Assessing the impact of typeface design in a text-rich automotive user interface

Text-rich driver–vehicle interfaces are increasingly common in new vehicles, yet the effects of different typeface characteristics on task performance in this brief off-road based glance context remains sparsely examined. Subjects completed menu selection tasks while in a driving simulator. Menu text was set either in a ‘humanist’ or ‘square grotesque’ typeface. Among men, use of the humanist typeface resulted in a 10.6% reduction in total glance time as compared to the square grotesque typeface. Total response time and number of glances showed similar reductions. The impact of typeface was either more modest or not apparent for women. Error rates for both males and females were 3.1% lower for the humanist typeface. This research suggests that optimised typefaces may mitigate some interface demands. Future work will need to assess whether other typeface characteristics can be optimised to further reduce demand, improve legibility, increase usability and help meet new governmental distraction guidelines

Malaria has no effect on birth weight in Rwanda

<p>Abstract</p> <p>Background</p> <p>Malaria has a negative effect on pregnancy outcome, causing low birth weight, premature birth and stillbirths, particularly in areas with high malaria transmission. In Rwanda, malaria transmission intensity ranges from high to nil, probably associated with variable altitudes. Overall, the incidence decreased over the last six years (2002–2007). Therefore, the impact of malaria on birth outcomes is also expected to vary over time and space.</p> <p>Methods</p> <p>Obstetric indicators (birth weight and pregnancy outcome) and malaria incidence were compared and analyzed to their association over time (2002–2007) and space. Birth data from 12,526 deliveries were collected from maternity registers of 11 different primary health centers located in different malaria endemic areas. Malaria data for the same communities were collected from the National Malaria Control Programme. Associations were sought with mixed effects models and logistic regression.</p> <p>Results</p> <p>In all health centres, a significant increase of birth weight over the years was observed (p < 0.001) with a significant seasonal fluctuation. Malaria incidence had no significant effect on birth weight. There was a slight but significant decreasing effect of malaria incidence on the occurrence of premature delivery (p-value 0.045) and still birth (p-value 0.009). Altitude showed a slight but significant negative correlation with birth weight. Overall, a decrease over the years of premature delivery (p = 0.010) and still birth (p = 0.036) was observed.</p> <p>Conclusion</p> <p>In Rwanda, birth weight and pregnancy outcome are not directly influenced by malaria, which is in contrast to many other studied areas. Although malaria incidence overall has declined and mean birth weight increased over the studied period, no direct association was found between the two. Socio-economic factors and improved nutrition could be responsible for birth weight changes in recent years.</p

Substantial Contribution of Submicroscopical Plasmodium falciparum Gametocyte Carriage to the Infectious Reservoir in an Area of Seasonal Transmission

BACKGROUND: Man to mosquito transmission of malaria depends on the presence of the sexual stage parasites, gametocytes, that often circulate at low densities. Gametocyte densities below the microscopical threshold of detection may be sufficient to infect mosquitoes but the importance of submicroscopical gametocyte carriage in different transmission settings is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Membrane feeding experiments were carried out on 80 children below 14 years of age at the end of the wet season in an area of seasonal malaria transmission in Burkina Faso. Gametocytes were quantified by microscopy and by Pfs25-based quantitative nucleic acid sequence-based amplification assay (QT-NASBA). The children's infectiousness was determined by membrane feeding experiments in which a venous blood sample was offered to locally reared Anopheles mosquitoes. Gametocytes were detected in 30.0% (24/80) of the children by microscopy compared to 91.6% (65/71) by QT-NASBA (p<0.001). We observed a strong association between QT-NASBA gametocyte density and infection rates (p = 0.007). Children with microscopically detectable gametocytes were more likely to be infectious (68.2% compared to 31.7% of carriers of submicroscopical gametocytes, p = 0.001), and on average infected more mosquitoes (13.2% compared to 2.3%, p<0.001). However, because of the high prevalence of submicroscopical gametocyte carriage in the study population, carriers of sub-microscopical gametocytes were responsible for 24.2% of the malaria transmission in this population. CONCLUSIONS/SIGNIFICANCE: Submicroscopical gametocyte carriage is common in an area of seasonal transmission in Burkina Faso and contributes substantially to the human infectious reservoir. Submicroscopical gametocyte carriage should therefore be considered when implementing interventions that aim to reduce malaria transmission

An epigenetic blockade of cognitive functions in the neurodegenerating brain

Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer’s disease [superscript 1]. The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge [superscript 2]. Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer’s-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer’s disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade.Stanley Medical Research InstituteNational Institute of Neurological Disorders and Stroke (U.S.) (RO1NS078839)Swiss National Science FoundationBard Richmond (Fellowship)Simons FoundationTheodor und Ida Herzog-Egli Foundatio

Crebinostat: A novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity

Long-term memory formation is known to be critically dependent upon de novo gene expression in the brain. As a consequence, pharmacological enhancement of the transcriptional processes mediating long-term memory formation provides a potential therapeutic strategy for cognitive disorders involving aberrant neuroplasticity. Here we focus on the identification and characterization of small molecule inhibitors of histone deacetylases (HDACs) as enhancers of CREB (cAMP response element-binding protein)-regulated transcription and modulators of chromatin-mediated neuroplasticity. Using a CREB reporter gene cell line, we screened a library of small molecules structurally related to known HDAC inhibitors leading to the identification of a probe we termed crebinostat that produced robust activation of CREB-mediated transcription. Further characterization of crebinostat revealed its potent inhibition of the deacetylase activity of recombinant class I HDACs 1, 2, 3, and class IIb HDAC6, with weaker inhibition of the class I HDAC8 and no significant inhibition of the class IIa HDACs 4, 5, 7, and 9. In cultured mouse primary neurons, crebinostat potently induced acetylation of both histone H3 and histone H4 as well as enhanced the expression of the CREB target gene Egr1 (early growth response 1). Using a hippocampus-dependent, contextual fear conditioning paradigm, mice systemically administered crebinostat for a ten day time period exhibited enhanced memory. To gain insight into the molecular mechanisms of memory enhancement by HDAC inhibitors, whole genome transcriptome profiling of cultured mouse primary neurons treated with crebinostat, combined with bioinformatic analyses of CREB-target genes, was performed revealing a highly connected protein–protein interaction network reflecting modules of genes important to synaptic structure and plasticity. Consistent with these findings, crebinostat treatment increased the density of synapsin-1 punctae along dendrites in cultured neurons. Finally, crebinostat treatment of cultured mouse primary neurons was found to upregulate Bdnf (brain-derived neurotrophic factor) and Grn (granulin) and downregulate Mapt (tau) gene expression—genes implicated in aging-related cognitive decline and cognitive disorders. Taken together, these results demonstrate that crebinostat provides a novel probe to modulate chromatin-mediated neuroplasticity and further suggests that pharmacological optimization of selective of HDAC inhibitors may provide an effective therapeutic approach for human cognitive disorders.National Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01NS051874)Stanley Medical Research InstituteHoward Hughes Medical Institut

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm&lt; 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

Mood is a key determinant of cognitive performance in community-dwelling older adults: a cross-sectional analysis

First Online: 06 October 2012Identification of predictors of cognitive trajectories through the establishment of composite or single-parameter dimensional categories of cognition and mood may facilitate development of strategies to improve quality of life in the elderly. Participants (n = 487, aged 50+ years) were representative of the Portuguese population in terms of age, gender, and educational status. Cognitive and mood profiles were established using a battery of neurocognitive and psychological tests. Data were subjected to principal component analysis to identify core dimensions of cognition and mood, encompassing multiple test variables. Dimensions were correlated with age and with respect to gender, education, and occupational status. Cluster analysis was applied to isolate distinct patterns of cognitive performance and binary logistic regression models to explore interrelationships between aging, cognition, mood, and socio-demographic characteristics. Four main dimensions were identified: memory, executive function, global cognitive status, and mood. Based on these, strong and weak cognitive performers were distinguishable. Cluster analysis revealed further distinction within these two main categories into very good, good, poor, and very poor performers. Mood was the principal factor contributing to the separation between very good and good, as well as poor and very poor, performers. Clustering was also influenced by gender and education, albeit to a lesser extent; notably, however, female gender × lower educational background predicted significantly poorer cognitive performance with increasing age. Mood has a significant impact on the rate of cognitive decline in the elderly. Gender and educational level are early determinants of cognitive performance in later life.This work was funded by the European Commission (FP7) “SwitchBox” (Contract HEALTH-F2-2010-259772). NCS is supported by a SwitchBox post-doctoral fellowship. We are thankful to all study participants. The authors would like to acknowledge all colleagues who assisted with participant recruitment and evaluation

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Southern Ocean Action Plan (2021-2030) in support of the United Nations Decade of Ocean Science for Sustainable Development

In 2017, the United Nations proclaimed a Decade of Ocean Science for Sustainable Development (hereafter referred to as the UN Ocean Decade) from 2021 until 2030 to support efforts to reverse the cycle of decline in ocean health. To achieve this ambitious goal, this initiative aims to gather ocean stakeholders worldwide behind a common framework that will ensure ocean science can fully support countries in creating improved conditions for sustainable development of the world’s oceans. The initiative strives to strengthen the international cooperation needed to develop the scientific research and innovative technologies that can connect ocean science with the needs of society at the global scale. Based on the recommendations in the Implementation Plan of the United Nations Decade of Ocean Science for Sustainable Development (Version 2.0, July 2021), the Southern Ocean community engaged in a stakeholder - oriented process to develop the Southern Ocean Action Plan. The Southern Ocean process engaged a broad community, which includes the scientific research community, the business and industry sector, and governance and management bodies. As part of this global effort, the Southern Ocean Task Force identified the needs of the Southern Ocean community to address the challenges related to the unique environmental characteristics and governance structure of the Southern Ocean. Through this community-driven process, we identified synergies within the Southern Ocean community and beyond in order to elaborate an Action Plan that provides a framework for Southern Ocean stakeholders to formulate and develop tangible actions and deliverables that support the UN Ocean Decade vision. Through the publication of this Action Plan, the Southern Ocean Task Force aims to mobilise the Southern Ocean community and inspire all stakeholders to seek engagement and leverage opportunities to deliver innovative solutions that maintain and foster the unique conditions of the Southern Ocean. This framework provides an initial roadmap to strengthen links between science, industry and policy, as well as to encourage internationally collaborative activities in order to address existing gaps in our knowledge and data coverage