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Online data collection offers a wide range of benefits including access to larger and more diverse populations, together with a reduction in the experiment cycle. Here we compare performance in a spatial memory task, in which participants had to estimate object locations following viewpoint shifts, using data from a controlled lab-based setting and from an unsupervised online sample. We found that the data collected in a conventional laboratory setting and those collected online produced very similar results, although the online data was more variable with standard errors being about 10% larger than those of the data collected in the lab. Overall, our findings suggest that spatial memory studies using static images can be successfully carried out online with unsupervised samples. However, given the higher variability of the online data, it is recommended that the online sample size is increased to achieve similar standard errors to those obtained in the lab. For the current study and data processing procedures, this would require an online sample 25% larger than the lab sample., PLoS ONE, 16 (11), ISSN:1932-6203

Licenced London taxi drivers have been found to show changes in the grey matter density of their hippocampus over the course of training and decades of navigation in London (UK). This has been linked to their learning and using of the ‘Knowledge of London’, the names and layout of over 26,000 streets and thousands of points of interest in London. Here we examined the process of how this knowledge is acquired and we detail key steps that include: systematic study of maps, travel on selected overlapping routes, the mental visualisation of places and the optimal use of subgoals. We provide the first map of the street network covered by the routes used to learn, allowing insight into where gaps in the network exist. The methods could be widely applied to aid spatial learning in the general population and may provide insights for artificial intelligence (AI) systems to efficiently learn new environments.

Our previous research highlighted a systematic bias in a spatial memory task, with participants correctly detecting object movements in the same direction as the perspective shift, whilst misjudging the direction of object movements if those were in the opposite direction to the perspective shift. The aim of the current study was to investigate if the introduction of perspective shifts results in systematic biases in object location estimations. To do so, we asked participants to encode the position of an object in a virtual room and to then estimate the object’s position following a perspective shift. In addition, by manipulating memory load (perception and memory condition) we investigated if the bias in object position estimates results from systematic distortions introduced in spatial memory. Overall, our results show that participants make systematic errors in estimating object positions in the same direction as the perspective shift. This bias was present in both the memory and the perception condition. We propose that the systematic bias in the same direction as the perspective shift is driven by difficulties in understanding the perspective shifts that may lead participants to use an egocentric representation of object positions as an anchor when estimating the object location following a perspective shift, thereby giving rise to a systematic shift in errors in the same direction as the perspective shift.

Successful navigation requires memorising and recognising the locations of objects across different perspectives. Although these abilities rely on hippocampal functioning, which is susceptible to degeneration in older adults, little is known about the effects of ageing on encoding and response strategies that are used to recognise spatial configurations. To investigate this, we asked young and older participants to encode the locations of objects in a virtual room shown as a picture on a computer screen. Participants were then shown a second picture of the same room taken from the same (0°) or a different perspective (45° or 135°) and had to judge whether the objects occupied the same or different locations. Overall, older adults had greater difficulty with the task than younger adults although the introduction of a perspective shift between encoding and testing impaired performance in both age groups. Diffusion modelling revealed that older adults adopted a more conservative response strategy, while the analysis of gaze patterns showed an age-related shift in visual-encoding strategies with older adults attending to more information when memorising the positions of objects in space. Overall, results suggest that ageing is associated with declines in spatial processing abilities, with older individuals shifting towards a more conservative decision style and relying more on encoding target object positions using room-based cues compared to younger adults, who focus more on encoding the spatial relationships among object clusters. Electronic supplementary material The online version of this article (10.3758/s13421-020-01089-3) contains supplementary material, which is available to authorized users.

© The Author(s) 2020. Ensuring that environments are designed to cater for those with decreasing orientation, perceptual and mobility skills, is an example of how environments are being changed to become more age and dementia friendly. However, environmental design should directly involve potential users of the environment to ensure that their views are accounted for. Four open-ended questions, focusing on orientation strategies, reasons for disorientation, and design preferences, were given to 32 older adults after they had completed a route learning task through an unfamiliar environment. A Content Analysis found a strong focus on participants’ ability to memorize routes based on verbally encoding the route and on their ability to remember landmarks, with the reports linking closely to cognitive theories of navigation. Design suggestions included the importance of a homely and welcoming environment, memorable features, and access to the outdoors. The findings can be used inform age and dementia friendly design principles.

Typically aged adults show reduced ability to learn a route compared to younger adults. In this experiment, we investigate the role of visual attention through eye-tracking and engagement of attentional resources in age-related route learning deficits. Participants were shown a route through a realistic virtual environment before being tested on their route knowledge. Younger and older adults were compared on their gaze behaviour during route learning and on their reaction time to a secondary probe task as a measure of attentional engagement. Behavioural results show a performance deficit in route knowledge for older adults compared to younger adults, which is consistent with previous research. We replicated previous findings showing that reaction times to the secondary probe task were longer at decision points than non-decision points, indicating stronger attentional engagement at navigationally relevant locations. However, we found no differences in attentional engagement and no differences for a range of gaze measures between age groups. We conclude that age-related changes in route learning ability are not reflected in changes in control of visual attention or regulation of attentional engagement. Electronic supplementary material The online version of this article (10.1007/s00426-019-01159-5) contains supplementary material, which is available to authorized users.

A 30 × 30m-resolution gridded dataset of forest plot identifiers was developed for the conterminous United States (CONUS) using a random forests machine-learning imputation approach. Forest plots from the US Forest Service Forest Inventory and Analysis program (FIA) were imputed to gridded c2014 landscape data provided by the LANDFIRE project using topographic, biophysical, and disturbance variables. The output consisted of a raster map of plot identifiers. From the plot identifiers, users of the dataset can link to a number of tree- and plot-level attributes stored in the accompanying tables and in the publicly available FIA DataMart, and then produce maps of any of these attributes, including number of trees per acre, tree species, and forest type. Of 67,141 FIA plots available, 62,758 of these (93.5%) were utilized at least once in imputation to 2,841,601,981 forested pixels in CONUS. Continuous high-resolution forest structure data at a national scale will be invaluable for analyzing carbon dynamics, habitat distributions, and fire effects., Measurement(s) forested area Technology Type(s) machine learning Factor Type(s) biophysical variables • geographic location • forest type • forest height • forest percent cover Sample Characteristic - Environment vegetation layer Sample Characteristic - Location United States of America Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.13285904

Cathepsin S (CatS) is a cysteine protease found in lysosomes of hematopoietic and microglial cells and in secreted form in the extracellular space. While CatS has been shown to contribute significantly to neuropathic pain, the precise mechanisms remain unclear. In this report, we describe JNJ-39641160, a novel non-covalent, potent, selective and orally-available CatS inhibitor that is peripherally restricted (non-CNS penetrant) and may represent an innovative class of immunosuppressive and analgesic compounds and tools useful toward investigating peripheral mechanisms of CatS in neuropathic pain. In C57BL/6 mice, JNJ-39641160 dose-dependently blocked the proteolysis of the invariant chain, and inhibited both T-cell activation and antibody production to a vaccine antigen. In the spared nerve injury (SNI) model of chronic neuropathic pain, in which T-cell activation has previously been demonstrated to be a prerequisite for the development of pain hypersensitivity, JNJ-39641160 fully reversed tactile allodynia in wild-type mice but was completely ineffective in the same model in CatS knockout mice (which exhibited a delayed onset in allodynia). By contrast, in the acute mild thermal injury (MTI) model, JNJ-39641160 only weakly attenuated allodynia at the highest dose tested. These findings support the hypothesis that blockade of peripheral CatS alone is sufficient to fully reverse allodynia following peripheral nerve injury and suggest that the mechanism of action likely involves interruption of T-cell activation and peripheral cytokine release. In addition, they provide important insights toward the development of selective CatS inhibitors for the treatment of neuropathic pain in humans.

Background Islam is the world's fastest growing religion and is projected to be the world's most popular religion by the end of the century. The growing population and increased mobility among Muslims make certain that healthcare providers anywhere will encounter Muslim patients in their clinical practice. The intersection of religion, culture, and gender for Muslim women has unique implications for their healthcare provision but remains understudied. Method We conducted this narrative review of the literature to describe the known barriers for Muslim women in accessing and receiving high quality healthcare, with an emphasis on what individual providers may do to heighten cultural awareness and sensitivity. Results Potential barriers discussed include modesty and privacy among Muslim women, gender preference for providers, family involvement in care, fatalism and predestination, maintaining religious practices during illness, low health literacy and language proficiency, preference for traditional remedies, fear of stereotype and discrimination, and limited healthcare access. Specific advice is included for healthcare providers. Conclusions When caring for Muslim women, healthcare providers' awareness of common barriers to effective care and methods of addressing them is valuable. Additionally, an appreciation of the diversity of religious practices, health beliefs, and preferences of Muslim women and their families will enable providers to engage this population with effective and culturally competent care.

To resolve some of the inconsistencies in existing research into spatial navigation in Autism Spectrum Disorder (ASD), we tested two large age- and ability-matched groups of ASD and typically developing (TD) participants for their spatial navigation abilities in a route learning task, which has been shown to shed light on the strategies participants employ when navigating complex environments. Participants studied a route through a virtual maze by watching a short video of a first-person perspective navigating a maze. The maze included four four-way intersections that were each marked with two unique landmarks in two corners of the intersection. At test, static images of the intersections, either as seen during the video or as approached from a different direction, were presented and participants had to indicate in which direction they would need to travel (straight, left or right) in order to follow the originally studied route. On both types of test trials, the ASD group performed worse and their difficulties were related to reduced cognitive flexibility. Eye-movement data and followup item-memory tests suggested that navigation difficulties may have been related to differences in attention during encoding and less spontaneous use of landmarks as cues for navigation. Spatial navigation performance was best predicted by memory for landmarks as well as by executive functions. The results are discussed in relation to theories of underlying navigation-related brain regions. More research is needed to disentangle the influence of executive functions, memory and attention on spatial navigation.

The dynamic charge acceptance (DCA) of modern lead-carbon batteries is one of the key parameters for their future application in micro- and mild-hybrid cars. This work elucidates the impact of the external surface area of carbon additives on the electrochemical performance of lead-carbon electrodes with respect to the DCA. Five specially synthesized amorphous hard carbon powders with different specific external surface area ranging from 13 m2 g−1 to 192 m2 g−1 were added to the negative active material of laboratory lead-carbon test cells. Results from cyclic voltammetry reveal that the specific external surface area of amorphous carbons exhibits a clear correlation to the electrochemical activity of lead-carbon electrodes. Firstly, an almost linear increase of the activity of the hydrogen evolution reaction with increasing specific external surface area of the carbon additive can be found. Secondly, the specific double-layer capacity of the negative active material is directly linked to the specific external surface area of the additive, as well. Thirdly, a clear correlation to the DCA can be established. In conclusion, a high specific external carbon surface in the negative active material seems to be a key to improve the dynamic charge acceptance of modern lead-carbon batteries.

The study investigated the impact of trauma exposure and of Post-Traumatic Stress Disorder (PTSD) on spatial processing and active navigation in a sample (n = 138) comprising civilians (n = 91), police officers (n = 22) and veterans (n = 27). Individuals with previous trauma exposure exhibited significantly poorer hippocampal-dependent (allocentric) navigation performance on active navigation in a virtual environment (the Alternative Route task) regardless of whether or not they had PTSD (scoring above 20 on the PTSD Diagnostic Scale). No effect of trauma exposure was found in static perspective taking (the Four Mountains task). Moreover, an associative information processing bias in those with PTSD interfered with ability to use hippocampal-dependent processing in active navigation. This study provides new evidence of impaired active navigation in individuals with trauma exposure and highlights the importance of considering the relationship between trauma and spatial processing in clinical and occupational settings.

Visual search experiments used in the field of psychology may be applied to investigate the relationship between environments and prey detection rates that could influence hunting behaviours in ancient humans. Two lab-based experiments were designed to examine the effects of differing virtual environments, representing Marine Isotope Stage 3 (MIS3) in Europe, on participants’ ability to locate prey. The results show that prey detection performance is highly influenced by vegetation structure, both in terms of the biome type (wooded vs. grassland environments) and the density of the vegetation (trees in wooded and shrubs in grassland environments). However, the density of vegetation has a greater relative effect in grassland than in wooded biomes. Closer examination of the transition between biomes (relative percentages of trees vs. shrubs) at the same vegetative density shows a non-linear relationship between prey detection performance and the relative tree to shrub percentages. Changes in the distribution of biomes occurred throughout the Quaternary. The composition of those biomes will have likely affected hominin hunting behaviours because of their intermediary effects on prey detection performance. This may, therefore, have played a role in the turn-overs of hunter-gatherer hominin populations during MIS3 and at other times in the Quaternary.

At the onset of a drug discovery program, the goal is to identify novel compounds with appropriate chemical features that can be taken forward as lead series. Here, we describe three prospective case studies, Bruton Tyrosine Kinase (BTK), RAR-Related Orphan Receptor γ t (RORγt), and Human Leukocyte Antigen DR isotype (HLA-DR) to illustrate the positive impact of high throughput virtual screening (HTVS) on the successful identification of novel chemical series. Each case represents a project with a varying degree of difficulty due to the amount of structural and ligand information available internally or in the public domain to utilize in the virtual screens. We show that HTVS can be effectively employed to identify a diverse set of potent hits for each protein system even when the gold standard, high resolution structural data or ligand binding data for benchmarking, is not available.

Deciding whether a place is the same or different than places encountered previously is a common task in daily navigation which requires to develop knowledge about the locations of objects (object-location binding) and to recognize places from different perspectives. These abilities rely on hippocampal functioning which is susceptible to increasing age. Thus, the question of the present study is how they both together impact on place recognition in aging. Forty people aged 20-29, 44 aged 60-69, and 32 aged 70-79 were presented with places consisting of four different objects during the encoding phase. In the test phase, they were then presented with a second place and had to decide whether it was the same or different. Test places were presented from different perspectives (0°, 30°, 60°) and with different object conditions (same, a swap of two objects, a substitution with a novel object). The sensitivity for detecting changes (d') decreased from 20-29 to 60-69 and to 70-79 years old, and with increasing perspective shifts. Importantly, older adults were less sensitive to object swapping than to object substitution, while young participants did not show any difference. Overall, these results suggest specific age-related difficulties in object-location binding in the context of place recognition.

Our ability to learn unfamiliar routes declines in typical and atypical ageing. The reasons for this\ud decline, however, are not well understood. Here we used eye-tracking to investigate how ageing\ud affects people’s ability to attend to navigationally relevant information and to select unique objects\ud as landmarks. We created short routes through a virtual environment, each comprised of four\ud intersections with two objects each, and we systematically manipulated the saliency and uniqueness\ud of these objects. While salient objects might be easier to memorise than non-salient objects, they\ud cannot be used as reliable landmarks if they appear more than once along the route. As cognitive\ud ageing affects executive functions and control of attention, we hypothesised that the process of\ud selecting navigationally relevant objects as landmarks might be affected as well. The behavioural\ud data showed that younger participants outperformed the older participants and the eye-movement\ud data revealed some systematic differences between age groups. Specifically, older adults spent less\ud time looking at the unique, and therefore navigationally relevant, landmark objects. Both young and\ud older participants, however, effectively directed gaze towards the unique and away from the nonunique objects, even if these were more salient. These findings highlight specific age-related\ud differences in the control of attention that could contribute to declining route learning abilities in\ud older age. Interestingly, route-learning performance in the older age group was more variable than\ud in the young age group with some older adults showing performance similar to the young group.\ud These individual differences in route learning performance were strongly associated with verbal and\ud episodic memory abilities.

Aging is accompanied by changes in general cognitive functioning which may impact the learning rate of older adults; however, this is often not controlled for in cognitive aging studies. We investigated the contribution of differences in learning rates to age-related differences in landmark knowledge acquired from route learning. In Experiment 1 we used a standard learning procedure in which participants received a fixed amount of exposure to a route. Consistent with previous research, we found age-related deficits in associative cue and landmark sequence knowledge. Experiment 2 controlled for differences in learning rates by using a flexible exposure learning procedure. Specifically, participants were trained to a performance criterion during route learning before being tested on the content of their route knowledge. While older adults took longer to learn the route than younger adults, the age-related differences in associative cue knowledge were abolished. The deficit in landmark sequence knowledge, however, remained. Experiment 3 replicated these results and introduced a test situation in which a deficit in landmark sequence knowledge yielded an increased likelihood of disorientation in older adults. The findings of this study suggest that age-related deficits in landmark associative cue knowledge are attenuated by controlling for learning rates. In contrast, landmark sequence knowledge deficits persist and are best explained by changes in the learning strategy of older adults to acquire task essential associative cue knowledge at the expense of supplementary sequence knowledge.

Environments need to be designed such that they support successful orientation for older adults and those with dementia who often experience marked difficulties in their orientation abilities. To better understand how environments can compensate for decreasing orientation skills, voice should be given directly to those experiencing dementia to describe how they find their way and to understand their design preferences. This study explored the navigational experiences and design preferences of older adults with memory difficulties living in a retirement development. In-depth semi-structured interviews with 13 older adults experiencing memory difficulties were conducted. All participants were residents of one retirement development in the United Kingdom. Questions began broadly, for example, to describe their experiences of navigating in their living environment, before discussing any specific navigation difficulties in detail. Thematic analysis identified three main themes: highlighting environmental design that causes disorientation, strategies to overcome disorientation, and residents’ suggestions to improve the design. The design suggestions were particularly informative, heavily focusing on the importance of having memorable and meaningful spaces which were favoured more than signage as an orientation aid. The findings demonstrate the need to consider environmental design to support orientation for those with memory difficulties. Of particular importance is the use of meaningful and relevant landmarks as orientation aids which can additionally stimulate conversation and increase wellbeing. Given the range of suggestions in dementia-friendly design guidelines aimed to support orientation, it is crucial to speak directly to those living in different environments to learn how they find their way around and what design works in their environment.

Virtual reality environments presented on tablets and smartphones have potential to aid the early diagnosis of conditions such as Alzheimer’s dementia by quantifying impairments in navigation performance. However, it is unclear whether performance on mobile devices can predict navigation errors in the real world. We compared the performance of 49 participants (25 females, 18-35 years old) at wayfinding and path integration tasks designed in our mobile app ‘Sea Hero Quest’ with their performance at similar tasks in a real-world environment. We first performed this experiment in the streets of London (UK) and replicated it in Paris (France). In both cities, we found a significant correlation between virtual and real-world wayfinding performance and a male advantage in both environments, although smaller in the real world (Cohen’s d in the game = 0.89, in the real world = 0.59). Results in London and Paris were highly similar, and controlling for familiarity with video games did not change the results. The strength of the correlation between real world and virtual environment increased with the difficulty of the virtual wayfinding task, indicating that Sea Hero Quest does not merely capture video gaming skills. The fact that the Sea Hero Quest wayfinding task has real-world ecological validity constitutes a step toward controllable, sensitive, safe, low-cost, and easy to administer digital cognitive assessment of navigation ability., PLoS ONE, 14 (3), ISSN:1932-6203

Objectives: To explore contemporary antibiotic management of infections caused by carbapenem-resistant Gram-negative bacteria in hospitals. Methods: Cross-sectional, internet-based questionnaire survey. We contacted representatives of all hospitals with more than 800 acute-care hospital beds in France, Greece, Israel, Italy, Kosovo, Slovenia, Spain and selected hospitals in the USA. We asked respondents to describe the most common actual practice at their hospital regarding management of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa through close-ended questions. Results: Between January and June 2017, 115 of 141 eligible hospitals participated (overall response rate 81.6%, country-specific rates 66.7%–100%). Most were tertiary-care (99/114, 86.8%), university-affiliated (110/115, 89.1%) hospitals and most representatives were infectious disease specialists (99/115, 86.1%). Combination therapy was prescribed in 114/115 (99.1%) hospitals at least occasionally. Respondents were more likely to consider combination therapy when treating bacteraemia, pneumonia and central nervous system infections and for Enterobacteriaceae, P. aeruginosa and A. baumannii similarly. Combination of a polymyxin with a carbapenem was used in most cases, whereas combinations of a polymyxin with tigecycline, an aminoglycoside, fosfomycin or rifampicin were also common. Monotherapy was used for treatment of complicated urinary tract infections, usually with an aminoglycoside or a polymyxin. The intended goal of combination therapy was to improve the effectiveness of the treatment and to prevent development of resistance. In general, respondents shared the misconception that combination therapy is supported by strong scientific evidence. Conclusions: Combination therapy was the preferred treatment strategy for infections caused by carbapenem-resistant Gram-negative bacteria among hospital representatives, even though high-quality evidence for carbapenem-based combination therapy is lacking. © 2018 European Society of Clinical Microbiology and Infectious Diseases

Alpha1 -adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α1A -adrenoceptors, and this study investigated whether the low affinity state of this receptor (α1L -adrenoceptor) is involved in mediating contractions of this tissue. The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [(3) H]tamsulosin binding experiments to identify the α1 -adrenoceptor subtype population present in the human vas deferens. The α1A -adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pKd = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α1D -adrenoceptor selective) gave a low affinity estimate (pKd = 6.7), whilst tamsulosin (α1A - and α1D -adrenoceptor selective) had a high affinity (pKd = 9.9). [(3) H]Tamsulosin bound to human vas deferens membranes with a high affinity (pKd = 10.0). Prazosin, RS17053 and BMY7378 competed with [(3) H]tamsulosin with low affinities for a single population of binding sites (pKd values of 8.5, 7.2 and 6.3, respectively). These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α1 -adrenoceptors which have the pharmacological properties of the putative α1L -adrenoceptor, the same functional receptor previously identified in the human prostate.

To investigate the impact of thermal annealing on the micro- and macrostructure of amorphous carbons two series of synthetic disordered porous carbons (carbon xerogels) were analyzed with respect to their structural properties after exposure to different annealing temperatures under argon between 800 and 2000 °C. One series has micro- and mesopores, while the second set of samples is micro- and macroporous only. Gas sorption measurements and small angle X-ray scattering (SAXS) were applied to determine characteristic parameters of the micro- and mesoporosity present and in particular to distinguish between accessible and inaccessible porosity. XRD-spectra were taken to analyze the size of the graphitic domains (microcrystallites) defining the micropores as intercrystalline voids. The macroscopic properties of the carbons were quantified in terms of their apparent density and their elastic modulus. The combination of these characterization methods yields a detailed picture of the inner structure of the porous carbons and the changes upon annealing. The experimental data reveal that the graphitic domains as well as the size of the micropores grow with the annealing temperature. However, for T > 1000 °C micropore accessibility is continuously decreasing and for T > 1800 °C practically no microporosity is detected with N 2 sorption analysis, while SAXS still shows significant micropore volume. At the same time the structure on the meso- and macroscale is almost unaffected.

© 2017 The Author(s) Research into the effects of cognitive aging on route navigation usually focuses on differences in learning performance. In contrast, we investigated age-related differences in route knowledge after successful route learning. One young and two groups of older adults categorized using different cut-off scores on the Montreal Cognitive Assessment (MoCA), were trained until they could correctly recall short routes. During the test phase, they were asked to recall the sequence in which landmarks were encountered (Landmark Sequence Task), the sequence of turns (Direction Sequence Task), the direction of turn at each landmark (Landmark Direction Task), and to identify the learned routes from a map perspective (Perspective Taking Task). Comparing the young participant group with the older group that scored high on the MoCA, we found effects of typical aging in learning performance and in the Direction Sequence Task. Comparing the two older groups, we found effects of early signs of atypical aging in the Landmark Direction and the Perspective Taking Tasks. We found no differences between groups in the Landmark Sequence Task. Given that participants were able to recall routes after training, these results suggest that typical and early signs of atypical aging result in differential memory deficits for aspects of route knowledge.

Human spatial ability is modulated by a number of factors, including age [1, 2, 3] and gender [4, 5]. Although a few studies showed that culture influences cognitive strategies [6, 7, 8, 9, 10, 11, 12, 13], the interaction between these factors has never been globally assessed as this requires testing millions of people of all ages across many different countries in the world. Since countries vary in their geographical and cultural properties, we predicted that these variations give rise to an organized spatial distribution of cognition at a planetary-wide scale. To test this hypothesis, we developed a mobile-app-based cognitive task, measuring non-verbal spatial navigation ability in more than 2.5 million people and sampling populations in every nation state. We focused on spatial navigation due to its universal requirement across cultures. Using a clustering approach, we find that navigation ability is clustered into five distinct, yet geographically related, groups of countries. Specifically, the economic wealth of a nation was predictive of the average navigation ability of its inhabitants, and gender inequality was predictive of the size of performance difference between males and females. Thus, cognitive abilities, at least for spatial navigation, are clustered according to economic wealth and gender inequalities globally, which has significant implications for cross-cultural studies and multi-center clinical trials using cognitive testing.

Planning routes using transportation network maps is a common task that has received little attention in the literature. Here, we present a novel eye-tracking paradigm to investigate psychological processes and mechanisms involved in such a route planning. In the experiment, participants were first presented with an origin and destination pair before we presented them with fictitious public transportation maps. Their task was to find the connecting route that required the minimum number of transfers. Based on participants' gaze behaviour, each trial was split into two phases: (1) the search for origin and destination phase, i.e., the initial phase of the trial until participants gazed at both origin and destination at least once and (2) the route planning and selection phase. Comparisons of other eye-tracking measures between these phases and the time to complete them, which depended on the complexity of the planning task, suggest that these two phases are indeed distinct and supported by different cognitive processes. For example, participants spent more time attending the centre of the map during the initial search phase, before directing their attention to connecting stations, where transitions between lines were possible. Our results provide novel insights into the psychological processes involved in route planning from maps. The findings are discussed in relation to the current theories of route planning.

The discovery of neuronal systems dedicated to computing spatial information, composed of functionally distinct cell types such as place and grid cells, combined with an extensive body of human-based behavioral and neuroimaging research has provided us with a detailed understanding of the brain's navigation circuit. In this review, we discuss emerging evidence from rodents, non-human primates, and humans that demonstrates how cognitive aging affects the navigational computations supported by these systems. Critically, we show 1) that navigational deficits cannot solely be explained by general deficits in learning and memory, 2) that there is no uniform decline across different navigational computations, and 3) that navigational deficits might be sensitive markers for impending pathological decline. Following an introduction to the mechanisms underlying spatial navigation and how they relate to general processes of learning and memory, the review discusses how aging affects the perception and integration of spatial information, the creation and storage of memory traces for spatial information, and the use of spatial information during navigational behavior. The closing section highlights the clinical potential of behavioral and neural markers of spatial navigation, with a particular emphasis on neurodegenerative disorders.

Background Spatial disorientation is one of the most common symptoms in Alzheimer's disease. However, detection of such symptoms is difficult as there are currently no global benchmarks of what constitutes healthy navigation behaviour on a mass population level. Methods To address this we worked with a global telecommunications company (Deutsche Telekom) and a game development company (Glitchers) to develop the mobile video game “Sea Hero Quest”, that tests spatial orientation on a mass population. Three different spatial tasks are examined in the game: way-finding, path integration and spatial working memory. The game to date has collected data in more than 2.7 million people worldwide, across an age range of 19-95, in 193 countries. Results Preliminary findings for the path integration levels of the game, which are targeted more towards egocentric navigation strategies.

Transitions of care between physicians and from inpatient to outpatient settings leave patients vulnerable to medical errors and adverse events. A transitions of care workshop consisting of 2 sessions, Sign-Out Success (SOS) and Transition To Home (TTH), taught sign-out and discharge skills to incoming internal medicine interns during orientation. The workshop used role-playing exercises, didactics, demonstrations, and peer and self-evaluations. Interns completed a survey at 3 months post workshop. Using pre-post workshop measures, SOS increased the quality of intern-rated sign-outs (P = .004). Interns reported more confidence in their ability to effectively sign out (P = .016) and a greater understanding of problems that might arise while on call (P = .012). TTH increased intern-reported confidence in their ability to communicate discharge instructions (P.001) and to verify patient understanding of instructions (P.001). A majority reported using SOS and TTH skills 3 months post workshop. This workshop may be replicable at other institutions.

The ability of two, scattering gold nanoparticles (GNPs) to plasmonically couple in a manner that is dependent on the interparticle separation has been exploited to measure nanometer-level displacements. However, despite broad applicability to monitoring biophysical dynamics, the long time scales (

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Pregnancy is accompanied by prolonged exposure to high estrogen levels. Animal studies have shown that estrogen influences navigation strategies and, hence, affects navigation performance. High estrogen levels are related to increased use of hippocampal-based allocentric strategies and decreased use of striatal-based egocentric strategies. In humans, associations between hormonal shifts and navigation strategies are less well studied. This study compared 30 peripartal women (mean age 28 years) to an age-matched control group on allocentric versus egocentric navigation performance (measured in the last month of pregnancy) and gray matter volume (measured within two months after delivery). None of the women had a previous pregnancy before study participation. Relative to controls, pregnant women performed less well in the egocentric condition of the navigation task, but not the allocentric condition. A whole-brain group comparison revealed smaller left striatal volume (putamen) in the peripartal women. Across the two groups, left striatal volume was associated with superior egocentric over allocentric performance. Limited by the cross-sectional study design, the findings are a first indication that human pregnancy might be accompanied by structural brain changes in navigation-related neural systems and concomitant changes in navigation strategy.

Previously, benzthiazole containing LTA4H inhibitors were discovered that were potent (1–3), but were associated with the potential for a hERG liability. Utilizing medicinal chemistry first principles (e.g., introducing rigidity, lowering c Log D) a new benzthiazole series was designed, congeners of 1–3, which led to compounds 7a, 7c, 12a–d which exhibited LTA4H IC50 = 3–6 nM and hERG Dofetilide Binding IC50 = 8.9–> >10 μM.

Background The prevalence of generalized transit delay and relation to symptoms in suspected gastroparesis, intestinal dysmotility, or slow transit constipation are unknown. Aims The aims of this study were (1) to define prevalence of generalized dysmotility using wireless motility capsules (WMC), (2) to relate to symptoms in suspected regional delay, (3) to compare results of WMC testing to conventional transit studies to quantify new diagnoses, and (4) to assess the impact of results of WMC testing on clinical decisions. Methods WMC transits were analyzed in 83 patients with suspected gastroparesis, intestinal dysmotility, or slow transit constipation. Results Isolated regional delays were observed in 32% (9% stomach, 5% small bowel, 18% colon). Transits were normal in 32% and showed generalized delays in 35%. Symptom profiles were similar with normal transit, isolated delayed gastric, small intestinal, and colonic transit, and generalized delay (P = NS). Compared to conventional tests, WMC showed discordance in 38% and provided new diagnoses in 53%. WMC testing influenced management in 67% (new medications 60%; modified nutritional regimens 14%; surgical referrals 6%) and eliminated needs for testing not already done including gastric scintigraphy (17%), small bowel barium transit (54%), and radioopaque colon marker tests (68%). Conclusions WMC testing defines localized and generalized transit delays with suspected gastroparesis, intestinal dysmotility, or slow transit constipation. Symptoms do not predict the results of WMC testing. WMC findings provide new diagnoses in [50%, may be discordant with conventional tests, and can influence management by changing treatments and eliminating needs for other tests. These findings suggest potential benefits of this method in suspected dysmotility syndromes and mandate prospective investigation to further define its clinical role.

Phenomena that occur in microdroplets are described to the undergraduate chemistry community. Droplets having a diameter in the micrometer range can have unique and interesting properties, which arise because of their small size and, especially, their high surface area-to-volume ratio. Students are generally unfamiliar with the characteristics of small droplets. However, with the increasing importance of miniaturization in chemistry and biochemistry, especially in the burgeoning field of microdroplet microfluidics, it would be beneficial for students to become aware of some of the features that differentiate chemistry on a small scale. To better acquaint students with these features, microdroplet systems that model microfluidics in a “stop-action” manner are described. Using a micropipet manipulation technique combined with video microscopy, chemical reactions and physical phenomena that occur in one or more individual water droplets surrounded by an immiscible liquid are shown. Real-time visualizations of the unfolding chemical phenomena at the single, isolated droplet level are provided. The outcomes of various types of physical and chemical phenomena, including redox reactions, precipitation reaction, interfacial extraction of metals, solubility of water in oils, and crystallization are illustrated. Each system is understood as a dramatic exploitation of the small size of microdroplets having a large surface area-to-volume ratio.

Path integration is a fundamental mechanism of spatial navigation. In non-human species, it is assumed to be an online process in which a homing vector is updated continuously during an outward journey. In contrast, human path integration has been conceptualized as a configural process in which travelers store working memory representations of path segments, with the computation of a homing vector only occurring when required. To resolve this apparent discrepancy, we tested whether humans can employ different path integration strategies in the same task. Using a triangle completion paradigm, participants were instructed either to continuously update the start position during locomotion (continuous strategy) or to remember the shape of the outbound path and to calculate home vectors on basis of this representation (configural strategy). While overall homing accuracy was superior in the configural condition, participants were quicker to respond during continuous updating, strongly suggesting that homing vectors were computed online. Corroborating these findings, we observed reliable differences in head orientation during the outbound path: when participants applied the continuous updating strategy, the head deviated significantly from straight ahead in direction of the start place, which can be interpreted as a continuous motor expression of the homing vector. Head orientation-a novel online measure for path integration-can thus inform about the underlying updating mechanism already during locomotion. In addition to demonstrating that humans can employ different cognitive strategies during path integration, our two-systems view helps to resolve recent controversies regarding the role of the medial temporal lobe in human path integration.

Despite the increased expansion into areas away from floodplains and the resulting increase in experimental timber tree management by small landholders, basic ecological knowledge about managing native tree species in secondary forests on terra firme sites in the Amazon basin is sparse. I examine the use of stand thinning as a technique for aiding the active reintroduction of a diverse assemblage of native tree species in a young successional forest on a terra firme plateau in northeastern Peru. I monitored the growth and survivorship of 17 native tree species across an experimental canopy gradient that I created by implementing seven 144 m2 replicates of each of four levels of stand thinning treatments (no trees removed, 60% of the stand basal area removed, 80% of the stand basal area removed, and 100% of the stand basal area removed). Seedlings were established from seeds in four seedling beds within each treatment replicate. The plants were monitered monthly for 13 months and then at 6 and 10 years fol...

Three of the most common methods to analyze sorption isotherms with respect to micropore volume and specific surface, respectively, are the Brunauer–Emmett–Teller (BET) theory, established for the specific surface area of meso- and macroporous materials, the t-plot-method, which separates micropore from multilayer adsorption and the micropore analysis based on the work of Dubinin and Radushkevich (DR). While BET-analysis is assumed to be sensitive to multilayer adsorption on the external surface area, the DR-method is expected to be in particular sensitive to the micropores. However, the data for a series of synthetic carbons investigated reveal that the values derived by both methods are equivalent, despite the different underlying assumptions.

We introduce Scaffold Explorer, an interactive tool that allows medicinal chemists to define hierarchies of chemical scaffolds and use them to explore their project data. Scaffold Explorer allows the user to construct a tree, where each node corresponds to a specific scaffold. Each node can have multiple children, each of which represents a more refined substructure relative to its parent node. Once the tree is defined, it can be mapped onto any collection of compounds and be used as a navigational tool to explore structure-activity relationships (SAR) across different chemotypes. The rich visual analytics of Scaffold Explorer afford the user a "bird's-eye" view of the chemical space spanned by a particular data set, map any physicochemical property or biological activity of interest onto the individual scaffold nodes, serve as an aggregator for the properties of the compounds represented by these nodes, and quickly distinguish promising chemotypes from less interesting or problematic ones. Unlike previous approaches, which focused on automated extraction and classification of scaffolds, the utility of the new tool rests on its interactivity and ability to accommodate the medicinal chemists' intuition by allowing the use of arbitrary substructures containing variable atoms, bonds, and/or substituents such as those employed in substructure search.

Cathepsin S has been of increasing interest as a target of medicinal chemistry efforts given its role in modulating antigen-presentation by major histocompatibility class II (MHC II) molecules as well as its involvement in extracellular proteolytic activities. Inhibition of the cathepsin S enzyme reduces degradation of the invariant chain, a crucial chaperon which also blocks peptide-binding by MHC II molecules, thereby decreasing antigen presentation to CD4(+) T-cells. Extracellular cathepsin S may also be involved in angiogenesis and initiation and/or maintenance of neuropathic pain by cleavage of the membrane-bound chemokine fractalkine (CX3CL1). Cathepsin S inhibitors have thus been suggested to hold potential as therapeutics for a variety of diseases. The initial development of cathepsin S inhibitors targeted irreversible, covalent inhibitors, but more recently the focus has been on reversible inhibitors, representing both covalent modifiers of the enzyme and, of late, noncovalent inhibitors. This review details advances in cathepsin S inhibitor design as reported in the primary literature since 2006, focusing especially on structure-activity relationships of the various covalent and noncovalent inhibitor series.