Publications by authors named "David McLean"

130 Publications

Intention and performance when reading aloud: Context is everything.

Conscious Cogn 2021 Sep 29;95:103211. Epub 2021 Sep 29.

Psychology Department, Cognition and Perception Unit (CPU), University of Waterloo, Canada.

A widely held account asserts that single words are automatically identified in the absence of an intent to process them in the form of identifying a task set, and implementing it. We provide novel evidence that there is no fixed relation between intention and visual word identification. Subjects were randomly cued on a trial-by-trial basis as to whether to read aloud a single target word (Go) or not (No-go). When the Go-No Go probability was 50% (Experiment 1) the effect of stimulus quality (bright vs. dim targets) was the same size as in a separate block of 100% Go trials. In Experiment 2, where the Go-No Go probability was 80% in the cued condition, the stimulus quality effect was smaller than in the block of all Go trials. These results can be understood in terms of Go trial probability moderating whether subjects (i) hold off beginning to process the target until an intention in the form of a Task Set has been implemented, or (ii) begin to identify the target during the time taken to implement a Task Set. The additivity of stimulus quality and cueing conditions in Experiment 1 support the view that target processing only begins when a Task Set is in place, whereas the under-additivity of stimulus quality and cueing condition in Experiment 2 supports the interpretation that target identification can start during the time that a Task Set is being implemented. Taken together with other results, we conclude that there is no fixed relation between an intention and word identification; context is everything.
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http://dx.doi.org/10.1016/j.concog.2021.103211DOI Listing
September 2021

Locomotor control: Inhibiting actions locally and senses globally.

Curr Biol 2021 Sep;31(17):R1035-R1037

Department of Neurobiology, Northwestern University, Evanston, IL 60201, USA. Electronic address:

Locomotion requires the segmental coordination of activity along the body. A new study in zebrafish reveals that spinal inhibitory interneurons are wired to execute different functions depending on whether their targets are nearby or further away.
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http://dx.doi.org/10.1016/j.cub.2021.07.050DOI Listing
September 2021

On the determination of eye gaze and arrow direction: Automaticity reconsidered.

Can J Exp Psychol 2021 Sep 7;75(3):261-278. Epub 2021 Jun 7.

Psychology Department, University of Waterloo.

It is a widely held view that the determination of eye gaze direction is "automatic" in various senses (e.g., innate; informationally encapsulated; triggered without intent). The determination of arrow direction is also held to be automatic (following a certain amount of learning) despite not being innate. The present experiments evaluate the automaticity assumption of both eyes and arrows in terms of an interference criterion. The results of 10 experiments support the inference that explicit judgements of eye gaze direction, when participants respond with a lateralized key press, are (a) neither automatic in the strong sense (they are interfered with by an uninformative, incongruent arrow in the display) and (b) nor are they are automatic in a weaker sense (uninformative, incongruent arrows interfere more strongly with the determination of eye gaze direction than uninformative, incongruent eyes interfere with the arrow direction task). However, the determination of arrow direction is also not strongly automatic, given that it is interfered with by irrelevant eyes. At least with respect to an interference criterion, the determination of eye gaze direction appears less prepotent than the determination of arrow direction, which itself is only weakly automatic. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/cep0000261DOI Listing
September 2021

Attention spreads between students in a learning environment.

J Exp Psychol Appl 2021 Jun 11;27(2):276-291. Epub 2021 Mar 11.

Department of Psychology.

We propose a novel phenomenon, defined as the spread of attentive (or inattentive) states among members of a group. We examined attention contagion in a learning environment in which pairs of undergraduate students watched a lecture video. Each pair consisted of a participant and a confederate trained to exhibit attentive behaviors (e.g., leaning forward) or inattentive behaviors (e.g., slouching). In Experiment 1, confederates sat in front of participants and could be seen. Relative to participants who watched the lecture with an inattentive confederate, participants with an attentive confederate: (a) self-reported higher levels of attentiveness, (b) behaved more attentively (e.g., took more notes), and (c) had better memory for lecture content. In Experiment 2, confederates sat behind participants. Despite confederates not being visible, participants were still aware of whether confederates were acting attentively or inattentively, and participants were still susceptible to attention contagion. Our findings suggest that distraction is one factor that contributes to the spread of inattentiveness (Experiment 1), but this phenomenon apparently can still occur in the absence of distraction (Experiment 2). We propose an account of how (in)attentiveness spreads across students and discuss practical implications regarding how learning is affected in the classroom. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/xap0000341DOI Listing
June 2021

Intersection of motor volumes predicts the outcome of ambush predation of larval zebrafish.

J Exp Biol 2021 03 1;224(Pt 5). Epub 2021 Mar 1.

Department of Biomedical Engineering, Northwestern University, Evaxnston, IL 60201, USA

Escape maneuvers are key determinants of animal survival and are under intense selection pressure. A number of escape maneuver parameters contribute to survival, including response latency, escape speed and direction. However, the relative importance of these parameters is context dependent, suggesting that interactions between parameters and predatory context determine the likelihood of escape success. To better understand how escape maneuver parameters interact and contribute to survival, we analyzed the responses of larval zebrafish () to the attacks of dragonfly nymphs (). We found that no single parameter explains the outcome. Instead, the relative intersection of the swept volume of the nymph's grasping organs with the volume containing all possible escape trajectories of the fish is the strongest predictor of escape success. In cases where the prey's motor volume exceeds that of the predator, the prey survives. By analyzing the intersection of these volumes, we compute the survival benefit of recruiting the Mauthner cell, a neuron in anamniotes devoted to producing escapes. We discuss how the intersection of motor volume approach provides a framework that unifies the influence of many escape maneuver parameters on the likelihood of survival.
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http://dx.doi.org/10.1242/jeb.235481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938803PMC
March 2021

Do eyes and arrows elicit automatic orienting? Three mutually exclusive hypotheses and a test.

Q J Exp Psychol (Hove) 2021 Jul 19;74(7):1164-1169. Epub 2021 Mar 19.

Cognition and Perception Unit (CPU), Psychology Department, University of Waterloo, Waterloo, Ontario, Canada.

Eyes in a schematic face and arrows presented at fixation can each cue an upcoming lateralized target such that responses to the target are faster to a valid than an invalid cue (sometimes claimed to reflect "automatic" orienting). One test of an automatic process concerns the extent to which it can be interfered with by another process. The present experiment investigates the ability of eyes and arrows to cue an upcoming target when both cues are present at the same time. On some trials they are congruent (both cues signal the same direction); on other trials they are incongruent (the two cues signal opposite directions). When the cues are congruent a valid cue produced faster response times than an invalid cue. In the incongruent case arrows are resistant to interference from eyes, whereas an incongruent arrow eliminates a cueing effect for eyes. The discussion elaborates briefly on the theoretical implications.
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http://dx.doi.org/10.1177/1747021821998572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189009PMC
July 2021

Orderly compartmental mapping of premotor inhibition in the developing zebrafish spinal cord.

Science 2020 10;370(6515):431-436

Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA.

In vertebrates, faster movements involve the orderly recruitment of different types of spinal motor neurons. However, it is not known how premotor inhibitory circuits are organized to ensure alternating motor output at different movement speeds. We found that different types of commissural inhibitory interneurons in zebrafish form compartmental microcircuits during development that align inhibitory strength and recruitment order. Axonal microcircuits develop first and provide the most potent premotor inhibition during the fastest movements, followed by perisomatic microcircuits, and then dendritic microcircuits that provide the weakest inhibition during the slowest movements. The conversion of a temporal sequence of neuronal development into a spatial pattern of inhibitory connections provides an "ontogenotopic" solution to the problem of shaping spinal motor output at different speeds of movement.
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http://dx.doi.org/10.1126/science.abb4608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229876PMC
October 2020

Society for Maternal-Fetal Medicine Special Statement: A maternal transport briefing form and checklist.

Am J Obstet Gynecol 2020 11 28;223(5):B12-B15. Epub 2020 Aug 28.

Society for Maternal-Fetal Medicine, 409 12 St. SW, Washington, DC 20024, USA.

When performing a maternal transport between two facilities, numerous pieces of information must be communicated between physicians, nurses, and transport personnel, including the health status of 2 patients (mother and fetus), availability of bed space and personnel in 2 units at the receiving facility (labor and delivery unit and neonatal intensive care unit), arrangements for transportation, and inpatient and outpatient records. The amount and complexity of information creates a risk of medical error due to communication lapses. A cognitive aid such as a standardized form can help the team prepare for a transfer and provide a consistent framework for a handoff briefing among healthcare professionals. SMFM presents a sample briefing form to ensure that key elements are communicated for every maternal transport. Practical suggestions are given to help facilities customize the form and implement it on their units.
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http://dx.doi.org/10.1016/j.ajog.2020.08.065DOI Listing
November 2020

Integration of Swimming-Related Synaptic Excitation and Inhibition by olig2 Eurydendroid Neurons in Larval Zebrafish Cerebellum.

J Neurosci 2020 04 5;40(15):3063-3074. Epub 2020 Mar 5.

Northwestern University Interdepartmental Neuroscience Program, and

The cerebellum influences motor control through Purkinje target neurons, which transmit cerebellar output. Such output is required, for instance, for larval zebrafish to learn conditioned fictive swimming. The output cells, called eurydendroid neurons (ENs) in teleost fish, are inhibited by Purkinje cells and excited by parallel fibers. Here, we investigated the electrophysiological properties of glutamatergic ENs labeled by the transcription factor Action potential firing and synaptic responses were recorded in current clamp and voltage clamp from olig2 neurons in immobilized larval zebrafish (before sexual differentiation) and were correlated with motor behavior by simultaneous recording of fictive swimming. In the absence of swimming, olig2 ENs had basal firing rates near 8 spikes/s, and EPSCs and IPSCs were evident. Comparing Purkinje firing rates and eurydendroid IPSC rates indicated that 1-3 Purkinje cells converge onto each EN. Optogenetically suppressing Purkinje simple spikes, while preserving complex spikes, suggested that eurydendroid IPSC size depended on presynaptic spike duration rather than amplitude. During swimming, EPSC and IPSC rates increased. Total excitatory and inhibitory currents during sensory-evoked swimming were both more than double those during spontaneous swimming. During both spontaneous and sensory-evoked swimming, the total inhibitory current was more than threefold larger than the excitatory current. Firing rates of ENs nevertheless increased, suggesting that the relative timing of IPSCs and EPSCs may permit excitation to drive additional eurydendroid spikes. The data indicate that olig2 cells are ENs whose activity is modulated with locomotion, suiting them to participate in sensorimotor integration associated with cerebellum-dependent learning. The cerebellum contributes to movements through signals generated by cerebellar output neurons, called eurydendroid neurons (ENs) in fish (cerebellar nuclei in mammals). ENs receive sensory and motor signals from excitatory parallel fibers and inhibitory Purkinje cells. Here, we report electrophysiological recordings from ENs of larval zebrafish that directly illustrate how synaptic inhibition and excitation are integrated by cerebellar output neurons in association with motor behavior. The results demonstrate that inhibitory and excitatory drive both increase during fictive swimming, but inhibition greatly exceeds excitation. Firing rates nevertheless increase, providing evidence that synaptic integration promotes cerebellar output during locomotion. The data offer a basis for comparing aspects of cerebellar coding that are conserved and that diverge across vertebrates.
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http://dx.doi.org/10.1523/JNEUROSCI.2322-19.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141884PMC
April 2020

Reconciling the functions of even-skipped interneurons during crawling, swimming, and walking.

Curr Opin Physiol 2019 Apr 5;8:188-192. Epub 2019 Mar 5.

Department of Neurobiology Northwestern University EVANSTON, IL USA.

In all bilaterally symmetric animals, movements across the body are coordinated by interneurons that traverse the midline. Recent work is beginning to tease apart the functional complexity of interneurons labeled by the homeodomain transcription factor even-skipped, which provide a phylogenetically-conserved source of commissural excitation during locomotion in both vertebrates and invertebrates. Here we review recent studies of the roles of even-skipped neurons during locomotion in flies (EL neurons), fishes, frogs, and mice (V0v neurons). Comparisons across species reveal commonalities, which include the functional organization of even-skipped circuits based on birth order, the link between increased muscular complexity and even-skipped neuron diversity, and the hierarchical organization of even-skipped circuits based on their control of escape versus exploratory movements. We discuss how stronger links between different species enable testable predictions to further the discovery of principles of locomotor network organization.
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http://dx.doi.org/10.1016/j.cophys.2019.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820970PMC
April 2019

Hierarchical control of locomotion by distinct types of spinal V2a interneurons in zebrafish.

Nat Commun 2019 09 13;10(1):4197. Epub 2019 Sep 13.

Department of Neurobiology, Northwestern University, Evanston, IL, 60208, USA.

In all vertebrates, excitatory spinal interneurons execute dynamic adjustments in the timing and amplitude of locomotor movements. Currently, it is unclear whether interneurons responsible for timing control are distinct from those involved in amplitude control. Here, we show that in larval zebrafish, molecularly, morphologically and electrophysiologically distinct types of V2a neurons exhibit complementary patterns of connectivity. Stronger higher-order connections from type I neurons to other excitatory V2a and inhibitory V0d interneurons provide timing control, while stronger last-order connections from type II neurons to motor neurons provide amplitude control. Thus, timing and amplitude are coordinated by distinct interneurons distinguished not by their occupation of hierarchically-arranged anatomical layers, but rather by differences in the reliability and probability of higher-order and last-order connections that ultimately form a single anatomical layer. These findings contribute to our understanding of the origins of timing and amplitude control in the spinal cord.
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http://dx.doi.org/10.1038/s41467-019-12240-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744451PMC
September 2019

An updated critique of the use of the Twin Spine Study (2009) to determine causation of low back disorder.

N Z Med J 2019 05 3;132(1494):57-59. Epub 2019 May 3.

Epidemiologist, London School of Hygiene and Tropical Medicine, UK.

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May 2019

Central and peripheral innervation patterns of defined axial motor units in larval zebrafish.

J Comp Neurol 2019 10 11;527(15):2557-2572. Epub 2019 Apr 11.

Interdepartmental Neuroscience Postbaccalaureate Research Education Program, Northwestern University, Evanston, Illinois.

Spinal motor neurons and the peripheral muscle fibers they innervate form discrete motor units that execute movements of varying force and speed. Subsets of spinal motor neurons also exhibit axon collaterals that influence motor output centrally. Here, we have used in vivo imaging to anatomically characterize the central and peripheral innervation patterns of axial motor units in larval zebrafish. Using early born "primary" motor neurons and their division of epaxial and hypaxial muscle into four distinct quadrants as a reference, we define three distinct types of later born "secondary" motor units. The largest is "m-type" units, which innervate deeper fast-twitch muscle fibers via medial nerves. Next in size are "ms-type" secondaries, which innervate superficial fast-twitch and slow fibers via medial and septal nerves, followed by "s-type" units, which exclusively innervate superficial slow muscle fibers via septal nerves. All types of secondaries innervate up to four axial quadrants. Central axon collaterals are found in subsets of primaries based on soma position and predominantly in secondary fast-twitch units (m, ms) with increasing likelihood based on number of quadrants innervated. Collaterals are labeled by synaptophysin-tagged fluorescent proteins, but not PSD95, consistent with their output function. Also, PSD95 dendrite labeling reveals that larger motor units receive more excitatory synaptic input. Collaterals are largely restricted to the neuropil, however, perisomatic connections are observed between motor units. These observations suggest that recurrent interactions are dominated by motor neurons recruited during stronger movements and set the stage for functional investigations of recurrent motor circuitry in larval zebrafish.
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http://dx.doi.org/10.1002/cne.24689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688944PMC
October 2019

Occupation and motor neuron disease: a New Zealand case-control study.

Occup Environ Med 2019 05 22;76(5):309-316. Epub 2019 Mar 22.

Centre for Public Health Research, Massey University, Wellington, New Zealand.

Objectives: To assess associations between occupation and motor neuron disease (MND).

Methods: We conducted a population-based case-control study with cases (n=321) recruited through the New Zealand Motor Neurone Disease Association and hospital discharge data. Controls (n=605) were recruited from the Electoral Roll. Information on personal and demographic details, lifestyle factors and a full occupational history was collected using questionnaires and interviews. Associations with ever/never employed and employment duration were estimated using logistic regression stratified by sex and adjusted for age, ethnicity, socioeconomic deprivation, education and smoking.

Results: Elevated risks were observed for field crop and vegetable growers (OR 2.93, 95% CI 1.10 to 7.77); fruit growers (OR 2.03, 95% CI 1.09 to 3.78); gardeners and nursery growers (OR 1.96, 95% CI 1.01 to 3.82); crop and livestock producers (OR 3.61, 95% CI 1.44 to 9.02); fishery workers, hunters and trappers (OR 5.62, 95% CI 1.27 to 24.97); builders (OR 2.90, 95% CI 1.41 to 5.96); electricians (OR 3.61, 95% CI 1.34 to 9.74); caregivers (OR 2.65, 95% CI 1.04 to 6.79); forecourt attendants (OR 8.31, 95% CI 1.79 to 38.54); plant and machine operators and assemblers (OR 1.42, 95% CI 1.01 to 2.01); telecommunications technicians (OR 4.2, 95% CI 1.20 to 14.64); and draughting technicians (OR 3.02, 95% CI 1.07 to 8.53). Industries with increased risks were agriculture (particularly horticulture and fruit growing), construction, non-residential care services, motor vehicle retailing, and sport and recreation. Positive associations between employment duration and MND were shown for the occupations fruit growers, gardeners and nursery growers, and crop and livestock producers, and for the horticulture and fruit growing industry.

Conclusions: This study suggests associations between MND and occupations in agriculture and several other occupations.
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http://dx.doi.org/10.1136/oemed-2018-105605DOI Listing
May 2019

Integrated one- and two-photon scanned oblique plane illumination (SOPi) microscopy for rapid volumetric imaging.

Opt Express 2018 May;26(10):13027-13041

Versatile, sterically accessible imaging systems capable of in vivo rapid volumetric functional and structural imaging deep in the brain continue to be a limiting factor in neuroscience research. Towards overcoming this obstacle, we present integrated one- and two-photon scanned oblique plane illumination (SOPi, /sōpī/) microscopy which uses a single front-facing microscope objective to provide light-sheet scanning based rapid volumetric imaging capability at subcellular resolution. Our planar scan-mirror based optimized light-sheet architecture allows for non-distorted scanning of volume samples, simplifying accurate reconstruction of the imaged volume. Integration of both one-photon (1P) and two-photon (2P) light-sheet microscopy in the same system allows for easy selection between rapid volumetric imaging and higher resolution imaging in scattering media. Using SOPi, we demonstrate deep, large volume imaging capability inside scattering mouse brain sections and rapid imaging speeds up to 10 volumes per second in zebrafish larvae expressing genetically encoded fluorescent proteins GFP or GCaMP6s. SOPi's flexibility and steric access makes it adaptable for numerous imaging applications and broadly compatible with orthogonal techniques for actuating or interrogating neuronal structure and activity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005676PMC
http://dx.doi.org/10.1364/OE.26.013027DOI Listing
May 2018

On the prospect of knowing: Providing solutions can reduce persistence.

J Exp Psychol Gen 2017 Dec;146(12):1677-1693

Psychological Clinical Science, University of Toronto.

Our willingness to persist in problem solving is often held up as a critical component in being successful. Allied against this ability, however, are a number of situational factors that undermine our persistence. In the present investigation, the authors examine 1 such factor-knowing that the answers to a problem are easily accessible. Does having answers to a problem available reduce our willingness to persist in solving it ourselves? Across 4 experiments, participants (university students from a large Canadian University) solved multisolution anagrams and were either provided the answers after giving up (and knew they would receive the answers) or not. Results demonstrated that individuals persisted for less time in the former condition. In addition, participants did not seem to be aware of the effect that answers had on their decisions to quit. Implications for our understanding of the role that access to answers has on persistence across a number of domains (e.g., education, Internet) are discussed. (PsycINFO Database Record
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http://dx.doi.org/10.1037/xge0000334DOI Listing
December 2017

Exposure to respirable crystalline silica in the construction industry-do we have a problem?

N Z Med J 2017 Dec 1;130(1466):78-82. Epub 2017 Dec 1.

Professor and Director, Centre for Public Health Research, Massey University.

Aims: To assess personal exposure to respirable dust and respirable crystalline silica (RCS) in New Zealand construction workers.

Methods: In a pilot study, 39 personal samples were collected from a cross-section of workers engaged in a range of tasks performed on construction sites that were expected to entail exposure to respirable crystalline silica. Nine static samples were taken at locations adjacent to these tasks. Particle size-selective sampling heads were used to collect the respirable fraction of airborne particulates. Dust concentrations were determined gravimetrically, while crystalline silica was analysed using x-ray diffraction.

Results: Almost half of the personal crystalline silica samples exceeded the New Zealand Workplace Exposure Standard (NZ WES), while 56% exceeded the more stringent international recommendation (ACGIH TLV). The tasks associated with the highest RCS levels were concrete grinding and cutting. Two of four static samples collected close to (silica-containing) Linea board cutting exceeded the ACGIH TLV for RCS, indicating the potential for bystander exposure.

Conclusions: A large proportion of workers performing common tasks in the construction industry may be exposed to levels of respirable dust and crystalline silica exceeding national standards and international recommendations. These results suggest that workers in this industry may be at risk of developing silica-related diseases, including silicosis, lung cancer, COPD and chronic renal disease. Action is required to improve dust control to reduce silica exposure and the associated health risks.
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December 2017

Occupational solvent exposure and risk of glioma in the INTEROCC study.

Br J Cancer 2017 Oct 14;117(8):1246-1254. Epub 2017 Sep 14.

Barcelona Institute for Global Health (ISGlobal), Barcelona 08036, Spain.

Background: The aetiology of glioma remains largely unknown. Occupational solvent exposure has been suggested as a putative cause of glioma, but past studies have been inconsistent. We examined the association between a range of solvents and glioma risk within the INTEROCC project, a study of brain tumours and occupational exposures based on data from seven national case-control studies conducted in the framework of the INTERPHONE study. We also investigated associations according to tumour grade.

Methods: Data from the seven countries were standardised and then combined into one aggregate data set. Pooled odds ratios (ORs) were estimated for adjusted models that included sex, age, country-region of residence and level of educational attainment. Exposures to any solvent or 11 specific solvents or subgroups were assessed using a modified version of the FINJEM job exposure matrix (JEM) specifically developed for the study, called INTEROCC-JEM.

Results: Analysis included 2000 glioma cases and 5565 controls. For glioma and ever/never exposure to any solvent, the OR was 0.91 (95% confidence interval: 0.74-1.11). All ORs were <1.0 for specific solvents/subgroups. There were no increases in risk according to high or low grade of tumour.

Conclusions: The results of this study show no consistent associations for any solvent exposures overall or by grade of tumour.
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http://dx.doi.org/10.1038/bjc.2017.285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674105PMC
October 2017

Visual Threat Assessment and Reticulospinal Encoding of Calibrated Responses in Larval Zebrafish.

Curr Biol 2017 Sep 7;27(18):2751-2762.e6. Epub 2017 Sep 7.

Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA; Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA; Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA. Electronic address:

All visual animals must decide whether approaching objects are a threat. Our current understanding of this process has identified a proximity-based mechanism where an evasive maneuver is triggered when a looming stimulus passes a subtended visual angle threshold. However, some escape strategies are more costly than others, and so it would be beneficial to additionally encode the level of threat conveyed by the predator's approach rate to select the most appropriate response. Here, using naturalistic rates of looming visual stimuli while simultaneously monitoring escape behavior and the recruitment of multiple reticulospinal neurons, we find that larval zebrafish do indeed perform a calibrated assessment of threat. While all fish generate evasive maneuvers at the same subtended visual angle, lower approach rates evoke slower, more kinematically variable escape responses with relatively long latencies as well as the unilateral recruitment of ventral spinal projecting nuclei (vSPNs) implicated in turning. In contrast, higher approach rates evoke faster, more kinematically stereotyped responses with relatively short latencies, as well as bilateral recruitment of vSPNs and unilateral recruitment of giant fiber neurons in fish and amphibians called Mauthner cells. In addition to the higher proportion of more costly, shorter-latency Mauthner-active responses to greater perceived threats, we observe a higher incidence of freezing behavior at higher approach rates. Our results provide a new framework to understand how behavioral flexibility is grounded in the appropriate balancing of trade-offs between fast and slow movements when deciding to respond to a visually perceived threat.
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http://dx.doi.org/10.1016/j.cub.2017.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703209PMC
September 2017

Lifetime occupational exposure to metals and welding fumes, and risk of glioma: a 7-country population-based case-control study.

Environ Health 2017 08 25;16(1):90. Epub 2017 Aug 25.

Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain.

Background: Brain tumor etiology is poorly understood. Based on their ability to pass through the blood-brain barrier, it has been hypothesized that exposure to metals may increase the risk of brain cancer. Results from the few epidemiological studies on this issue are limited and inconsistent.

Methods: We investigated the relationship between glioma risk and occupational exposure to five metals - lead, cadmium, nickel, chromium and iron- as well as to welding fumes, using data from the seven-country INTEROCC study. A total of 1800 incident glioma cases and 5160 controls aged 30-69 years were included in the analysis. Lifetime occupational exposure to the agents was assessed using the INTEROCC JEM, a modified version of the Finnish job exposure matrix FINJEM.

Results: In general, cases had a slightly higher prevalence of exposure to the various metals and welding fumes than did controls, with the prevalence among ever exposed ranging between 1.7 and 2.2% for cadmium to 10.2 and 13.6% for iron among controls and cases, respectively. However, in multivariable logistic regression analyses, there was no association between ever exposure to any of the agents and risk of glioma with odds ratios (95% confidence intervals) ranging from 0.8 (0.7-1.0) for lead to 1.1 (0.7-1.6) for cadmium. Results were consistent across models considering cumulative exposure or duration, as well as in all sensitivity analyses conducted.

Conclusions: Findings from this large-scale international study provide no evidence for an association between occupational exposure to any of the metals under scrutiny or welding fumes, and risk of glioma.
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http://dx.doi.org/10.1186/s12940-017-0300-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574088PMC
August 2017

Melanin quantification by in vitro and in vivo analysis of near-infrared fluorescence.

Pigment Cell Melanoma Res 2018 01 5;31(1):31-38. Epub 2017 Nov 5.

Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.

Objective measurements of melanin can provide important information for differentiating melanoma from benign pigmented lesions and in assessing pigmentary diseases. Herein, we evaluate near-infrared (NIR) fluorescence as a possible tool to quantify melanin. Various concentrations of in vitro Sepia melanin in tissue phantoms were measured with NIR fluorescence and diffuse reflectance spectroscopy. Similar optic measurements were conducted in vivo on 161 normal human skin sites. Diffuse reflectance spectroscopy was used to quantify the melanin content via Stamatas-Kollias algorithm. At physiologic concentrations, increasing in vitro melanin concentrations demonstrated higher fluorescence that was linearly correlated (R  = 0.99, p < .001). At higher concentrations, the fluorescence signal plateaued. A linear relationship was also observed with melanin content in human skin (R  = 0.59, p < .001). Comparing the fluorescence and reflectance signals with in vitro and in vivo samples, the estimated melanin concentration in human skin ranged between 0 and 1.25 mg/ml, consistent with previous quantitative studies involving invasive methods.
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http://dx.doi.org/10.1111/pcmr.12624DOI Listing
January 2018

Distinct responses of Purkinje neurons and roles of simple spikes during associative motor learning in larval zebrafish.

Elife 2017 05 25;6. Epub 2017 May 25.

Department of Neurobiology, Northwestern University, Evanston, United States.

To study cerebellar activity during learning, we made whole-cell recordings from larval zebrafish Purkinje cells while monitoring fictive swimming during associative conditioning. Fish learned to swim in response to visual stimulation preceding tactile stimulation of the tail. Learning was abolished by cerebellar ablation. All Purkinje cells showed task-related activity. Based on how many complex spikes emerged during learned swimming, they were classified as multiple, single, or zero complex spike (MCS, SCS, ZCS) cells. With learning, MCS and ZCS cells developed increased climbing fiber (MCS) or parallel fiber (ZCS) input during visual stimulation; SCS cells fired complex spikes associated with learned swimming episodes. The categories correlated with location. Optogenetically suppressing simple spikes only during visual stimulation demonstrated that simple spikes are required for acquisition and early stages of expression of learned responses, but not their maintenance, consistent with a transient, instructive role for simple spikes during cerebellar learning in larval zebrafish.
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http://dx.doi.org/10.7554/eLife.22537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444900PMC
May 2017

Solvent neurotoxicity in vehicle collision repair workers in New Zealand.

Neurotoxicology 2016 12 11;57:223-229. Epub 2016 Oct 11.

Centre for Public Health Research, Massey University, Wellington, New Zealand.

Objectives: To assess whether solvent use and workplace practices in the vehicle collision repair industry are associated with symptoms of neurotoxicity in spray painters and panel beaters (auto body repair workers).

Methods: Neurobehavioural symptoms were assessed using a cross-sectional study design in 370 vehicle collision repair and 211 reference workers using the EUROQUEST questionnaire. Full-shift airborne solvent levels were measured in a subset (n=92) of collision repair workers.

Results: Solvent exposures were higher in spray painters than in panel beaters, but levels were below current international exposure standards. Collision repair workers were more likely to report symptoms of neurotoxicity than reference workers with ORs of 2.0, 2.4 and 6.4 (all p<0.05) for reporting ≥5, ≥10 and ≥15 symptoms respectively. This trend was generally strongest for panel beaters (ORs of 2.1, 3.3 and 8.2 for ≥5, ≥10 and ≥15 symptoms respectively). Associations with specific symptom domains showed increased risks for neurological (OR 4.2), psychosomatic (OR 3.2), mood (OR 2.1), memory (OR 2.9) and memory and concentration symptoms combined (OR 2.4; all p<0.05). Workers who had worked for 10-19 years or 20+ years in the collision repair industry reported consistently more symptoms than those who had only worked less than 10 years even after adjusting for age. However, those who worked more than 20 years generally reported fewer symptoms than those who worked 10-19 years, suggesting a possible healthy worker survivor bias.

Conclusions: Despite low airborne solvent exposures, vehicle collision repair spray painters and panel beaters continue to be at risk of symptoms of neurotoxicity.
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http://dx.doi.org/10.1016/j.neuro.2016.10.005DOI Listing
December 2016

Answers at your fingertips: Access to the Internet influences willingness to answer questions.

Conscious Cogn 2015 Dec 2;37:91-102. Epub 2015 Sep 2.

Department of Psychology, University of Waterloo, Canada. Electronic address:

Recent technological advances have given rise to an information-gathering tool unparalleled by any in human history-the Internet. Understanding how access to such a powerful informational tool influences how we think represents an important question for psychological science. In the present investigation we examined the impact of access to the Internet on the metacognitive processes that govern our decisions about what we "know" and "don't know." Results demonstrated that access to the Internet influenced individuals' willingness to volunteer answers, which led to fewer correct answers overall but greater accuracy when an answer was offered. Critically, access to the Internet also influenced feeling-of-knowing, and this accounted for some (but not all) of the effect on willingness to volunteer answers. These findings demonstrate that access to the Internet can influence metacognitive processes, and contribute novel insights into the operation of the transactive memory system formed by people and the Internet.
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http://dx.doi.org/10.1016/j.concog.2015.08.008DOI Listing
December 2015

Peeling back the layers of locomotor control in the spinal cord.

Curr Opin Neurobiol 2015 Aug 25;33:63-70. Epub 2015 Mar 25.

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address:

Vertebrate locomotion is executed by networks of neurons within the spinal cord. Here, we describe recent advances in our understanding of spinal locomotor control provided by work using optical and genetic approaches in mice and zebrafish. In particular, we highlight common observations that demonstrate simplification of limb and axial motor pool coordination by spinal network modularity, differences in the deployment of spinal modules at increasing speeds of locomotion, and functional hierarchies in the regulation of locomotor rhythm and pattern. We also discuss the promise of intersectional genetic strategies for better resolution of network components and connectivity, which should help us continue to close the gap between theory and function.
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http://dx.doi.org/10.1016/j.conb.2015.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523447PMC
August 2015

Neuromodulation: letting sources of spinal dopamine speak for themselves.

Curr Biol 2015 Feb;25(4):R146-8

Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA. Electronic address:

A recent study of dopaminergic neurons in the brain of larval zebrafish has important implications for interpreting the natural actions of neuromodulators in the spinal cord.
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http://dx.doi.org/10.1016/j.cub.2015.01.001DOI Listing
February 2015

Real-time visualization of melanin granules in normal human skin using combined multiphoton and reflectance confocal microscopy.

Photodermatol Photoimmunol Photomed 2015 May 17;31(3):141-8. Epub 2015 Feb 17.

Imaging Unit, Integrative Oncology Department, British Columbia Cancer Agency Research Centre, Vancouver, British Columbia, Canada; Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada; Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Recent advances in biomedical optics have enabled dermal and epidermal components to be visualized at subcellular resolution and assessed noninvasively. Multiphoton microscopy (MPM) and reflectance confocal microscopy (RCM) are noninvasive imaging modalities that have demonstrated promising results in imaging skin micromorphology, and which provide complementary information regarding skin components. This study assesses whether combined MPM/RCM can visualize intracellular and extracellular melanin granules in the epidermis and dermis of normal human skin.

Methods: We perform MPM and RCM imaging of in vivo and ex vivo skin in the infrared domain. The inherent three-dimensional optical sectioning capability of MPM/RCM is used to image high-contrast granular features across skin depths ranging from 50 to 90 μm. The optical images thus obtained were correlated with conventional histologic examination including melanin-specific staining of ex vivo specimens.

Results: MPM revealed highly fluorescent granular structures below the dermal-epidermal junction (DEJ) region. Histochemical staining also demonstrated melanin-containing granules that correlate well in size and location with the granular fluorescent structures observed in MPM. Furthermore, the MPM fluorescence excitation wavelength and RCM reflectance of cell culture-derived melanin were equivalent to those of the granules.

Conclusion: This study suggests that MPM can noninvasively visualize and quantify subepidermal melanin in situ.
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http://dx.doi.org/10.1111/phpp.12161DOI Listing
May 2015

Systematic shifts in the balance of excitation and inhibition coordinate the activity of axial motor pools at different speeds of locomotion.

J Neurosci 2014 Oct;34(42):14046-54

Department of Neurobiology, Northwestern University, Evanston, Illinois 60625

An emerging consensus from studies of axial and limb networks is that different premotor populations are required for different speeds of locomotion. An important but unresolved issue is why this occurs. Here, we perform voltage-clamp recordings from axial motoneurons in larval zebrafish during "fictive" swimming to test the idea that systematic differences in the biophysical properties of axial motoneurons are associated with differential tuning in the weight and timing of synaptic drive, which would help explain premotor population shifts. We find that increases in swimming speed are accompanied by increases in excitation preferentially to lower input resistance (Rin) motoneurons, whereas inhibition uniformly increases with speed to all motoneurons regardless of Rin. Additionally, while the timing of rhythmic excitatory drive sharpens within the pool as speed increases, there are shifts in the dominant source of inhibition related to Rin. At slow speeds, anti-phase inhibition is larger throughout the pool. However, as swimming speeds up, inhibition arriving in-phase with local motor activity increases, particularly in higher Rin motoneurons. Thus, in addition to systematic differences in the weight and timing of excitation related to Rin and speed, there are also speed-dependent shifts in the balance of different sources of inhibition, which is most obvious in more excitable motor pools. We conclude that synaptic drive is differentially tuned to the biophysical properties of motoneurons and argue that differences in premotor circuits exist to simplify the coordination of activity within spinal motor pools during changes in locomotor speed.
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http://dx.doi.org/10.1523/JNEUROSCI.0514-14.2014DOI Listing
October 2014

Selective responses to tonic descending commands by temporal summation in a spinal motor pool.

Neuron 2014 Aug 24;83(3):708-21. Epub 2014 Jul 24.

Interdepartmental Neuroscience Program, Northwestern University, Evanston, IL 60208, USA; Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA. Electronic address:

Motor responses of varying intensities rely on descending commands to heterogeneous pools of motoneurons. In vertebrates, numerous sources of descending excitatory input provide systematically more drive to progressively less excitable spinal motoneurons. While this presumably facilitates simultaneous activation of motor pools, it is unclear how selective patterns of recruitment could emerge from inputs weighted this way. Here, using in vivo electrophysiological and imaging approaches in larval zebrafish, we find that, despite weighted excitation, more excitable motoneurons are preferentially activated by a midbrain reticulospinal nucleus by virtue of longer membrane time constants that facilitate temporal summation of tonic drive. We confirm the utility of this phenomenon by assessing the activity of the midbrain and motoneuron populations during a light-driven behavior. Our findings demonstrate that weighted descending commands can generate selective motor responses by exploiting systematic differences in the biophysical properties of target motoneurons and their relative sensitivity to tonic input.
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http://dx.doi.org/10.1016/j.neuron.2014.06.021DOI Listing
August 2014

Clinical Raman measurements under special ambient lighting illumination.

J Biomed Opt 2014 ;19(11):111609

British Columbia Cancer Research Center, Imaging Unit-Integrative Oncology Department, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, CanadabUniversity of British Columbia and Vancouver Coastal Health Research Institute, Photomedicine Institute, Department.

One challenge in facing the application of biomedical Raman spectroscopy is that the Raman signal is acquired in a dark operation room. It is inconvenient for both the operator and the patient because it is difficult for the operator to accurately and precisely locate the target in the dark environment, and the patient feels uncomfortable in such a setting. In this note, we propose a method to implement biomedical Raman measurement with an illumination source, by multiple filtering of the illumination and the collection optics. Experimental results are demonstrated on skin Raman measurement under 785-nm excitation.
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http://dx.doi.org/10.1117/1.JBO.19.11.111609DOI Listing
January 2015
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