Effects of Lidocaine and Articaine on Neuronal Survival and Recovery

The local anesthetics lidocaine and articaine are among the most widely used drugs in the dentist’s arsenal, relieving pain by blocking voltage-dependent Naþ channels and thus preventing transmission of the pain signal. Given reports of infrequent but prolonged paresthesias with 4% articaine, we compared its neurotoxicity and functional impairment by screening cultured neural SH-SY5Y cells with formulations used in patients (2% lidocaine + 1:100,000 epinephrine or 4% articaine + 1:100,000 epinephrine) and with pure formulations of the drugs. Voltage-dependent sodium channels Na(v)1.2 and Na(v)1.7 were expressed in SH-SY5Y cells. To test the effects on viability, cells were exposed to drugs for 5 minutes, and after washing, cells were treated with the ratiometric Live/Dead assay. Articaine had no effect on the survival of SH-SY5Y cells, while lidocaine produced a significant reduction only when used as pure powder. To determine reversibility of blockage, wells were exposed to drugs for 5 minutes and returned for medium for 30 minutes, and the calcium elevation induced by depolarizing cells with a high-potassium solution was measured using the calcium indicator Fura-2. High potassium raised calcium in control SH-SY5Y cells and those treated with articaine, but lidocaine treatment significantly reduced the response. In conclusion, articaine does not damage neural cells more than lidocaine in this in vitro model. While this does not question the safety of lidocaine used clinically, it does suggest that articaine is no more neurotoxic, at least in the in vitro setting. © 2018 by the American Dental Society of Anesthesiology

Best practices for using drones in seabird monitoring and research

Over the past decade, drones have become increasingly popular in environmental biology and have been used to study wildlife on all continents. Drones have become of global importance for surveying breeding seabirds by providing opportunities to transform monitoring techniques and allow new research on some of the most threatened birds. However, such fast-changing and increasingly available technology presents challenges to regulators responding to requests to carry out surveys and to researchers ensuring their work follows best practice and meets legal and ethical standards. Following a workshop convened at the 14th International Seabird Group Conference and a subsequent literature search, we collate information from over 100 studies and present a framework to ensure drone-seabird surveys are safe, effective, and within the law. The framework comprises eight steps: (1) Objectives and Feasibility; (2) Technology and Training; (3) Site Assessment and Permission; (4) Disturbance Mitigation; (5) Pre-deployment Checks; (6) Flying; (7) Data Handling and Analysis; and (8) Reporting. The audience is wide-ranging with sections having relevance for different users, including prospective and experienced drone-seabird pilots, landowners, and licensors. Regulations vary between countries and are frequently changing, but common principles exist. Taking-off, landing, and conducting in-flight changes in altitude and speed at ≥ 50 m from the study area, and flying at ≥ 50 m above ground-nesting seabirds/horizontal distance from vertical colonies, should have limited disturbance impact on many seabird species; however, surveys should stop if disturbance occurs. Compared to automated methods, manual or semi-automated image analyses are, at present, more suitable for infrequent drone surveys and surveys of relatively small colonies. When deciding if drone-seabird surveys are an appropriate monitoring method long-term, the cost, risks, and results obtained should be compared to traditional field monitoring where possible. Accurate and timely reporting of surveys is essential to developing adaptive guidelines for this increasingly common technology

Best practices for using drones in seabird monitoring and research

Over the past decade, drones have become increasingly popular in environmental biology and have been used to study wildlife on all continents. Drones have become of global importance for surveying breeding seabirds by providing opportunities to transform monitoring techniques and allow new research on some of the most threatened birds. However, such fast-changing and increasingly available technology presents challenges to regulators responding to requests to carry out surveys and to researchers ensuring their work follows best practice and meets legal and ethical standards. Following a workshop convened at the 14th International Seabird Group Conference and a subsequent literature search, we collate information from over 100 studies and present a framework to ensure drone-seabird surveys are safe, effective, and within the law. The framework comprises eight steps: (1) Objectives and Feasibility; (2) Technology and Training; (3) Site Assessment and Permission; (4) Disturbance Mitigation; (5) Pre-deployment Checks; (6) Flying; (7) Data Handling and Analysis; and (8) Reporting. The audience is wide-ranging with sections having relevance for different users, including prospective and experienced drone-seabird pilots, landowners, and licensors. Regulations vary between countries and are frequently changing, but common principles exist. Taking-off, landing, and conducting in-flight changes in altitude and speed at ≥ 50 m from the study area, and flying at ≥ 50 m above ground-nesting seabirds/horizontal distance from vertical colonies, should have limited disturbance impact on many seabird species; however, surveys should stop if disturbance occurs. Compared to automated methods, manual or semi-automated image analyses are, at present, more suitable for infrequent drone surveys and surveys of relatively small colonies. When deciding if drone-seabird surveys are an appropriate monitoring method long-term, the cost, risks, and results obtained should be compared to traditional field monitoring where possible. Accurate and timely reporting of surveys is essential to developing adaptive guidelines for this increasingly common technology

The genomic landscape of juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 and CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and therefore be candidates for experimental therapies. In addition, there have been few other molecular pathways identified aside from the Ras/MAPK pathway to serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia in order to expand our knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, gene splicing, the polycomb repressive complex 2 (PRC2) and transcription. Importantly, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome

Increased food production and reduced water use through optimized crop distribution

Growing demand for agricultural commodities for food, fuel and other uses is expected to be met through an intensification of production on lands that are currently under cultivation. Intensification typically entails investments in modern technology - such as irrigation or fertilizers - and increases in cropping frequency in regions suitable for multiple growing seasons. Here we combine a process-based crop water model with maps of spatially interpolated yields for 14 major food crops to identify potential differences in food production and water use between current and optimized crop distributions. We find that the current distribution of crops around the world neither attains maximum production nor minimum water use. We identify possible alternative configurations of the agricultural landscape that, by reshaping the global distribution of crops within current rainfed and irrigated croplands based on total water consumption, would feed an additional 825 million people while reducing the consumptive use of rainwater and irrigation water by 14% and 12%, respectively. Such an optimization process does not entail a loss of crop diversity, cropland expansion or impacts on nutrient and feed availability. It also does not necessarily invoke massive investments in modern technology that in many regions would require a switch from smallholder farming to large-scale commercial agriculture with important impacts on rural livelihoods

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe