It’s all about time : Precision and accuracy of Emotiv event-marking for ERPD research

Background The use of consumer-grade electroencephalography (EEG) systems for research purposes has become more prevalent. In event-related potential (ERP) research, it is critical that these systems have precise and accurate timing. The aim of the current study was to investigate the timing reliability of event-marking solutions used with Emotiv commercial EEG systems. Method We conducted three experiments. In Experiment 1 we established a jitter threshold (i.e. the point at which jitter made an event-marking method unreliable). To do this, we introduced statistical noise to the temporal position of event-marks of a pre-existing ERP dataset (recorded with a research-grade system, Neuroscan SynAmps2 at 1,000 Hz using parallel-port event-marking) and calculated the level at which the waveform peaks differed statistically from the original waveform. In Experiment 2 we established a method to identify ‘true’ events (i.e. when an event should appear in the EEG data). We did this by inserting 1,000 events into Neuroscan data using a custom-built event-marking system, the ‘Airmarker’, which marks events by triggering voltage spikes in two EEG channels. We used the lag between Airmarker events and events generated by Neuroscan as a reference for comparisons in Experiment 3. In Experiment 3 we measured the precision and accuracy of three types of Emotiv event-marking by generating 1,000 events, 1 s apart. We measured precision as the variability (standard deviation in ms) of Emotiv events and accuracy as the mean difference between Emotiv events and true events. The three triggering methods we tested were: (1) Parallel-port-generated TTL triggers; (2) Arduino-generated TTL triggers; and (3) Serial-port triggers. In Methods 1 and 2 we used an auxiliary device, Emotiv Extender, to incorporate triggers into the EEG data. We tested these event-marking methods across three configurations of Emotiv EEG systems: (1) Emotiv EPOC+ sampling at 128 Hz; (2) Emotiv EPOC+ sampling at 256 Hz; and (3) Emotiv EPOC Flex sampling at 128 Hz. Results In Experiment 1 we found that the smaller P1 and N1 peaks were attenuated at lower levels of jitter relative to the larger P2 peak (21 ms, 16 ms, and 45 ms for P1, N1, and P2, respectively). In Experiment 2, we found an average lag of 30.96 ms for Airmarker events relative to Neuroscan events. In Experiment 3, we found some lag in all configurations. However, all configurations exhibited precision of less than a single sample, with serial-port-marking the most precise when paired with EPOC+ sampling at 256 Hz. Conclusion All Emotiv event-marking methods and configurations that we tested were precise enough for ERP research as the precision of each method would provide ERP waveforms statistically equivalent to a research-standard system. Though all systems exhibited some level of inaccuracy, researchers could easily account for these during data processing

Case study: auditory brain responses in a minimally verbal child with autism and cerebral palsy

An estimated 30% of individuals with autism spectrum disorders (ASD) remain minimally verbal into late childhood, but research on cognition and brain function in ASD focuses almost exclusively on those with good or only moderately impaired language. Here we present a case study investigating auditory processing of GM, a nonverbal child with ASD and cerebral palsy. At the age of 8 years, GM was tested using magnetoencephalography (MEG) whilst passively listening to speech sounds and complex tones. Where typically developing children and verbal autistic children all demonstrated similar brain responses to speech and nonspeech sounds, GM produced much stronger responses to nonspeech than speech, particularly in the 65–165 ms (M50/M100) time window post-stimulus onset. GM was retested aged 10 years using electroencephalography (EEG) whilst passively listening to pure tone stimuli. Consistent with her MEG response to complex tones, GM showed an unusually early and strong response to pure tones in her EEG responses. The consistency of the MEG and EEG data in this single case study demonstrate both the potential and the feasibility of these methods in the study of minimally verbal children with ASD. Further research is required to determine whether GM's atypical auditory responses are characteristic of other minimally verbal children with ASD or of other individuals with cerebral palsy

Self-concept in poor readers : A systematic review and meta-analysis

Background The aims of this systematic review and meta-analyses were to determine if there is a statistically reliable association between poor reading and poor self-concept, and if such an association is moderated by domain of self-concept, type of reading impairment, or contextual factors including age, gender, reading instruction, and school environment. Methodology We searched 10 key databases for published and unpublished studies, as well as reference lists of included studies, and studies that cited included studies. We calculated standardised mean differences (SMDs) and 95% confidence intervals for one primary outcome (average self-concept) and 10 secondary outcomes (10 domains of self-concept). We assessed the data for risk of bias, heterogeneity, sensitivity, reporting bias, and quality of evidence. Results Thirteen studies with 3,348 participants met our selection criteria. Meta-analyses revealed statistically significant SMDs for average self-concept (−0.57) and five domains of self-concept (reading/writing/spelling: −1.03; academic: −0.67; math: −0.64; behaviour: −0.32; physical appearance: −0.28). The quality of evidence for the primary outcome was moderate, and for secondary outcomes was low, due to lack of data. Conclusions These outcomes suggest a probable moderate association between poor reading and average self-concept; a possible strong association between poor reading and reading-writing-spelling self-concept; and possible moderate associations between poor reading and self-concept in the self-concept domains of academia, mathematics, behaviour, and physical appearance

The Lick AGN Monitoring Project: Reverberation Mapping of Optical Hydrogen and Helium Recombination Lines

We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range ~10^6-10^7M_sun and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in the broad Hbeta emission, which we have previously reported. We present here the light curves for the Halpha, Hgamma, HeII 4686, and HeI 5876 emission lines and the time lags for the emission-line responses relative to changes in the continuum flux. Combining each emission-line time lag with the measured width of the line in the variable part of the spectrum, we determine a virial mass of the central supermassive black hole from several independent emission lines. We find that the masses are generally consistent within the uncertainties. The time-lag response as a function of velocity across the Balmer line profiles is examined for six of the AGNs. Finally we compare several trends seen in the dataset against the predictions from photoionization calculations as presented by Korista & Goad. We confirm several of their predictions, including an increase in responsivity and a decrease in the mean time lag as the excitation and ionization level for the species increases. Further confirmation of photoionization predictions for broad-line gas behavior will require additional monitoring programs for these AGNs while they are in different luminosity states. [abridged]Comment: 37 pages, 18 figures and 15 tables, accepted for publication in the Astrophysical Journa

Discovery of potent and selective MRCK inhibitors with therapeutic effect on skin cancer

The myotonic dystrophy-related Cdc42-binding kinases MRCKα and MRCKβ contribute to the regulation of actin-myosin cytoskeleton organization and dynamics, acting in concert with the Rho-associated coiled-coil kinases ROCK1 and ROCK2. The absence of highly potent and selective MRCK inhibitors has resulted in relatively little knowledge of the potential roles of these kinases in cancer. Here we report the discovery of the azaindole compounds BDP8900 and BDP9066 as potent and selective MRCK inhibitors that reduce substrate phosphorylation, leading to morphological changes in cancer cells along with inhibition of their motility and invasive character. In over 750 human cancer cell lines tested, BDP8900 and BDP9066 displayed consistent anti-proliferative effects with greatest activity in hematological cancer cells. Mass spectrometry identified MRCKα S1003 as an autophosphorylation site, enabling development of a phosphorylation-sensitive antibody tool to report on MRCKα status in tumor specimens. In a two-stage chemical carcinogenesis model of murine squamous cell carcinoma, topical treatments reduced MRCKα S1003 autophosphorylation and skin papilloma outgrowth. In parallel work, we validated a phospho-selective antibody with the capability to monitor drug pharmacodynamics. Taken together, our findings establish an important oncogenic role for MRCK in cancer, and they offer an initial preclinical proof of concept for MRCK inhibition as a valid therapeutic strategy

Clinical utilization of genomics data produced by the international Pseudomonas aeruginosa consortium

The International Pseudomonas aeruginosa Consortium is sequencing over 1000 genomes and building an analysis pipeline for the study of Pseudomonas genome evolution, antibiotic resistance and virulence genes. Metadata, including genomic and phenotypic data for each isolate of the collection, are available through the International Pseudomonas Consortium Database (http://ipcd.ibis.ulaval.ca/). Here, we present our strategy and the results that emerged from the analysis of the first 389 genomes. With as yet unmatched resolution, our results confirm that P. aeruginosa strains can be divided into three major groups that are further divided into subgroups, some not previously reported in the literature. We also provide the first snapshot of P. aeruginosa strain diversity with respect to antibiotic resistance. Our approach will allow us to draw potential links between environmental strains and those implicated in human and animal infections, understand how patients become infected and how the infection evolves over time as well as identify prognostic markers for better evidence-based decisions on patient care

Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling

Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression

Combined Vemurafenib and Combimetinib in BRAF-Mutated Melanoma

Background The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.Methods We randomly assigned 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and placebo (control group). The primary end point was investigator-assessed progression-free survival.Results The median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68;

Evolution of the Toarcian (Early Jurassic) carbon-cycle and global climatic controls on local sedimentary processes (Cardigan Bay Basin, UK)

The late Early Jurassic Toarcian Stage represents the warmest interval of the Jurassic Period, with an abrupt rise in global temperatures of up to ∼7 °C in mid-latitudes at the onset of the early Toarcian Oceanic Anoxic Event (T-OAE; ∼183 Ma). The T-OAE, which has been extensively studied in marine and continental successions from both hemispheres, was marked by the widespread expansion of anoxic and euxinic waters, geographically extensive deposition of organic-rich black shales, and climatic and environmental perturbations. Climatic and environmental processes following the T-OAE are, however, poorly known, largely due to a lack of study of stratigraphically well-constrained and complete sedimentary archives. Here, we present integrated geochemical and physical proxy data (high-resolution carbon-isotope data (δ13C), bulk and molecular organic geochemistry, inorganic petrology, mineral characterisation, and major- and trace-element concentrations) from the biostratigraphically complete and expanded entire Toarcian succession in the Llanbedr (Mochras Farm) Borehole, Cardigan Bay Basin, Wales, UK. With these data, we (1) construct the first high-resolution biostratigraphically calibrated chemostratigraphic reference record for nearly the complete Toarcian Stage, (2) establish palaeoceanographic and depositional conditions in the Cardigan Bay Basin, (3) show that the T-OAE in the hemipelagic Cardigan Bay Basin was marked by the occurrence of gravity-flow deposits that were likely linked to globally enhanced sediment fluxes to continental margins and deeper marine (shelf) basins, and (4) explore how early Toarcian (tenuicostatum and serpentinum zones) siderite formation in the Cardigan Bay Basin may have been linked to low global oceanic sulphate concentrations and elevated supply of iron (Fe) from the hinterland, in response to climatically induced changes in hydrological cycling, global weathering rates and large-scale sulphide and evaporite deposition