PRIMA1 mutation: A new cause of nocturnal frontal lobe epilepsy

Objective Nocturnal frontal lobe epilepsy (NFLE) can be sporadic or autosomal dominant; some families have nicotinic acetylcholine receptor subunit mutations. We report a novel autosomal recessive phenotype in a single family and identify the causative gene. Methods Whole exome sequencing data was used to map the family, thereby narrowing exome search space, and then to identify the mutation. Results Linkage analysis using exome sequence data from two affected and two unaffected subjects showed homozygous linkage peaks on chromosomes 7, 8, 13, and 14 with maximum LOD scores between 1.5 and 1.93. Exome variant filtering under these peaks revealed that the affected siblings were homozygous for a novel splice site mutation (c.93+2T>C) in the PRIMA1 gene on chromosome 14. No additional PRIMA1 mutations were found in 300 other NFLE cases. The c.93+2T>C mutation was shown to lead to skipping of the first coding exon of the PRIMA1 mRNA using a minigene system. Interpretation PRIMA1 is a transmembrane protein that anchors acetylcholinesterase (AChE), an enzyme hydrolyzing acetycholine, to membrane rafts of neurons. PRiMA knockout mice have reduction of AChE and accumulation of acetylcholine at the synapse; our minigene analysis suggests that the c.93+2T>C mutation leads to knockout of PRIMA1. Mutations with gain of function effects in acetylcholine receptor subunits cause autosomal dominant NFLE. Thus, enhanced cholinergic responses are the likely cause of the severe NFLE and intellectual disability segregating in this family, representing the first recessive case to be reported and the first PRIMA1 mutation implicated in disease

High-time Resolution Astrophysics and Pulsars

The discovery of pulsars in 1968 heralded an era where the temporal characteristics of detectors had to be reassessed. Up to this point detector integration times would normally be measured in minutes rather seconds and definitely not on sub-second time scales. At the start of the 21st century pulsar observations are still pushing the limits of detector telescope capabilities. Flux variations on times scales less than 1 nsec have been observed during giant radio pulses. Pulsar studies over the next 10 to 20 years will require instruments with time resolutions down to microseconds and below, high-quantum quantum efficiency, reasonable energy resolution and sensitive to circular and linear polarisation of stochastic signals. This chapter is review of temporally resolved optical observations of pulsars. It concludes with estimates of the observability of pulsars with both existing telescopes and into the ELT era.Comment: Review; 21 pages, 5 figures, 86 references. Book chapter to appear in: D.Phelan, O.Ryan & A.Shearer, eds.: High Time Resolution Astrophysics (Astrophysics and Space Science Library, Springer, 2007). The original publication will be available at http://www.springerlink.co

Fracture parameter inversion from passive seismic shear-wave splitting: A validation study using full-waveform numerical synthetics

Fractures are pervasive features within the Earth's crust and they have a significant influence on the multi-physical response of the subsurface. The presence of coherent fracture sets often leads to observable seismic anisotropy enabling seismic techniques to remotely locate and characterise fracture systems. Since fractures play a critical role in the geomechanical and fluid-flow response, there has been significant interest in quantitatively imaging in situ fractures for improved hydro-mechanical modelling. In this study we assess the robustness of inverting for fracture properties using shear-wave splitting measurements. We show that it is feasible to invert shear-wave splitting measurements to quantitatively estimate fracture strike and fracture density assuming an effective medium fracture model. Although the SWS results themselves are diagnostic of fracturing, the fracture inversion allows placing constraints on the physical properties of the fracture system. For the single seismic source case and optimum receiver array geometry, the inversion for strike has average errors of between 11° and 25°, whereas for density has average errors between 65% and 80% for the single fracture set and 30% and 90% for the double fracture sets. For real microseismic datasets, the range in magnitude of microseismicity (i.e., frequency content), spatial distribution and variable source mechanisms suggests that the inversion of fracture properties from SWS measurements is feasible

Nitrogen deposition and prey nitrogen uptake control the nutrition of the carnivorous plant Drosera rotundifolia

This article was accepted for publication in the journal, Science of the Total Environment [© Elsevier B.V] and the definitive version is available at: http://dx.doi.org/10.1016/j.scitotenv.2015.01.067Nitrogen (N) deposition has important negative impacts on natural and semi-natural ecosystems, impacting on biotic interactions across trophic levels. Low-nutrient systems are particularly sensitive to changes in N inputs and are therefore more vulnerable to N deposition. Carnivorous plants are often part of these ecosystems partly because of the additional nutrients obtained from prey. We studied the impact of N deposition on the nutrition of the carnivorous plant Drosera rotundifolia growing on 16 ombrotrophic bogs across Europe. We measured tissue N, phosphorus (P) and potassium (K) concentrations and prey and root N uptake using a natural abundance stable isotope approach. Our aim was to test the impact of N deposition on D. rotundifolia prey and root N uptake, and nutrient stoichiometry. D. rotundifolia root N uptake was strongly affected by N deposition, possibly resulting in reduced N limitation. The contribution of prey N to the N contained in D. rotundifolia ranged from 20 to 60%. N deposition reduced the maximum amount of N derived from prey, but this varied below this maximum. D. rotundifolia tissue N concentrations were a product of both root N availability and prey N uptake. Increased prey N uptake was correlated with increased tissue P concentrations indicating uptake of P from prey. N deposition therefore reduced the strength of a carnivorous plant–prey interaction, resulting in a reduction in nutrient transfer between trophic levels. We suggest that N deposition has a negative impact on D. rotundifolia and that responses to N deposition might be strongly site specific

Analysis of fracture induced scattering of microseismic shear-waves

Fractures are pervasive features within the Earth’s crust and have a significant influence on the multi-physical response of the subsurface. The presence of coherent fracture sets often leads to observable seismic scattering enabling seismic techniques to remotely locate and characterise fracture systems. In this study, we confirm the general scale-dependence of seismic scattering and provide new results specific to shear-wave propagation. We do this by generating full waveform synthetics using finite-difference wave simulation within an isotropic background model containing explicit fractures. By considering a suite of fracture models having variable fracture density and fracture size, we examine the widening effect of wavelets due to scattering within a fractured medium by using several different approaches, such as root-mean-square envelope analysis, shear-wave polarisation distortion, differential attenuation analysis and peak frequency shifting. The analysis allows us to assess the scattering behavior of parametrised models in which the propagation direction is either normal or parallel to the fracture surfaces. The quantitative measures show strong observable deviations for fractures size on the order of or greater than the dominant seismic wavelength within the Mie and geometric scattering regime for both propagation normal and parallel to fracture strike. The results suggest that strong scattering is symptomatic of fractures having size on the same order of the probing seismic wave

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.</p

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol�which is a marker of cardiovascular risk�changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95 credible interval 3.7 million�4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world. © 2020, The Author(s), under exclusive licence to Springer Nature Limited

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)