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2. |
- Danaei, Goodarz, et al.
(författare)
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Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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3. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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4. |
- Pakpour, Amir H., et al.
(författare)
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Psychometric properties and measurement invariance of the Weight Self-Stigma Questionnaire and Weight Bias Internalization Scale in children and adolescents
- 2019
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Ingår i: International Journal of Clinical and Health Psychology. - : Elsevier. - 1697-2600 .- 2174-0852. ; 19:2, s. 150-159
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objective: Given the negative consequences of weight bias, including internalized weight stigma, on health outcomes, two instruments—the Weight Self-Stigma Questionnaire (WSSQ) and Weight Bias Internalization Scale (WBIS)—have been developed. However, their psychometric properties are yet to be tested for Asian pediatric populations.Method: Participants aged 8 to 12 years (N = 287; 153 boys) completed the WSSQ and the WBIS, and they were classified into either a group with overweight or a group without overweight based on self-reported weight and height.Results: Both WSSQ and WBIS had their factor structures supported by confirmatory factor analyses (CFAs). The measurement invariance of two-factor structure was further supported for WSSQ across gender and weight status. The measurement invariance of single-factor structure was supported for WBIS across gender but not across weight status.Conclusions: WSSQ and WBIS were both valid to assess the internalization of weight bias. However, the two instruments demonstrated different properties and should be applied in different situations.
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5. |
- Reitsma, Marissa B., et al.
(författare)
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Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015 : a systematic analysis from the Global Burden of Disease Study 2015
- 2017
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 389:10082, s. 1885-1906
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Tidskriftsartikel (refereegranskat)abstract
- Background The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. Methods We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). Findings Worldwide, the age-standardised prevalence of daily smoking was 25.0% (95% uncertainty interval [UI] 24.2-25.7) for men and 5.4% (5.1-5.7) for women, representing 28.4% (25.8-31.1) and 34.4% (29.4-38.6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11.5% of global deaths (6.4 million [95% UI 5.7-7.0 million]) were attributable to smoking worldwide, of which 52.2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. Interpretation The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years.
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6. |
- Rhind, Nicholas, et al.
(författare)
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Comparative Functional Genomics of the Fission Yeasts
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 332:6032, s. 930-936
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Tidskriftsartikel (refereegranskat)abstract
- The fission yeast clade-comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus-occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.
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7. |
- Tsai, Meng-Che, et al.
(författare)
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Attitudes toward and beliefs about obese persons across Hong Kong and Taiwan : wording effects and measurement invariance
- 2019
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Ingår i: Health and Quality of Life Outcomes. - : BioMed Central. - 1477-7525. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The psychosocial consequences of obesity are important but often underrated. The Attitudes Toward Obese Persons (ATOP) and Beliefs About Obese Persons (BAOP) scales used to measure weight-related bias have little psychometric information, especially in East Asian contexts. The objective of this study was to use rigorous statistical methods to demonstrate the psychometric properties of these two instruments in Hong Kong and Taiwanese college students.METHODS: A convenience sample of 707 students was recruited from the universities in Hong Kong and Taiwan. Several competing confirmatory factor analyses (CFAs) were conducted to confirm the factorial structure of the ATOP and BAOP. The best fit models for the ATOP and BAOP were chosen for the examination of the measurement invariance across subcultures. We then compared configurable models with or without loading and/or intercept constrained before correlating the latent constructs between the best models for the ATOP and BAOP.RESULTS: The comparison in multiple CFAs found that the model with one factor and two correlated-wording-method factors outperformed the other models for both the ATOP and BOAP. However, the internal consistency was suboptimal (ATOP: α = .56 to .80; BTOP: α = .57 to .65) and the measurement invariance was somewhat unsupported among the Hong Kong and Taiwan samples. Moreover, after controlling wording effects, the latent construct of the ATOP was moderately associated with that of BAOP (r = .356; p < .001).CONCLUSION: Chinese versions of the ATOP and BAOP can be treated as a unidimensional factor for use in Hong Kong and Taiwan university students. However, further refinements of both instruments may be needed before using them to capture the social attitudes and beliefs toward obesity individuals, which is expected to advance our understanding of weight-related bias in East Asian contexts.
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8. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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9. |
- Ahorsu, Daniel K., et al.
(författare)
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A prospective study on the link between weight-related self-stigma and binge eating : Role of food addiction and psychological distress
- 2020
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Ingår i: International Journal of Eating Disorders. - : John Wiley & Sons. - 0276-3478 .- 1098-108X. ; 53:3, s. 442-450
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This prospective study investigated the link between weight-related self-stigma and binge eating by (a) examining the temporal association between weight-related self-stigma and binge eating; (b) investigating the mediating role of food addiction in the association between weight-related self-stigma and binge eating; and (c) examining the mediating role of psychological distress in the association between weight-related self-stigma and binge eating.METHOD: Participants comprised 1,497 adolescents (mean = 15.1 years; SD = 6.0). Body mass index and weight bias were assessed at baseline; psychological distress (i.e., depression, anxiety, and stress) assessed and food addiction at 3 months; and binge eating at 6 months. The mediation model was analyzed using Model 4 in the PROCESS macro for SPSS with 10,000 bootstrapping resamples.RESULTS: There was no significant direct association between weight-related self-stigma and binge eating. However, food addiction and psychological distress significantly mediated the association between weight-related self-stigma and binge eating.DISCUSSION: These findings highlight the indirect association between weight-related self-stigma and binge eating via food addiction and psychological distress. Consequently, intervention programs targeting food addiction and psychological distress among adolescents may have significant positive effects on outcomes for weight-related self-stigma and binge eating. The findings will be beneficial to researchers and healthcare professionals working with adolescents during this critical developmental period.
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11. |
- Asplund, Matthias, et al.
(författare)
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Assessment of the data quality of wayside wheel profile measurements
- 2016
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Ingår i: International Journal of COMADEM. - 1363-7681. ; 19:3, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the behaviour and the condition of a railway wheel in relation to performance and safety criteria, the wheel profile can be measured. This can be achieved using manual methods or automatic systems mounted along the railway track. Such systems have the advantage that they can measure a vast number of profiles, enabling new possibilities of performing statistical analyses of the results and pinpointing bad wheels at an early stage. These wayside measurement systems are, however, subjected to different environmental conditions that can affect the data quality of the measurement. If one is to be able to use automatic wheel profile measurements, the data quality has to be controlled in order to facilitate maintenance decisions. This paper proposes a method for the data quality assessment of an automatic wayside condition monitoring system measuring railway rolling stock wheels. The purpose of the assessment method proposed in this paper is to validate individual wheel profile measurements to ensure the accuracy of the wheel profile measurement data and hence the following data analysis. The method consists of a check routine based on the paired t-test, which uses a hypothesis test to verify if the null hypotheses are true. The check routine compares measurements of passing wheels rolling to a certain destination with measurements of the same wheels returning from that destination. The routine of comparing measurements of the same wheel, which is performed by four sensors (one on each side of each rail), will ensure that the sensors generate the same data for the same sample. A case study is presented which shows how the method can detect a faulty setup of the measurement system and prevent incorrect interpretations of the data from different measurement units in the same system. The paper ends with a discussion and conclusions concerning the improvements that are presented.
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12. |
- Asplund, Matthias, et al.
(författare)
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Enhancing the quality of data from a wheel profile measurement system : a proposed approach
- 2015
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Konferensbidrag (refereegranskat)abstract
- This investigation proposes a method for increasing the quality of data from an automatic condition monitoring system for railway rolling stock wheels, in order to assure the right data quality for further use of the data. The data quality improvement is used to ensure a higher reliability of the data analysis and to propose a new check routine to ensure that the sensors generate the same data for the same sample. A case study on field data shows how the data from different measurement setups differ for three of four measurements and why this check routine is needed. The paper ends with a discussion and conclusions concerning the improvements that are presented.
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13. |
- Bailey-Wilson, Joan E, et al.
(författare)
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Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families
- 2012
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Ingår i: BMC Medical Genetics. - London : BioMed Central. - 1471-2350. ; 13, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
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14. |
- Bemani, Ali, 1986-
(författare)
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Collaborative Predictive Maintenance for Smart Manufacturing : From Wireless Control to Federated Learning
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Industry 4.0 represents a significant shift in the industrial landscape, aimed at improving efficiency, productivity, and competitiveness. This shift involves the digitalization of industries, impacting manufacturing and maintenance processes. A pivotal element of this transformation is the development of Cyber-Physical Systems (CPS) that seamlessly connect the physical factory floor with the digital realm. These systems monitor real-time data from the physical world and prepare feedback from the digital space, necessitating the harmonious integration of computation and communication, especially through wireless technology. Simultaneously, Machine Learning (ML) methods are advancing across various domains. The proliferation of wireless sensors and the Internet of Things, particularly within the CPS framework, generates substantial data. To address challenges such as latency, device resource limitations, and privacy concerns associated with centralized cloud processing, there is a shift towards edge computing, enabling distributed learning algorithms.This dissertation tackles these challenges with four innovative methods that combine wireless technology, control systems, and distributed ML in the context of Industry 4.0. These methods aim to harness the potential of this digital transformation, making Predictive Maintenance (PdM) in industries smarter and more efficient. The first method, parallel event-triggering, is designed for multi-agent systems in industrial environments. It utilizes distributed event-based state estimation to enhance control performance and reduce network resource consumption. The second and third methods are developed for collaborative PdM using wireless communication in a federated approach. The second method focuses on real-time anomaly detection while preserving asset privacy at the edge level, and the third method optimizes remaining useful life prediction from sequential data within a federated learning framework. Both federated approaches enhance efficiency, simplify communication, and improve local model convergence. The fourth method introduces an innovative approach to collaborative PdM, utilizing over-the-air computation at the edge level. This approach offers low latency and improved spectral efficiency. The optimization challenges at the edge level are addressed by using a modified gradient descent approach, which effectively handles noisy communication channels and improves the convergence of ML algorithms. All four methods proposed in this thesis underwent a comprehensive evaluation,and the experimental findings demonstrate their effectiveness in achieving their intended objectives.
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15. |
- Butler, Geraldine, et al.
(författare)
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Evolution of pathogenicity and sexual reproduction in eight Candida genomes.
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 459:7247, s. 657-62
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Tidskriftsartikel (refereegranskat)abstract
- Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.
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17. |
- Chen, Haizhou, et al.
(författare)
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An integrated approach to evaluate the measurement capability and acceptability of acoustic emission sensors
- 2024
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Ingår i: Measurement science and technology. - : Institute of Physics. - 0957-0233 .- 1361-6501. ; 2:25132
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Tidskriftsartikel (refereegranskat)abstract
- Acoustic emission (AE) is a pivotal technique in condition-based maintenance (CBM) and recent years have witnessed a significant surge in the deployment of AE sensors in industrial applications. With this increase in availability, there comes a substantial challenge: evaluating the measurement capability of sensors within specific applications. As such, this study identifies a critical need for a structured approach to evaluate the measurement capabilities of AE sensors and subsequently judge their acceptability against guideline criteria. To address this need, we present an integrated approach that systematically guides the capability evaluation of AE sensors, incorporating both qualitative and quantitative analyses. The qualitative analysis aims to scrutinize the diagnostic accuracy of sensors by assessing the detectability of features critical for diagnostics. The quantitative analysis leverages the Gage repeatability and reproducibility (Gage R&R) to statistically evaluate sensor characteristics. A comprehensive experimental study further investigates the impact of measurement sources on the sensors’ repeatability, and reproducibility. This study illustrates the qualitative findings regarding sensor’s diagnostic accuracy in both time and frequency domains, revealing promising performance in diagnostic-based evaluations. In quantitative analysis, we demonstrate the results of sensor capability in terms of repeatability and reproducibility, providing the variations of different sources in statistics-based evaluations. We thoroughly investigate the influence of significant factors, quantifying their contributions to the sensor’s measurement capability. Furthermore, we introduce metrics designed to assess sensor’s acceptability, according to explicit acceptance and rejection criteria. Our experimental results affirm that root mean square measurements are within acceptable ranges for both sensors, while spectral entropy (SE) measurements for PK15I sensor satisfy the acceptable level. For HZ136I sensor, however, SE measurements are deemed conditionally acceptable. Ultimately, the proposed approach provides a robust framework for the comprehensive evaluation of AE sensor measurement capabilities, offering invaluable guidance for sensor selection and enhancement in industrial applications.
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18. |
- Christensen, G Bryce, et al.
(författare)
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Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.
- 2010
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.
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19. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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20. |
- Enshaei, Nastaran, et al.
(författare)
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ICPHM’23 Benchmark Vibration Dataset Applicable in Machine Learning for Systems’ Health Monitoring
- 2024
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Ingår i: 2024 IEEE International Conference on Prognostics and Health Management (ICPHM). - : IEEE.
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Konferensbidrag (refereegranskat)abstract
- Vibration signal analysis is an effective tool for fault diagnosis in industrial/manufacturing machinery. Gearboxes are a fundamental component of many industrial machines, and their failure can cause significant downtime, production losses, and safety hazards. Analyzing vibration signals makes it possible to detect, classify, and diagnose faults in gearboxes, enabling timely maintenance and preventing catastrophic failures. Vibration signals are sensitive to changes in the operating conditions and internal components of gearboxes, making them a reliable indicator of potential faults. This paper introduces a new vibration signal data set, referred to as VibraFault, which has been the focus of the ICPHM23 data challenge. The dataset contains vibration signals acquired from a test rig consisting of a driving motor, a two-stage planetary gearbox, a two-stage parallel gearbox, and a magnetic brake. The experiments include various operating conditions and focus on common sun gear faults on the planetary gearbox, such as surface wear, chipped, crack, and tooth-missing. For each operating condition, normal and fault vibration signals have been recorded at a sampling frequency of 10 kHz. Vibration signals have been collected in three directions to facilitate more comprehensive research studies on mapping between different types of faults and the system’s vibration response. The dataset has the potential to promote research in fault diagnosis, particularly in the development of advanced solutions based on Machine Learning (ML) and Deep Neural Networks (DNN).
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21. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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22. |
- Furberg, Helena, et al.
(författare)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Tidskriftsartikel (refereegranskat)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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23. |
- Garcia-Closas, Montserrat, et al.
(författare)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Tidskriftsartikel (refereegranskat)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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24. |
- Günaydin, Gökce, et al.
(författare)
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Impact of Q-Griffithsin anti-HIV microbicide gel in non-human primates : In situ analyses of epithelial and immune cell markers in rectal mucosa
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Natural-product derived lectins can function as potent viral inhibitors with minimal toxicity as shown in vitro and in small animal models. We here assessed the effect of rectal application of an anti-HIV lectin-based microbicide Q-Griffithsin (Q-GRFT) in rectal tissue samples from rhesus macaques. E-cadherin(+) cells, CD4(+) cells and total mucosal cells were assessed using in situ staining combined with a novel customized digital image analysis platform. Variations in cell numbers between baseline, placebo and Q-GRFT treated samples were analyzed using random intercept linear mixed effect models. The frequencies of rectal E-cadherin(+) cells remained stable despite multiple tissue samplings and Q-GRFT gel (0.1%, 0.3% and 1%, respectively) treatment. Whereas single dose application of Q-GRFT did not affect the frequencies of rectal CD4(+) cells, multi-dose Q-GRFT caused a small, but significant increase of the frequencies of intra-epithelial CD4(+) cells (placebo: median 4%; 1% Q-GRFT: median 7%) and of the CD4(+) lamina propria cells (placebo: median 30%; 0.1-1% Q-GRFT: median 36-39%). The resting time between sampling points were further associated with minor changes in the total and CD4(+) rectal mucosal cell levels. The results add to general knowledge of in vivo evaluation of anti-HIV microbicide application concerning cellular effects in rectal mucosa.
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25. |
- Handmark, Moa, et al.
(författare)
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STEMI, Revascularization, and Peak Troponin by Adverse Pregnancy Outcomes in Women With Myocardial Infarction
- 2024
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Ingår i: JACC: Advances. - 2772-963X. ; 3:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women with a history of adverse pregnancy outcomes have a higher risk of coronary heart disease. Emerging evidence suggests that women with a history of preeclampsia have a different pattern of overall coronary atherosclerosis and that they at the time of myocardial infarction (MI) more frequently present with ST-segment elevation MI (STEMI) compared to women with no such history.OBJECTIVES: The purpose of this study was to determine whether among women with MI, those with a history of adverse pregnancy outcomes are more likely to present with STEMI or other clinical characteristics indicating a more severe myocardial injury.METHODS: The study sample consisted of 8,320 women aged ≤65 years with first MI in Sweden 2007 to 2022. Regression models were used to estimate the association between adverse pregnancy outcomes (hypertensive disorders of pregnancy [non-preeclamptic hypertension and preeclampsia], small for gestational age [SGA] infant, and preterm delivery) and STEMI, invasive revascularization, and high troponin, while considering known predictors of coronary heart disease.RESULTS: In total, 3,128 (38%) of women suffered STEMI. The adjusted OR of presenting with STEMI were higher in women with a history of preterm preeclampsia (OR: 1.40; 95% CI: 1.05-1.88), or an SGA infant (OR: 1.30; 95% CI: 1.13-1.50) compared to women with no such history, as well as for in-hospital revascularization. Stratified by infarct type, troponin levels did not differ by adverse pregnancy outcome history.CONCLUSIONS: Among women with a first MI, a history of preterm preeclampsia or SGA infant were associated with STEMI and invasive revascularization.
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26. |
- He, Zhiyi, et al.
(författare)
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Deep transfer multi-wavelet auto-encoder for intelligent fault diagnosis of gearbox with few target training samples
- 2020
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Ingår i: Knowledge-Based Systems. - : Elsevier. - 0950-7051 .- 1872-7409. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- Lack of typical fault samples remains a huge challenge for intelligent fault diagnosis of gearbox. In this paper, a novel approach named deep transfer multi-wavelet auto-encoder is presented for gearbox intelligent fault diagnosis with few training samples. Firstly, new-type deep multi-wavelet auto-encoder is designed for learning important features of the collected vibration signals of gearbox. Secondly, high-quality auxiliary samples are selected based on similarity measure to well pre-train a source model sharing similar characteristics with the target domain. Thirdly, parameter knowledge acquired from the source model is transferred to target model using very few target training samples. Transfer diagnosis cases for different fault severities and compound faults of gearbox confirm the feasibility of the proposed approach even if the working conditions have significant changes.
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27. |
- Jin, Guangfu, et al.
(författare)
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Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis : evidence from the International Consortium for Prostate Cancer Genetics (ICPCG)
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:7, s. 1095-1103
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Tidskriftsartikel (refereegranskat)abstract
- Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.
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28. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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29. |
- Kapoor, Pooja Middha, et al.
(författare)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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30. |
- Lange, Jane M., et al.
(författare)
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Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts
- 2020
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Ingår i: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 126:3, s. 583-592
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Tidskriftsartikel (refereegranskat)abstract
- Background Active surveillance (AS) is an accepted means of managing low-risk prostate cancer. Because of the rarity of downstream events, data from existing AS cohorts cannot yet address how differences in surveillance intensity affect metastasis and mortality. This study projected the comparative benefits of different AS schedules in men diagnosed with prostate cancer who had Gleason score (GS) <= 6 disease and risk profiles similar to those in North American AS cohorts. Methods Times of GS upgrading were simulated based on AS data from the University of Toronto, Johns Hopkins University, the University of California at San Francisco, and the Canary Pass Active Surveillance Cohort. Times to metastasis and prostate cancer death, informed by models from the Scandinavian Prostate Cancer Group 4 trial, were projected under biopsy surveillance schedules ranging from watchful waiting to annual biopsies. Outcomes included the risk of metastasis, the risk of death, remaining life-years (LYs), and quality-adjusted LYs. Results Compared with watchful waiting, AS biopsies reduced the risk of prostate cancer metastasis and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively; and 5-year biopsies reduced the risk of metastasis and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. There was little difference between annual and 5-year biopsy schedules in terms of LYs (range of differences, 0.04-0.16 LYs) and quality-adjusted LYs (range of differences, -0.02 to 0.09 quality-adjusted LYs). Conclusions Among men diagnosed with GS <= 6 prostate cancer, obtaining a biopsy every 3 or 4 years appears to be an acceptable alternative to more frequent biopsies. Reducing surveillance intensity for those who have a low risk of progression reduces the number of biopsies while preserving the benefit of more frequent schedules.
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31. |
- Li, Xin, et al.
(författare)
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Intelligent fault diagnosis of bevel gearboxes using semi-supervised probability support matrix machine and infrared imaging
- 2023
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Ingår i: Reliability Engineering & System Safety. - : Elsevier. - 0951-8320 .- 1879-0836. ; 230
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Tidskriftsartikel (refereegranskat)abstract
- Fault diagnosis is of great significance to ensure the reliability and safety of complex bevel gearbox systems. Most existing intelligent fault diagnosis approaches of bevel gearboxes are designed with vibration monitoring. However, the collected vibration data are vulnerable to noise pollution and machinery operating conditions. Besides, traditional fault diagnosis models highly rely on numerous labeled samples, and neglect the high cost of label annotation in real-world applications. Therefore, a novel fault diagnosis approach based on semi-supervised probability support matrix machine (SPSMM) and infrared imaging is proposed for bevel gearboxes in this paper, which has the following properties. Firstly, SPSMM classifies 2D matrix data directly without vectorization, thus fully utilizing the spatial information in infrared images. Secondly, a probability output strategy is designed for SPSMM to calculate the posterior class probability estimation of matrix inputs, and consequently enhance the diagnostic accuracy and robustness of the model. Thirdly, a semi-supervised learning (SSL) framework is proposed for SPSMM to carry out sample transfer from the unlabeled sample pool to the labeled sample pool, which can effectively alleviate the problem of insufficient labeled samples. The superiority of the proposed diagnosis approach is demonstrated with an infrared imaging dataset of a bevel gearbox.
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32. |
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33. |
- Lin, Annie, et al.
(författare)
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Coronary Artery Restenosis in Women by History of Preeclampsia
- 2022
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Ingår i: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 11:18
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Tidskriftsartikel (refereegranskat)abstract
- Background: A history of preeclampsia is associated with increased risk of coronary artery disease and experimental evidence suggests that a history of preeclampsia also increases the risk of restenosis. However, the extent to which a history of preeclampsia is associated with risk of restenosis after percutaneous coronary intervention in women is unknown.Methods and Results: We included 6065 parous women aged <= 65 years with first percutaneous coronary intervention on 9452 segments 2006 to 2017, linking nationwide data on percutaneous coronary intervention and delivery history in Sweden. Main outcomes were clinical restenosis and target lesion revascularization within 2 years. We accounted for segment-, procedure-, and patient-related potential predictors of restenosis in proportional hazards regression models. Restenosis occurred in 345 segments (3.7%) and target lesion revascularization was performed on 383 patients (6.3%). A history of preeclampsia was neither significantly associated with risk of restenosis (predictor-accounted hazard ratio [HR], 0.71 [95% CI, 0.41-1.23]) nor target lesion revascularization (0.74 [95% CI, 0.51-1.07]) compared with a normotensive pregnancy history. When term and preterm preeclampsia were investigated separately, segments in women with a history of term preeclampsia had a lower risk of restenosis (predictor-accounted HR, 0.45 [95% CI, 0.21-0.94]). A history of preeclampsia was not significantly associated with death by any cause within 2 years of the index procedure (predictor-accounted HR 1.06, [95% CI, 0.62-1.80]).Conclusions: A history of preeclampsia was not associated with increased risk of restenosis but instead some evidence pointed to a decreased risk. To facilitate future studies and allow for replication, concomitant collection of data on pregnancy complication history and percutaneous coronary intervention outcomes in women is warranted.
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34. |
- Lin, Chung-Ying, et al.
(författare)
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Association of quality of life with internet use and weight stigma across individuals with obesity and those without obesity : Role of self-perception
- 2024
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Ingår i: Acta Psychologica. - : Elsevier. - 0001-6918 .- 1873-6297. ; 244
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Tidskriftsartikel (refereegranskat)abstract
- Weight status, weight stigma, and internet use are important factors impacting quality of life (QoL). However, little is known regarding how these factors interact in their association with QoL, and it is important to understand how self-perceived obesity and body mass index (BMI)-defined obesity may differentially impact QoL. We aimed to assess the associations between weight status (obesity vs. non-obesity, including both self-perceived and BMI-defined), weight stigma, internet use, and QoL. Cross-sectional data from the Taiwan Social Change Survey (N = 1604; mean age = 49.22; 52.93 % women) were used. All participants were classified as having obesity or not having obesity according to both self-perceived (self-perceived as ‘too fat’) and BMI-defined (≧27 kg/m2 as obesity) weight status. Results showed that the group with obesity (both BMI-defined and self-perceived) had significantly more internet time and lower physical QoL than the group without obesity. Those with self-perceived obesity, but not those with BMI-defined obesity, sought health information via the internet and used social media significantly more than the group without obesity. More internet time was associated with worse physical and mental QoL for the group with obesity regardless of BMI-defined or self-perceived status. Moreover, weight stigma was associated with worse mental QoL for the group with self-perceived obesity, but not for the group with BMI-defined obesity. Accordingly, being a person with obesity (self-defined, or based upon BMI) was associated with more internet time and poorer QoL. People with self-perceived obesity may have increased experience of weight stigma and greater internet use, factors that may contribute to their impaired QoL.
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35. |
- Lin, Daniel W., et al.
(författare)
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Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:9, s. 1928-1936
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer. Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 top-ranking SNPs (P <= 0.01, FDR <= 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients. Results: Five SNPs were validated (P <= 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2-1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (P(trend) = 0.001), adjusting for clinicopathologic factors known to influence prognosis. Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer. Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated. Cancer Epidemiol Biomarkers Prev; 20(9); 1928-36. (C)2011 AACR.
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36. |
- Lin, Janet
(författare)
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Bayesian Reliability with MCMC : Opportunities and Challenges
- 2016
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Ingår i: Current Trends in Reliability, Availability, Maintainability and Safety. - Cham : Encyclopedia of Global Archaeology/Springer Verlag. - 9783319235967 - 9783319235974 ; , s. 575-585
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Konferensbidrag (refereegranskat)abstract
- The recent proliferation of Markov Chain Monte Carlo (MCMC) approaches has led to the use of the Bayesian inference in a wide variety of fields, including reliability engineering. With the current (and future) proliferation of new products, old problems continue to hamper us, while new challenges keep appearing. In Bayesian reliability, these include but are not limited to: (1) achieving and making use of prior information; (2) applying small data sets or system operating/environmental (SOE) data with big and complex data; and (3) making posterior inferences from high-dimensional numerical integration. To deal with old problems while meeting new challenges, this paper proposes an improved procedure for Bayesian reliability inference with MCMC, discussing modern reliability data and noting some applications where the Bayesian reliability approach with MCMC can be used. It also explores opportunities to use Bayesian reliability models to create stronger statistical methods from prior to posterior. Finally, it outlines some practical concerns and remaining challenges for future research.
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37. |
- Lin, Janet, et al.
(författare)
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Data analysis of heavy haul wagon axle loads on Malmbanan line, Sweden : A case study for LKAB
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The research presented in this report was carried out by Operation and Maintenance Engineering at Luleå University of Technology (LTU) from November 2015 to April 2016. LKAB initiated the research study and provided financial support. The purpose of this research was to support LKAB and Trafikverket in their operational strategy review and optimization of future axle load implementations. It developed five research questions and answered them by analyzing the data for the Malmbanan iron ore train axle loads for 2015.Data analysis comprises four parts. In the first part (section 2), the analysis focuses on axle loads of all loaded trains operating at three different terminals: Kiruna, Malmberget, and Svappavaara. In addition, it examines the differences of three weighing locations in Kiruna, five weighing locations in Malmberget and four weighing locations in Svappavaara (12 weighing locations). Based on these results, the analysis in the second part (section 3) focuses on the heavy haul wagon. Wagon loads are evaluated and predicted for different loading rules (31.0 and 32.5 tons separately). To optimize the current loading rules, the third part of the analysis (section 4) proposes a novel approach to optimize the wagon axle loads: “three sigma prediction”. Under this approach, Kiruna, Malmberget and Svappavaara can set new target loads based on various risk levels. In the fourth and final part of the data analysis (section 5), a comparison study is carried out by collecting axle load data for the test train (with a 32.5 ton axle load) using three different measurement systems in Malmberget, Sävast and Sunderbyn. Finally, sections 6 and 7 summarize the results and make some recommendations for future work. The work presented in this report should give LKAB and Trafikverket a good overview of the load distribution for the ore trains operating on Malmbanan line. It can serve as input into the process of evaluating possible changes in axle load limits. It also gives LKAB a base from which to identify and work with optimization of the various loading places to load trains more efficiently and save costs.
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38. |
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39. |
- Lin, Janet (Jing), et al.
(författare)
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Guest editorial
- 2019
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Ingår i: International Journal of COMADEM. - : COMADEM International. - 1363-7681. ; 22:3, s. 3-3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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40. |
- Lin, Jing (Janet), et al.
(författare)
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IN2CLOUD : A novel concept for collaborative management of big railway data
- 2017
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Ingår i: Frontiers of Engineering Management. - : Higher Education Press. - 2095-7513 .- 2096-0255. ; 4:4, s. 428-436
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Tidskriftsartikel (refereegranskat)abstract
- In the EU Horizon 2020 Shift2Rail Multi-Annual Action Plan, the challenge of railway maintenance is generating knowledge from data and/or information. Therefore, we promote a novel concept called “IN2CLOUD,” which comprises three sub-concepts, to address this challenge: 1) A hybrid cloud, 2) an intelligent cloud with hybrid cloud learning, and 3) collaborative management using asset-related data acquired from the intelligent hybrid cloud. The concept is developed under the assumption that organizations want/need to learn from each other (including domain knowledge and experience) but do not want to share their raw data or information. IN2CLOUD will help the movement of railway industry systems from “local” to “global” optimization in a collaborative way. The development of cutting-edge intelligent hybrid cloud-based solutions, including information technology (IT) solutions and related methodologies, will enhance business security, economic sustainability, and decision support in the field of intelligent asset management of railway assets.
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41. |
- Lophatananon, Artitaya, et al.
(författare)
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Height, selected genetic markers and prostate cancer risk : results from the PRACTICAL consortium.
- 2017
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 117:5, s. 734-743
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer.METHODS: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions.RESULTS: The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm are at a 22% increased risk as compared to men with height <173 cm (OR 1.22, 95% CI 1.01-1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group.CONCLUSIONS: There was no evidence of gene-environment interaction between height and the selected candidate SNPs.Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.
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42. |
- Lozano, Rafael, et al.
(författare)
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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
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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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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43. |
- Lu, Lingyi, et al.
(författare)
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Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG
- 2012
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 72:4, s. 410-426
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD?=?1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS. In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS. Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD cores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS. These results will be useful in prioritizing future susceptibility gene discovery efforts in thiscommon cancer. Prostate 72: 410-426, 2012. (C) 2011 Wiley Periodicals, Inc.
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44. |
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45. |
- Norrbin, Per, et al.
(författare)
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Infrastructure robustness for railway systems
- 2016
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Ingår i: International Journal of Performability Engineering. - 0973-1318. ; 12:3, s. 249-264
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Tidskriftsartikel (refereegranskat)abstract
- In the railway industry, most maintenance approaches are based on certain “specified conditions”, e.g., RAMS (Reliability, Availability, Maintainability and Safety) and Risk. But the reality is more complex. Instead of the assumed conditions, “unfavorable conditions” may occur from either natural or operational causes, where robustness can be an effective approach. To adequately consider “unfavorable conditions” and to reduce “uncertainties” in railway maintenance, this study conducts a holistic examination of railway infrastructure robustness. It gives an overview of robustness and discusses some relevant studies. It then develops a new road map for railway infrastructure robustness, including a novel definition and a new framework of robustness management, based on continuous improvement. It explores the opportunities of applying the road map to the infrastructure of railway systems and outlines some practical concerns and remaining challenges for future research. The results provide guidelines for other research into robust infrastructure in railway maintenance.
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46. |
- Saari, Esi
(författare)
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KPI framework for maintenance management through eMaintenance : Development, implementation, assessment, and optimization
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Performance measurement is critical if any organization wants to thrive. The motivation for the thesis originated from the project “Key Performance Indicators (KPI) for control and management of maintenance process through eMaintenance (in Swedish: Nyckeltal för styrning och uppföljning av underhållsverksamhet m h a eUnderhåll)”, initiated and financed by a mining company in Sweden. The main purpose of this project is to propose an integrated KPI system for the mining company’s maintenance process through eMaintenance, including development, implementation, assessment, and optimization.There are gaps in the research, however, resulting in the following challenges. First, no KPI framework considers both technical and soft KPIs, so developing a system is problematic. Second, few studies have focused on implementing KPI measurement through eMaintenance. Third, there are gaps in KPI assessment. In assessing system availability, for example, the current analytical (e.g., Markov/semi-Markov) or simulation approaches (e.g., Monte Carlo simulation-based) cannot handle complicated state changes or are computationally expensive. In addition, few researchers have revealed the connections between technical and soft KPIs. For those soft KPIs for which the distribution of data collected from eMaintenance systems (e.g., work orders) is not easily determined, studies are insufficient. Fourth, the current continuous improvement process for the KPIs is very time-consuming. In short, there is a need for a new approach.The thesis develops an integrated KPI framework consisting of technical KPIs (linked to machines) and soft KPIs (linked to maintenance workflow) to control and monitor the entire maintenance process to achieve the overall goals of the organization. The proposed KPI framework makes use of four hierarchical levels and has 134 KPIs divided into technical and soft KPIs as follows: asset operation management has 23 technical KPIs, maintenance process management has 85 soft KPIs and maintenance resources management has 26 soft KPIs.The thesis discusses the proposed KPI framework; it lists the KPIs and provides timelines, definitions and general formulas for each specified KPI. Results will be used by the mining company to guide the implementation of the proposed KPIs in an eMaintenance environment.To suggest novel approaches to KPI assessment, the thesis takes system availability in the operational stage as an example. It proposes parametric Bayesian approaches to assess system availability. With these approaches, Mean Time to Failure (MTTF) and Mean Time to Repair (MTTR) can be treated as distributions instead of being “averaged” by point estimation. This better reflects reality. Markov Chain Monte Carlo (MCMC) approach is adopted to take advantage of both analytical and simulation methods. Because of MCMC’s high dimensional numerical integral calculation, the selection of prior information and descriptions of reliability/maintainability can be more flexible and realistic. The limitations of data sample size can also be compensated for. In the case studies, Time to Failure (TTF) and Time to Repair (TTR) are determined using a Bayesian Weibull model and a Bayesian lognormal model, respectively. The proposed approach can integrate analytical and simulation methods for system availability assessment and could be applied to other technical problems in asset management (e.g., other industries, other systems). By comparing the results with and without considering the threshold for censoring data, the research shows the connection between technical and soft KPIs, and suggests the threshold can be used as a monitoring line for continuous improvement in the mining company. For those soft KPIs for which the distribution of data collected from the eMaintenance system (e.g., work orders) is not easily determined, other approaches, such as time series analysis (if the data are “fast moving”), the Croston method (if the data are “intermittent”), or the bootstrap method (if the data are “slow moving”) could be applied. To ensure the KPI framework can be improved continuously, the thesis performs a comparison study to find the gaps between current and proposed KPIs in the mining company. It adapts a roadmap from the railway industry to show how optimization can be promoted by reviewing and improving the KPI framework.Results from this study will be applied to the company and guide its development, implementation and assessment of the KPIs through eMaintenance with continuous improvement. The proposed approaches could also be applied to other technical problems in asset management (e.g., other industries, other system).
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47. |
- Shu, Xiang, et al.
(författare)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Tidskriftsartikel (refereegranskat)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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48. |
- Szulkin, Robert, et al.
(författare)
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Prediction of individual genetic risk to prostate cancer using a polygenic score.
- 2015
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 75:13, s. 1467-74
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction.METHODS: We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls.RESULTS: The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk.CONCLUSIONS: Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction.
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49. |
- Teerlink, Craig C., et al.
(författare)
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Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease
- 2014
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Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 133:3, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p a parts per thousand currency sign 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.
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50. |
- Vos, Theo, et al.
(författare)
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Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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