Can shared surfaces be safely negotiated by blind and partially sighted people?

‘Shared Space’ schemes are designed to remove the physical distinction between pedestrian space and traffic space in the street environment to encourage more pedestrians to use the area. They may also make it easier for people with wheelchairs, prams or similar to negotiate the space. However, by removing the kerbs, blind and partially sighted people lose one of the key references that they normally use to know they are in a safe space away from vehicles and to navigate around the area. This study is intended to understand what people with visual impairments need from a surface to make it clearly detectable, given that it should not be a barrier to progress for people with other mobility limitations. With this information, some surfaces were tested to determine their suitability as a delineator. Approach and/or Methodology An experimental approach was adopted. People with mobility impairments and blind and partially sighted people were recruited. All participants used the normal street environment unaccompanied. The blind and partially sighted participants included people who use a guide dog, those who use a long cane and those who use no assistive device. The people with mobility impairments all used some form of mobility aid for example walking stick or wheelchair. The tests were run in the pedestrian testing facility PAMELA at UCL. The top surface of the test facility was predominantly concrete paving slab, but with test surfaces discretely located. The task for all participants was to travel from one designated place in the test area to another. For some of these trials the participant would encounter one of the test surfaces, but on other trials they would not. After each trial the participants were asked to rate how easy it was to detect a change in surface, or how easy it was to pass over the surface. The different surfaces included blister paving, corduroy paving, a central delineator, slopes, roughened surfaces, and traditional kerb upstands of different heights. Results or Expected Results None of the 400mm wide surfaces was detected by all participants. Changes in level through slopes were considered both positively and negatively, some people asking for steeper gradients and some less steep. Kerb heights below 60mm were not reliably detectable by blind or partially sighted people and are an obstacle to people in wheelchairs. Further tests on more surfaces are in process and the results will be incorporated into this paper. Conclusion Early suggestions for detectable surfaces – proposed in UK schemes - have been either a barrier to people with mobility impairments, or difficult to detect for blind and partially sighted people or both. The work presented in this paper shows the difficulty in finding a suitable dual purpose surface, yet clarifies the design requirements for shared space delineators for people with mobility impairments and blind or partially sighted people. This work has reinforced the point that 400mm width is insufficient to be used as a tactile surface. Further conclusions will be made after the additional surface tests. Topic Code: Ca C. Accessibility concerns and solutions for those with cognitive and sensory impairment a. Pedestrian safety at crossings and intersection

Merlin Phosphorylation by p21-activated Kinase 2 and Effects of Phosphorylation on Merlin Localization

The Nf2 tumor suppressor gene product merlin is related to the membrane-cytoskeleton linker proteins of the band 4.1 superfamily, including ezrin, radixin, and moesin (ERMs). Merlin is regulated by phosphorylation in a Rac/cdc42-dependent fashion. We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2. This is demonstrated by biochemical fractionation, use of active and dominant-negative mutants of PAK2, and immunodepletion. By using wild-type and mutated forms of merlin and phospho-directed antibodies, we show that phosphorylation of merlin at serine 518 leads to dramatic protein relocalization. Neurofibromatosis type 2 (NF2)1 is an inherited disorder characterized by the development of Schwann cell tumors of the eighth cranial nerve. Mutations and loss of heterozygosity of theNF2 gene have been detected in NF2 patients and in various sporadic tumors, including schwannomas, meningiomas, and ependymomas (1). In further support of a role for NF2 in tumor suppression, mice heterozygous for an Nf2 mutation are predisposed to a wide variety of tumors with high metastatic potential (2). In a separate model in which Nf2 is inactivated specifically in Schwann cells, mice develop schwannomas and Schwann cell hyperplasia (3). The longest and predominant splice form of the Nf2gene codes for a 595-amino acid protein highly similar to the band 4.1 family of proteins. It is most closely related to the ERM proteins,moesin, ezrin, and radixin. The ERM proteins are thought to function as cell membrane-cytoskeleton linkers and are localized to cortical actin structures near the plasma membrane such as microvilli, membrane ruffles, and lamellipodia (4, 5). Likewise, merlin is localized to cortical actin structures, in patterns that partially overlap with the ERMs (1). It has been proposed that intramolecular binding of the N-terminal and C-terminal domains conformationally regulates the ERM proteins by masking binding sites for interacting proteins. The ERMs can also form homodimers and heterodimers, among themselves and with merlin, adding an additional level of complexity to the regulation of these proteins (6). The recently solved crystal structure of the moesin N/C-terminal complex strengthens this model of conformational regulation (7). Given the sequence and, most likely, structural similarities of merlin to the ERM proteins, it is possible that merlin itself could be regulated in a similar fashion. Recent studies (8, 9) have implicated additional factors in the regulation of the ERMs, including phospholipids and phosphorylation. Previous work from our group and others (10, 11) has shown that merlin is differentially phosphorylated as well and that merlin protein levels are affected by growth conditions such as cell confluency, loss of adhesion, or serum deprivation. Merlin is found in an hypophosphorylated form when the combination of cellular and environmental conditions are growth-inhibitory (10). ERMs can be phosphorylated by Rho kinase, and this phosphorylation can affect intramolecular association and cellular localization. Phosphorylation and/or phospholipids may promote the transition of the proteins to an active form by “opening” intra- and intermolecular associations. These active monomers can then bind to other interacting proteins and the actin cytoskeleton and induce actin-rich membrane projections (5,8, 12, 13). The induction of merlin phosphorylation by activated alleles of the Rho family GTPases has also been examined. Interestingly, although activated Rho did not induce noticeable phosphorylation of merlin, activated forms of Rac and cdc42 did. The site of Rac-induced phosphorylation was determined to be a serine at position 518; mutation of serine 518 results in reduced basal phosphorylation and eliminated Rac-induced phosphorylation (11). Although Rac and cdc42 are implicated in the regulation of many pathways, they are most associated with regulation of cytoskeleton reorganization and gene expression (for recent reviews see Refs.14-16). In light of the data demonstrating that activated Rac/cdc42 leads to phosphorylation and possible inactivation of merlin, the elucidation of the responsible effector pathways and their effects on merlin function are of major importance. Understanding this regulation of merlin could lead to a more complete appreciation of the effects of merlin loss in tumors

The Psychology of Trial Judging

Trial court judges play a crucial role in the administration of justice for both criminal and civil matters. Although psychologists have studied juries for many decades, they have paid relatively little attention to judges. Recent writings, however, suggest that there is increasing interest in the psychology of judicial decision making. In this article, I review several selected areas of judicial behavior in which decisions appear to be influenced by psychological dispositions, but I caution that a mature psychology of judging field will need to consider the influence of the bureaucratic court setting in which judges are embedded, judges’ legal training, and the constraints of legal precedent

Analysis of Neural-BOLD Coupling Through Four Models of the Neural Metabolic Demand

The coupling of the neuronal energetics to the blood-oxygen-level-dependent (BOLD) response is still incompletely understood. To address this issue, we compared the fits of four plausible models of neurometabolic coupling dynamics to available data for simultaneous recordings of the local field potential and the local BOLD response recorded from monkey primary visual cortex over a wide range of stimulus durations. The four models of the metabolic demand driving the BOLD response were: direct coupling with the overall LFP; rectified coupling to the LFP; coupling with a slow adaptive component of the implied neural population response; and coupling with the non-adaptive intracellular input signal defined by the stimulus time course. Taking all stimulus durations into account, the results imply that the BOLD response is most closely coupled with metabolic demand derived from the intracellular input waveform, without significant influence from the adaptive transients and nonlinearities exhibited by the LFP waveform

Research Review: Neural response to threat in children, adolescents, and adults after child maltreatment – a quantitative meta‐analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136280/1/jcpp12651_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136280/2/jcpp12651.pd

When Ecology Needs Economics and Economics Needs Ecology: Interdisciplinary Exchange in the Age of Humans

Evidence that humans play a dominant role in most ecosystems forces scientists to confront systems that contain factors transgressing traditional disciplinary boundaries. However, it is an open question whether this state of affairs should encourage interdisciplinary exchange or integration. With two case studies, we show that exchange between ecologists and economists is preferable, for epistemological and policy-oriented reasons, to their acting independently. We call this “exchange gain.” Our case studies show that theoretical exchanges can be less disruptive to current theory than commonly thought—valuable exchange does not necessarily require disciplinary integration

A Powerful New Quantitative Genetics Platform, Combining Caenorhabditis elegans High-Throughput Fitness Assays with a Large Collection of Recombinant Strains.

The genetic variants underlying complex traits are often elusive even in powerful model organisms such as Caenorhabditis elegans with controlled genetic backgrounds and environmental conditions. Two major contributing factors are: (1) the lack of statistical power from measuring the phenotypes of small numbers of individuals, and (2) the use of phenotyping platforms that do not scale to hundreds of individuals and are prone to noisy measurements. Here, we generated a new resource of 359 recombinant inbred strains that augments the existing C. elegans N2xCB4856 recombinant inbred advanced intercross line population. This new strain collection removes variation in the neuropeptide receptor gene npr-1, known to have large physiological and behavioral effects on C. elegans and mitigates the hybrid strain incompatibility caused by zeel-1 and peel-1, allowing for identification of quantitative trait loci that otherwise would have been masked by those effects. Additionally, we optimized highly scalable and accurate high-throughput assays of fecundity and body size using the COPAS BIOSORT large particle nematode sorter. Using these assays, we identified quantitative trait loci involved in fecundity and growth under normal growth conditions and after exposure to the herbicide paraquat, including independent genetic loci that regulate different stages of larval growth. Our results offer a powerful platform for the discovery of the genetic variants that control differences in responses to drugs, other aqueous compounds, bacterial foods, and pathogenic stresses

The human fear-circuitry and fear-induced fainting in healthy individuals The paleolithic-threat hypothesis

The Paleolithic-Threat hypothesis reviewed here posits that habitual efferent fainting can be traced back to fear-induced allelic polymorphisms that were selected into some genomes of anatomically, mitochondrially, and neurally modern humans (Homo sapiens sapiens) in the Mid-Paleolithic because of the survival advantage they conferred during periods of inescapable threat. We posit that during Mid-Paleolithic warfare an encounter with “a stranger holding a sharp object” was consistently associated with threat to life. A heritable hard- wired or firm-wired (prepotentiated) predisposition to abruptly increase vagal tone and collapse flaccidly rather than freeze or attempt to flee or fight in response to an approaching sharp object, a minor injury, or the sight of blood, polymorphism for the hemodynamically “paradoxical” flaccid- immobility in response to these stimuli may have increased some non-combatants’ chances of survival. This is consistent with the unusual age and sex pattern of fear-induced fainting. The Paleolithic-Threat hypothesis also predicts a link to various hypo-androgenic states (e.g. low dehydroxyepiandrosterone-sulfate. We offer five predictions testable via epidemiological, clinical, and ethological/primatological methods. The Paleolithic-Threat hypothesis has implications for research in the aftermath of man-made disasters, such as terrorism against civilians, a traumatic event in which this hypothesis predicts epidemics of fear-induced faintin

Survival strategies in arctic ungulates

Arctic ungulates usually neither freeze nor starve to death despite the rigours of winter. Physiological adaptations enable them to survive and reproduce despite long periods of intense cold and potential undernutrition. Heat conservation is achieved by excellent insulation combined with nasal heat exchange. Seasonal variation in fasting metabolic rate has been reported in several temperate and sub-arctic species of ungulates and seems to occur in muskoxen. Surprisingly, there is no evidence for this in reindeer. Both reindeer and caribou normally maintain low levels of locomotor activity in winter. Light foot loads are important for reducing energy expenditure while walking over snow. The significance and control of selective cooling of the brain during hard exercise (e.g. escape from predators) is discussed. Like other cervids, reindeer and caribou display a pronounced seasonal cycle of appetite and growth which seems to have an intrinsic basis. This has two consequences. First, the animals evidently survive perfectly well despite enduring negative energy balance for long periods. Second, loss of weight in winter is not necessarily evidence of undernutrition. The main role of fat reserves, especially in males, may be to enhance reproductive success. The principal role of fat reserves in winter appears to be to provide a supplement to, rather than a substitute for, poor quality winter forage. Fat also provides an insurance against death during periods of acute starvation