Exogenous Visual Orienting Is Associated with Specific Neurotransmitter Genetic Markers: A Population-Based Genetic Association Study

Background: Currently, there is a sense that the spatial orienting of attention is related to genotypic variations in cholinergic genes but not to variations in dopaminergic genes. However, reexamination of associations with both cholinergic and dopaminergic genes is warranted because previous studies used endogenous rather than exogenous cues and costs and benefits were not analyzed separately. Examining costs (increases in response time following an invalid precue) and benefits (decreases in response time following a valid pre-cue) separately could be important if dopaminergic genes (implicated in disorders such as attention deficit disorder) independently influence the different processes of orienting (e.g., disengage, move, engage). Methodology/Principal Findings: We tested normal subjects (N = 161) between 18 and 61 years. Participants completed a computer task in which pre-cues preceded the presence of a target. Subjects responded (with a key press) to the location of the target (right versus left of fixation). The cues could be valid (i.e., appear where the target would appear) or invalid (appear contralateral to where the target would appear). DNA sequencing assays were performed on buccal cells to genotype known genetic markers and these were examined for association with task scores. Here we show significant associations between visual orienting and genetic markers (on COMT, DAT1, and APOE; R 2 s from 4 % to 9%). Conclusions/Significance: One measure in particular – the response time cost of a single dim, invalid cue – was associate

Open Babel: An open chemical toolbox

Background: A frequent problem in computational modeling is the interconversion of chemical structures between different formats. While standard interchange formats exist (for example, Chemical Markup Language) and de facto standards have arisen (for example, SMILES format), the need to interconvert formats is a continuing problem due to the multitude of different application areas for chemistry data, differences in the data stored by different formats (0D versus 3D, for example), and competition between software along with a lack of vendorneutral formats. Results: We discuss, for the first time, Open Babel, an open-source chemical toolbox that speaks the many languages of chemical data. Open Babel version 2.3 interconverts over 110 formats. The need to represent such a wide variety of chemical and molecular data requires a library that implements a wide range of cheminformatics algorithms, from partial charge assignment and aromaticity detection, to bond order perception and canonicalization. We detail the implementation of Open Babel, describe key advances in the 2.3 release, and outline a variety of uses both in terms of software products and scientific research, including applications far beyond simple format interconversion. Conclusions: Open Babel presents a solution to the proliferation of multiple chemical file formats. In addition, it provides a variety of useful utilities from conformer searching and 2D depiction, to filtering, batch conversion, and substructure and similarity searching. For developers, it can be used as a programming library to handle chemical data in areas such as organic chemistry, drug design, materials science, and computational chemistry. It is freely available under an open-source license fro

Balancing the immune response in the brain: IL-10 and its regulation

Background: The inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental to the host. A growing body of evidence places non-resolved inflammation at the core of various pathologies, from cancer to neurodegenerative diseases. It is therefore not surprising that the immune system has evolved several regulatory mechanisms to achieve maximum protection in the absence of pathology. Main body: The production of the anti-inflammatory cytokine interleukin (IL)-10 is one of the most important mechanisms evolved by many immune cells to counteract damage driven by excessive inflammation. Innate immune cells of the central nervous system, notably microglia, are no exception and produce IL-10 downstream of pattern recognition receptors activation. However, whereas the molecular mechanisms regulating IL-10 expression by innate and acquired immune cells of the periphery have been extensively addressed, our knowledge on the modulation of IL-10 expression by central nervous cells is much scattered. This review addresses the current understanding on the molecular mechanisms regulating IL-10 expression by innate immune cells of the brain and the implications of IL-10 modulation in neurodegenerative disorders. Conclusion: The regulation of IL-10 production by central nervous cells remains a challenging field. Answering the many remaining outstanding questions will contribute to the design of targeted approaches aiming at controlling deleterious inflammation in the brain.We acknowledge the Portuguese Foundation for Science and Technology (FCT) for providing a PhD grant to DLS (SFRH/BD/88081/2012) and a post-doctoral fellowship to SR (SFRH/BPD/72710/2010). DS, AGC and SR were funded by FEDER through the Competitiveness Factors Operational Programme (COMPETE) and National Funds through FCT under the scope of the project POCI-01-0145-FEDER007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The MS lab was financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT in the framework of the project “Institute for Research and Innovation in Health Sciences ” (POCI-01-0145-FEDER-007274). MS is a FCT Associate Investigator. The funding body had no role in the design of the study and collection, analysis, and interpretation of the data and in writing the manuscript

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Dispersion statistics and a sampling plan for Helicoverpa (Lepidoptera : Noctuidae) on fresh-market tomatoes (Lycopersicon esculentum)

Helicoverpa spp. is the primary pest in the Australian fresh-market tomato industry. We describe the spatial distribution of Helicoverpa spp. eggs on fresh-market tomato crops in the Goulburn Valley region of Victoria, and present a sequential sampling plan for monitoring population densities. The distribution of Helicoverpa spp. eggs was highly contagious, as indicated by a Taylor\u27s b-value of 1.59. This high level of contagion meant that relatively large sample sizes would need to be collected to obtain an estimate of population density. High-precision sampling plans generally necessitated impractical sample sizes, and thus the plan we present is a relatively low-precision level plan (SE/mean = 0.3). Nonetheless, this level of precision is considered adequate for most agronomic scenarios. The plan was validated using a statistical re-sampling approach. The level of precision achieved was generally close to the nominal level. Likewise, the number of samples collected generally showed little departure from the theoretically calculated minimum sample size.<br /

The effects of competition on medical service provision

We explore how competition between physicians affects medical service provision. Previous research has shown that, without competition, physicians deviate from patient-optimal treatment under payment systems like capitation and fee-for-service. While competition might reduce these distortions, physicians usually interact with each other repeatedly over time and only a fraction of patients switches providers at all. Both patterns might prevent competition to work in the desired direction. To analyze the behavioral effects of competition, we develop a theoretical benchmark which is then tested in a controlled laboratory experiment. Experimental conditions vary physician payment and patient characteristics. Real patients benefit from treatment decisions made in the experiment. Our results reveal that, in line with the theoretical prediction, introducing competition can reduce overprovision and underprovision, respectively. The observed effects depend on patient characteristics and the payment system, though. Tacit collusion is observed and particularly pronounced with fee-for-service payment, but it appears to be less frequent than in related experimental research on price competition.In der vorliegenden Studie untersuchen wir, wie sich Wettbewerb zwischen Ärzten auf deren Behandlungsentscheidungen auswirkt. Bisherige Forschungsergebnisse zeigen, dass ohne Wettbewerb die Behandlungsentscheidungen von Ärzten bei klassischen Vergütungssystemen wie der Einzelleistungsvergütung oder der Kopfpauschale von den patientenoptimalen Entscheidungen abweichen. Während diese Abweichungen grundsätzlich durch Wettbewerb reduziert werden könnten, ist davon auszugehen, dass Ärzte typischerweise wiederholt miteinander interagieren und dass nur ein Teil der Patienten den Arzt wechselt. Beides könnte die positiven Effekte des Wettbewerbs verringern. Um die Verhaltenswirkungen von Wettbewerb zu analysieren, entwickeln wir ein spieltheoretisches Modell, das wir mit Hilfe kontrollierter Laborexperimente testen. Die experimentellen Anordnungen variieren bezüglich der Arztvergütung und der Charakteristika der Patienten. Reale Patienten profitieren von den im Experiment getroffenen Behandlungsentscheidungen. Unsere Ergebnisse zeigen, dass Wettbewerb im Einklang mit der theoretischen Prognose Überbehandlung und Unterbehandlung reduzieren kann. Die beobachteten Effekte hängen jedoch von den Charakteristika der Patienten und der Arztvergütung ab. Wir finden auch stillschweigende Kollusion, insbesondere bei der Einzelleistungsvergütung. Diese tritt jedoch in geringerem Ausmaß auf als in vergleichbaren experimentellen Studien zum Preiswettbewerb