Carotid atherosclerosis and a reduced likelihood for lowered cognitive Performance in a Canadian first nations population

Background: We investigated the associations among cardiovascular risk factors, carotid atherosclerosis and cognitive function in a Canadian First Nations population. Methods: Individuals aged ≥18 years, without stroke, nonpreg- nant and with First Nations status were assessed by the Trail Making Test Parts A and B. Results were combined into a Trail Making Test executive function score (TMT-exec). Doppler ultrasonography assessed carotid stenosis and plaque volume. Anthropometric, vascular and metabolic risk factors were assessed by interview, clinical examinations and blood tests. Results: For 190 individuals with TMT-exec scores, the median age of the population was 39 years. Compared to the reference group, individuals with elevated levels of left carotid stenosis (LCS) and total carotid stenosis (TCS) were less likely to demonstrate lowered cognitive performance [LCS, odds ratio (OR): 0.47, 95% confidence interval (CI): 0.24-0.96; TCS, OR: 0.40, 95% CI: 0.20-0.80]. No effect was shown for plaque volume. In structural equation modeling, we found that for every 1-unit change in the anthropometric factor in kg/m2, there was a 0.86-fold decrease in the percent of TCS (p \u3c 0.05). Conclusions: Individuals with elevated levels of LCS and TCS were less likely to demonstrate lowered performance. There was some suggestion that TCS mediates the effect of anthropometric risk factors on cognitive function. Copyright © 2009 S. Karger AG, Basel

A controlled crossover trial of fendluramine in autism

Introduction: Against a background of variable results achieved by the treatment of childhood autism with dopaminergic agonists or antagonists, and opiate antagonists and mild behavioural improvements achieved following treatment with fenfluramine (Geller et al., 1982; Ritvo et al., 1984 among others) a 12 month double-blind crossover trial of fenfluramine was undertaken. [the d-isomer releases serotonin, the l-isomer modestly blocks dopamine receptors.] Methods: Six female and 14 male children and adolescents with autism were enrolled (median 9y; range 5-17 years of age) in a trial run over a 1 month baseline, 5 months of treatment, 2 months placebo, and 5 months of treatment. Parent diaries were kept. Various tests and rating scales for development, verbal and noverbal abilities along with measures of blood serotonin, urinary catecholamines and auditory event-related potentials (ERPs) were measured at 6-month intervals. Results: a) With fenfluramine treatment children lost weight, blood serotonin decreased by 60% and urinary catecholamine levels fell (25-45%, but dopamine utilization (HVA/DA) increased 2-4-fold. b) Under fenfluramine some autistic subjects improved on measures of cognitive and language function. Two mute subjects began to speak, but for the group overall the improvements did not prove significant. [British Ability Scale, Reynell developmental language and Vineland social maturity scale improvements were significant.] c) Treatment improved early stages of information processing, but impaired later stages as measured in the ERP (i.e. early negative going excitatory vs. later positive going inhibitory response, respectively in 7 patients). The early negativity changes (especially over the right hemisphere) correlated inversely with HVA/DA actvivity. d) Side effects reported included lethargy and irritability.. Conclusions: While individuals showed marked reductions of stereotypies, hyperactivity, and improvements on develepmental and cognitive measures, the absence of clear group-wide effects suggests that fenfluramine would have but a limited place in the management of some patients with autism

Disparate associations of a functional promoter polymorphism in PCK1 with carotid wall ultrasound traits

Background and Purpose - Cytosolic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32), encoded by PCK1, catalyzes the first committed step in gluconeogenesis. We previously showed that a -232C\u3eG promoter polymorphism within a cis-acting element required for basal and cAMP-mediated PCK1 gene transcription results in loss of negative regulation by insulin, contributing to worsened metabolic control in the context of insulin resistance. We hypothesized that this polymorphism would be associated with carotid atherosclerosis in a sample of 150 aboriginal Canadians. Methods - Dependent variables were 2 distinct carotid traits, namely intima-media thickness (IMT) assessed using B-mode ultrasound and total carotid plaque volume (TPV) assessed using 3D ultrasound. Results - Multivariate analysis showed significant but opposite associations of PCK1 genotype with these traits. Specifically, subjects with the PCK1-232G/G genotype had more carotid IMT (0.80±0.02 versus 0.73±0.03 mm; P=0.007) but less TPV (0.10±0.09 versus 0.38±0.13; P=0.03) than subjects with other genotypes. Conclusions - The findings connect the key enzyme in gluconeogenesis with atherosclerosis. The meaning of the opposing associations of PCK1 genotype with IMT and TPV is unclear; more work is required to confirm whether these might be distinct quantitative traits with different biological determinants. © 2005 American Heart Association, Inc

Isotopic evolution of prehistoric magma sources of Mt. Etna, Sicily: Insights from the Valle Del Bove

Mount Etna in NE Sicily occupies an unusual tectonic position in the convergence zone between the African and Eurasian plates, near the Quaternary subduction-related Aeolian arc and above the down-going Ionian oceanic slab. Magmatic evolution broadly involves a transition from an early tholeiitic phase (~ 500 ka) to the current alkaline phase. Most geochemical investigations have focussed on either historic (> 130-years old) or recent (< 130-years old) eruptions of Mt. Etna or on the ancient basal lavas (ca. 500 ka). In this study, we have analysed and modelled the petrogenesis of alkalic lavas from the southern wall of the Valle del Bove, which represent a time span of Mt. Etna’s prehistoric magmatic activity from ~ 85 to ~ 4 ka. They exhibit geochemical variations that distinguish them as six separate lithostratigraphic and volcanic units. Isotopic data (143Nd/144Nd = 0.51283–0.51291; 87Sr/86Sr = 0.70332–0.70363; 176Hf/177Hf = 0.28288–0.28298; 206Pb/204Pb = 19.76–20.03) indicate changes in the magma source during the ~ 80 kyr of activity that do not follow the previously observed temporal trend. The oldest analysed Valle del Bove unit (Salifizio-1) erupted basaltic trachyandesites with variations in 143Nd/144Nd and 87Sr/86Sr ratios indicating a magma source remarkably similar to that of recent Etna eruptions, while four of the five subsequent units have isotopic compositions resembling those of historic Etna magmas. All five magma batches are considered to be derived from melting of a mixture of spinel lherzolite and pyroxenite (± garnet). In contrast, the sixth unit, the main Piano Provenzana formation (~ 42–30 ka), includes the most evolved trachyandesitic lavas (58–62 wt% SiO2) and exhibits notably lower 176Hf/177Hf, 143Nd/144Nd, and 206Pb/204Pb ratios than the other prehistoric Valle del Bove units. This isotopic signature has not yet been observed in any other samples from Mt. Etna and we suggest that the parental melts of the trachyandesites were derived predominantly from ancient pyroxenite in the mantle source of Etna

Genetic variation in PPARG encoding peroxisome proliferator-activated receptor γ associated with carotid atherosclerosis

Background and Purpose-Peroxisome proliferator-activated receptor γ is a crucial molecule in atherogenesis because it is associated with metabolic risk factors such as obesity and diabetes and also plays a key role in subcellular metabolism of arterial wall macrophage foam cells. Genetic variation in PPARG has been associated with metabolic and cardiovascular end points. Methods-We investigated the relationship between 2 common PPARG polymorphisms, namely P12A and c.1431C\u3eT, and carotid atherosclerosis in a sample of 161 Canadian aboriginal people. Dependent variables were carotid intima media thickness (IMT), assessed using B-mode ultrasonography, and total carotid plaque volume (TPV), assessed using 3D ultrasound. Results-Using multivariate analysis, we found that subjects with ≥ 1 PPARG A12 allele had less carotid IMT than others (0.72±0.03 versus 0.80±0.02 mm; P=0.0045), with no between-genotype difference in TPV. In contrast, subjects with the PPARG c.1431T allele had greater TPV than others (124±18.4 versus 65.1±23.7 mm3; P=0.0079), with no between-genotype difference in IMT. Conclusions-The findings show an association between PPARG genotypes and carotid arterial phenotypes, and further reflect the prevailing view that the PPARG A12 allele protects against deleterious phenotypes. Also, whereas IMT and TPV are somewhat correlated with each other, they might also represent distinct traits with discrete determinants representing different stages of atherogenesis

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

University-industry relationships and open innovation: Towards a research agenda

Accepted versio

The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed

Solving math problems: Where and why does the solution process go astray?

Wetensch. publicatieFaculteit der Sociale Wetenschappe