A Framework for Assessing the Rationality of Judgments in Carcinogenicity Hazard Identification

Arguing that guidelines for identifying carcinogens now lack a philosophically rigorous framework, the authors present an alternative that draws clear attention to the process of reasoning towards judgments of carcinogenicity

Brainstem Control Of Three-dimensional Eye Movements

This thesis examines the neural mechanisms that generate torsional and vertical eye movements, and how they handle the kinematics of three-dimensional rotations. Three-dimensional eye rotations were recorded in alert monkeys, and the midbrain was studied using single unit recording, electrical microstimulation, and pharmacological inactivation.;The direction of VOR slow phases was usually opposite to that of head rotation, as required for optimal visual stabilization. However, direction errors sometimes occurred because of low gain about a head-fixed torsional axis. This axis was orthogonal to Listing\u27s plane of saccadic eye positions, which suggests that saccades and the VOR share the same coordinate system. As predicted by the laws of rotational kinematics, even slow phase axes with zero torsional components produced torsional violations of Listing\u27s law. This proves that mechanics of the plant are not responsible for Listing\u27s law. Furthermore, the final positions were held. This signifies that the eye velocity signal is multiplied by position feedback before entering the oculomotor integrator. Finally, these violations of Listing\u27s law were corrected by VOR quick phases.;Microstimulation and inactivation of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) demonstrated two right riMLF burst neuron populations that generate clockwise-upward-rightward and clockwise-downward-leftward rotations respectively, and two left riMLF populations for counterclockwise-upward-leftward and counterclockwise-downward-rightward rotations. The torsional axes of eye rotation evoked by riMLF stimulation were orthogonal to Listing\u27s plane, whereas axes that remained after riMLF inactivation aligned with Listing\u27s plane. This suggests that the neural coordinates of motor systems reflect their behavioral constraints.;The neural integrator, which generates the eye position signal, is central to oculomotor control. Post-saccadic drift during inactivation of the midbrain interstitial nucleus of Cajal (INC) showed that this nucleus is the integrator for vertical and torsional eye positions. Stimulation showed that the right INC controls clockwise rotations and the left INC controls counterclockwise rotations. Simulations of the drift suggested that the INC distributes integration over parallel independent neural compartments. This makes the integrator more computationally robust, and suggests a similar role for the modular connectivity observed throughout the brain

A Computational Model to Account for Dynamics of Spatial Updating of Remembered Visual Targets across Slow and Rapid Eye Movements

Despite the ever-changing visual scene on the retina between eye movements, our perception of the visual world is constant and unified. It is generally believed that this space constancy is due to the brain’s ability of spatial updating. Although many efforts have been made to discover the mechanism underlying spatial updating across eye movements, still there are many unanswered questions about the neuronal mechanism of this phenomenon. We developed a state space model for updating gaze-centered spatial information. To explore spatial updating, we considered two kinds of eye movements, saccade and smooth pursuit. The inputs to our proposed model are: a corollary discharge signal, an eye position signal and 2D visual topographic maps of visual stimuli. The state space is represented by a radial basis function neural network and we can obtain a topographic map of the remembered visual target in its hidden layer. Finally, the decoded location of the remembered target is the output of the model. We trained the model on the double step saccade-saccade and pursuit-saccade tasks. Training this model revealed that the receptive fields of state-space units are remapped predictively during saccades and updated continuously during smooth pursuit. Moreover, during saccades, receptive fields also expanded (to our knowledge, this predicted expansion has not yet been reported in the published literature). We believe that incorporating this model can shed light on the underlying neural mechanism for Trans-saccadic perception

The role of areas MT+/V5 and SPOC in spatial and temporal control of manual interception: an rTMS study

Manual interception, such as catching or hitting an approaching ball, requires the hand to contact a moving object at the right location and at the right time. Many studies have examined the neural mechanisms underlying the spatial aspects of goal-directed reaching, but the neural basis of the spatial and temporal aspects of manual interception are largely unknown. Here, we used repetitive transcranial magnetic stimulation (rTMS) to investigate the role of the human middle temporal visual motion area (MT+/V5) and superior parieto-occipital cortex (SPOC) in the spatial and temporal control of manual interception. Participants were required to reach-to-intercept a downward moving visual target that followed an unpredictably curved trajectory, presented on a screen in the vertical plane. We found that rTMS to MT+/V5 influenced interceptive timing and positioning, whereas rTMS to SPOC only tended to increase the spatial variance in reach end points for selected target trajectories. These findings are consistent with theories arguing that distinct neural mechanisms contribute to spatial, temporal, and spatiotemporal control of manual interception

Brief communication: Thwaites Glacier cavity evolution

Between 2014 and 2017, ocean melt eroded a large cavity beneath and along the western margin of the fast-flowing core of Thwaites Glacier. Here we show that from2017 to the end of 2020 the cavity persisted but did not ex-pand. This behaviour, of melt concentrated at the groundingline within confined sub-shelf cavities, fits with prior observations and modelling studies. We also show that acceleration and thinning of Thwaites Glacier grounded ice continued, with an increase in speed of 400 m a−1and a thinning rate of at least 1.5 m a−1, between 2012 and 2020

Boundary Crossing: Networked Policing and Emergent “Communities of Practice” in Safeguarding Children

Child safeguarding has come to the forefront of public debate in the UK in the aftermath of a series of highly publicised incidents of child sexual exploitation and abuse. These have exposed the inadequacies and failings of inter-organisational relations between police and key partners. While the discourse of policing partnerships is now accepted wisdom, progress has been distinctly hesitant. This paper contributes to understanding both the challenges and opportunities presented through working across organisational boundaries in the context of safeguarding children. It draws on a study of relations within one of the largest Safeguarding Children partnerships in England, developing insights from Etienne Wenger regarding the potential of ‘communities of practice’ that innovate on the basis of everyday learning through ‘boundary work’. We demonstrate how such networked approaches expose the differential power relations and sites of conflict between organisations but also provide possibilities to challenge introspective cultures and foster organisational learning. We argue that crucial in cultivating effective ‘communities of practice’ are: shared commitment and purpose; relations of trust; balanced exchange of information and resources; mutual respect for difference; and an open and mature dialogue over possible conflicts. Boundary crossing can open opportunities to foster increased reflexivity among policing professionals, prompting critical self-reflection on values, ongoing reassessment of assumptions and questioning of terminology. Yet, there is an inherent tension in that the learning and innovative potential afforded by emergent ‘communities of practice’ derives from the coexistence and interplay between both the depth of knowledge within practices and active boundaries across practices

Human parietal reach region primarily encodes intrinsic visual direction, not extrinsic movement direction, in a visual motor dissociation task.

Posterior parietal cortex (PPC) participates in the planning of visuospatial behaviors, including reach movements, in gaze-centered coordinates. It is not known if these representations encode the visual goal in retinal coordinates, or the movement direction relative to gaze. Here, by dissociating the intrinsic retinal stimulus from the extrinsic direction of movement, we show that PPC employs a visual code. Using delayed pointing and event-related functional magnetic resonance imaging, we identified a cluster of PPC regions whose activity was topographically (contralaterally) related to the direction of the planned movement. We then switched the normal visual-motor spatial relationship by adapting subjects to optical left/right reversing prisms. With prisms, movement-related PPC topography reversed, remaining tied to the retinal image. Thus, remarkably, the PPC region in each hemisphere now responded more for planned ipsilateral pointing movements. Other non-PPC regions showed the opposite world- or motor-fixed pattern. These findings suggest that PPC primarily encodes not motor commands but movement goals in visual coordinates

Gut inflammation provides a respiratory electron acceptor for Salmonella.

Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen