Applying System Analysis and System Dynamics Modelling In Complex Research Projects - The Case Of VALUMICS

VALUMICS is a Horizon 2020 project funded by the European Commission (2017-2021). The project structure is highly integrated and transdisciplinary, building on the expertise of over 30 specialists in various fields of research including knowledge integration through systems analysis and system dynamics modelling, food science, supply chain management, life cycle assessment, logistics, economics and social science. The aim of the project is to analyze the dynamics of food supply systems using a structural analysis including system analysis and perform system simulations using system dynamics. The VALUMICS research approach and the project design are explained and it is justified why system analysis is needed to obtain an understanding of the complex connections and interactions of the distinct parts of food systems. Patterns will be recognized and thus causes and effects of complex relations within the selected food supply system and networks will be identified. This understanding of the functioning of the system can in turn be used to identify policy interventions

System Dynamics Modelling and System Analysis Applied in Complex Research Projects - the Case of VALUMICS

VALUMICS is a Horizon 2020 project funded by the European Commission (2017-2021). The project structure is highly integrated and transdisciplinary, building on the expertise of over 30 specialists in various fields of research including knowledge integration through systems analysis and system dynamics modelling, food science, supply chain management, life cycle assessment, logistics, economics and social science. The aim of the project is to analyze the dynamics of food supply- and value chain systems using a structural analysis including system analysis and perform system simulations using system dynamics. The VALUMICS research approach and the project design are explained and it is justified why system analysis is needed to obtain an understanding of the complex connections and interactions of the distinct parts of food systems. Patterns will be recognized and thus causes and effects of complex relations within the selected food supply system and networks will be identified. This understanding of the functioning of the system can in turn be used to identify policy interventions

Modeling of Integrated Supply-, Value- and Decision Chains within Food Systems

This paper presents a work in progress on the development of a mental model of a food system using system analysis. The aim is to be able to use this model to create a mathematical simulation model that can be used to identify policy intervention opportunities, specifically focusing on the resilience, integrity and sustainability of food supply networks. The traditional view of food systems as supply chains with a downstream physical flow of products is extended to include the associated upstream flow of money and the decision chains that link these flows. Central to this work is the idea that supply systems are driven by profit and regulated by market dynamics and that these factors generate the underlying feedback structure of the system. Studying the structure of such systems as integrated supply-, value- and decision chains has underscored their complexity and the need for further, more food system specific research

Maternal diet in early and late pregnancy in relation to weight gain

To access Publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To identify dietary factors related to the risk of gaining weight outside recommendations for pregnancy weight gain and birth outcome.Design:An observational study with free-living conditions.Subjects:Four hundred and ninety five healthy pregnant Icelandic women. METHODS: The dietary intake of the women was estimated with a semiquantitative food frequency questionnaire covering food intake together with lifestyle factors for the previous 3 months. Questionnaires were filled out at between 11 and 15 weeks and between 34 and 37 weeks gestation. Comparison of birth outcome between the three weight gain groups was made with ANOVA and Bonferroni post hoc tests. Dietary factors related to at least optimal and excessive weight gain during pregnancy were represented with logistic regression controlling for potential confounding. RESULTS: Of the women, 26% gained suboptimal and 34% excessive weight during pregnancy. Women in late pregnancy with at least optimal, compared with women with suboptimal, weight gain were eating more (OR = 3.32, confidence interval (CI)=1.81-6.09, P < 0.001) and drinking more milk (OR = 3.10, CI = 1.57-6.13, P = 0.001). The same dietary factors were related to excessive, compared with optimal, weight gain. Furthermore, eating more sweets early in pregnancy increased the risk of gaining excessive weight (OR=2.52, CI=1.10-5.77, P=0.029). Women with a body mass index of 25.0-29.9 kg/m(2) before pregnancy were most likely to gain excessive weight (OR = 7.37, CI 4.13-13.14, P < 0.001). Women gaining suboptimal weight gave birth to lighter children (P < 0.001) and had shorter gestation (P = 0.008) than women gaining optimal or excessive weight. CONCLUSION: Women who are overweight before pregnancy should get special attention regarding lifestyle modifications affecting consequent weight gain during pregnancy. They are most likely to gain excessive weight and therefore most likely to suffer pregnancy and delivery complications and struggle with increasing overweight and obesity after giving birth

Invasive infections due to Streptococcus pyogenes: seasonal variation of severity and clinical characteristics, Iceland, 1975 to 2012.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageEpidemiology and clinical characteristics of invasive Group A streptococcal infections (IGASI) are highly variable. Long-term studies are needed to understand the interplay between epidemiology and virulence. In a population-based study of IGASI in Iceland from 1975 to 2012, 288 cases were identified by positive cultures from normally sterile body sites. Charts were reviewed retrospectively and emm-types of viable Streptococcus pyogenes isolates (n=226) determined. Comparing the first and last decade of the study period, IGASI incidence increased from 1.09 to 3.96 cases per 100,000 inhabitants per year. The most common were emm types 1 (25%), 28 (11%) and 89 (11%); emm1 strains were most likely to cause severe infections. Infections in adults were significantly more likely to be severe during the seasonal peak from January to April (risk ratio: 2.36, 95% confidence interval: 1.34–4.15). Significant seasonal variability in severity was noted among patients with diagnosis of sepsis, respiratory infection and cellulitis, with 38% of severe infections in January to April compared with 16% in other months (p<0.01). A seasonal increase in severity of IGASI suggested that generalised seasonal increase in host susceptibility, rather than introduction of more virulent strains may play a role in the pathogenesis of these potentially fatal infections.Icelandic Center for Research, Rannis/100436021 Landspitali University Hospital Science Fun

BRCA2 mutation carriers, reproductive factors and breast cancer risk

BACKGROUND: Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear. METHODS: In a case–control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis. RESULTS: An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years. CONCLUSION: The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: Common diseases often have an inflammatory component reflected by associated markers such as serum C-reactive protein (CRP) levels. Circulating CRP levels have also been associated with adipose tissue as well as with specific CRP genotypes. We examined the interaction between measures of body mass index (BMI), waist circumference and fat percent (total fat measured by bioimpedance) with genotypes of the CRP gene in the determination of CRP levels. METHODS: The first 2296 participants (mean age 76+/-6 years, 42% men) in the Age, Gene/Environment Susceptibility-Reykjavik Study, a multidisciplinary epidemiological study to determine risk factors in aging, were genotyped for 10 single nucleotide polymorphisms (SNPs) in the CRP gene. General linear models with age and terms for interaction of CRP genotypes with BMI, waist circumference and percent fat were used to evaluate the association of genotypes to CRP levels (high-sensitivity method, range 0-10 mg l(-1)) in men and women separately. RESULTS: We focused on the SNP rs1205 that represents the allele that captures the strongest effects of the gene on CRP levels. Carriers of the rs1205 G allele had significantly higher CRP levels than noncarriers in a dose-dependent manner. Compared to the AA genotype, the slope of the increase in CRP with increasing BMI (P=0.045) and waist circumference (P=0.014) was different for the G allele carriers and of similar magnitude in both men and women. The rs1205 interactions were not significant for fat mass percent, suggesting a possible association with fat localization. CONCLUSIONS: This study further illuminates the known association between measures of adiposity and CRP levels and is shown to be dependent on variation in the rs1205 SNP of the CRP gene. The correlated increase in CRP levels with adiposity is accentuated by presence of the G allele

Individual risk assessment and information technology to optimise screening frequency for diabetic retinopathy.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.AIMS/HYPOTHESIS: The aim of this study was to reduce the frequency of diabetic eye-screening visits, while maintaining safety, by using information technology and individualised risk assessment to determine screening intervals. METHODS: A mathematical algorithm was created based on epidemiological data on risk factors for diabetic retinopathy. Through a website, www.risk.is , the algorithm receives clinical data, including type and duration of diabetes, HbA(1c) or mean blood glucose, blood pressure and the presence and grade of retinopathy. These data are used to calculate risk for sight-threatening retinopathy for each individual's worse eye over time. A risk margin is defined and the algorithm recommends the screening interval for each patient with standardised risk of developing sight-threatening retinopathy (STR) within the screening interval. We set the risk margin so that the same number of patients develop STR within the screening interval with either fixed annual screening or our individualised screening system. The database for diabetic retinopathy at the Department of Ophthalmology, Aarhus University Hospital, Denmark, was used to empirically test the efficacy of the algorithm. Clinical data exist for 5,199 patients for 20 years and this allows testing of the algorithm in a prospective manner. RESULTS: In the Danish diabetes database, the algorithm recommends screening intervals ranging from 6 to 60 months with a mean of 29 months. This is 59% fewer visits than with fixed annual screening. This amounts to 41 annual visits per 100 patients. CONCLUSION: Information technology based on epidemiological data may facilitate individualised determination of screening intervals for diabetic eye disease. Empirical testing suggests that this approach may be less expensive than conventional annual screening, while not compromising safety. The algorithm determines individual risk and the screening interval is individually determined based on each person's risk profile. The algorithm has potential to save on healthcare resources and patients' working hours by reducing the number of screening visits for an ever increasing number of diabetic patients in the world

Genomic and phenotypic analysis of BRCA2 mutated breast cancers reveals co-occurring changes linked to progression

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Inherited mutations in the BRCA2 gene greatly increase the risk of developing breast cancer. Consistent with an important role for BRCA2 in error-free DNA repair, complex genomic changes are frequently observed in tumors derived from BRCA2 mutation carriers. Here, we explore the impact of DNA copy-number changes in BRCA2 tumors with respect to phenotype and clinical staging of the disease. METHODS: Breast tumors (n = 33) derived from BRCA2 999del5 mutation carriers were examined in terms of copy-number changes with high-resolution aCGH (array comparative genomic hybridization) containing 385 thousand probes (about one for each 7 kbp) and expression of phenotypic markers on TMAs (tissue microarrays). The data were examined with respect to clinical parameters including TNM staging, histologic grade, S phase, and ploidy. RESULTS: Tumors from BRCA2 carriers of luminal and basal/triple-negative phenotypes (TNPs) differ with respect to patterns of DNA copy-number changes. The basal/TNP subtype was characterized by lack of pRb (RB1) coupled with high/intense expression of p16 (CDKN2A) gene products. We found increased proportions of Ki-67-positive cells to be significantly associated with loss of the wild-type (wt) BRCA2 allele in luminal types, whereas BRCA2wt loss was less frequent in BRCA2 tumors displaying basal/TNP phenotypes. Furthermore, we show that deletions at 13q13.1, involving the BRCA2wt allele, represents a part of a larger network of co-occurring genetic changes, including deletions at 6q22.32-q22.33, 11q14.2-q24.1, and gains at 17q24.1. Importantly, copy-number changes at these BRCA2-linked networking regions coincide with those associated with advanced progression, involving the capacity to metastasize to the nodes or more-distant sites at diagnosis. CONCLUSIONS: The results presented here demonstrate divergent paths of tumor evolution in BRCA2 carriers and that deletion of the wild-type BRCA2 allele, together with co-occurring changes at 6 q, 11 q, and 17 q, are important events in progression toward advanced disease.Eimskipafelag University Minningarsjodur Bergthoru Magnusdottur and Jakobs J Bjarnasonar Gongum Saman Icelandic Cancer Research Fund SKI Icelandic Centre for Research RANNIS The University of Icelan