The effects of scopolamine upon control of attention and memory in humans

Research into the effects of scopolamine hydrobromide, a post­synaptic cholinergic receptor blocking drug, upon cognition in humans has been conducted for at least two decades. In that time, a distinct pattern of effects has emerged. Within a dose range of 0.3 to 1.2 mg (oral), scopolamine has been found to impair the acquisition of new information in verbal and spatial learning tasks, to reduce stimulus sensitivity in tests of vigilance and to impair selective attention. Generally it is thought that information retrieval, both of newly learned and autobiographical material, is unaffected by this drug. A primary reason for research interest in scopolamine is that the effects have been found to resemble the pattern of impairment found in advanced age, and particularly in Alzheimer's Disease (AD). This is often referred to as the 'Scopolamine model of dementia'. Coupled with the observation of extensive damage to CNS cholinergic neurons in AD, the hypothesis has emerged that acetylcholine activity influences many important cognitive processes. Recent theoretical analyses of cognitive loss in AD have proposed that there is a selective impairment to effortful (i.e. active, conscious) processes, whereas the more automatic (i.e. reflexive, unconscious) aspects of cognition remain intact. If the scopolamine model is to remain valid in this perspective, then it should be possible to show that, in normal humans, the effects of the drug are specific to effortful cognitive control processes. This thesis describes six experiments designed to test this prediction. It is presented in three parts. In Part I, two experiments examined the effects of O. 6mg and O. 9mg oral scopolamine upon the control of attention to targets in visual space. Results confirmed the prediction that the ability to detect stimuli in high probability locations on a VDU is impaired, while detection of stimuli in low probability locations is enhanced. It was argued that the drug broadened the attentional focus, and that this is due to a general reduction in cognitive control. In Part II, two studies sought to find evidence that the drug impairs the active selection of information from semantic memory. Here, subjects were not provided with material to learn, but rather were asked to sustain the retrieval of items from natural semantic categories for extended periods (8 to 12 min). In the second study of this pair, subjects were also constrained as to the type of retrieval strategy they could use. Results failed to confirm the prediction. The drug had no main or interactive effects on active control over semantic memory retrieval. In Part III, two studies tested the prediction that scopolamine would selectively impair the more difficult, controlled aspects of encoding and retrieval following presentation of verbal material (i.e. an episodic memory task) in two sensory modalities (auditory and visual). Subjects were required to recall lists of words, and to actively group their recall on the basis of the items' sensory modality. The first study found that the drug impaired recall, but not recognition, and did not have an effect on more automatic phenomena such as word priming effects and the recall advantage for auditory material. In addition, there was some evidence from statistical interactions that the drug impaired subjects' ability to actively cluster the presented material on the basis of input modality. The second experiment examined effects of scopolamine upon list learning and modality clustering when subjects were given five attempts to recall the same i terns. This experiment introduced two levels of task difficulty, by varying the extent to which item input modality was consistent across learning trials. Pilot testing (non-drug) revealed that list learning and clustering ability were significantly impaired in the variable, as compared to consistent, modality condition. In the full experiment, scopolamine impaired total recall but not recognition. The drug did not directly effect subjects' ability to group items on the basis of modality, and the size of the drug effect on immediate recall was similar for both the easy (i.e. consistent modality) and difficult (i.e. variable modality) learning trials. There were some interactions between drug and task variables which indicated a weak effect upon attention Taken together, these six experiments show the following pattern. Control over visual attention is impaired by scopolamine, and this agrees with some previous research. However, this reduction in cognitive control appears to be specific, rather than general, since the attempts to find an effect of the drug on active control of retrieval from semantic memory and the conscious organisation of material in episodic memory were unsuccessful. In theoretical terms, this series of experiments does not support the view that anticholinergic drug effects are specific to effortful processing. It was argued that the pattern of drug effects observed here is not simply due to low potency of a O. 9mg oral dose. Numerous previous experiments have observed subtle effects of scopolamine 0.9mg oral (and lower doses) on various measures of cognitive function. It was concluded that a low to moderate dose of oral scopolamine does have selective effects on different cognitive processes, but that this selectivity is not related to the amount of cognitive effort involved in the tasks. This work has identified some important limits to the scopolamine model of dementia, and extended research with this drug into several domains of human memory not previously examined. The implications for future research are discussed

OrthoFiller: utilising data from multiple species to improve the completeness of genome annotations.

Background Complete and accurate annotation of sequenced genomes is of paramount importance to their utility and analysis. Differences in gene prediction pipelines mean that genome annotations for a species can differ considerably in the quality and quantity of their predicted genes. Furthermore, genes that are present in genome sequences sometimes fail to be detected by computational gene prediction methods. Erroneously unannotated genes can lead to oversights and inaccurate assertions in biological investigations, especially for smaller-scale genome projects, which rely heavily on computational prediction. Results Here we present OrthoFiller, a tool designed to address the problem of finding and adding such missing genes to genome annotations. OrthoFiller leverages information from multiple related species to identify those genes whose existence can be verified through comparison with known gene families, but which have not been predicted. By simulating missing gene annotations in real sequence datasets from both plants and fungi we demonstrate the accuracy and utility of OrthoFiller for finding missing genes and improving genome annotations. Furthermore, we show that applying OrthoFiller to existing “complete” genome annotations can identify and correct substantial numbers of erroneously missing genes in these two sets of species. Conclusions We show that significant improvements in the completeness of genome annotations can be made by leveraging information from multiple species

Texture Determination from Ultrasonic Wave Speeds for Hexagonal Close Pack and Cubic Materials

Crystallographic texture in polycrystalline hexagonal close pack (HCP) and cubic materials, often developed during thermomechanical deformations, has profound effects on properties at the macroscopic or component level. In this talk, a novel theoretical convolution model is presented, which couples the single crystal wave speed (the kernel function) with the polycrystal crystallographic orientation distribution function to give the resultant polycrystal wave speed function. Firstly developed on HCP [1] and then successfully extended to general anisotropic materials [2], the theoretical model expresses the three functions as harmonic expansions, thus enabling the calculation of any one of them when the other two are known. Hence, the forward problem of determination of polycrystal wave speed is solved for all crystal systems. Verifications are provided on various textures, showing near-perfect representation of the sensitivity of wave speed to texture as well as quantitative predictions of polycrystal wave speed. More importantly, the model also presents a solution to the long-standing inverse problem of detecting texture using ultrasound, with proof of principle established where the wave velocities propagating in groups of HCP and cubic polycrystals with different known textures are computationally calculated, and then the texture information is recovered solely from simulated velocities through the model, and the results show good agreements with the original textures. With possibilities of developing a powerful tool for bulk texture measurement and wave propagation studies in general for HCP, cubic materials now shown, further experimental validations of the proposed model are then conducted. A series of samples cut from typical HCP and cubic materials, including commercially pure (CP) Ti, copper, Ti-6Al-4V, are examined by carefully designed experimental setup for the measurement of the angular variations of ultrasonic wave velocities. Texture information of the samples are extracted out from these measured velocities using the model, for the comparison and calibration against the set of information of the same samples measured independently by the well-established neutron diffraction technique. This part of the research is still ongoing and we hope to be able to show results soon

Modeling predictors of risky drug use behavior among male street laborers in urban Vietnam

BACKGROUND: The application of theoretical frameworks for modeling predictors of drug risk among male street laborers remains limited. The objective of this study was to test a modified version of the IMB (Information-Motivation-Behavioral Skills Model), which includes psychosocial stress, and compare this modified version with the original IMB model in terms of goodness-of-fit to predict risky drug use behavior among this population. METHODS: In a cross-sectional study, social mapping technique was conducted to recruit 450 male street laborers from 135 street venues across 13 districts of Hanoi city, Vietnam, for face-to-face interviews. Structural equation modeling (SEM) was used to analyze data from interviews. RESULTS: Overall measures of fit via SEM indicated that the original IMB model provided a better fit to the data than the modified version. Although the former model was able to predict a lesser variance than the latter (55% vs. 62%), it was of better fit. The findings suggest that men who are better informed and motivated for HIV prevention are more likely to report higher behavioral skills, which, in turn, are less likely to be engaged in risky drug use behavior. CONCLUSIONS: This was the first application of the modified IMB model for drug use in men who were unskilled, unregistered laborers in urban settings. An AIDS prevention program for these men should not only distribute information and enhance motivations for HIV prevention, but consider interventions that could improve self-efficacy for preventing HIV infection. Future public health research and action may also consider broader factors such as structural social capital and social policy to alter the conditions that drive risky drug use among these men

Trauma Exposure and Mental Health Problems Among Adults in Central Vietnam: A Randomized Cross-Sectional Survey

Background: There is relatively little evidence about the psychological and social impacts of trauma exposure in the general population in East Asian countries. Vietnam has a long history of war and poverty, is prone to natural disasters and has high mortality related to traffic accidents. The mental health systems may be inadequate to cope with the resultant trauma.Objectives: This research examines the lifetime prevalence of single and multiple traumas and the association between trauma exposure and depression, anxiety and post-traumatic stress disorder (PTSD) among a randomly selected sample of the adult population in Thua Thien-Hue province in central Vietnam.Methods: Six hundred and eight Vietnamese adults aged 18 years or older participated in the survey. The main tools in the face-to-face interview included the Life Event Checklist (LEC) to measure trauma exposure, the Hospital Anxiety and Depression Scale (HADS) and the PTSD Checklist for DSM-IV (PCL-IV). Hierarchical multiple logistic regression was used to examine associations between trauma exposure and mental health.Results: Forty seven percent of the participants experienced at least one traumatic event in their lifetime and about half of these people were exposed to multiple traumas. The prevalence of depression, anxiety, and PTSD symptoms among the total sample was 12.7, 15.5, and 6.9%, respectively. Prevalence of PTSD among those reporting trauma exposure was 14.8%. Exposure to a higher number of trauma types was associated with increased risk of having depression, anxiety, and PTSD symptoms. Interpersonal traumas were strongly associated with symptoms of all three mental disorders while non-interpersonal traumas were only associated with depressive symptoms.Conclusion: Our findings indicate high burden of lifetime trauma and mental ill health in the adult population of central Vietnam and show a cumulative effect of multiple traumas on symptoms of the three mental disorders. Interpersonal trauma appears to have a more harmful effect on mental health than non-interpersonal trauma. Efforts to improve mental health in Vietnam should focus on reducing risk of preventable interpersonal trauma in every stage of life, and more broadly, ensure greater availability of trauma-sensitive mental health programs and services

Analytical solution of the Gross-Neveu model at finite density

Recent numerical calculations have shown that the ground state of the Gross-Neveu model at finite density is a crystal. Guided by these results, we can now present the analytical solution to this problem in terms of elliptic functions. The scalar potential is the superpotential of the non-relativistic Lame Hamiltonian. This model can also serve as analytically solvable toy model for a relativistic superconductor in the Larkin-Ovchinnikov-Fulde-Ferrell phase.Comment: 5 pages, no figures, revtex; vs2: appendix with analytical proof of self-consistency adde

Evaluating Southern Ocean biological production in two ocean biogeochemical models on daily to seasonal timescales using satellite chlorophyll and O2 / Ar observations

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biogeosciences 12 (2015): 681-695, doi:10.5194/bg-12-681-2015.We assess the ability of ocean biogeochemical models to represent seasonal structures in biomass and net community production (NCP) in the Southern Ocean. Two models are compared to observations on daily to seasonal timescales in four different sections of the region. We use daily satellite fields of chlorophyll (Chl) as a proxy for biomass and in situ observations of O2 and Ar supersaturation (ΔO2 / Ar) to estimate NCP. ΔO2 / Ar is converted to the flux of biologically generated O2 from sea to air (O2 bioflux). All data are aggregated to a climatological year with a daily resolution. To account for potential regional differences within the Southern Ocean, we conduct separate analyses of sections south of South Africa, around the Drake Passage, south of Australia, and south of New Zealand. We find that the models simulate the upper range of Chl concentrations well, underestimate spring levels significantly, and show differences in skill between early and late parts of the growing season. While there is a great deal of scatter in the bioflux observations in general, the four sectors each have distinct patterns that the models pick up. Neither model exhibits a significant distinction between the Australian and New Zealand sectors and between the Drake Passage and African sectors. South of 60° S, the models fail to predict the observed extent of biological O2 undersaturation. We suggest that this shortcoming may be due either to problems with the ecosystem dynamics or problems with the vertical transport of oxygen.This work was supported in part by funding from the National Aeronautic and Space Administration (NASA NNX08AF12G) and the National Science Foundation (NSF OPP-0823101)

Evaluation of the Southern Ocean O2/Ar-based NCP estimates in a model framework

Author Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Biogeosciences 118 (2013): 385–399, doi:10.1002/jgrg.20032.The sea-air biological O2 flux assessed from measurements of surface O2 supersaturation in excess of Ar supersaturation (“O2 bioflux”) is increasingly being used to constrain net community production (NCP) in the upper ocean mixed layer. In making these calculations, one generally assumes that NCP is at steady state, mixed layer depth is constant, and there is no O2 exchange across the base of the mixed layer. The object of this paper is to evaluate the magnitude of errors introduced by violations of these assumptions. Therefore, we examine the differences between the sea-air biological O2 flux and NCP in the Southern Ocean mixed layer as calculated using two ocean biogeochemistry general circulation models. In this approach, NCP is considered a known entity in the prognostic model, whereas O2 bioflux is estimated using the model-predicted O2/Ar ratio to compute the mixed layer biological O2 saturation and the gas transfer velocity to calculate flux. We find that the simulated biological O2 flux gives an accurate picture of the regional-scale patterns and trends in model NCP. However, on local scales, violations of the assumptions behind the O2/Ar method lead to significant, non-uniform differences between model NCP and biological O2 flux. These errors arise from two main sources. First, venting of biological O2 to the atmosphere can be misaligned from NCP in both time and space. Second, vertical fluxes of oxygen across the base of the mixed layer complicate the relationship between NCP and the biological O2 flux. Our calculations show that low values of O2 bioflux correctly register that NCP is also low (<10 mmol m−2 day−1), but fractional errors are large when rates are this low. Values between 10 and 40 mmol m−2 day−1 in areas with intermediate mixed layer depths of 30 to 50 m have the smallest absolute and relative errors. Areas with O2 bioflux higher than 30 mmol m−2 day−1 and mixed layers deeper than 40 m tend to underestimate NCP by up to 20 mmol m−2 day−1. Excluding time periods when mixed layer biological O2 is undersaturated, O2 bioflux underestimates time-averaged NCP by 5%–15%. If these time periods are included, O2 bioflux underestimates mixed layer NCP by 20%–35% in the Southern Ocean. The higher error estimate is relevant if one wants to estimate seasonal NCP since a significant amount of biological production takes place when mixed layer biological O2 is undersaturated.This work was supported in part by funding from the National Aeronautic and Space Administration (NASA NNX08AF12G) and National Science Foundation (NSF OPP-0823101)

Production and Use of Ceramics in the First Millennium BC: Jebel Moya, Sudan

The site of Jebel Moya, situated in the center of the southern Gezira Plain in southcentral Sudan, has an occupational sequence spanning at least five millennia until around 2000 years ago. Renewed excavation is shedding new light on its occupational chronology and socioeconomic history, including activities such as burial, savanna herding, and domesticated sorghum cultivation practices dating to at least the mid-third millennium BC. In the present study, predominantly final phase pottery sherds from the first millennium BC to the start of the first millennium AD (Assemblage 3) have been analyzed via a combination of thin section petrography and instrumental geochemistry to determine their raw materials and place of manufacture and reconstruct their manufacturing technology. Organic residue analysis was also conducted to identify the products processed within vessels found at the site. The results suggest the existence of a well-developed local ceramic craft tradition that persisted for over one thousand years. Pots from Assemblage 3 were used to process, store, and consume animal and plant products, thus reinforcing emerging evidence for early agro-pastoral activities