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- Mayén, Ana Lucia, et al.
(author)
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A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk
- 2022
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 37:9, s. 915-929
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Journal article (peer-reviewed)abstract
- Background: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. Objective: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. Methods: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. Results: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. Conclusions: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.
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- Skold, AE, et al.
(author)
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Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived dendritic cells and in vivo in cynomolgus macaques
- 2012
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 120:4, s. 768-777
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Journal article (peer-reviewed)abstract
- TLR3 is a key receptor for recognition of double-stranded RNA and initiation of immune responses against viral infections. However, hyperactive responses can have adverse effects, such as virus-induced asthma. Strategies to prevent TLR3-mediated pathology are therefore desired. We investigated the effect of single-stranded DNA oligonucleotides (ssDNA-ODNs) on TLR3 activation. Human monocyte-derived dendritic cells up-regulate maturation markers and secrete proinflammatory cytokines on treatment with the synthetic TLR3 ligand polyinosine-polycytidylic acid (poly I:C). These events were inhibited in cultures with ssDNA-ODNs. Poly I:C activation of nonhematopoietic cells was also inhibited by ssDNA-ODNs. The uptake of poly I:C into cells was reduced in the presence of ssDNA-ODNs, preventing TLR3 engagement from occurring. To confirm this inhibition in vivo, we administered ssDNA-ODNs and poly I:C, alone or in combination, via the intranasal route in cynomolgus macaques. Proinflammatory cytokines were detected in nasal secretions in the poly I:C group, while the levels were reduced in the groups receiving ssDNA-ODNs or both substances. Our results demonstrate that TLR3-triggered immune activation can be modulated by ssDNA-ODNs and provide evidence of dampening proinflammatory cytokine release in the airways of cynomolgus macaques. These findings may open novel perspectives for clinical strategies to prevent or treat inflammatory conditions exacerbated by TLR3 signaling.
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- Andersson, Viktor, 1994, et al.
(author)
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A Novel Method for On-Line Characterization of Alkali Release and Thermal Stability of Materials Used in Thermochemical Conversion Processes
- 2022
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In: Energies. - : MDPI AG. - 1996-1073. ; 15:12
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Journal article (peer-reviewed)abstract
- Alkali metal compounds are released during the thermal conversion of biofuels and fossil fuels and have a major impact on the efficiency of conversion processes. Herein, we describe a novel method for the simultaneous characterization of alkali release and mass loss from materials used in combustion and gasification processes including solid fuels, fluidized bed materials, and catalysts for gas reforming. The method combines the thermogravimetric analysis of selected samples with the on-line measurement of alkali release using a surface ionization detector. The technique builds on the careful treatment of alkali processes during transport from a sample to the downstream alkali monitor including the losses of alkali in the molecular form to hot walls, the formation of nanometer-sized alkali-containing particles during the cooling of exhaust gases, aerosol particle growth, and diffusion losses in sampling tubes. The performance of the setup was demonstrated using biomass samples and fluidized bed material from an industrial process. The emissions of alkali compounds during sample heating and isothermal conditions were determined and related to the simultaneous thermogravimetric analysis. The methodology was concluded to provide new evidence regarding the behavior of alkali in key processes including biomass pyrolysis and gasification and ash interactions with fluidized beds. The implications and further improvements of the technique are discussed.
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- Ananthaseshan, Sharan
(author)
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Vascular related pathologies in cardiovascular disease and cancer
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Cardiovascular disease (CVD) and cancer are the leading causes of death worldwide. A damaged endothelium is one of the factors contributing towards these diseases. This thesis focused on understanding the implications of alterations to the physiological endothelium resulting in pathologies related to vascular disease and cancer metastasis. Functional healing response occurs in the diseased vessel wall aimed at restoring the vessel after an injury. Existing studies state that vascular progenitor cells contribute to the injured vasculature and aid in the repair process. Yet the mechanisms underlying the amalgamation of the cells to the endothelium, their origin and functions have not been clear. Through Study 1 using animal models of arterial injury, we examined the role of bone marrow derived cells in arterial repair and the mechanisms behind it. We observed that bone marrow-derived cells, helped in the initial stages of arterial injury and were subsequently eliminated from the artery wall. They localized in the arterial intima and most them were of endothelial phenotype. Additionally, bone marrow-derived cells did not fuse with the intima but could differentiate into vascular cells. This helped them adjust in the vessel wall and meet the needs of their new microenvironment. Fascinatingly, local delivery of bone marrow-derived endothelial cells to the sites of arterial injury caused a 1.4-fold decrease of the intimal lesion area. These results define the role of BM derived endothelial cells in the development of intimal lesions post vascular injury and this information contributes to the existing understanding of the pathogenesis of intimal hyperplasia. Hemodynamic forces are a cause of a dysfunctional endothelium. A turbulent blood flow could result in vascular disease. Studies have shown that red blood cell distribution (RDW) width as a risk factor for death in cancer and CVD. RDW is one of the haematological parameters commonly reported as part of a complete blood count An RDW higher than normal is termed as anisocytosis. Anisocytosis has been traditionally used, in combination with the red blood cell corpuscular volume, to diagnose chronic inflammatory status in the body. It has been never studied before if anisocytosis is just factor that reflects chronic inflammation in the body, or is factor that directly affects it. Hence in Study 2, we hypothesized that anisocytosis leads to changes in blood flow affecting interaction between blood and vascular endothelium at the bifurcation of arteries. We found that a high RDW is a predictive factor for the interaction between cellular components of blood and vascular wall. These interactions can lead to increased inflammation in the vessels and initiation of thrombosis. Put together, we suggest that anisocytosis measured by RDW is a predictive factor of vascular diseases. Cancer metastasis is one of the major causes of mortality and arises also due to a damaged endothelium. In Study 3 we investigated the role of murine cytomegalovirus(MCMV) in colon cancer progression using MCMV infected and non-infected animal models. Our results indicate that MCMV did not affect tumor growth but increases the incidence of metastasis to the lungs. Additionally, using microarray analysis we found cytokeratins 1, 2 and 14 to be upregulated 100 times in the infected models compared to the non-infected. We speculate that in our case metastasis is mediated possibly through a cytokeratin mediated pathway. The mechanism for dissemination is under investigation. In Study 4, we investigated the effect of C/EBPβ on metastasis and the relationship between C/EBPβ expression and overall survival of breast cancer patients. We found that decrease in C/EBPβ expression was related to shorter overall survival of breast cancer patients. Loss of C/EBPβ also, affected tumor growth, morphology and lung metastasis in murine 4T1 breast cancer model. Furthermore, inhibition of C/EBPβ resulted in an augmented expression of MHCII and CD45+, CD3+ and CD4+ lymphocytes accumulation in the tumors. Additional experiments established the role of inflammation in C/EBPβ-mediated metastasis formation.
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- Ask, Maria
(author)
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Mechanical tests on claystone from Ocean Drilling Program Hole 1070A (Leg 173) : implications for elevatedpore-fluid pressure in sediments within the ocean-continent transition zone, West Iberia
- 2001
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In: Marine Geology. - 0025-3227 .- 1872-6151. ; 177:3, s. 395-410
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Journal article (peer-reviewed)abstract
- Laboratory geotechnical deformation tests on a claystone test specimen from 619 m depth in Ocean Drilling Program Hole 1070A provide evidence of low effective yield stresses and capillary pressures (1.2–1.5 MPa) in the sediment section near the acoustic basement. Effects from negative pore-fluid pressure, and the presence of expansive clay minerals probably account for the drastic change in the mechanical behavior of the sample below and above the yield stress. The results from the geotechnical tests, together with high porosity values, suggest that the pore-fluid pressure is high in these basal sediments. The intense fracture/vein development in the basement suggests that the pore-fluids originate from deeper sections in the basement. Porosity anomalies are found near the basement in three boreholes drilled in the western part of the Iberia Margin. The anomalies are interpreted to signal elevated pore-fluid pressure. Consequently, a zone of overpressure possibly exists in the western part of the ocean-transition zone of the West Iberia margin, which thickens towards the west.
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- Westman, Anton, 1972-, et al.
(author)
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Validity of injury reporting among active Swedish skydivers
- 2009
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Other publication (other academic/artistic)abstract
- Objective: Evaluation of a national compulsory reporting system for skydiving injuries.Design: Self-report survey.Setting: The Swedish Parachute Association (SFF).Subjects: All persons renewing a Swedish skydiving license 2008 (n=1049).Main outcome measures: Sensitivity was measured as the proportion of injury events fulfilling the reporting criterion that were actually reported; Specificity was measured as the proportion of false positives in relation to the defined gold standard. Self-stated bone fractures, shoulder dislocations and cruciate ligament injuries were labeled as non-minor injuries.Results: The response rate was 100%. The overall sensitivity of the reporting system 2006/2007 was 0.37 (95% confidence interval (CI) 0.24-0.51). With selfstated non-minor injuries as the target for reporting, the sensitivity was 0.67 (95% CI 0.43-0.85). No significant effect on reporting was found for gender, age, license level, years in the sport, total number of jumps or club affiliation. The specificity was 0.91 (95% CI 0.83-0.95).Conclusions: The low sensitivity will yield false low incidence calculations, but risk comparisons related to the candidate predictor variables appear reasonably valid. The false positive reporting warrants assortment of incoming data and a clarification of the reporting criterions. We propose the addition of “hospitalization Yes/No” in future reporting and endorse coordinating skydiving data collection in the Nordic countries. Further studies on attitudes to reporting are necessary to understand the drivers and constraints for achieving a more complete notification of skydiving injuries.
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