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- Benatar, Michael, et al.
(författare)
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Preventing amyotrophic lateral sclerosis : insights from pre-symptomatic neurodegenerative diseases
- 2022
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 145:1, s. 27-44
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Forskningsöversikt (refereegranskat)abstract
- Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis. While much is still unknown, advances in other neurodegenerative diseases offer valuable insights. Indeed, it is increasingly clear that the well-recognized clinical syndromes of Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy and frontotemporal dementia are also each preceded by a pre-symptomatic or prodromal period of varying duration, during which the underlying disease process unfolds, with associated compensatory changes and loss of inherent system redundancy. Key insights from these diseases highlight opportunities for discovery in amyotrophic lateral sclerosis. The development of biomarkers reflecting amyloid and tau has led to a shift in defining Alzheimer's disease based on inferred underlying histopathology. Parkinson's disease is unique among neurodegenerative diseases in the number and diversity of non-genetic biomarkers of pre-symptomatic disease, most notably REM sleep behaviour disorder. Huntington's disease benefits from an ability to predict the likely timing of clinically manifest disease based on age and CAG-repeat length alongside reliable neuroimaging markers of atrophy. Spinal muscular atrophy clinical trials have highlighted the transformational value of early therapeutic intervention, and studies in frontotemporal dementia illustrate the differential role of biomarkers based on genotype. Similar advances in amyotrophic lateral sclerosis would transform our understanding of key events in pathogenesis, thereby dramatically accelerating progress towards disease prevention. Deciphering the biology of pre-symptomatic amyotrophic lateral sclerosis relies on a clear conceptual framework for defining the earliest stages of disease. Clinically manifest amyotrophic lateral sclerosis may emerge abruptly, especially among those who harbour genetic mutations associated with rapidly progressive amyotrophic lateral sclerosis. However, the disease may also evolve more gradually, revealing a prodromal period of mild motor impairment preceding phenoconversion to clinically manifest disease. Similarly, cognitive and behavioural impairment, when present, may emerge gradually, evolving through a prodromal period of mild cognitive impairment or mild behavioural impairment before progression to amyotrophic lateral sclerosis. Biomarkers are critically important to studying pre-symptomatic amyotrophic lateral sclerosis and essential to efforts to intervene therapeutically before clinically manifest disease emerges. The use of non-genetic biomarkers, however, presents challenges related to counselling, informed consent, communication of results and limited protections afforded by existing legislation. Experiences from pre-symptomatic genetic testing and counselling, and the legal protections against discrimination based on genetic data, may serve as a guide. Building on what we have learned - more broadly from other pre-symptomatic neurodegenerative diseases and specifically from amyotrophic lateral sclerosis gene mutation carriers - we present a road map to early intervention, and perhaps even disease prevention, for all forms of amyotrophic lateral sclerosis.
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- BOSTROM, D, et al.
(författare)
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A SOLID-STATE EMF METHOD TO DETERMINE EQUILIBRIUM OXYGEN PARTIAL PRESSURES OF SLOW REACTING CHEMICAL-SYSTEMS AT HIGH-TEMPERATURES
- 1989
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Ingår i: HIGH TEMPERATURE SCIENCE. - 0018-1536. ; 28, s. 235-244
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Tidskriftsartikel (refereegranskat)abstract
- In solid state emf measurements on sluggish systems, difficulties to achieve stable and reproducible values have been encountered. There are many indications that these problems are owing to the small, but obviously not negligible, transport of oxygen through the electrolyte. In the present work, an improved galvanic cell arrangement, here called the "zero point" method, has been developed. The principles of this method are to approach zero emf for the sample cell, containing a sluggish system, by an adjustable reference gas phase, and determine the oxygen partial pressure in the reference gas phase, initially made up of a H2/CO2 mixture, by a reference cell, containing a fast reacting metal-metaloxide equilibrium system, which is unaffected by the oxygen permeation. The following equilibrium, with a recognized slow reaction rate, was chosen as a test system to demonstrate the "zero point" method Co(s) + Cr2O3 (s) + 1/2O2 (g) reversible CoCr2O4 (s)
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- Haglund, B, et al.
(författare)
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Is moist snuff use associated with excess risk of IHD or stroke? A longitudinal follow-up of snuff users in Sweden
- 2007
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 35:6, s. 618-622
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Tidskriftsartikel (refereegranskat)abstract
- Background: The potential risks of Swedish moist snuff (snus) are debated and studies have shown diverging results. Aims: The aim of this study is to investigate whether there is any excess risk of ischaemic heart disease (IHD) and stroke from snuff use. Methods: The Swedish Survey of Living Conditions from 1988—89 was record-linked to the Swedish Cause of Death Register and the Swedish Hospital Discharge Register to investigate excess mortality and hospitalization from IHD and stroke. A Poisson regression model was used and incidence rate ratios (IRRs) for snuff and smoking were calculated controlling for age, physical activity, self-reported health, number of longstanding illnesses, residential area, and socioeconomic position. Results: Among snuff users there were no excess risks of mortality or hospitalization from IHD (IRR 0.8; 0.5—1.2,) or stroke (IRR 1.1; 0.7—1.8), but, as expected, clear excess risks were found for smokers (IRR 1.7; 1.4—2.1 for IHD, and IRR 1.4; 1.0—1.9 for stroke). Conclusions: This study has not shown any excess risk among users of snuff for IHD or stroke. If there is a risk associated with snuff it is evidently much lower than those associated with smoking.
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- Hahn, A, et al.
(författare)
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Climate induced changes as registered in inorganic and organic sediment components from Laguna Potrok Aike (Argentina) during the past 51 ka
- 2013
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 71, s. 154-166
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Tidskriftsartikel (refereegranskat)abstract
- Total organic carbon, total inorganic carbon, biogenic silica content and total organic carbon/total nitrogen ratios of the Laguna Potrok Aike lacustrine sediment record are used to reconstruct the environmental history of south-east Patagonia during the past 51 ka in high resolution. High lake level conditions are assumed to have prevailed during the Last Glacial, as sediments are carbonate-free. Increased runoff linked to permafrost and reduced evaporation due to colder temperatures and reduced influence of Southern Hemispheric Westerlies (SHIN) may have caused these high lake levels with lake productivity being low and organic matter mainly of algal or cyanobacterial origin. Aquatic moss growth and diatom blooms occurred synchronously with southern hemispheric glacial warming events such as the Antarctic A-events, the postglacial warming following the LGM and the Younger Dryas chronozone. During these times, a combination of warmer climatic conditions with related thawing permafrost could have increased the allochthonous input of nutrients and in combination with warmer surface waters increased aquatic moss growth and diatom production. The SHW were not observed to affect southern Patagonia during the Last Glacial. The Holocene presents a completely different lacustrine system because (a) permafrost no longer inhibits infiltration nor emits meltwater pulses and (b) the positioning of the SHW over the investigated area gives rise to strong and dry winds. Under these conditions total organic carbon, total organic carbon/total nitrogen ratios and biogenic silica cease to be first order productivity indicators. On the one hand, the biogenic silica is influenced by dissolution of diatoms due to higher salinity and pH of the lake water under evaporative stress characterizing low lake levels. On the other hand, total organic carbon and total organic carbon/total nitrogen profiles are influenced by reworked macrophytes from freshly exposed lake level terraces during lowstands. Total inorganic carbon remains the most reliable proxy for climatic variations during the Holocene as high precipitation of carbonates can be linked to low lake levels and high autochthonous production. The onset of inorganic carbon precipitation has been associated with the southward shift of the SHW over the latitudes of Laguna Potrok Aike. The refined age-depth model of this record suggests that this shift occurred around 9.4 cal. ka BP. (c) 2012 Elsevier Ltd. All rights reserved.
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- Hahn, A., et al.
(författare)
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Comparative study of infrared techniques for fast biogeochemical sediment analyses
- 2011
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Ingår i: Geochemistry Geophysics Geosystems. - Washington, DC : AGU and the Geochemical Society. - 1525-2027. ; 12, s. Q10003-
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of sediment samples in the visible to mid infrared (IR) region requires small amounts of sample material and enables rapid and cost efficient geochemical analysis of mineral and organic sediment components. Here we use geochemical properties (total organic and inorganic carbon, biogenic silica, total nitrogen) from the ICDP deep drilling project PASADO to compare three different IR spectroscopy techniques: Diffuse Reflectance Fourier Transform IR Spectrometry (DRIFTS), Attenuated Total Reflectance Fourier Transform IR Spectroscopy (ATR-FTIRS) and Visible Near IR Spectroscopy (VNIRS). ATR-FTIRS and VNIRS are more rapid techniques compared to DRIFTS. Results show that calibration models developed using DRIFTS are most robust (correlation coefficient: R = 0.92 for TIC, R = 0.84 for BSi, R = 0.97 for TOC, R = 0.95 for TN). However, good statistical performance was also obtained by using ATR-FTIRS and VNIRS. When time and costs are limiting factors, these tools may be given preference for rapid biogeochemical screening.
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| 10. |
- Pearson, Emma J., et al.
(författare)
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A lacustrine GDGT-temperature calibration from the Scandinavian Arctic to Antarctic : Renewed potential for the application of GDGT-paleothermometry in lakes
- 2011
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Ingår i: Geochimica et Cosmochimica Acta. - Oxford : Elsevier BV. - 0016-7037 .- 1872-9533. ; 75:20, s. 6225-6238
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative climate reconstructions are fundamental to understand long-term trends in natural climate variability and to test climate models used to predict future climate change. Recent advances in molecular geochemistry have led to calibrations using glycerol dialkyl glycerol tetraethers (GDGTs), a group of temperature-sensitive membrane lipids found in Archaea and bacteria. GDGTs have been used to construct temperature indices for oceans (TEX(86) index) and soils (MBT/CBT index). The aim of this study is to examine GDGT-temperature relationships and assess the potential of constructing a GDGT-based palaeo-thermometer for lakes. We examine GDGT-temperature relationships using core top sediments from 90 lakes across a north-south transect from the Scandinavian Arctic to Antarctica including sites from Finland, Sweden, Siberia, the UK, Austria, Turkey, Ethiopia, Uganda, Chile, South Georgia and the Antarctic Peninsula. We examine a suite of 15 GDGTs, including compounds used in the TEX(86) and MBT/CBT indices and reflecting the broad range of GDGT inputs to small lake systems. GDGTs are present in varying proportions in all lakes examined. The TEX(86) index is not applicable to our sites because of the large relative proportions of soil derived and methanogenic components. Similarly, the MBT/CBT index is also not applicable and predicts temperatures considerably lower than those measured. We examine relationships between individual GDGT compounds and temperature, pH, conductivity and water depth. Temperature accounts for a large and statistically independent fraction of variation in branched GDGT composition. We propose a GDGT-temperature regression model with high accuracy and precision (R(2) = 0.88; RMSE = 2.0 degrees C; RMSEP = 2.1 degrees C) for use in lakes based on a subset of branched GDGT compounds and highlight the potential of this new method for reconstructing past temperatures using lake sediments. (C) 2011 Elsevier Ltd. All rights reserved.
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