Objectives
To determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade‐long follow‐up period.
Design
Prospective cohort study.
...Setting
Betula Study, Umeå, Sweden.
Participants
A population‐based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).
Measurements
Olfactory performance using the Scandinavian Odor‐Identification Test (SOIT) and self‐reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.
Results
Within the 10‐year follow‐up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71–0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health‐related and cognitive variables (HR = 0.92, 95% CI = 0.87–0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87–0.97, P = .001). Similar results were obtained for self‐reported olfactory dysfunction.
Conclusion
Poor odor identification and poor self‐reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.
The need for deep decarbonisation in the energy intensive basic materials industry is increasingly recognised. In light of the vast future potential for renewable electricity the implications of ...electrifying the production of basic materials in the European Union is explored in a what-if thought-experiment. Production of steel, cement, glass, lime, petrochemicals, chlorine and ammonia required 125 TW-hours of electricity and 851 TW-hours of fossil fuels for energetic purposes and 671 TW-hours of fossil fuels as feedstock in 2010. The resulting carbon dioxide emissions were equivalent to 9% of total greenhouse gas emissions in EU28. A complete shift of the energy demand as well as the resource base of feedstocks to electricity would result in an electricity demand of 1713 TW-hours about 1200 TW-hours of which would be for producing hydrogen and hydrocarbons for feedstock and energy purposes. With increased material efficiency and some share of bio-based materials and biofuels the electricity demand can be much lower. Our analysis suggest that electrification of basic materials production is technically possible but could have major implications on how the industry and the electric systems interact. It also entails substantial changes in relative prices for electricity and hydrocarbon fuels.
•Energy intensive basic materials industry has a high share in EU greenhouse gas emissions.•Decarbonising these industries is very important, but still relatively unexplored.•Electrification is possible regarding renewable energy resources and technologies.•Combination with energy and materials efficiency, biofuels and CCS is crucial.•Electrification needs very high amounts of electricity and strong policies.
Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules.
In two prospective, open-label, controlled, randomized, crossover ...pilot studies, 39 prevalent hemodialysis (HD) patients were studied in four dialysis treatments as follows: study 1, three MCO prototype dialyzers (AA, BB and CC with increasing permeability) and one high-flux dialyzer in HD; and study 2, two MCO prototype dialyzers (AA and BB) in HD and high-flux dialyzers in HD and hemodiafiltration (HDF). Primary outcome was lambda free light chain (λFLC) overall clearance. Secondary outcomes included overall clearances and pre-to-post-reduction ratios of middle and small molecules, and safety of MCO HD treatments.
MCO HD provided greater λFLC overall clearance least square mean (standard error) as follows: study 1: MCO AA 8.5 (0.54), MCO BB 11.3 (0.51), MCO CC 15.0 (0.53) versus high-flux HD 3.6 (0.51) mL/min; study 2: MCO AA 10.0 (0.58), MCO BB 12.5 (0.57) versus high-flux HD 4.4 (0.57) and HDF 6.2 (0.58) mL/min. Differences between MCO and high-flux dialyzers were consistently significant in mixed model analysis (each P < 0.001). Reduction ratios of λFLC were greater for MCO. Clearances of α1-microglobulin, complement factor D, kappa FLC (κFLC) and myoglobin were generally greater with MCO than with high-flux HD and similar to or greater than clearances with HDF. Albumin loss was moderate with MCO, but greater than with high-flux HD and HDF.
MCO HD removes a wide range of middle molecules more effectively than high-flux HD and even exceeds the performance of high-volume HDF for large solutes, particularly λFLC.
•We identify archetypal transition pathways in four industries.•We assess the feasibility of pathways in terms of conditions and potential.•The maturity of pathways varies significantly.•Sensitivity ...to learning and branching points key for future policy.
Analyses of the future for manufacturing and heavy industries in a climate constrained world many times focus on technological innovations in the early stages of the value chain, assuming few significant changes are plausible, wanted, or necessary throughout the rest of the value chain. Complex questions about competing interests, different ways of organising resource management, production, consumption, and integrating value chains are thus closed down to ones about efficiencies, pay-back times, and primary processing technologies. In this analysis, we move beyond this to identify archetypal pathways that span across value chains in four emissions intensive industries: plastics, steel, pulp and paper, and meat and dairy. The pathways as presented in the present paper were inductively identified in a multi-stage process throughout a four-year European research project. The identified archetypal pathways are i) production and end-use optimisation, ii) electrification with CCU, iii) CCS, iv) circular material flows, and v) diversification of bio-feedstock use.
The pathways are at different stages of maturity and furthermore their maturity vary across sectors. The pathways show that decarbonisation is likely to force value chains to cross over traditional boundaries. This implies that an integrated industrial and climate policy must handle both sectoral specificities and commonalities for decarbonised industrial development.
Amyloid-β (Aβ) protofibrils are known intermediates of the in vitro Aβ aggregation process and the protofibrillogenic Arctic mutation (APPE693G) provides clinical support for a pathogenic role of Aβ ...protofibrils in Alzheimer's disease (AD). To verify their in vivo relevance and to establish a quantitative Aβ protofibril immunoassay, Aβ conformation dependent monoclonal antibodies were generated. One of these antibodies, mAb158 (IgG2a), was used in a sandwich ELISA to specifically detect picomolar concentrations of Aβ protofibrils without interference from Aβ monomers or the amyloid precursor protein (APP). The specificity and biological significance of this ELISA was demonstrated using cell cultures and transgenic mouse models expressing human APP containing the Swedish mutation (APPKN670/671ML), or the Swedish and Arctic mutation in combination. The mAb158 sandwich ELISA analysis revealed presence of Aβ protofibrils in both cell and animal models, proving that Aβ protofibrils are formed not only in vitro, but also in vivo. Furthermore, elevated Aβ protofibril levels in the Arctic-Swedish samples emphasize the usefulness of the Arctic mutation as a model of enhanced protofibril formation. This assay provides a novel tool for investigating the role of Aβ protofibrils in AD and has the potential of becoming an important diagnostic assay.
Five-year changes in episodic and semantic memory were examined in a sample of 829 participants (35-80 years). A cohort-matched sample (
N
= 967) was assessed to control for practice effects. For ...episodic memory, cross-sectional analyses indicated gradual age-related decrements, whereas the longitudinal data revealed no decrements before age 60, even when practice effects were adjusted for. Longitudinally, semantic memory showed minor increments until age 55, with smaller decrements in old age as compared with episodic memory. Cohort differences in educational attainment appear to account for the discrepancies between cross-sectional and longitudinal data. Collectively, the results show that age trajectories for episodic and semantic memory differ and underscore the need to control for cohort and retest effects in cross-sectional and longitudinal studies, respectively.
This paper provides an overview of methodologies used for quantitative evaluations of security of supply. The studied material is mainly based on peer-reviewed articles and the methodologies are ...classified according to which stage in the supply chain their main focus is directed to, as well as their scientific background. Our overview shows that a broad variety of approaches is used, but that there are still some important gaps, especially if the aim is to study energy security in a future-oriented way.
First, there is a need to better understand how sources of insecurity can develop over time and how they are affected by the development of the energy system. Second, the current tendency to study the security of supply for each energy carrier separately needs to be complemented by comparisons of different energy carrier's supply chains. Finally, the mainly static perspective on system structure should be complemented with perspectives that to a greater extent take the systems' adaptive capacity and transformability into account, as factors with a potential to reduce the systems vulnerabilities. Furthermore, it may be beneficial to use methodological combinations, conduct more thorough sensitivity analysis and alter the mind-set from securing energy flows to securing energy services.
•We classify a broad range of methodologies in a framework.•Different methodologies give conflicting recommendations on how to increase security.•Methodological combinations could be used to identify robust policies.
Point mutations in the amyloid precursor protein gene (
) cause familial Alzheimer's disease (AD) by increasing generation or altering conformation of amyloid β (Aβ). Here, we describe the
mutation ...(Δ690-695), the first reported deletion causing autosomal dominant AD. Affected individuals have an age at symptom onset in their early forties and suffer from a rapidly progressing disease course. Symptoms and biomarkers are typical of AD, with the exception of normal cerebrospinal fluid (CSF) Aβ42 and only slightly pathological amyloid-positron emission tomography signals. Mass spectrometry and Western blot analyses of patient CSF and media from experimental cell cultures indicate that the
mutation alters APP processing by increasing β-secretase cleavage and affecting α-secretase cleavage. Furthermore, in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated Aβ, AβUpp1-42
, accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain.
Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain ...networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n
=
287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior–posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to
mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
► We report causal role of WM integrity in age-related differences in processing speed. ► Age related decreases in FA and increases in MD were observed. ► The anterior section of the corpus callosum was more susceptible to aging. ► Compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging.
Alzheimer's disease (AD) neuropathology is associated with neuroinflammation, but there are few useful biomarkers. Mutant variants of triggering receptor expressed on myeloid cells 2 (TREM2) have ...recently been linked to late-onset AD and other neurodegenerative disorders. TREM2, a microglial receptor, is involved in innate immunity. A cleaved fragment, soluble TREM2 (sTREM2), is present in the cerebrospinal fluid (CSF).
We developed and used a novel enzyme-linked immunosorbent assay to investigate the potential value of CSF sTREM2 as an AD biomarker in two independent cohorts: an AD/mild cognitive impairment (MCI)/control cohort (n = 100) and an AD/control cohort (n = 50).
We found no significant difference in sTREM2 levels between groups of controls and patients with AD or MCI. However, among all controls there was a positive correlation between sTREM2 and age (Spearman rho = 0.50; p < 0.001; n = 75). In the AD/MCI/control cohort, CSF sTREM2 correlated positively with total Tau (T-tau) (Spearman rho 0.57; p < 0.001; n = 50), phosphorylated Tau (P-tau) (Spearman rho 0.63; p < 0.001; n = 50) and amyloid-β1-42 (Aβ42) (Spearman rho 0.35; p = 0.01; n = 50) in control subjects. Among controls with a CSF Aβ42 above a cut-off value (700 pg/ml) in this cohort, the positive correlation between sTREM2 and Aβ42 was stronger (Spearman rho = 0.44; p = 0.002; n = 46).
sTREM2 in CSF correlates with aging in controls, and with the neurodegenerative markers CSF T-tau/P-tau among controls who are negative for AD CSF core biomarkers Aβ42, T-tau or P-tau.
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