| 51. |
- Marklund, Matti, et al.
(författare)
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Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality : An Individual-Level Pooled Analysis of 30 Cohort Studies
- 2019
-
Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 139:21, s. 2422-2436
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.Methods:We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).Results:In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15198 incident cardiovascular events occurred among 68659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.Conclusions:In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.
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| 52. |
- Merritt, Melissa A, et al.
(författare)
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Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition : a cohort study
- 2015
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. Methods: The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled > 500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. Results: During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (>= 15 years versus < 12; 0.90; 0.85-0.96; P for trend = 0.038). Conclusions: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.
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| 53. |
- Muller, D. C., et al.
(författare)
-
No association between circulating concentrations of vitamin D and risk of lung cancer : an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3)
- 2018
-
Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 29:6, s. 1468-1475
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3).Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables.Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology.Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.
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| 54. |
- Ogunbode, Charles, et al.
(författare)
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Climate anxiety, wellbeing and pro-environmental action : Correlates of negative emotional responses to climate change in 32 countries
- 2022
-
Ingår i: Journal of Environmental Psychology. - : Academic Press. - 0272-4944 .- 1522-9610. ; 84
-
Tidskriftsartikel (refereegranskat)abstract
- This study explored the correlates of climate anxiety in a diverse range of national contexts. We analysed cross-sectional data gathered in 32 countries (N = 12,246). Our results show that climate anxiety is positively related to rate of exposure to information about climate change impacts, the amount of attention people pay to climate change information, and perceived descriptive norms about emotional responding to climate change. Climate anxiety was also positively linked to pro-environmental behaviours and inversely related to mental wellbeing. Notably, climate anxiety had a significant inverse association with mental wellbeing in 31 out of 32 countries, and with pro-environmental behaviour in 24 countries, it only predicted environmental activism in 12 countries. Our findings highlight contextual boundaries to engagement in environmental action as an antidote to climate anxiety, and the broad international significance of negative climate-related emotions as a plausible threat to wellbeing.
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| 55. |
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| 56. |
- Ricceri, Fulvio, et al.
(författare)
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Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC)
- 2015
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:4, s. 940-948
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Tidskriftsartikel (refereegranskat)abstract
- Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer. What's new? For the first time, researchers have used cohort data to show that people who survive breast cancer have a higher risk of developing another cancer later. By collecting data on 10,000 breast cancer patients over 11 years, these authors calculated a 30% boost in the patients' risk of developing a second primary malignancy, particularly colorectal cancer, lymphoma, melanoma, endometrial cancer, and kidney cancer. These findings, plus the data they collected on risk factors such as age, smoking, body mass index, and others, will help guide clinicians in screening procedures and follow up care for breast cancer patients.
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| 57. |
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| 58. |
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| 59. |
- Singh, Amika S, et al.
(författare)
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Effects of physical activity interventions on cognitive and academic performance in children and adolescents : a novel combination of a systematic review and recommendations from an expert panel
- 2019
-
Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 53, s. 640-647
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To summarise the current evidence on the effects of physical activity (PA) interventions on cognitive and academic performance in children, and formulate research priorities and recommendations. DESIGN: Systematic review (following PRISMA guidelines) with a methodological quality assessment and an international expert panel. We based the evaluation of the consistency of the scientific evidence on the findings reported in studies rated as of high methodological quality. DATA SOURCES: PubMed, PsycINFO, Cochrane Central, Web of Science, ERIC, and SPORTDiscus. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: PA-intervention studies in children with at least one cognitive or academic performance assessment. RESULTS: Eleven (19%) of 58 included intervention studies received a high-quality rating for methodological quality: four assessed effects of PA interventions on cognitive performance, six assessed effects on academic performance, and one on both. All high-quality studies contrasted the effects of additional/adapted PA activities with regular curriculum activities. For cognitive performance 10 of 21 (48%) constructs analysed showed statistically significant beneficial intervention effects of PA, while for academic performance, 15 of 25 (60%) analyses found a significant beneficial effect of PA. Across all five studies assessing PA effects on mathematics, beneficial effects were reported in six out of seven (86%) outcomes.Experts put forward 46 research questions. The most pressing research priority cluster concerned the causality of the relationship between PA and cognitive/academic performance. The remaining clusters pertained to PA characteristics, moderators and mechanisms governing the 'PA-performance' relationship and miscellaneous topics. CONCLUSION: There is currently inconclusive evidence for the beneficial effects of PA interventions on cognitive and overall academic performance in children. We conclude that there is strong evidence for beneficial effects of PA on maths performance.The expert panel confirmed that more 'high-quality' research is warranted. By prioritising the most important research questions and formulating recommendations we aim to guide researchers in generating high-quality evidence. Our recommendations focus on adequate control groups and sample size, the use of valid and reliable measurement instruments for physical activity and cognitive performance, measurement of compliance and data analysis. PROSPERO REGISTRATION NUMBER: CRD42017082505.
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| 60. |
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| 61. |
- Yan, C., et al.
(författare)
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Size-dependent influence of NOx on the growth rates of organic aerosol particles
- 2020
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:22
-
Tidskriftsartikel (refereegranskat)abstract
- Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.
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| 62. |
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| 63. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 64. |
- Agustin, Sanchez-Arcilla, et al.
(författare)
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Introduction
- 2008
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Ingår i: Journal of Hydraulic Research. - 0022-1686. ; 46:2, s. 179-182
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 65. |
- Allen, Katherine H., et al.
(författare)
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Assistive Applications, Accessibility, and Disability Ethics in HRI
- 2024
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Ingår i: COMPANION OF THE 2024 ACM/IEEE INTERNATIONAL CONFERENCE ON HUMAN-ROBOT INTERACTION, HRI 2024 COMPANION. - : Association for Computing Machinery (ACM). - 9798400703232 ; , s. 1305-1307
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Konferensbidrag (refereegranskat)abstract
- This full-day workshop addresses the problems of accessibility in HRI and the interplay of ethical considerations for disability-centered design and research, accessibility concerns for disabled researchers, and the design of assistive HRI technologies. We invite authors to submit extended abstracts (up to 2 pages, excluding references) and short papers (up to 4 pages, excluding references) on a range of topics relevant to ethics, accessibility, and assistive applications in HRI, including critical reflections on methodologies, design papers on human-centered or anti-ableist assistive technology, and papers from those outside the HRI community who may have insight to share on these concerns. The workshop will use a hybrid format to allow participants who due to disability, geographic, financial, or other constraints, are unable to travel, and will feature keynote speakers, panel discussions, and breakout sessions.
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| 66. |
- Antoniou, Antonis C., et al.
(författare)
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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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| 67. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 68. |
- Balea, A, et al.
(författare)
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Morphology, properties and recyclability of modified fibres and papers with different chemicals at laboratory and pilot plant trials
- 2015
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Ingår i: 46th Congresso Annuale Aticelca, May 28-29, Sestri Levante-Genova, Italy. - : Aticelca. ; , s. 23-31
-
Konferensbidrag (refereegranskat)abstract
- Fibre+ (2012-2015) is a European project aiming to develop potential treatments for recovered fibre modification capable of improving the recyclability and the properties of recycled papers. This study reports on the results on fibre morphology, paper properties and recyclability of fibres and papers modified with different chemicals and approaches from both laboratory and pilot plant trials. Sixteen modification chemical agents were studied in a set of laboratory trials. The raw material used was 100% recycled paper grade from old corrugated board containers (OCC). The laboratory analysis to evaluate the effectiveness of fibre modifications treatments included FBRM for pre-screening of chemicals, preparation of laboratory control and modified handsheets to a target grammage of 80 g/m2, and measurement of the fibre morphology, recyclability and mechanical and physical properties of the modified handsheets. Based on the results of laboratory testing, Fibre+ modifications pilot plant trials were carried out at a FEX paper machine. Furthermore the effect of the better dispersion of the cPAM using an ECOWIRL was studied. The overall laboratory and pilot plant results were promising for further implementation of the Fibre+ modifications at industrial scale and projection of improvements of fibre and paper properties on the performance of packaging products thereof
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| 69. |
- Brandau, Benedikt, et al.
(författare)
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Angular dependence of coaxial and quasi-coaxial monitoring systems for process radiation analysis in laser materials processing
- 2022
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Ingår i: Optics and lasers in engineering. - : Elsevier. - 0143-8166 .- 1873-0302. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- Process monitoring is becoming increasingly important in laser-based manufacturing and is of particular importance in the field of additive manufacturing [e.g. Laser Powder Bed Fusion (LPBF)]. Process monitoring enables a reduction of production costs and a lower time-to-market. Furthermore, the data can be used to create a digital twin of the workpiece. There are already many established processing head-integrated monitoring systems for such applications as the multispectral analysis of process radiation. However, the monitoring of complex signals in systems with F-Theta scanner lenses is very challenging and requires specially adapted optics or measuring sensors.In this paper a potential arrangement for spectroscopy-based process monitoring in pre-objective scanning is presented. The process radiation was monitored using a coaxial and a quasi-coaxial observation system. The measurements were carried out on both a solid and a powder coated sample of 2.4668 (Inconel 718) to show the potential use of these systems in laser-based additive manufacturing. In order to obtain comprehensive data about the process signal, the process zone was analyzed at different angles of incidence (AOI) of the laser using a high-speed camera (HSI) and a spectrometer. The connection between the HSI and the spectral measurements is discussed. The ionization of the material and the formation of a plasma was observed and found to lose intensity as the angle of incidence increases. A model of the system that demonstrates the intensity of the emitted radiation of the plasma was created. It enables the measured values to be corrected. The corrected measurement data can be used to detect impurities or a non-ideal energy input across the entire processing field, which is a move towards robust process monitoring.
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| 70. |
- Candido-dos-Reis, Francisco J, et al.
(författare)
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Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer
- 2015
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 21:3, s. 7-652
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
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| 71. |
- Cho, Yoon Shin, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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| 72. |
- Coppo, Rosanna, et al.
(författare)
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Is there long-term value of pathology scoring in immunoglobulin A nephropathy? : A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update
- 2020
-
Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 35:6, s. 1002-1009
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up.Methods: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)].Results: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%).Conclusion: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.
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| 73. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 74. |
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| 75. |
- El-Seedi, Hesham R., et al.
(författare)
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Naturally occurring xanthones; latest investigations : isolation, structure elucidation and chemosystematic significance
- 2009
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 16:20, s. 2581-2626
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Forskningsöversikt (refereegranskat)abstract
- In this review, an updated literature survey covering the reports of naturally occurring xanthones in the period of 2005-2008 is presented. In some 143 studies, the isolation of 264 different xanthones from 36 plant species (representing 15 genera in 6 families of higher plants), 7 species of fungi, and 1 lichen species were reported. Of these, 122 compounds were isolated for the first time from nature. We discuss plant origin, the way of separation, and spectral analysis done for structure elucidation, along with a brief discussion of the chemosystematic significance.
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| 76. |
- Fang, Jun, et al.
(författare)
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Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
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| 77. |
- Gascón-Garrido, P, et al.
(författare)
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Resistance of wood modified with different technologies against Mediterranean termites (Reticulitermes spp.)
- 2013
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Ingår i: International Biodeterioration & Biodegradation. - : Elsevier BV. - 0964-8305 .- 1879-0208. ; 82, s. 13-16
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Tidskriftsartikel (refereegranskat)abstract
- A laboratory no-choice test following the standard EN-117 was conducted to evaluate the efficacy of wood modified with different technologies against subterranean termites of the genus Reticulitermes spp. European beech modified with DMDHEU, acetylated radiata pine, and furfurylated Southern yellow pine were used for termite testing. Before the bioassay, half the number of the specimens (including controls) was subjected to an accelerated aging test according to EN-84. The specimens were exposed for 8 wk to the termites. Additionally, mass losses were measured. The results indicated that the feeding pressure was sufficient according to EN-117 for a valid test. Acetylated wood and DMDHEU-modified wood were classified as durable, showing excellent termite resistance. Furfurylated wood was resistant in the case of non-leached specimens; however, the leaching process led to a classification of non-durable. Thus, the new modification technologies open a real possibility of their use in the Mediterranean region as alternative preventive treatments against subterranean termites.
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| 78. |
- Greve, Anders M., et al.
(författare)
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Contrasting Hemodynamic Mechanisms of Losartan- vs. Atenolol-Based Antihypertensive Treatment : A LIFE Study
- 2012
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 25:9, s. 1017-1023
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Pharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP). METHODS Data from all patients with at least two echocardiographic examinations in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) echocardiographic substudy (n = 801); high-risk patients on losartan- vs. atenolol-based antihypertensive therapy. Echocardiography was performed annually for 4 years to measure stroke index (SI), heart rate, cardiac index (CI), conduit artery stiffness assessed as pulse pressure/stroke index (PP/SI) and total peripheral resistance index (TPRI). RESULTS Atenolol- and losartan-based therapy reduced BP similarly (cumulative difference in mean brachial blood pressure 0.3 mm Hg, P = 0.65). After 4 years the cumulative means of SI and heart rate were 1.8 ml/m(2) higher and 5.7 beats/min lower on atenolol-based treatment, respectively (both P < 0.001). This kept CI below baseline in atenolol-treated patients, whereas in the losartan group CI was unchanged from baseline throughout the study. TPRI was decreased more and remained lower in the losartan group (cumulative difference in mean TPRI 287 dynes/sec(-5)/cm/m(2), P < 0.001). These findings partly explained univariate differences in systolic- and diastolic function indices between the two treatments; fully adjusted losartan was only associated with a smaller left atrial diameter (cumulative mean difference 0.07 cm; 95% confidence intervals, -0.13 to -0.01, P = 0.03). CONCLUSIONS Contrasting hemodynamics impacted cardiac response to similar reductions in brachial BP on losartan- vs. atenolol-based therapy. The similar reduction of PP/SI suggests that the antihypertensive regimens used in the LIFE study had comparable effects on arterial stiffness (LIFE study; NCT00338260)
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| 79. |
- Gu, Chaoyi, 1992, et al.
(författare)
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Omega-3 and-6 Fatty Acids Alter the Membrane Lipid Composition and Vesicle Size to Regulate Exocytosis and Storage of Catecholamines
- 2024
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Ingår i: ACS CHEMICAL NEUROSCIENCE. - 1948-7193. ; 15:4, s. 816-826
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Tidskriftsartikel (refereegranskat)abstract
- The two essential fatty acids, alpha-linolenic acid and linoleic acid, and the higher unsaturated fatty acids synthesized from them are critical for the development and maintenance of normal brain functions. Deficiencies of these fatty acids have been shown to cause damage to the neuronal development, cognition, and locomotor function. We combined electrochemistry and imaging techniques to examine the effects of the two essential fatty acids on catecholamine release dynamics and the vesicle content as well as on the cell membrane phospholipid composition to understand how they impact exocytosis and by extension neurotransmission at the single-cell level. Incubation of either of the two fatty acids reduces the size of secretory vesicles and enables the incorporation of more double bonds into the cell membrane structure, resulting in higher membrane flexibility. This subsequently affects proteins regulating the dynamics of the exocytotic fusion pore and thereby affects exocytosis. Our data suggest a possible pathway whereby the two essential fatty acids affect the membrane structure to impact exocytosis and provide a potential treatment for diseases and impairments related to catecholamine signaling.
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| 80. |
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| 81. |
- Holmberg, Anders R, et al.
(författare)
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Development of a novel poly bisphosphonate conjugate for treatment of skeletal metastasis and osteoporosis.
- 2010
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Ingår i: International journal of oncology. - : Spandidos Publications. - 1791-2423 .- 1019-6439. ; 37:3, s. 563-567
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Tidskriftsartikel (refereegranskat)abstract
- Advanced stage prostate and breast cancer frequently metastasize to the skeleton (approximately 75%). An additional complication in these patients, that further affects the bones, is that their hormonal treatment, induces osteoporosis. Bisphosphonates (bpns) are standard drugs against osteoporosis and have been shown to have clinically significant anti-tumor effects. This study describes the development of a new polybisphosphonate conjugate (ODX) with enhanced dual efficacy i.e. with anti-bone resorption and anti-tumor properties. Zoledronic acid (Zometa) was used as a positive control (at equimolar concentrations). Alendronic acid and aminoguanidine were conjugated to oxidized dextran with subsequent reductive amination (on average approximately 8 alendronate and approximately 50 guanidine moieties per conjugate). ODX was tested in a bone resorption assay for its capacity to inhibit bone resorbing osteoclasts (bone organ culture from neonatal mice, 45Ca labelled bone mineral). Tumor cell toxicity was studied on prostate (PC3) and breast cancer (MDA231, MDA453) cell cultures. Two methods were employed, a fluorescent cytotoxicity assay (FMCA) and an apoptosis assay (Annexin V assay). In the bone resorption assay, Zometa and ODX showed very similar potency with 50% osteoclast inhibition at approximately 20 nM and 100% at 0.2 microM. In the FMCA, IC50 for ODX was at approximately 2 microM and 25 microM for Zometa (PC3). In the apoptosis assay, ODX induced approximately 85-97% apoptosis at 10 microM in both cell lines, while Zometa failed to induce any significant apoptosis in any of the cell lines at the tested concentration range (10 nM-10 microM). ODX appears to be a promising drug candidate with high dual efficacy for the treatment of bone metastasis and osteoporosis. It has both potent osteoclast inhibiting properties and enhanced anti-tumor efficacy.
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| 82. |
- Horning, A. M., et al.
(författare)
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DNA Methylation Screening of Primary Prostate Tumors Identifies SRD5A2 and CYP11A1 as Candidate Markers for Assessing Risk of Biochemical Recurrence
- 2015
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Ingår i: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 75:15, s. 1790-1801
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Altered DNA methylation in CpG islands of gene promoters has been implicated in prostate cancer (PCa) progression and can be used to predict disease outcome. In this study, we determine whether methylation changes of androgen biosynthesis pathway (ABP)-related genes in patients' plasma cell-free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR). METHODS. Methyl-binding domain capture sequencing (MBDCap-seq) was used to identify differentially methylated regions (DMRs) in primary tumors of patients who subsequently developed BCR or not, respectively. Methylation pyrosequencing of candidate loci was validated in cfDNA samples of 86 PCa patients taken at and/or post-radical prostatectomy (RP) using univariate and multivariate prediction analyses. RESULTS. Putative DMRs in 13 of 30 ABP-related genes were found between tumors of BCR (n = 12) versus no evidence of disease (NED) (n = 15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci-SRD5A2 and CYP11A1, which also correlated with their decreased expression, in tumors with subsequent BCR development. Their aberrant cfDNA methylation was also associated with detectable levels of PSA taken after patients' post-RP. Multivariate analysis of the change in cfDNA methylation at all of CpG sites measured along with patient's treatment history predicted if a patient will develop BCR with 77.5% overall accuracy. CONCLUSIONS. Overall, increased DNA methylation of SRD5A2 and CYP11A1 related to androgen biosynthesis functions may play a role in BCR after patients' RP. The correlation between aberrant cfDNA methylation and detectable PSA in post-RP further suggests their utility as predictive markers for PCa recurrence. (C) 2015 Wiley Periodicals, Inc.
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| 83. |
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| 84. |
- Jimenez-del-Toro, Oscar, et al.
(författare)
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Cloud-Based Evaluation of Anatomical Structure Segmentation and Landmark Detection Algorithms : VISCERAL Anatomy Benchmarks
- 2016
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Ingår i: IEEE Transactions on Medical Imaging. - : Institute of Electrical and Electronics Engineers (IEEE). - 0278-0062 .- 1558-254X. ; 35:11, s. 2459-2475
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Tidskriftsartikel (refereegranskat)abstract
- Variations in the shape and appearance of anatomical structures in medical images are often relevant radiological signs of disease. Automatic tools can help automate parts of this manual process. A cloud-based evaluation framework is presented in this paper including results of benchmarking current state-of-the-art medical imaging algorithms for anatomical structure segmentation and landmark detection: the VISCERAL Anatomy benchmarks. The algorithms are implemented in virtual machines in the cloud where participants can only access the training data and can be run privately by the benchmark administrators to objectively compare their performance in an unseen common test set. Overall, 120 computed tomography and magnetic resonance patient volumes were manually annotated to create a standard Gold Corpus containing a total of 1295 structures and 1760 landmarks. Ten participants contributed with automatic algorithms for the organ segmentation task, and three for the landmark localization task. Different algorithms obtained the best scores in the four available imaging modalities and for subsets of anatomical structures. The annotation framework, resulting data set, evaluation setup, results and performance analysis from the three VISCERAL Anatomy benchmarks are presented in this article. Both the VISCERAL data set and Silver Corpus generated with the fusion of the participant algorithms on a larger set of non-manually-annotated medical images are available to the research community.
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| 85. |
- Johnstone, Devon L., et al.
(författare)
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Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ : Report of seven new subjects and review of the literature
- 2020
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 43:6, s. 1321-1332
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Tidskriftsartikel (refereegranskat)abstract
- We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Transfection of wildtype PIGQ cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of PIGQ-related disease and provide the first functional evidence in human cells of defective GPI-anchoring due to pathogenic variants in PIGQ.
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| 86. |
- Kielmann, B, et al.
(författare)
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Decay resistance of ash, beech and maple wood modified with N-methylol melamine and a metal complex dye
- 2014
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Ingår i: International Biodeterioration & Biodegradation. - : Elsevier BV. - 0964-8305 .- 1879-0208. ; 89, s. 110-114
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluated the decay resistance of ash (Fraxinus excelsior L.), beech (Fagus sylvatica L.), and maple (Acer platanoides L.) wood impregnated by a full cell process with N-methylol melamine (NMM) and combined NMM-metal complex dye (NMM-BS) in aqueous solutions. Basidiomycete decay testing involved incubation with Coniophora puteana (brown rot) and Trametes versicolor (white rot) according to a modified EN 113 (1996) standard, while for the soft rot fungal resistance was evaluated following the standard ENv 807 (2001). NMM and NMM-BS modifications at a WPG range of 7–11% provided decay protection against brown rot resulting in a mass loss less than the required limit (3%). The NMM and NMM-BS modified wood showed increased resistance to white rot decay; however, a higher WPG is needed to prohibit attack from this hardwood specific fungus. The metal-complex dye alone revealed biocidal effects against basidiomycetes. An increased WPG in NMM or NMM-BS had a positive impact against soft rot decay and the lowest mass losses after 32 weeks of exposure were obtained with NMM modification at about 18–21% WPG. NMM modification at this WPG range, however, was not sufficient to protect the wood from soft rot decay. The wood of beech and maple showed slightly higher resistance to all decay types than ash, probably due to the poorer degree of modification of the latter.
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| 87. |
- Kielmann, B, et al.
(författare)
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Modification of three hardwoods with an N-methylol melamine compound and a metal-complex dye
- 2014
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Ingår i: Wood Science and Technology. - : Springer Science and Business Media LLC. - 0043-7719 .- 1432-5225. ; 48:1, s. 123-136
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluated the combined modification and staining of ash, beech and maple wood with a low molecular weight N-methylol melamine compound (NMM) and a metal-complex dye. Wood samples were treated with aqueous solutions of 10, 20 and 30 wt% NMM and 5 wt% of the dye. The treatment caused the fixation of the water-soluble dye by the NMM resin. Vacuum pressure impregnation of unsealed wood blocks did not result in different solution uptake and weight percent gain after curing among the three species, but sealing of the surfaces of the wood blocks to allow penetration only into one direction revealed easiest penetrability of beech followed by maple and ash. UV micro-spectrophotometry and light microscopy indicated that NMM was partly deposited in the cell wall and partly in the lumens. Penetration of the metal-complex dye was shown by means of X-ray micro-analysis (SEM–EDX). The study shows that a combined resin modification and staining of the three wood species tested is possible and that NMM causes fixation of the water-soluble dye.
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| 88. |
- Kielmann, B, et al.
(författare)
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Strength changes in ash, beech and maple wood modified with a N-methylol melamine compound and a metal-complex dye
- 2013
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Ingår i: Wood research. - 1336-4561. ; 58:3, s. 343-350
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Tidskriftsartikel (refereegranskat)abstract
- Ash, beech and maple wood was modified with aqueous solutions of methylated N-methylol melamine (NMM) and a metal-complex dye (BS) consisting of 10, 20, and 30 % NMM and 5 % BS. Static bending strength and stiffness, impact bending strength and hardness were examined to evaluate the suitability of modified wood for structural uses. The combined NMMBS modification resulted in significant higher dynamic (MOEdyn) and static (MOE) moduli of elasticity for all species. Beech and maple exhibited enhanced static bending strength (MOR), while that of ash was unchanged. The higher stiffness and strength of NMM-BS modified wood is attributed to its higher wood density and lower EMC and to the stiff character of NMM resin incorporated in the wood matrix. Impact bending strength decreased substantially after modification as a result of reduced pliability of treated wood. Brinell hardness significantly increased with the weight percent gain (WPG) due to modification, and, unlike the other properties, it was positively correlated with the WPG.
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| 89. |
- Klabunde, C, et al.
(författare)
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Participation rates for organized colorectal cancer screening programmes: an international comparison
- 2015
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Ingår i: Journal of medical screening. - : SAGE Publications. - 1475-5793 .- 0969-1413. ; 22:3, s. 119-126
-
Tidskriftsartikel (refereegranskat)abstract
- Participation, an indicator of screening programme acceptance and effectiveness, varies widely in clinical trials and population-based colorectal cancer (CRC) screening programmes. We aimed to assess whether CRC screening participation rates can be compared across organized guaiac fecal occult blood test (G-FOBT)/fecal immunochemical test (FIT)-based programmes, and what factors influence these rates. Methods Programme representatives from countries participating in the International Cancer Screening Network were surveyed to describe their G-FOBT/FIT-based CRC screening programmes, how screening participation is defined and measured, and to provide participation data for their most recent completed screening round. Results Information was obtained from 15 programmes in 12 countries. Programmes varied in size, reach, maturity, target age groups, exclusions, type of test kit, method of providing test kits and use, and frequency of reminders. Coverage by invitation ranged from 30–100%, coverage by the screening programme from 7–67.7%, overall uptake/participation rate from 7–67.7%, and first invitation participation from 7–64.3%. Participation rates generally increased with age and were higher among women than men and for subsequent compared with first invitation participation. Conclusion Comparisons among CRC screening programmes should be made cautiously, given differences in organization, target populations, and interpretation of indicators. More meaningful comparisons are possible if rates are calculated across a uniform age range, by gender, and separately for people invited for the first time vs. previously.
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| 90. |
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| 91. |
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| 92. |
- Mai, Tam T., et al.
(författare)
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An overview of grid-edge control with the digital transformation
- 2021
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Ingår i: Electrical Engineering. - : Springer Science and Business Media LLC. - 1432-0487 .- 0948-7921. ; 103:4, s. 1989-2007
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Tidskriftsartikel (refereegranskat)abstract
- Distribution networks are evolving to become more responsive with increasing integration of distributed energy resources (DERs) and digital transformation at the grid edges. This evolution imposes many challenges to the operation of the network, which then calls for new control and operation paradigms. Among others, a so-called grid-edge control is emerging to harmonise the coexistence of the grid control system and DER’s autonomous control. This paper provides a comprehensive overview of the grid-edge control with various control architectures, layers, and strategies. The challenges and opportunities for such an approach at the grid edge with the integration of DERs and digital transformation are summarised. The potential solutions to support the network operation by using the inherent controllability of DER and the availability of the digital transformation at the grid edges are discussed.
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| 93. |
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| 94. |
- Omar, Hany A., et al.
(författare)
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Immunomodulatory MicroRNAs in cancer: targeting immune checkpoints and the tumor microenvironment
- 2019
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Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 286:18, s. 3540-3557
-
Forskningsöversikt (refereegranskat)abstract
- Cancer immunotherapy represents a promising new era in cancer management due to the relatively high safety margins and selectivity, compared to the classical cancer chemotherapeutic agents. However, there is an imperative need to overcome tumor resistance in order to improve clinical outcomes and maximize the benefits of cancer immunotherapy. The interaction between the programmed cell death-1 (PD-1) receptor and its ligand PD-L1 is a vital immune checkpoint that is often adopted by cancer cells to undergo immune evasion. PD-1/PD-L1 signaling is regulated at multiple levels through the crosstalk with other immune targets or relevant signaling partners involved in the cancer progression. Among the significant epigenetic players that are implicated in modulating the immune system are microRNAs (miRNAs). A complex system of these noncoding RNAs regulates the gene expression at the post-transcriptional level and plays a significant role in the modulation of both innate and the adaptive immune systems. The expression profile of immune-modulatory miRNAs might be useful as a predictive biomarker for the response and clinical outcomes in cancer immunotherapy. Therefore, in the current review, we highlighted the role of miRNAs in cancer immune evasion through a critical discussion of their impact on key immune checkpoints as well as the role of miRNAs in cancer progression and resistance.
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| 95. |
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| 96. |
- Peden, John F., et al.
(författare)
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A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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| 97. |
- Pettersson, John H.-O. 1981-, et al.
(författare)
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Re-visiting the evolution, dispersal and epidemiology of Zika virus in Asia
- 2018
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Ingår i: Emerging Microbes & Infections. - : Nature Publishing Group. - 2222-1751. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Based on serological evidence and viral isolation, Zika virus (ZIKV) has circulated for many years relatively benignly in a sylvatic cycle in Africa and an urban cycle in South East Asia (SEA). With the recent availability of limited but novel Indian ZIKV sequences to add to the plethora of SEA sequences, we traced the phylogenetic history and spatio-temporal dispersal pattern of ZIKV in Asia prior to its explosive emergence in the Pacific region and the Americas. These analyses demonstrated that the introduction and dispersal of ZIKV on the Pacific islands were preceded by an extended period of relatively silent transmission in SEA, enabling the virus to expand geographically and evolve adaptively before its unanticipated introduction to immunologically naive populations on the Pacific islands and in the Americas. Our findings reveal new features of the evolution and dispersal of this intriguing virus and may benefit future disease control strategies.
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| 98. |
- Pham, Thi Anh Mai, et al.
(författare)
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Evaluation of screening algorithms to detect rectal colonization with carbapenemase-producing Enterobacterales in a resource-limited setting
- 2024
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Ingår i: JAC - Antimicrobial Resistance. - : OXFORD UNIV PRESS. - 2632-1823. ; 6:3
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To improve and rationalize the detection of carbapenemase-producing Enterobacterales (CPE) in rectal swabs in a high-prevalence and resource-constrained setting, addressing surveillance challenges typically encountered in laboratories with limited resources.Methods A point prevalence survey (PPS) was conducted on 15 August 2022, in a provincial children's hospital in northern Vietnam. Rectal swab samples of all admitted children were collected and plated on a selective medium for carbapenem-resistant Enterobacterales (CRE). Species identification and antimicrobial susceptibility testing (AST) were performed by MALDI-TOF, and VITEK2 XL and interpreted according to CLSI breakpoints (2022). Carbapenemases were detected by the carbapenem inactivation method (CIM) and quantitative real-time PCR (qRT-PCR).Results Rectal swab samples were obtained from 376 patients. Of 178 isolates growing on the CRE screening agar, 140 isolates were confirmed as Enterobacterales of which 118 (84.3%) isolates were resistant to meropenem and/or ertapenem. CIM and PCR showed that 90/118 (76.3%) were carbapenemase producers. Overall, 83/367 (22.6%) were colonized by CPE. Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae complex were the most common CPE detected, with NDM as the predominant carbapenemase (78/90; 86.7%). Phenotypic resistance to meropenem was the best predictor of CPE production (sensitivity 85.6%, specificity 100%) compared with ertapenem resistance (95.6% sensitivity, 36% specificity). CIM was 100% concordant with PCR in detecting carbapenemases.Conclusions These findings underscore the effectiveness of meropenem resistance as a robust indicator of the production of carbapenemases and the reliability of the CIM method to detect such carbapenemases in resource-limited settings where the performance of molecular methods is not possible.
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| 99. |
- Philipsen, Mai H., et al.
(författare)
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Distinct Cholesterol Localization in Glioblastoma Multiforme Revealed by Mass Spectrometry Imaging
- 2023
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Ingår i: ACS Chemical Neuroscience. - 1948-7193. ; 14:9, s. 1602-1609
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults and is highly resistant to chemo- and radiotherapies. GBM has been associated with alterations in lipid contents, but lipid metabolism reprogramming in tumor cells is not fully elucidated. One of the key hurdles is to localize the lipid species that are correlated with tumor growth and invasion. A better understanding of the localization of abnormal lipid metabolism and its vulnerabilities may open up to novel therapeutic approaches. Here, we use time-of-flight secondary ion mass spectrometry (ToF-SIMS) to spatially probe the lipid composition in a GBM biopsy from two regions with different histopathologies: one region with most cells of uniform size and shape, the homogeneous part, and the other with cells showing a great variation in size and shape, the heterogeneous part. Our results reveal elevated levels of cholesterol, diacylglycerols, and some phosphatidylethanolamine in the homogeneous part, while the heterogeneous part was dominated by a variety of fatty acids, phosphatidylcholine, and phosphatidylinositol species. We also observed a high expression of cholesterol in the homogeneous tumor region to be associated with large cells but not with macrophages. Our findings suggest that ToF-SIMS can distinguish in lipid distribution between parts within a human GBM tumor, which can be linked to different molecular mechanisms.
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| 100. |
- Philipsen, Mai H., et al.
(författare)
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Mapping the chemistry of hair strands by mass spectrometry imaging - A Review
- 2021
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Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049. ; 26:24
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Tidskriftsartikel (refereegranskat)abstract
- Hair can record chemical information reflecting our living conditions, and, therefore, strands of hair have become a potent analytical target within the biological and forensic sciences. While early efforts focused on analyzing complete hair strands in bulk, high spatial resolution mass spectrometry imaging (MSI) has recently come to the forefront of chemical hair-strand analysis. MSI techniques offer a localized analysis, requiring fewer de-contamination procedures per default and making it possible to map the distribution of analytes on and within individual hair strands. Applying the techniques to hair samples has proven particularly useful in investigations quantifying the exposure to, and uptake of, toxins or drugs. Overall, MSI, combined with optimized sample preparation protocols, has improved precision and accuracy for identifying several elemental and molecular species in single strands of hair. Here, we review different sample preparation protocols and use cases with a view to make the methodology more accessible to researchers outside of the field of forensic science. We conclude that-although some challenges remain, including contamination issues and matrix effects-MSI offers unique opportunities for obtaining highly resolved spatial information of several compounds simultaneously across hair surfaces.
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