Geospatial big data and cartography : research challenges and opportunities for making maps that matter

Geospatial big data present a new set of challenges and opportunities for cartographic researchers in technical, methodological, and artistic realms. New computational and technical paradigms for cartography are accompanying the rise of geospatial big data. Additionally, the art and science of cartography needs to focus its contemporary efforts on work that connects to outside disciplines and is grounded in problems that are important to humankind and its sustainability. Following the development of position papers and a collaborative workshop to craft consensus around key topics, this article presents a new cartographic research agenda focused on making maps that matter using geospatial big data. This agenda provides both long-term challenges that require significant attention as well as short-term opportunities that we believe could be addressed in more concentrated studies.PostprintPeer reviewe

Perilipin 2 (PLIN2)-Deficiency Does Not Increase Cholesterol-Induced Toxicity in Macrophages

Interventions on macrophages/foam cells to redirect intracellular cholesterol towards efflux pathways could become a very valuable addition to our therapeutic arsenal against atherosclerosis. However, certain manipulations of the cholesteryl ester cycle, such as the inhibition of ACAT1, an ER-resident enzyme that re-esterifies cholesterol, are not well tolerated. Previously we showed that targeting perilipin-2 (PLIN2), a major lipid droplet (LD)-associated protein in macrophages, prevents foam cell formation and protects against atherosclerosis. Here we have assessed the tolerance of PLIN2-deficient bone marrow derived macrophages (BMM) to several lipid loading conditions similar to the found during atherosclerosis development, including exposure to modified low-density lipoprotein (mLDL) and 7-ketocholesterol (7-KC), a free cholesterol (FC) metabolite, in media with or without cholesterol acceptors. BMM isolated from mice that do or do not express PLIN2 were tested for apoptosis (TUNEL and cleaved caspase-3), ER stress (CHOP induction and XBP-1 splicing), and inflammation (TNF-α and IL-6 mRNA levels). Like in other cell types, PLIN2 deficiency impairs LD buildup in BMM. However, while most stress parameters were elevated in macrophages under ACAT inhibition and 7-KC loading, PLIN2 inactivation was well tolerated. The data support the safety of targeting PLIN2 to prevent foam cell formation and atherosclerosis

Manipulation of Pre-Target Activity on the Right Frontal Eye Field Enhances Conscious Visual Perception in Humans

The right Frontal Eye Field (FEF) is a region of the human brain, which has been consistently involved in visuo-spatial attention and access to consciousness. Nonetheless, the extent of this cortical site’s ability to influence specific aspects of visual performance remains debated. We hereby manipulated pre-target activity on the right FEF and explored its influence on the detection and categorization of low-contrast near-threshold visual stimuli. Our data show that pre-target frontal neurostimulation has the potential when used alone to induce enhancements of conscious visual detection. More interestingly, when FEF stimulation was combined with visuo-spatial cues, improvements remained present only for trials in which the cue correctly predicted the location of the subsequent target. Our data provide evidence for the causal role of the right FEF pre-target activity in the modulation of human conscious vision and reveal the dependence of such neurostimulatory effects on the state of activity set up by cue validity in the dorsal attentional orienting network

Frontal Non-Invasive Neurostimulation Modulates Antisaccade Preparation in Non-Human Primates

A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes

Does clinical examination aid in the diagnosis of urinary tract infections in women? A systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Clinicians should be aware of the diagnostic values of various symptoms, signs and antecedents. This information is particularly important in primary care settings, where sophisticated diagnostic approaches are not always feasible. The aim of the study is to determine the probability that various symptoms, signs, antecedents and tests predict urinary tract infection (UTI) in women.</p> <p>Methods</p> <p>We conducted a systematic search of the MEDLINE and EMBASE databases to identify articles published in all languages through until December 2008. We particularly focused on studies that examined the diagnostic accuracy of at least one symptom, sign or patient antecedent related to the urinary tract. We included studies where urine culture, a gold standard, was preformed by primary care providers on female subjects aged at least 14 years. A meta-analysis of the likelihood ratio was performed to assess variables related to the urinary tract symptoms.</p> <p>Results</p> <p>Of the 1, 212 articles identified, 11 met the selection criteria. Dysuria, urgency, nocturia, sexual activity and urgency with dysuria were weak predictors of urinary tract infection, whereas increases in vaginal discharge and suprapubic pain were weak predictors of the absence of infection. Nitrites or leukocytes in the dipstick test are the only findings that clearly favored a diagnosis of UTI.</p> <p>Conclusions</p> <p>Clinical findings do not aid in the diagnosis of UTI among women who present with urinary symptoms. Vaginal discharge is a weak indicator of the absence of infection. The urine dipstick test was the most reliable tool for detecting UTI.</p

Muscle Dystroglycan Organizes the Postsynapse and Regulates Presynaptic Neurotransmitter Release at the Drosophila Neuromuscular Junction

International audienceBACKGROUND: The Dystrophin-glycoprotein complex (DGC) comprises dystrophin, dystroglycan, sarcoglycan, dystrobrevin and syntrophin subunits. In muscle fibers, it is thought to provide an essential mechanical link between the intracellular cytoskeleton and the extracellular matrix and to protect the sarcolemma during muscle contraction. Mutations affecting the DGC cause muscular dystrophies. Most members of the DGC are also concentrated at the neuromuscular junction (NMJ), where their deficiency is often associated with NMJ structural defects. Hence, synaptic dysfunction may also intervene in the pathology of dystrophic muscles. Dystroglycan is a central component of the DGC because it establishes a link between the extracellular matrix and Dystrophin. In this study, we focused on the synaptic role of Dystroglycan (Dg) in Drosophila. METHODOLOGY/PRINCIPAL FINDINGS: We show that Dg was concentrated postsynaptically at the glutamatergic NMJ, where, like in vertebrates, it controls the concentration of synaptic Laminin and Dystrophin homologues. We also found that synaptic Dg controlled the amount of postsynaptic 4.1 protein Coracle and alpha-Spectrin, as well as the relative subunit composition of glutamate receptors. In addition, both Dystrophin and Coracle were required for normal Dg concentration at the synapse. In electrophysiological recordings, loss of postsynaptic Dg did not affect postsynaptic response, but, surprisingly, led to a decrease in glutamate release from the presynaptic site. CONCLUSION/SIGNIFICANCE: Altogether, our study illustrates a conservation of DGC composition and interactions between Drosophila and vertebrates at the synapse, highlights new proteins associated with this complex and suggests an unsuspected trans-synaptic function of Dg

Contrasting Responses to Harvesting and Environmental Drivers of Fast and Slow Life History Species

According to their main life history traits, organisms can be arranged in a continuum from fast (species with small body size, short lifespan and high fecundity) to slow (species with opposite characteristics). Life history determines the responses of organisms to natural and anthropogenic factors, as slow species are expected to be more sensitive than fast species to perturbations. Owing to their contrasting traits, cephalopods and elasmobranchs are typical examples of fast and slow strategies, respectively. We investigated the responses of these two contrasting strategies to fishing exploitation and environmental conditions (temperature, productivity and depth) using generalized additive models. Our results confirmed the foreseen contrasting responses of cephalopods and elasmobranchs to natural (environment) and anthropogenic (harvesting) influences. Even though a priori foreseen, we did expect neither the clear-cut differential responses between groups nor the homogeneous sensitivity to the same factors within the two taxonomic groups. Apart from depth, which affected both groups equally, cephalopods and elasmobranchs were exclusively affected by environmental conditions and fishing exploitation, respectively. Owing to its short, annual cycle, cephalopods do not have overlapping generations and consequently lack the buffering effects conferred by different age classes observed in multi-aged species such as elasmobranchs. We suggest that cephalopods are sensitive to short-term perturbations, such as seasonal environmental changes, because they lack this buffering effect but they are in turn not influenced by continuous, long-term moderate disturbances such as fishing because of its high population growth and turnover. The contrary would apply to elasmobranchs, whose multi-aged population structure would buffer the seasonal environmental effects, but they would display strong responses to uninterrupted harvesting due to its low population resilience. Besides providing empirical evidence to the theoretically predicted contrasting responses of cephalopods and elasmobranchs to disturbances, our results are useful for the sustainable exploitation of these resourcesVersión del editor4,411

Large-Scale Pathway-Based Analysis of Bladder Cancer Genome-Wide Association Data from Five Studies of European Background

Pathway analysis of genome-wide association studies (GWAS) offer a unique opportunity to collectively evaluate genetic variants with effects that are too small to be detected individually. We applied a pathway analysis to a bladder cancer GWAS containing data from 3,532 cases and 5,120 controls of European background (n = 5 studies). Thirteen hundred and ninety-nine pathways were drawn from five publicly available resources (Biocarta, Kegg, NCI-PID, HumanCyc, and Reactome), and we constructed 22 additional candidate pathways previously hypothesized to be related to bladder cancer. In total, 1421 pathways, 5647 genes and ∼90,000 SNPs were included in our study. Logistic regression model adjusting for age, sex, study, DNA source, and smoking status was used to assess the marginal trend effect of SNPs on bladder cancer risk. Two complementary pathway-based methods (gene-set enrichment analysis [GSEA], and adapted rank-truncated product [ARTP]) were used to assess the enrichment of association signals within each pathway. Eighteen pathways were detected by either GSEA or ARTP at P≤0.01. To minimize false positives, we used the I2 statistic to identify SNPs displaying heterogeneous effects across the five studies. After removing these SNPs, seven pathways (‘Aromatic amine metabolism’ [PGSEA = 0.0100, PARTP = 0.0020], ‘NAD biosynthesis’ [PGSEA = 0.0018, PARTP = 0.0086], ‘NAD salvage’ [PARTP = 0.0068], ‘Clathrin derived vesicle budding’ [PARTP = 0.0018], ‘Lysosome vesicle biogenesis’ [PGSEA = 0.0023, PARTP<0.00012], ’Retrograde neurotrophin signaling’ [PGSEA = 0.00840], and ‘Mitotic metaphase/anaphase transition’ [PGSEA = 0.0040]) remained. These pathways seem to belong to three fundamental cellular processes (metabolic detoxification, mitosis, and clathrin-mediated vesicles). Identification of the aromatic amine metabolism pathway provides support for the ability of this approach to identify pathways with established relevance to bladder carcinogenesis