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1.
  • Stanaway, Jeffrey D., et al. (författare)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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2.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
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3.
  • Lozano, Rafael, et al. (författare)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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4.
  • Murray, Christopher J. L., et al. (författare)
  • Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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5.
  • Arian, Fatemeh, et al. (författare)
  • Myocardial Function Prediction After Coronary Artery Bypass Grafting Using MRI Radiomic Features and Machine Learning Algorithms
  • 2022
  • Ingår i: Journal of digital imaging. - : Springer Nature. - 0897-1889 .- 1618-727X. ; 35:6, s. 1708-1718
  • Tidskriftsartikel (refereegranskat)abstract
    • The main aim of the present study was to predict myocardial function improvement in cardiac MR (LGE-CMR) images in patients after coronary artery bypass grafting (CABG) using radiomics and machine learning algorithms. Altogether, 43 patients who had visible scars on short-axis LGE-CMR images and were candidates for CABG surgery were selected and enrolled in this study. MR imaging was performed preoperatively using a 1.5-T MRI scanner. All images were segmented by two expert radiologists (in consensus). Prior to extraction of radiomics features, all MR images were resampled to an isotropic voxel size of 1.8 × 1.8 × 1.8 mm3. Subsequently, intensities were quantized to 64 discretized gray levels and a total of 93 features were extracted. The applied algorithms included a smoothly clipped absolute deviation (SCAD)–penalized support vector machine (SVM) and the recursive partitioning (RP) algorithm as a robust classifier for binary classification in this high-dimensional and non-sparse data. All models were validated with repeated fivefold cross-validation and 10,000 bootstrapping resamples. Ten and seven features were selected with SCAD-penalized SVM and RP algorithm, respectively, for CABG responder/non-responder classification. Considering univariate analysis, the GLSZM gray-level non-uniformity-normalized feature achieved the best performance (AUC: 0.62, 95% CI: 0.53–0.76) with SCAD-penalized SVM. Regarding multivariable modeling, SCAD-penalized SVM obtained an AUC of 0.784 (95% CI: 0.64–0.92), whereas the RP algorithm achieved an AUC of 0.654 (95% CI: 0.50–0.82). In conclusion, different radiomics texture features alone or combined in multivariate analysis using machine learning algorithms provide prognostic information regarding myocardial function in patients after CABG.
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7.
  • Koushki, Mehdi, et al. (författare)
  • Screening the critical protein subnetwork to delineate potential mechanisms and protective agents associated with arsenic-induced cutaneous squamous cell carcinoma: A toxicogenomic study
  • 2024
  • Ingår i: Food and Chemical Toxicology. - 1873-6351 .- 0278-6915. ; 185
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies show that complex mechanisms are involved in arsenic-induced malignant transformation of cells. This study aimed to decipher molecular mechanisms associated with arsenic-induced cutaneous squamous cell carcinoma (cSCC) and suggest potential protective factors. RNA-seq-based differentially expressed genes between arsenic-exposed human keratinocytes (HaCaT) and controls were used to construct a protein-protein interaction (PPI) network and discover critical subnetwork-based mechanisms. Protective compounds against arsenic toxicity were determined and their target interactions in the core sub-network were identified by the comparative toxicogenomic database (CTD). The binding affinity between the effective factor and target was calculated by molecular docking. A total of 15 key proteins were screened out as critical arsenic-responsive subnetwork (FN1, IL-1A, CCN2, PECAM1, FGF5, EDN1, FGF1, PXDN, DNAJB9, XBP1, ERN1, PDIA4, DNAJB11, FOS, PDIA6) and 7 effective protective agents were identified (folic acid, quercetin, zinc, acetylcysteine, methionine, catechin, selenium). The GeneMANIA predicted detailed interactions of the subnetwork and revealed terms related to unfolded protein response as the main processes. FN1, IL1A and CCN2, as top significant genes, had good docking affinity with folic acid and quercetin, as selected key compounds. Integration of gene expression and protein-protein interaction related to arsenic exposure in cSCC explored the potential mechanisms and protective agents.
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8.
  • Narooie-Nejad, Mehrnaz, et al. (författare)
  • Loss of function mutations in the gene encoding latent transforming growth factor beta binding protein 2, LTBP2, cause primary congenital glaucoma
  • 2009
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:20, s. 3969-3977
  • Tidskriftsartikel (refereegranskat)abstract
    • Glaucoma is a heterogeneous group of optic neuropathies that manifests by optic nerve head cupping or degeneration of the optic nerve, resulting in a specific pattern of visual field loss. Glaucoma leads to blindness if left untreated, and is considered the second leading cause of blindness worldwide. The subgroup primary congenital glaucoma (PCG) is characterized by an anatomical defect in the trabecular meshwork, and age at onset in the neonatal or infantile period. It is the most severe form of glaucoma. CYP1B1 was the first gene genetically linked to PCG, and CYP1B1 mutations are the cause of disease in 20-100% of patients in different populations. Here, we report that LTBP2 encoding latent transforming growth factor beta binding protein 2 is a PCG causing gene, confirming results recently reported. A disease-associated locus on chromosome 14 was identified by performing whole genome autozygosity mapping in Iranian PCG families using high density single nucleotide polymorphism chips, and two disease-segregating loss of function mutations in LTBP2, p.Ser472fsX3 and p.Tyr1793fsX55, were observed in two families while sequencing candidate genes in the locus. The p.Tyr1793fsX55 mutation affects an amino acid close to the C-terminal of the encoded protein. Subsequently, LTBP2 expression was shown in human eyes, including the trabecular meshwork and ciliary processes that are thought to be relevant to the etiology of PCG.
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9.
  • Rezaei, Fatemeh, et al. (författare)
  • Anatomical and morphological characteristics of beech wood after CO2-laser cutting
  • 2022
  • Ingår i: Wood Material Science & Engineering. - : Taylor & Francis Group. - 1748-0272 .- 1748-0280. ; 17:6, s. 459-468
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to characterize the surface quality of beech wood (Fagus sylvatica L.) cut by a CO2-laser. Boards were conditioned to a low (about 8% moisture content), 12% and a high, (about 18% moisture content). Laser cutting was performed at varying processing parameters, i.e. cutting speed, gas pressure and focal-point position. A confocal microscope was used to determine the average surface roughness perpendicular to the grain. The anatomical structures of the laser-cut surfaces were examined with scanning electron microscope. The result showed that smoother surfaces were obtained at the low moisture content when processed at a gas pressure of 21 bar. Focal-point positioning did only have an effect on the surface roughness at 12% moisture content whereas the value was substantially lower for focal-point positioned on the surface. The surfaces cut at 18% moisture content, and at a cutting speed of 3.5 m/min generated a rougher surface than cut at low moisture content and at a lower speed. Laser cutting produced a rougher surface as compared to sawn surface (circular saw). The structural integrity of the laser-cut surface was more intact when the wood was having high moisture content and processed at a high cutting speed.
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10.
  • Rezaei, Fatemeh, et al. (författare)
  • Delay and Stability Analysis of Caching in Heterogeneous Cellular Networks
  • 2016
  • Ingår i: 2016 23RD INTERNATIONAL CONFERENCE ON TELECOMMUNICATIONS (ICT). - : IEEE. - 9781509019908
  • Konferensbidrag (refereegranskat)abstract
    • In this paper, we propose a general delay and stability performance analysis in Heterogeneous Cellular Caching Networks (HCCNs), based on queuing theory. We introduce new performance metrics in HCCNs and propose an optimization problem which minimizes the average experienced delay for users by ensuring the stability of the network. In addition, from the design perspective, we address the problem of finding the minimum cache size for the small cell base stations (SBSs) for having a tolerable average delay and also a stable network. Finally, the analytic expressions derived in this paper are validated through real trace-driven experiments on traffic of YouTube video requests.
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11.
  • Rezaei, Fatemeh, et al. (författare)
  • Performance Analysis of Heterogeneous Cellular Caching Networks With Overlapping Small Cells
  • 2022
  • Ingår i: IEEE Transactions on Vehicular Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9545 .- 1939-9359. ; 71:2, s. 1941-1951
  • Tidskriftsartikel (refereegranskat)abstract
    • Caching at network edges has attracted more and more research interests recently for the purpose of alleviating the network traffic pressure especially in backhaul links and improving user experience. We study Heterogeneous Cellular Caching Networks (HCCNs) consisting of macro cells in which N small cell base stations (SBSs) equipped with cache memory operate in conjunction with the macro cell base station (MBS). We provide closed-form expressions of the MBS and SBSs utilization factors and average user-experienced-delay in HCCNs with overlapping coverage regions, considering general traffic models for the request arrivals based on the Independent Reference Model (IRM) and renewal traffic models. Moreover, we propose a novel caching scheme in HCCNs, namely Cooperative Most Popular Caching (CMPC), which outperforms the existing schemes in terms of delay. Subsequently, we present the bandwidth assignment problem aiming to minimize the average user-experienced-delay under stability and cache size constraints in HCCNs with overlapping coverage regions and stochastic request arrivals. Finally, the analytic results are validated through numerical results and real trace-driven experiments.
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12.
  • Rezaei, Fatemeh, et al. (författare)
  • The Characteristics of Glued Tensile Shear Strength Constituted of Wood Cut by CO2 Laser
  • 2023
  • Ingår i: Journal of Renewable Materials. - : Tech Science Press. - 2164-6325 .- 2164-6341. ; 11:8, s. 3277-3296
  • Tidskriftsartikel (refereegranskat)abstract
    • The performance of engineered wood products is highly associated with proper bonding and an efficient cutting method. This paper investigates the influence of CO2 laser cutting on the wetting properties, the modified chemical component of the laser-cut surface, and the strength and adhesive penetration near the bondline. Beechwood is cut by the laser with varying processing parameters, cutting speeds, gas pressures, and focal point positions. The laser-cut samples were divided into two groups, sanded and non-sanded samples. Polyvinyl acetate adhesive (PVAc) was used to bond the groups of laser-cut samples. After assembly with cold pressing, the tensile shear test was carried out. Numerical modelling was carried out to determine the partial elongation and shear strain of the glue line. Based on this, the shear modulus and linear elasticity of the glue line were estimated. Scanning electron microscopy was used to assess the adhesive penetration into the porosity structure of the laser-cut samples, and the depth of the heat-affected zone. The laser-cut surface was analysed by Fourier transform infrared spectroscopy. The wetting properties of the laser-cut surface were investigated by using a contact angle goniometer. The numerical model of the strain-stress curve confirmed the experimental model. The highest modulus of the linear elasticity of the glue in the numerical calculation belongs to the joint containing laser-cut samples at a gas pressure of 21 (bar). The penetration depth of PVAc adhesive into the porosity structure of the laser-cut samples was similar to that of sawn samples. The deepest heat-affected zone in the laser-cut samples was 150 µm. A PVAc drop disappeared immediately on the laser-cut surface without sanding, but gradually on the sanded surface. In contrast, the drop on the sawn surface remained with an angle of 32°–48°. The degradation of hemicellulose and lignin was proven by the lower intensity of the C=O and C-O Bonds, compared to the sawn surface. 
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13.
  • Rezaei, Fatemeh, et al. (författare)
  • Water uptake and permeability in sapwood and heartwood of hydro-thermally proceed Turkey oak
  • 2024
  • Ingår i: Wood Material Science & Engineering. - : Taylor & Francis. - 1748-0272 .- 1748-0280. ; 19:3, s. 803-810
  • Tidskriftsartikel (refereegranskat)abstract
    • This study aimed to investigate the combined effect of steaming and heating on the equilibrium moisture content (EMC) of Turkey oak (Quercus cerris L.) wood over a nine-year period. The study also aimed to determine the impact of steaming on water absorption and water permeability, crucial for the durability of the species against environmental factors. The specimens underwent thermal modification with and without steaming, then were stored under laboratory conditions for ten years. The mass of the specimens was monitored throughout the ten-year period. To measure the water uptake capacity, the specimens were soaked in water for 120 hours. The water permeability of the specimens was assessed using a pressurised chamber. The results showed that the moisture content of thermally-modified oak was constant under laboratory conditions after nine years, further improved by steam treatment. The research also revealed that the steamed wood absorbed more water during water submersion compared to the unmodified wood. When the steaming treatment was applied, there was a significant increase in permeability in the sapwood compared to the heartwood, due to anatomical variations. Despite this, statistical noise, and material variability, alongside tylosis presence, underline the need for examining more specimens in future studies.
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14.
  • Rezaei Moghadam, Adel, et al. (författare)
  • Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress
  • 2015
  • Ingår i: BMC Complementary and Alternative Medicine. - : BioMed Central. - 1472-6882. ; 15:246
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Methotrexate (MTX) is an antimetabolite broadly used in treatment of cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its application. We investigated hepatoprotective effects of turmeric in MTX-induced liver toxicity. Methods: All experiments were performed on male Wistar albino rats that were randomly divided into six groups. Group one received saline orally for 30 days (control group), groups two and three received turmeric extract (100, 200 mg/kg respectively) orally for 30 days, group four received single dose, of MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at day 30. Four days after MTX injection animals were sacrificed and evaluated. Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers of biliary function), albumin (reflect liver synthetic function) as well as the plasma TAS concentration (antioxidant defenses) were determined. The cellular antioxidant defense activities were examined in liver tissue samples using SOD, CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In addition, liver damage was evaluated histopathologically. Results: MTX significantly induced liver damage (P less than 0.05) and decreased its antioxidant capacity, while turmeric was hepatoprotective. Liver tissue microscopic evaluation showed that MTX treatment induced severe centrilobular and periportal degeneration, hyperemia of portal vein, increased artery inflammatory cells infiltration and necrosis, while all of histopathological changes were attenuated by turmeric (200 mg/kg). Conclusion: Turmeric extract can successfully attenuate MTX-hepatotoxicity. The effect is partly mediated through extracts antinflammatory activity.
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