Dose-related effects of alcohol on cognitive functioning

We assessed the suitability of six applied tests of cognitive functioning to provide a single marker for dose-related alcohol intoxication. Numerous studies have demonstrated that alcohol has a deleterious effect on specific areas of cognitive processing but few have compared the effects of alcohol across a wide range of different cognitive processes. Adult participants (N = 56, 32 males, 24 females aged 18–45 years) were randomized to control or alcohol treatments within a mixed design experiment involving multiple-dosages at approximately one hour intervals (attained mean blood alcohol concentrations (BACs) of 0.00, 0.048, 0.082 and 0.10%), employing a battery of six psychometric tests; the Useful Field of View test (UFOV; processing speed together with directed attention); the Self-Ordered Pointing Task (SOPT; working memory); Inspection Time (IT; speed of processing independent from motor responding); the Traveling Salesperson Problem (TSP; strategic optimization); the Sustained Attention to Response Task (SART; vigilance, response inhibition and psychomotor function); and the Trail-Making Test(TMT; cognitive flexibility and psychomotor function). Results demonstrated that impairment is not uniform across different domains of cognitive processing and that both the size of the alcohol effect and the magnitude of effect change across different dose levels are quantitatively different for different cognitive processes. Only IT met the criteria for a marker for wide-spread application: reliable dose-related decline in a basic process as a function of rising BAC level and easy to use non-invasive task properties.Mathew J. Dry, Nicholas R. Burns, Ted Nettelbeck, Aaron L. Farquharson and Jason M. Whit

Linking seed size and number to trait syndromes in trees

Aim Our understanding of the mechanisms that maintain forest diversity under changing climate can benefit from knowledge about traits that are closely linked to fitness. We tested whether the link between traits and seed number and seed size is consistent with two hypotheses, termed the leaf economics spectrum and the plant size syndrome, or whether reproduction represents an independent dimension related to a seed size–seed number trade-off. Location Most of the data come from Europe, North and Central America and East Asia. A minority of the data come from South America, Africa and Australia. Time period 1960–2022. Major taxa studied Trees. Methods We gathered 12 million observations of the number of seeds produced in 784 tree species. We estimated the number of seeds produced by individual trees and scaled it up to the species level. Next, we used principal components analysis and generalized joint attribute modelling (GJAM) to map seed number and size on the tree traits spectrum. Results Incorporating seed size and number into trait analysis while controlling for environment and phylogeny with GJAM exposes relationships in trees that might otherwise remain hidden. Production of the large total biomass of seeds [product of seed number and seed size; hereafter, species seed productivity (SSP)] is associated with high leaf area, low foliar nitrogen, low specific leaf area (SLA) and dense wood. Production of high seed numbers is associated with small seeds produced by nutrient-demanding species with softwood, small leaves and high SLA. Trait covariation is consistent with opposing strategies: one fast-growing, early successional, with high dispersal, and the other slow-growing, stress-tolerant, that recruit in shaded conditions. Main conclusions Earth system models currently assume that reproductive allocation is indifferent among plant functional types. Easily measurable seed size is a strong predictor of the seed number and species seed productivity. The connection of SSP with the functional traits can form the first basis of improved fecundity prediction across global forests

Masting is uncommon in trees that depend on mutualist dispersers in the context of global climate and fertility gradients

The benefits of masting (volatile, quasi-synchronous seed production at lagged intervals) include satiation of seed predators, but these benefits come with a cost to mutualist pollen and seed dispersers. If the evolution of masting represents a balance between these benefits and costs, we expect mast avoidance in species that are heavily reliant on mutualist dispersers. These effects play out in the context of variable climate and site fertility among species that vary widely in nutrient demand. Meta-analyses of published data have focused on variation at the population scale, thus omitting periodicity within trees and synchronicity between trees. From raw data on 12 million tree-years worldwide, we quantified three components of masting that have not previously been analysed together: (i) volatility, defined as the frequency-weighted year-to-year variation; (ii) periodicity, representing the lag between high-seed years; and (iii) synchronicity, indicating the tree-to-tree correlation. Results show that mast avoidance (low volatility and low synchronicity) by species dependent on mutualist dispersers explains more variation than any other effect. Nutrient-demanding species have low volatility, and species that are most common on nutrient-rich and warm/wet sites exhibit short periods. The prevalence of masting in cold/dry sites coincides with climatic conditions where dependence on vertebrate dispersers is less common than in the wet tropics. Mutualist dispersers neutralize the benefits of masting for predator satiation, further balancing the effects of climate, site fertility and nutrient demands

Deep broadband observations of the distant gamma-ray blazar PKS 1424+240

We present deep VERITAS observations of the blazar PKS 1424+240, along with contemporaneous Fermi Large Area Telescope, Swift X-ray Telescope, and Swift UV Optical Telescope data between 2009 February 19 and 2013 June 8. This blazar resides at a redshift of z ≥ 0.6035, displaying a significantly attenuated gamma-ray flux above 100 GeV due to photon absorption via pair-production with the extragalactic background light. We present more than 100 hr of VERITAS observations over three years, a multiwavelength light curve, and the contemporaneous spectral energy distributions. The source shows a higher flux of (2.1 ± 0.3) × 10-7 photons m-2 s -1 above 120 GeV in 2009 and 2011 as compared to the flux measured in 2013, corresponding to (1.02 ± 0.08) × 10-7 photons m-2 s-1 above 120 GeV. The measured differential very high energy (VHE; E ≥ 100 GeV) spectral indices are Γ = 3.8 ± 0.3, 4.3 ± 0.6 and 4.5 ± 0.2 in 2009, 2011, and 2013, respectively. No significant spectral change across the observation epochs is detected. We find no evidence for variability at gamma-ray opacities of greater than τ = 2, where it is postulated that any variability would be small and occur on timescales longer than a year if hadronic cosmic-ray interactions with extragalactic photon fields provide a secondary VHE photon flux. The data cannot rule out such variability due to low statistics. © 2014. The American Astronomical Society. All rights reserved.

Deep broadband observations of the distant gamma-ray blazar PKS 1424+240

We present deep VERITAS observations of the blazar PKS 1424+240, along with contemporaneous Fermi Large Area Telescope, Swift X-ray Telescope, and Swift UV Optical Telescope data between 2009 February 19 and 2013 June 8. This blazar resides at a redshift of z ≥ 0.6035, displaying a significantly attenuated gamma-ray flux above 100 GeV due to photon absorption via pair-production with the extragalactic background light. We present more than 100 hr of VERITAS observations over three years, a multiwavelength light curve, and the contemporaneous spectral energy distributions. The source shows a higher flux of (2.1 ± 0.3) × 10 photons m s above 120 GeV in 2009 and 2011 as compared to the flux measured in 2013, corresponding to (1.02 ± 0.08) × 10 photons m s above 120 GeV. The measured differential very high energy (VHE; E ≥ 100 GeV) spectral indices are Γ = 3.8 ± 0.3, 4.3 ± 0.6 and 4.5 ± 0.2 in 2009, 2011, and 2013, respectively. No significant spectral change across the observation epochs is detected. We find no evidence for variability at gamma-ray opacities of greater than τ = 2, where it is postulated that any variability would be small and occur on timescales longer than a year if hadronic cosmic-ray interactions with extragalactic photon fields provide a secondary VHE photon flux. The data cannot rule out such variability due to low statistics. © 2014. The American Astronomical Society. All rights reserved.. -7 -2 -1 -7 -2 -

Fermi Observations of the LIGO Event GW170104

We present the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) observations of the LIGO binary black hole merger (BBH) event GW170104. No candidate electromagnetic counterpart was detected by either GBM or LAT. A detailed analysis of the GBM and LAT data over timescales from seconds to days covering the Laser Interferometer Gravitational-wave Observatory (LIGO) localization region is presented. The resulting flux upper bound from the GBM is (5.2-9.4). x. 10(-7) erg cm(-2) s(-1) in the 10-1000 keV range and from the LAT is (0.2-90). x. 10(-9) erg cm(-2) s(-1) in the 0.1-1 GeV range. We also describe the improvements to our automated pipelines and analysis techniques for searching for and characterizing the potential electromagnetic counterparts for future gravitational-wave events from Advanced LIGO/Virgo

Updated report on tools to measure outcomes of clinical trials in fragile X syndrome

Abstract Objective Fragile X syndrome (FXS) has been the neurodevelopmental disorder with the most active translation of preclinical breakthroughs into clinical trials. This process has led to a critical assessment of outcome measures, which resulted in a comprehensive review published in 2013. Nevertheless, the disappointing outcome of several recent phase III drug trials in FXS, and parallel efforts at evaluating behavioral endpoints for trials in autism spectrum disorder (ASD), has emphasized the need for re-assessing outcome measures and revising recommendations for FXS. Methods After performing an extensive database search (PubMed, Food and Drug Administration (FDA)/National Institutes of Health (NIH)’s www.ClinicalTrials.gov , etc.) to determine progress since 2013, members of the Working Groups who published the 2013 Report evaluated the available outcome measures for FXS and related neurodevelopmental disorders using the COSMIN grading system of levels of evidence. The latter has also been applied to a British survey of endpoints for ASD. In addition, we also generated an informal classification of outcome measures for use in FXS intervention studies as instruments appropriate to detect shorter- or longer-term changes. Results To date, a total of 22 double-blind controlled clinical trials in FXS have been identified through www.ClinicalTrials.gov and an extensive literature search. The vast majority of these FDA/NIH-registered clinical trials has been completed between 2008 and 2015 and has targeted the core excitatory/inhibitory imbalance present in FXS and other neurodevelopmental disorders. Limited data exist on reliability and validity for most tools used to measure cognitive, behavioral, and other problems in FXS in these trials and other studies. Overall, evidence for most tools supports a moderate tool quality grading. Data on sensitivity to treatment, currently under evaluation, could improve ratings for some cognitive and behavioral tools. Some progress has also been made at identifying promising biomarkers, mainly on blood-based and neurophysiological measures. Conclusion Despite the tangible progress in implementing clinical trials in FXS, the increasing data on measurement properties of endpoints, and the ongoing process of new tool development, the vast majority of outcome measures are at the moderate quality level with limited information on reliability, validity, and sensitivity to treatment. This situation is not unique to FXS, since reviews of endpoints for ASD have arrived at similar conclusions. These findings, in conjunction with the predominance of parent-based measures particularly in the behavioral domain, indicate that endpoint development in FXS needs to continue with an emphasis on more objective measures (observational, direct testing, biomarkers) that reflect meaningful improvements in quality of life. A major continuous challenge is the development of measurement tools concurrently with testing drug safety and efficacy in clinical trials