sampled three days later. The range in estimates highlights the utility of increased sampling to get a more complete understanding of the temporal variability of emissions and to identify emission sources within facilities. In addition, hourly on-site activity data would provide insight to the observed temporal variability in emissions and make a comparison to reported emissions more straightforward

Tuneable electron-magnon coupling of ferromagnetic surface states in PdCoO2

Funding: We gratefully acknowledge support from the European Research Council (through the QUESTDO project, 714193), the Royal Society, the Max Planck Society, and the UKRI Engineering and Physical Sciences Research Council (Grant No. EP/S005005/1). V.S., O.J.C., and L.B. acknowledge the EPSRC for PhD studentship support through Grants EP/L015110/1, EP/K503162/1, and EP/G03673X/1, respectively. I.M. and D.C. acknowledge studentship support from the International Max-Planck Research School for Chemistry and Physics of Quantum Materials.Controlling spin wave excitations in magnetic materials underpins the burgeoning field of magnonics. Yet, little is known about how magnons interact with the conduction electrons of itinerant magnets, or how this interplay can be controlled. Via a surface-sensitive spectroscopic approach, we demonstrate a strong and highly-tuneable electron-magnon coupling at the Pd-terminated surface of the delafossite oxide PdCoO2, where a polar surface charge mediates a Stoner transition to itinerant surface ferromagnetism. We show how the coupling can be enhanced 7-fold with increasing surface disorder, and concomitant charge carrier doping, becoming sufficiently strong to drive the system into a polaronic regime, accompanied by a significant quasiparticle mass enhancement. Our study thus sheds new light on electron-magnon interactions in solid-state materials, and the ways in which these can be controlled.Publisher PDFPeer reviewe