235 research outputs found

    Starting a new anti-seizure medication in drug-resistant epilepsy: Add-on or substitute?

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    Objectives: Randomized studies in drug-resistant epilepsy (DRE) typically involve addition of a new anti-seizure medication (ASM). However, in clinical practice, if the patient is already taking multiple ASMs, then substitution of one of the current ASMs commonly occurs, despite little evidence supporting this approach. Methods: Longitudinal prospective study of seizure outcome after commencing a previously untried ASM in patients with DRE. Multivariable time-to-event and logistic regression models were used to evaluate outcomes by whether the new ASM was introduced by addition or substitution. Results: A total of 816 ASM changes in 436 adult patients with DRE between 2010 and 2018 were analyzed. The new ASM was added on 407 (50.1%) occasions and substituted on 409 (49.9%). Mean patient follow-up was 3.2 years. Substitution was more likely if the new ASM was enzyme-inducing or in patients with a greater number of concurrent ASMs. ASM add-on was more likely if a γ-aminobutyric acid (GABA) agonist was introduced or if the patient had previously trialed a higher number of ASMs. The rate of discontinuation due to lack of tolerability was similar between the add-on and substitution groups. No difference between the add-on and substitution ASM introduction strategies was observed for the primary outcome of ≥50% seizure reduction at 12 months. Significance: Adding or substituting a new ASM in DRE has the same influence on seizure outcomes. The findings confirm that ASM alterations in DRE can be individualized according to concurrent ASM therapy and patient characteristics

    How diet portfolio shifts combined with land-based climate change mitigation strategies could reduce climate burdens in Germany

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    Many studies have analysed the environmental impact of vegan, vegetarian, or reduced meat diets. To date, literature has not evaluated how diet shifts affect environmental impacts by utilising portfolios which reflect personal nutrition preferences. Further, changing diets could alter the available land for non-food uses. This paper defines novel diet portfolios to outline alternative diet transitions and choices within the population and finds their effect on greenhouse gas (GHG) emissions, primary energy use, and land use in Germany. The aim of this study is to capture how these diet shifts affect land availability and increase the options for land-based climate change mitigation strategies. To do so, a contextualisation is made to compare the use of freed-up land for afforestation or biomethane production (with and without carbon capture and storage). The investigated diet portfolios lead to a reduction of the investigated impacts (GHG emissions: 7–67%; energy use: 5–46%; land use: 6–64%). Additionally, afforestation of freed-up land from each diet portfolio leads to further emission removals of 4–37%. In comparison, using the land to produce energy crops for biomethane production could lead to 2–23% further CO2-eq emission reductions when replacing fossil methane. If biomethane production is paired with carbon capture and storage, emission abatement is increased to 3–34%. This research indicates various short-term pathways to reduce GHG emissions with portfolio diet shifts. Utilising freed-up land for climate change mitigation strategies could prove essential to meet climate targets, but trade-offs with, e.g. biodiversity and ecosystem services exist and should be considered

    Skin Cancer and UV Exposure-Related Behaviors Among Appalachian and Non-Appalachian Adults

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    Introduction: Appalachian communities experience elevated rates of cancer incidence and mortality relative to other regions in the U.S. Specifically, melanoma mortality rates are higher in Appalachia compared to the national average, despite comparable incidence rates. Purpose: To examine differences in self-reported history of skin cancer and prevalence of two UV exposure behaviors between Appalachian and non-Appalachian adults in a nationally representative sample. Methods: Data are from four cross-sectional cycles of the Health Information National Trends Survey (2011–2014) (N=14,451). We examined sunscreen use and tanning bed use, and self-reported history of melanoma and non-melanoma skin cancer. Descriptive and weighted multivariable analyses were conducted to examine sunscreen and tanning bed use, controlling for sociodemographic characteristics. Results: Approximately 8% of the study sample resided in Appalachia (n=1,015). Self-reported melanoma (0.6%) and non-melanoma (3.2%) skin cancer histories were low among Appalachians and did not differ statistically from non-Appalachians (p\u3e0.05). Only 21.2% of Appalachians reported using sunscreen often or always when going outside for more than one hour on a warm, sunny day compared to 27.4% of non-Appalachians (p\u3c0.05). In separate multivariable logistic regressions, Appalachians reported lower odds of sunscreen use compared to non-Appalachian (OR=0.76, p=0.04), but there were no regional differences in tanning bed use (OR=1.48, p=0.23) when controlling for sociodemographics and general health status. Implications: Appalachians had comparable histories of self-reported melanoma and non-melanoma skin cancer but were less likely to report sunscreen use than non-Appalachians. Enhanced communication efforts to promote sunscreen use and other UV protection behaviors in Appalachia may be valuable

    Is language ability associated with behaviors of concern in autism? A systematic review

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    This review systematically synthesized evidence on the association between structural language ability and behaviors of concern (BoC) in autism. Four databases were searched for studies that included >10 autistic participants, measures of structural language (content and/or form of language) and BoC, and an analysis of their association. BoCs included self-injurious behavior (SIB), aggression, tantrums, and externalizing behavior. Methodological quality of studies were assessed using the Newcastle Ottawa Scale. Forty-five publications (n = 11,961) were included. Forty studies were cross-sectional and five were prospective cohort studies. Over 70% of the studies investigating expressive language and SIB (n = 10), aggression (n = 5), tantrums (n = 3), and externalizing behavior (n = 17) reported an inverse association, where lower expressive language ability was associated with increased BoC. Eleven out of sixteen studies of combined expressive and receptive language reported an inverse relationship with SIB or aggression. All outcomes were rated as moderate to very low certainty of evidence. This review highlights evidence showing an inverse association between expressive or combined language ability and SIB, and externalizing behavior in autism. However, further high-quality studies that use standardized, consistent measures of language and behavior and investigate longitudinal associations are needed. Early detection and support for reduced structural language difficulties have substantial potential to assist in reducing BoC

    A model for cost- and greenhouse gas optimal material and energy allocation of biomass and hydrogen

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    BENOPT, an optimal material and energy allocation model is presented, which is used to assess cost-optimal and/or greenhouse gas abatement optimal allocation of renewable energy carriers across power, heat and transport sectors. A high level of detail on the processes from source to end service enables detailed life-cycle greenhouse gas and cost assessments. Pareto analyses can be performed, as well as thorough sensitivity analyses. The model is designed to analyse optimal biomass and hydrogen usage, as a complement to integrated assessment and power system models

    Adjuvant immunotherapy increases β cell regenerative factor Reg2 in the pancreas of diabetic mice

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    Insulin-producing β cells can partially regenerate in adult pancreatic tissues, both in human and animal models of type 1 diabetes (T1D). Previous studies have shown that treatment with mycobacterial adjuvants such as CFA and bacillus Calmette-Guérin prevents induction and recurrence of T1D in NOD mice with partial recovery of β cell mass. In this study, we investigated factors involved in the regeneration of β cells in the pancreas of NOD mice during diabetes development and after treatment with adjuvants. The Regeneration (Reg) gene family is known to be involved in regeneration of various tissues including β cells. Reg2 expression was found to be upregulated in pancreatic islets both during diabetes development and as a result of adjuvant treatment in diabetic NOD mice and in C57BL/6 mice made diabetic by streptozotocin treatment. The upregulation of Reg2 by adjuvant treatment was independent of signaling through MyD88 and IL-6 because it was not altered in MyD88 or IL-6 knockout mice. We also observed upregulation of Reg2 in the pancreas of diabetic mice undergoing β cell regenerative therapy with exendin-4 or with islet neogenesis-associated protein. Reg2 expression following adjuvant treatment correlated with a reduction in insulitis, an increase in insulin secretion, and an increase in the number of small islets in the pancreas of diabetic NOD mice and with improved glucose tolerance tests in streptozotocin-treated diabetic C57BL/6 mice. In conclusion, adjuvant immunotherapy regulates T1D in diabetic mice and induces Reg2-mediated regeneration of β cells. Copyright © 2010 by The American Association of Immunologists, Inc

    Expression of fatty acid and triacylglycerol synthesis genes in interspecific hybrids of oil palm

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    © 2020, The Author(s). Evaluation of transcriptome data in combination with QTL information has been applied in many crops to study the expression of genes responsible for specific phenotypes. In oil palm, the mesocarp oil extracted from E. oleifera × E. guineensis interspecific hybrids is known to have lower palmitic acid (C16:0) content compared to pure African palms. The present study demonstrates the effectiveness of transcriptome data in revealing the expression profiles of genes in the fatty acid (FA) and triacylglycerol (TAG) biosynthesis processes in interspecific hybrids. The transcriptome assembly yielded 43,920 putative genes of which a large proportion were homologous to known genes in the public databases. Most of the genes encoding key enzymes involved in the FA and TAG synthesis pathways were identified. Of these, 27, including two candidate genes located within the QTL associated with C16:0 content, showed differential expression between developmental stages, populations and/or palms with contrasting C16:0 content. Further evaluation using quantitative real-time PCR revealed that differentially expressed patterns are generally consistent with those observed in the transcriptome data. Our results also suggest that different isoforms are likely to be responsible for some of the variation observed in FA composition of interspecific hybrids

    Thiosquaramides: pH switchable anion transporters

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    The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquar-amides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH

    Future renewable energy targets in the EU: Impacts on the German transport

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    The transport sector is at the center of discussions on accelerating the energy transition due to its still increasing contribution to greenhouse gas emissions worldwide; therefore, the EU has set binding targets for the use of renewable energy in transport through the Renewable Energy Directive. To analyze the economic impact of these targets, we developed an optimization model that considers bio- and electricity-based fuel options, various transport sectors, and future policy requirements. Our study of the German transport sector found that imported alternative fuels play a key role in reducing fossil fuel usage. We also identify two technological and managerial obstacles: policymakers need to prioritize the rapid electrification of vehicles in the near future; and in the distant future, more attention is needed in research for new technologies in commercial transport. Although our findings are tailored to Germany, the employed approach can be transferred to other models and countries

    Mariprofundus ferrooxydans PV-1 the First Genome of a Marine Fe(II) Oxidizing Zetaproteobacterium

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    © The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e25386, doi:10.1371/journal.pone.0025386.Mariprofundus ferrooxydans PV-1 has provided the first genome of the recently discovered Zetaproteobacteria subdivision. Genome analysis reveals a complete TCA cycle, the ability to fix CO2, carbon-storage proteins and a sugar phosphotransferase system (PTS). The latter could facilitate the transport of carbohydrates across the cell membrane and possibly aid in stalk formation, a matrix composed of exopolymers and/or exopolysaccharides, which is used to store oxidized iron minerals outside the cell. Two-component signal transduction system genes, including histidine kinases, GGDEF domain genes, and response regulators containing CheY-like receivers, are abundant and widely distributed across the genome. Most of these are located in close proximity to genes required for cell division, phosphate uptake and transport, exopolymer and heavy metal secretion, flagellar biosynthesis and pilus assembly suggesting that these functions are highly regulated. Similar to many other motile, microaerophilic bacteria, genes encoding aerotaxis as well as antioxidant functionality (e.g., superoxide dismutases and peroxidases) are predicted to sense and respond to oxygen gradients, as would be required to maintain cellular redox balance in the specialized habitat where M. ferrooxydans resides. Comparative genomics with other Fe(II) oxidizing bacteria residing in freshwater and marine environments revealed similar content, synteny, and amino acid similarity of coding sequences potentially involved in Fe(II) oxidation, signal transduction and response regulation, oxygen sensation and detoxification, and heavy metal resistance. This study has provided novel insights into the molecular nature of Zetaproteobacteria.Funding has been provided by the NSF Microbial Observatories Program (KJE, DE), NSF’s Science and Technology Program, by the Gordon and Betty Moore Foundation (KJE), the College of Letters, Arts, and Sciences at the University of Southern California (KJE), and by the NASA Astrobiology Institute (KJE, DE). Advanced Light Source analyses at the Lawrence Berkeley National Lab are supported by the Office of Science, Basic Energy Sciences, Division of Materials Science of the United States Department of Energy (DE-AC02-05CH11231)
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