Recent progress in the development of polyethylene/metal‐oxide nanocomposites for extruded high‐voltage direct‐current (HVDC) cables with ultrahigh electric insulation properties is presented. This ...is a promising technology with the potential of raising the upper voltage limit in today's underground/submarine cables, based on pristine polyethylene, to levels where the loss of energy during electric power transmission becomes low enough to ensure intercontinental electric power transmission. The development of HVDC insulating materials together with the impact of the interface between the particles and the polymer on the nanocomposites electric properties are shown. Important parameters from the atomic to the microlevel, such as interfacial chemistry, interfacial area, and degree of particle dispersion/aggregation, are discussed. This work is placed in perspective with important work by others, and suggested mechanisms for improved insulation using nanoparticles, such as increased charge trap density, adsorption of impurities/ions, and induced particle dipole moments are considered. The effects of the nanoparticles and of their interfacial structures on the mechanical properties and the implications of cavitation on the electric properties are also discussed. Although the main interest in improving the properties of insulating polymers has been on the use of nanoparticles, leading to nanodielectrics, it is pointed out here that larger microscopic hierarchical metal‐oxide particles with high surface porosity also impart good insulation properties. The impact of the type of particle and its inherent properties (purity and conductivity) on the nanocomposite dielectric and insulating properties are also discussed based on data obtained by a newly developed technique to directly observe the charge distribution on a nanometer scale in the nanocomposite.
Recent progress in the development of polyethylene/metal‐oxide nanocomposites with “optimal” interfaces for the next generation of extruded high‐voltage direct‐current cables with ultralow transmission loss is presented. This is the most promising way of delivering clean and renewable energy from remote areas to more densely populated regions.
Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and glatiramer ...acetate (GA), the magnitude of potential risk increase is not well established in real-world populations. Even less is known about infection risk associated with rituximab, which is extensively used off-label to treat MS in Sweden.
To examine the risk of serious infections associated with disease-modifying treatments for MS.
This nationwide register-based cohort study was conducted in Sweden from January 1, 2011, to December 31, 2017. National registers with prospective data collection from the public health care system were used. All Swedish patients with relapsing-remitting MS whose data were recorded in the Swedish MS register as initiating treatment with rituximab, natalizumab, fingolimod, or interferon beta and GA and an age-matched and sex-matched general population comparator cohort were included.
Treatment with rituximab, natalizumab, fingolimod, and interferon beta and GA.
Serious infections were defined as all infections resulting in hospitalization. Additional outcomes included outpatient treatment with antibiotic or herpes antiviral medications. Adjusted hazard ratios (HRs) were estimated in Cox regressions.
A total of 6421 patients (3260 taking rituximab, 1588 taking natalizumab, 1535 taking fingolimod, and 2217 taking interferon beta/GA) were included, plus a comparator cohort of 42 645 individuals. Among 6421 patients with 8600 treatment episodes, the mean (SD) age at treatment start ranged from 35.0 (10.1) years to 40.4 (10.6) years; 6186 patients were female. The crude rate of infections was higher in patients with MS taking interferon beta and GA than the general population (incidence rate, 8.9 95% CI, 6.4-12.1 vs 5.2 95% CI, 4.8-5.5 per 1000 person-years), and higher still in patients taking fingolimod (incidence rate, 14.3 95% CI, 10.8-18.5 per 1000 person-years), natalizumab (incidence rate, 11.4 95% CI, 8.3-15.3 per 1000 person-years), and rituximab (incidence rate, 19.7 95% CI, 16.4-23.5 per 1000 person-years). After confounder adjustment, the rate remained significantly higher for rituximab (HR, 1.70 95% CI, 1.11-2.61) but not fingolimod (HR, 1.30 95% CI, 0.84-2.03) or natalizumab (HR, 1.12 95% CI, 0.71-1.77) compared with interferon beta and GA. In contrast, use of herpes antiviral drugs during rituximab treatment was similar to that of interferon beta and GA and lower than that of natalizumab (HR, 1.82 1.34-2.46) and fingolimod (HR, 1.71 95% CI, 1.27-2.32).
Patients with MS are at a generally increased risk of infections, and this differs by treatment. The rate of infections was lowest with interferon beta and GA; among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections. The different risk profiles should inform the risk-benefit assessments of these treatments.
Nanostructured biological materials inspire the creation of materials with tunable mechanical properties. Strong cellulose nanofibrils derived from bacteria or wood can form ductile or tough networks ...that are suitable as functional materials. Here, we show that freeze-dried bacterial cellulose nanofibril aerogels can be used as templates for making lightweight porous magnetic aerogels, which can be compacted into a stiff magnetic nanopaper. The 20-70-nm-thick cellulose nanofibrils act as templates for the non-agglomerated growth of ferromagnetic cobalt ferrite nanoparticles (diameter, 40-120 nm). Unlike solvent-swollen gels and ferrogels, our magnetic aerogel is dry, lightweight, porous (98%), flexible, and can be actuated by a small household magnet. Moreover, it can absorb water and release it upon compression. Owing to their flexibility, high porosity and surface area, these aerogels are expected to be useful in microfluidics devices and as electronic actuators.
The prevalence of type 2 diabetes (T2D) is higher in black Africans than their European counterparts. This review summarizes the research exploring the pathogenesis of T2D in populations of African ...ancestry compared to white Europeans and shows that the pathogenesis differs by ethnicity. Black Africans present with a phenotype of low insulin sensitivity and hyperinsulinaemia as a result of increased insulin secretion and reduced hepatic insulin clearance. Whether hyperinsulinaemia precedes insulin resistance or is merely a compensatory mechanism is yet to be determined. Black Africans have lower visceral adipose tissue and ectopic fat deposition and greater peripheral (gluteo‐femoral) fat deposition than their European counterparts. This suggests that black Africans are more sensitive to the effects of ectopic fat deposition, or alternatively, that ectopic fat is not an important mediator of T2D in black Africans. Importantly, ethnic disparities in T2D risk factors may be confounded by differences in sociocultural and lifestyle factors. Future longitudinal and dietary intervention studies, in combination with genetic analyses, are needed for a better understanding of the pathophysiology of T2D in black Africans. This will be key for effective prevention and management strategies.
Content List ‐ Read more articles from the symposium: “Obesity and Type 2 Diabetes: Understanding the Role of Ethnicity”.
Alzheimer's disease (AD) brain tissue can act as a seed to accelerate aggregation of amyloid-β (Aβ) into plaques in AD transgenic mice. Aβ seeds have been hypothesized to accelerate plaque formation ...in a prion-like manner of templated seeding and intercellular propagation. However, the structure(s) and location(s) of the Aβ seeds remain unknown. Moreover, in contrast to tau and α-synuclein, an in vitro system with prion-like Aβ has not been reported. Here we treat human APP expressing N2a cells with AD transgenic mouse brain extracts to induce inclusions of Aβ in a subset of cells. We isolate cells with induced Aβ inclusions and using immunocytochemistry, western blot and infrared spectroscopy show that these cells produce oligomeric Aβ over multiple replicative generations. Further, we demonstrate that cell lysates of clones with induced oligomeric Aβ can induce aggregation in previously untreated N2a APP cells. These data strengthen the case that Aβ acts as a prion-like protein, demonstrate that Aβ seeds can be intracellular oligomers and for the first time provide a cellular model of nucleated seeding of Aβ.
•Prion-like propagation of amyloid beta in cell culture•Intracellular amyloid beta can induce prion-like cellular propagation.•The intracellular seed is consistent with a high molecular weight oligomer.
Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set ...of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve AUC = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (P
CSF < 4 × 10−5, P
plasma < 4 × 10−5), and plasma CCL20 was associated with disease severity (P = 4 × 10−5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.
Background:
Both smoking and exposure to passive smoking have repeatedly been associated with increased multiple sclerosis (MS) risk, but have never before been studied together. We assessed the ...public health impact of these factors.
Methods:
In a Swedish population-based case-control study (2455 cases, 5336 controls), we calculated odds ratios of developing MS associated with different categories of tobacco smoke exposure, together with 95% confidence intervals, by using logistic regression. The excess proportion of cases attributable to smoking and passive smoking was calculated as a percentage.
Results:
Both smoking and exposure to passive smoking contribute to MS risk in a dose-dependent manner. At the population level, 20.4% of all cases were attributable to smoke exposure. Among subjects carrying the genetic risk factor HLA-DRB1*15 but lacking HLA-A*02, 41% of the MS cases were attributable to smoking.
Conclusions:
From a public health perspective, the impact of smoking and passive smoking on MS risk is considerable. Preventive measures in order to reduce tobacco smoke exposure are, therefore, essential. In particular, individuals with a history of MS in the family should be informed regarding the impact of smoking on the risk of MS, and the importance of preventing their children from being exposed to passive smoke.
During the past 40 years brain tissue grafting techniques have been used both to study fundamental neurobiological questions and to treat neurological diseases. Motor symptoms of Parkinson's disease ...are largely due to degeneration of midbrain dopamine neurones. Because the nigrostriatal pathology is relatively focused anatomically, Parkinson's disease is considered the ideal candidate for brain repair by neural grafting and dopamine neurone transplantation for it has led the way in the neural transplantation research field. In this mini‐review, we briefly highlight four important areas of development. First, we describe marked functional benefits up to 18 years after transplantation surgery in patients with Parkinson's disease. This is proof‐of‐principle that, using optimal techniques and patient selection, grafted dopamine neurones can work in humans and the duration of the benefit exceeds placebo effects associated with surgery. Second, we describe that eventually protein aggregates containing α‐synuclein, identical to Lewy bodies, develop inside foetal dopamine neurones transplanted to patients with Parkinson's disease. This gives clues about pathogenetic mechanisms operating in Parkinson's disease, and also raises the question whether neural graft function will eventually decline as the result of the disease process. Third, we describe new emerging sources of transplantable dopamine neurones derived from pluripotent stem cells or reprogrammed adult somatic cells. Fourth, we highlight an important European Union‐funded multicentre clinical trial involving transplantation of foetal dopamine neurones in Parkinson's disease. We describe the design of this ongoing trial and how it can impact on the overall future of cell therapy in Parkinson's disease.
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