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2.
  • Wuttke, Matthias, et al. (author)
  • A catalog of genetic loci associated with kidney function from analyses of a million individuals
  • 2019
  • In: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
  • Journal article (peer-reviewed)abstract
    • Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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3.
  • 2019
  • Journal article (peer-reviewed)
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4.
  • Gorski, Mathias, et al. (author)
  • Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
  • 2021
  • In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
  • Journal article (peer-reviewed)abstract
    • Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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5.
  • Pattaro, Cristian, et al. (author)
  • Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
  • 2016
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Journal article (peer-reviewed)abstract
    • Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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6.
  • Carlsson, Sigrid, 1982, et al. (author)
  • Who and when should we screen for prostate cancer? Interviews with key opinion leaders.
  • 2015
  • In: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13
  • Journal article (peer-reviewed)abstract
    • Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine's 'Spotlight on Prostate Cancer' article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world's key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts' views and give their own personal opinions on PSA screening.
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7.
  • Carrière, Yves, et al. (author)
  • Crop rotation mitigates impacts of corn rootworm resistance to transgenic Bt corn
  • 2020
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:31, s. 18385-18392
  • Journal article (peer-reviewed)abstract
    • Transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt) can suppress pests and reduce insecticide sprays, but their efficacy is reduced when pests evolve resistance. Although farmers plant refuges of non-Bt host plants to delay pest resistance, this tactic has not been sufficient against the western corn rootworm, Diabrotica virgifera virgifera. In the United States, some populations of this devastating pest have rapidly evolved practical resistance to Cry3 toxins and Cry34/35Ab, the only Bt toxins in commercially available corn that kill rootworms. Here, we analyzed data from 2011 to 2016 on Bt corn fields producing Cry3Bb alone that were severely damaged by this pest in 25 cropreporting districts of Illinois, Iowa, and Minnesota. The annual mean frequency of these problem fields was 29 fields (range 7 to 70) per million acres of Cry3Bb corn in 2011 to 2013, with a cost of $163 to $227 per damaged acre. The frequency of problem fields declined by 92% in 2014 to 2016 relative to 2011 to 2013 and was negatively associated with rotation of corn with soybean. The effectiveness of corn rotation for mitigating Bt resistance problems did not differ significantly between crop-reporting districts with versus without prevalent rotation-resistant rootworm populations. In some analyses, the frequency of problem fields was positively associated with planting of Cry3 corn and negatively associated with planting of Bt corn producing both a Cry3 toxin and Cry34/35Ab. The results highlight the central role of crop rotation for mitigating impacts of D. v. virgifera resistance to Bt corn.
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8.
  • Dall'Era, Marc A., et al. (author)
  • Active surveillance for early-stage prostate cancer : review of the current literature
  • 2008
  • In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 112:8, s. 1650-9
  • Journal article (peer-reviewed)abstract
    • The natural history of prostate cancer is remarkably heterogeneous and, at this time, not completely understood. The widespread adoption and application of prostate-specific antigen (PSA) screening has led to a dramatic shift toward the diagnosis of low-volume, nonpalpable, early-stage tumors. Autopsy and early observational studies have shown that approximately 1 in 3 men aged >50 years has histologic evidence of prostate cancer, with a significant portion of tumors being small and possibly clinically insignificant. Utilizing the power of improved contemporary risk stratification schema to better identify patients with a low risk of cancer progression, several centers are gaining considerable experience with active surveillance and delayed, selective, and curative therapy. A literature review was performed to evaluate the rationale behind active surveillance for prostate cancer and to describe the early experiences from surveillance protocols. It appears that a limited number of men on active surveillance have required treatment, with the majority of such men having good outcomes after delayed selective intervention for progressive disease. The best candidates for active surveillance are being defined, as are predictors of active treatment. The psychosocial ramifications of surveillance for prostate cancer can be profound and future needs and unmet goals will be discussed.
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9.
  • Gorski, Mathias, et al. (author)
  • Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
  • 2022
  • In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
  • Journal article (peer-reviewed)abstract
    • Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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10.
  • Okada, Yukinori, et al. (author)
  • Genetics of rheumatoid arthritis contributes to biology and drug discovery
  • 2014
  • In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
  • Journal article (peer-reviewed)abstract
    • A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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11.
  • Sawcer, Stephen, et al. (author)
  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
  • 2011
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
  • Journal article (peer-reviewed)abstract
    • Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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12.
  • Van Deerlin, Vivian M, et al. (author)
  • Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
  • 2010
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
  • Journal article (peer-reviewed)abstract
    • Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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14.
  • Bennett, Alexander, et al. (author)
  • Prevalence and Impact of Fall-Risk-Increasing Drugs, Polypharmacy, and Drug-Drug Interactions in Robust Versus Frail Hospitalised Falls Patients : A Prospective Cohort Study
  • 2014
  • In: Drugs & Aging. - : Springer Science and Business Media LLC. - 1170-229X .- 1179-1969. ; 31:3, s. 225-232
  • Journal article (peer-reviewed)abstract
    • Background Several measures of medication exposure are associated with adverse outcomes in older people. Exposure to and the clinical outcomes of these measures in robust versus frail older inpatients are not known. Objective In older robust and frail patients admitted to hospital after a fall, we investigated the prevalence and clinical impact of fall-risk-increasing drugs (FRIDs), total number of medications, and drug-drug interactions (DDIs). Methods Patients >= 60 years of age admitted with a fall to a tertiary referral teaching hospital in Sydney were recruited and frailty was assessed. Data were collected at admission, discharge, and 2 months after admission. Results A total of 204 patients were recruited (mean age 80.5 +/- 8.3 years), with 101 robust and 103 frail. On admission, compared with the robust, frail participants had significantly higher mean +/- SD number of FRIDs (frail 3.4 +/- 2.2 vs. robust 1.6 +/- 1.5, P < 0.0001), total number of medications (9.8 +/- 4.3 vs. 4.4 +/- 3.3, P < 0.0001), and DDI exposure (35 vs. 5 %, P = 0.001). Number of FRIDs on discharge was significantly associated with recurrent falls [odds ratio (OR) 1.7 (95 % confidence interval [CI] 1.3-2.1)], which were most likely to occur with 1.5 FRIDs in the frail and 2.5 FRIDs in the robust. Number of medications on discharge was also associated with recurrent falls [OR 1.2 (1.0-1.3)], but DDIs were not. Conclusion Exposure to FRIDs and other measures of high-risk medication exposures is common in older people admitted with falls, especially the frail. Number of FRIDs and to a lesser extent total number of medicines at discharge were associated with recurrent falls.
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15.
  • Bruford, Elspeth A., et al. (author)
  • HUGO Gene Nomenclature Committee (HGNC) recommendations for the designation of gene fusions
  • 2021
  • In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 35:11, s. 3040-3043
  • Journal article (peer-reviewed)abstract
    • Gene fusions have been discussed in the scientific literature since they were first detected in cancer cells in the early 1980s. There is currently no standardized way to denote the genes involved in fusions, but in the majority of publications the gene symbols in question are listed either separated by a hyphen (-) or by a forward slash (/). Both types of designation suffer from important shortcomings. HGNC has worked with the scientific community to determine a new, instantly recognizable and unique separator—a double colon (::)—to be used in the description of fusion genes, and advocates its usage in all databases and articles describing gene fusions.
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16.
  • Bruinsma, Sophie M, et al. (author)
  • Expert consensus document : Semantics in active surveillance for men with localized prostate cancer - results of a modified Delphi consensus procedure
  • 2017
  • In: Nature Reviews Urology. - : Springer Science and Business Media LLC. - 1759-4820 .- 1759-4812. ; 14:5, s. 312-322
  • Research review (peer-reviewed)abstract
    • Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if ≥70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.
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17.
  • Carriere, Yves, et al. (author)
  • Governing evolution : A socioecological comparison of resistance management for insecticidal transgenic Bt crops among four countries
  • 2020
  • In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 49:1, s. 1-16
  • Research review (peer-reviewed)abstract
    • Cooperative management of pest susceptibility to transgenic Bacillus thuringiensis (Bt) crops is pursued worldwide in a variety of forms and to varying degrees of success depending on context. We examine this context using a comparative socioecological analysis of resistance management in Australia, Brazil, India, and the United States. We find that a shared understanding of resistance risks among government regulators, growers, and other actors is critical for effective governance. Furthermore, monitoring of grower compliance with resistance management requirements, surveillance of resistance, and mechanisms to support rapid implementation of remedial actions are essential to achieve desirable outcomes. Mandated resistance management measures, strong coordination between actors, and direct linkages between the group that appraises resistance risks and growers also appear to enhance prospects for effective governance. Our analysis highlights factors that could improve current governance systems and inform other initiatives to conserve susceptibility as a contribution to the cause of public good.
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18.
  • Carroll, Christopher, et al. (author)
  • Hypoxia Generated by Avian Embryo Growth Induces the HIF-α Response and Critical Vascularization
  • 2021
  • In: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9, s. 1-15
  • Journal article (peer-reviewed)abstract
    • Cancer research has transformed our view on cellular mechanisms for oxygen sensing. It has been documented that these mechanisms are important for maintaining animal tissues and life in environments where oxygen (O2) concentrations fluctuate. In adult animals, oxygen sensing is governed by the Hypoxia Inducible Factors (HIFs) that are stabilized at low oxygen concentrations (hypoxia). However, the importance of hypoxia itself during development and for the onset of HIF-driven oxygen sensing remains poorly explored. Cellular responses to hypoxia associates with cell immaturity (stemness) and proper tissue and organ development. During mammalian development, the initial uterine environment is hypoxic. The oxygenation status during avian embryogenesis is more complex since O2 continuously equilibrates across the porous eggshell. Here, we investigate HIF dynamics and use microelectrodes to determine O2 concentrations within the egg and the embryo during the first four days of development. To determine the increased O2 consumption rates, we also obtain the O2 transport coefficient (DO2) of eggshell and associated inner and outer shell membranes, both directly (using microelectrodes in ovo for the first time) and indirectly (using water evaporation at 37.5°C for the first time). Our results demonstrate a distinct hypoxic phase (<5% O2) between day 1 and 2, concurring with the onset of HIF-α expression. This phase of hypoxia is demonstrably necessary for proper vascularization and survival. Our indirectly determined DO2 values are about 30% higher than those determined directly. A comparison with previously reported values indicates that this discrepancy may be real, reflecting that water vapor and O2 may be transported through the eggshell at different rates. Based on our obtained DO2 values, we demonstrate that increased O2 consumption of the growing embryo appears to generate the phase of hypoxia, which is also facilitated by the initially small gas cell and low membrane permeability. We infer that the phase of in ovo hypoxia facilitates correct avian development. These results support the view that hypoxic conditions, in which the animal clade evolved, remain functionally important during animal development. The study highlights that insights from the cancer field pertaining to the cellular capacities by which both somatic and cancer cells register and respond to fluctuations in O2 concentrations can broadly inform our exploration of animal development and success.
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19.
  • Carroll, Eero, 1970-, et al. (author)
  • Mutual benefit societies, institutional design, and the emergence of public sickness insurance programs : A comparative analysis of six European nations
  • Other publication (other academic/artistic)abstract
    • Prior research has tended to explain social insurance design in terms of purposive political strategy.  Yet previous structures of class representation, rather than strategic politics only, explain why early welfare states segregated or integrated provision on a class basis. In investigating Europe’s pre-1900 public sickness insurance programs, we find that “inclusionary” Belgian and Swedish insurance laws reflected the class-transcension of these countries’ mutualist organizations.  “Exclusionary,” occupationally segregated German and Austro-Hungarian laws reflected the fragmented corporatism of benefit organizations there.  In France, however, statist segregation of mutuals was partly upheld even against the background of more lateral mutualist traditions.  Finally, Denmark’s class-transcending mutualist movement could not prevent a more “exclusionary” law’s emergence—here based on targeting, or means testing. Categorical programs, especially those incorporating the “third sector“, cause political problems—particularly when third-sector organizing is not correspondingly categorical.  This should trouble contemporary politicians combining inclusionary and exclusionary programs and/or rhetoric.
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20.
  • Carroll, Harriet A., et al. (author)
  • Hydration status affects thirst and salt preference but not energy intake or postprandial ghrelin in healthy adults : A randomised crossover trial
  • 2019
  • In: Physiology and Behavior. - : Elsevier BV. - 0031-9384. ; 212
  • Journal article (peer-reviewed)abstract
    • Background: Few studies have investigated the effect of hydration status on appetite for food in healthy adults. Prior work suggests hydration status does not alter appetite or energy intake, with mixed findings regarding appetite hormone secretion. However, an extensive investigation into both the psychological and physiological appetitive responses to hydration status has never been conducted. Objective: To investigate the effect of hydration status on multiple facets of appetite. Design: After 3 days pre-trial standardization, a range of appetite tasks were conducted when hypohydrated (HYPO) and euhydrated (EUHY) in 16 healthy participants (8 men). Hydration status was manipulated via dehydration in a heat tent for 60 min and subsequent fluid restriction (HYPO) or replacement (EUHY). The next day, a food reward computer task was completed followed by an ad libitum pasta meal. Pre- and post-prandial visual analogue scales assessing hunger, fullness, and flavour desires (sweet, salty, savoury and fatty) were additionally completed. Blood samples were taken the previous day before the hydration interventions in a euhydrated state, and in the fasted and post-prandial state during HYPO and EUHY. Results: HYPO induced -1.9 ± 1.2% body mass change, compared to -0.2 ± 0.6%, with accompanying changes in markers of hypohydration which were not seen during EUHY. A higher desire for foods was associated with a higher water content but the association was weaker in EUHY compared to HYPO, (β= -0.33 mm/g of food water content, p < 0.001) in the food reward task. Visual analogue scales showed similar hunger and fullness between interventions, but during HYPO there was consistently higher thirst (average range in difference 27–32 mm across all time points) and lower fasted desire for salt (−23, 95% CI −10, −35 mm). Ad libitum energy intake (HYPO 1953 ± 742 kJ, EUHY 2027 ± 926 kJ; p = 0.542) and post-prandial ghrelin concentrations (HYPO 180 ± 65 pg mL−1, EUHY 188 ± 71 pg mL−1; p = 0.736) were similar by hydration status. Conclusions: An acute manipulation to hydration status altered desire for salt and foods of differing water contents, but did not influence energy intake at an ad libitum pasta meal. Further research should investigate whether these appetites would alter food choice.
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21.
  • Carroll, Joseph, et al. (author)
  • Biocultural Theory: The Current State of Knowledge
  • 2017
  • In: Evolutionary Behavioral Sciences. - : American Psychological Association (APA). - 2330-2925 .- 2330-2933. ; 11:1, s. 1-15
  • Journal article (peer-reviewed)abstract
    • Biocultural theory is an integrative research program designed to investigate the causal interactions between biological adaptations and cultural constructions. From the biocultural perspective, cultural processes are rooted in the biological necessities of the human life cycle: specifically human forms of birth, growth, survival, mating, parenting, and sociality. Conversely, from the biocultural perspective, human biological processes are constrained, organized, and developed by culture, which includes technology, culturally specific socioeconomic and political structures, religious and ideological beliefs, and artistic practices such as music, dance, painting, and storytelling. Establishing biocultural theory as a program that self-consciously encompasses the different particular forms of human evolutionary research could help scholars and scientists envision their own specialized areas of research as contributions to a coherent, collective research program. This article argues that a mature biocultural paradigm needs to be informed by at least 7 major research clusters: (a) gene-culture coevolution; (b) human life history theory; (c) evolutionary social psychology; (d) anthropological research on contemporary hunter-gatherers; (e) biocultural socioeconomic and political history; (f) evolutionary aesthetics; and (g) biocultural research in the humanities (religions, ideologies, the history of ideas, and the arts). This article explains the way these research clusters are integrated in biocultural theory, evaluates the level of development in each cluster, and locates current biocultural theory within the historical trajectory of the social sciences and the humanities.
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22.
  • Corneille, Olivier, et al. (author)
  • POINT OF VIEW Beware ‘persuasive communication devices’ when writing and reading scientific articles
  • 2023
  • In: eLife. - 2050-084X. ; 12
  • Journal article (peer-reviewed)abstract
    • Authors rely on a range of devices and techniques to attract and maintain the interest of readers, and to convince them of the merits of the author’s point of view. However, when writing a scientific article, authors must use these ‘persuasive communication devices’ carefully. In particular, they must be explicit about the limitations of their work, avoid obfuscation, and resist the temptation to oversell their results. Here we discuss a list of persuasive communication devices and we encourage authors, as well as reviewers and editors, to think carefully about their use.
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23.
  • Elsik, Christine G., et al. (author)
  • The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
  • 2009
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
  • Journal article (peer-reviewed)abstract
    • To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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25.
  • Hung, Ryan, et al. (author)
  • Systematic Review of the Clinical Course, Natural History, and Prognosis for Pediatric Mild Traumatic Brain Injury : Results of the International Collaboration on Mild Traumatic Brain Injury Prognosis
  • 2014
  • In: Archives of Physical Medicine and Rehabilitation. - : Elsevier. - 0003-9993 .- 1532-821X. ; 95:3, Suppl, s. S174-S191
  • Research review (peer-reviewed)abstract
    • ObjectiveTo synthesize the best available evidence on prognosis after pediatric mild traumatic brain injury (MTBI).Data SourcesWe searched MEDLINE, Embase, PsycINFO, CINAHL, and SPORTDiscus (2001–2012), as well as reference lists of eligible articles, and relevant systematic reviews and meta-analyses.Study SelectionControlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 MTBI pediatric cases. After 77,914 records were screened for the entire review, 299 studies were eligible and assessed for scientific rigor.Data ExtractionEligible studies were critically appraised using the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles into evidence tables.Data SynthesisEvidence from 25 accepted articles was synthesized qualitatively according to SIGN criteria, and prognostic information was prioritized according to design as exploratory or confirmatory. Most studies show that postconcussion symptoms and cognitive deficits resolve over time. Limited evidence suggests that postconcussion symptoms may persist in those with lower cognitive ability and intracranial pathology on neuroimaging. Preliminary evidence suggests that the risk of epilepsy is increased for up to 10 years after MTBI; however, there is insufficient high-quality evidence at this time to support this link.ConclusionsCommon post-MTBI symptoms and deficits in children are not specific to MTBI and appear to resolve with time; however, limited evidence suggests that children with intracranial pathology on imaging may experience persisting symptoms or deficits. Well-designed, long-term studies are needed to confirm these findings.
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26.
  • Ishigaki, Kazuyoshi, et al. (author)
  • Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis
  • 2022
  • In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:11, s. 1640-1651
  • Journal article (peer-reviewed)abstract
    • Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
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27.
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28.
  • Jalloh, Mohamed F., et al. (author)
  • Evidence of behaviour change during an Ebola virus disease outbreak, Sierra Leone
  • 2020
  • In: Bulletin of the World Health Organization. - : World Health Organization. - 0042-9686 .- 1564-0604. ; 98:5, s. 330-340
  • Journal article (peer-reviewed)abstract
    • Objective To evaluate changes in Ebola-related knowledge, attitudes and prevention practices during the Sierra Leone outbreak between 2014 and 2015.Methods Four cluster surveys were conducted: two before the outbreak peak (3499 participants) and two after (7104 participants). We assessed the effect of temporal and geographical factors on 16 knowledge, attitude and practice outcomes.Findings Fourteen of 16 knowledge, attitude and prevention practice outcomes improved across all regions from before to after the outbreak peak. The proportion of respondents willing to: (i) welcome Ebola survivors back into the community increased from 60.0% to 89.4% (adjusted odds ratio, aOR: 6.0; 95% confidence interval, CI: 3.9–9.1); and (ii) wait for a burial team following a relative’s death increased from 86.0% to 95.9% (aOR: 4.4; 95% CI: 3.2–6.0). The proportion avoiding unsafe traditional burials increased from 27.3% to 48.2% (aOR: 3.1; 95% CI: 2.4–4.2) and the proportion believing spiritual healers can treat Ebola decreased from 15.9% to 5.0% (aOR: 0.2; 95% CI: 0.1–0.3). The likelihood respondents would wait for burial teams increased more in high-transmission (aOR: 6.2; 95% CI: 4.2–9.1) than low-transmission (aOR: 2.3; 95% CI: 1.4–3.8) regions. Self-reported avoidance of physical contact with corpses increased in high but not low-transmission regions, aOR: 1.9 (95% CI: 1.4–2.5) and aOR: 0.8 (95% CI: 0.6–1.2), respectively.Conclusion Ebola knowledge, attitudes and prevention practices improved during the Sierra Leone outbreak, especially in high-transmission regions. Behaviourally-targeted community engagement should be prioritized early during outbreaks.
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29.
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30.
  • Lange, Jane M., et al. (author)
  • Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts
  • 2020
  • In: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 126:3, s. 583-592
  • Journal article (peer-reviewed)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.
  • Mah, Jean K, et al. (author)
  • A multinational study on motor function in early-onset FSHD.
  • 2018
  • In: Neurology. - 1526-632X. ; 90:15
  • Journal article (peer-reviewed)abstract
    • To investigate motor function associations with age, sex, and D4Z4 repeats among participants with early-onset facioscapulohumeral muscular dystrophy (FSHD) type 1 as defined by weakness onset before 10 years of age.We collected standardized motor assessments, including manual muscle testing (MMT), quantitative muscle testing, functional motor evaluations, and clinical severity scores (CSSs), at 12 Cooperative International Neuromuscular Research Group centers. To measure associations, we used linear regression models adjusted for sex, evaluation age, age at onset of weakness, and D4Z4 repeats.Among 52 participants (60% female, mean age 22.9 ± 14.7 years), weakness was most pronounced in the shoulder and abdominal musculature. Older enrollment age was associated with greater CSSs (p = 0.003). When adjusted for enrollment age, sex, and D4Z4 repeats, younger age at onset of facial weakness was associated with greater CSSs, slower velocities in timed function tests, and lower MMT scores (p < 0.05).Significant clinical variability was observed in early-onset FSHD. Earlier age at onset of facial weakness was associated with greater disease severity. Longitudinal assessments are needed to determine the rate of disease progression in this population.
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32.
  • Marini, Lorenzo, et al. (author)
  • Climate drivers of bark beetle outbreak dynamics in Norway spruce forests
  • 2017
  • In: Ecography. - : Wiley. - 0906-7590 .- 1600-0587. ; 40:12, s. 1426-1435
  • Journal article (peer-reviewed)abstract
    • Bark beetles are among the most devastating biotic agents affecting forests globally and several species are expected to be favored by climate change. Given the potential interactions of insect outbreaks with other biotic and abiotic disturbances, and the potentially strong impact of changing disturbance regimes on forest resources, investigating climatic drivers of destructive bark beetle outbreaks is of paramount importance. We analyzed 17 time-series of the amount of wood damaged by Ips typographus, the most destructive pest of Norway spruce forests, collected across 8 European countries in the last three decades. We aimed to quantify the relative importance of key climate drivers in explaining timber loss dynamics, also testing for possible synergistic effects. Local outbreaks shared the same drivers, including increasing summer rainfall deficit and warm temperatures. Large availability of storm-felled trees in the previous year was also strongly related to an increase in timber loss, likely by providing an alternative source of breeding material. We did not find any positive synergy among outbreak drivers. On the contrary, the occurrence of large storms reduced the positive effect of warming temperatures and rainfall deficit. The large surplus of breeding material likely boosted I. typographus population size above the density threshold required to colonize and kill healthy trees irrespective of other climate triggers. Importantly, we found strong negative density dependence in I. typographus that may provide a mechanism for population decline after population eruptions. Generality in the effects of complex climatic events across different geographical areas suggests that the large-scale drivers can be used as early warning indicators of increasing local outbreak probability. Ecography
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33.
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34.
  • Paulsson, Björn, et al. (author)
  • An overview of wheel–rail interface related research in the European project INNOTRACK including issues in technical and economical validation
  • 2009
  • In: Proceedings 8th International Conference on Contact Mechanics and Wear of Rail/Wheel Systems. ; , s. 8 pp-
  • Conference paper (peer-reviewed)abstract
    • The INNOTRACK project (www.innotrack.eu) is a European research project within the 6th Framework Programme. The aim of the INNOTRACK project is to deliver innovative track-related solutions to reduce life cycle costs and improve the reliability, availability, maintainability and safety of the rail sector. The current paper gives an overview of work in INNOTRACK of relevance for the CM2009 conference. The work presented in this paper focuses on innovative processes and methodologies. Topics discussed concern rail selection, installation, inspection and maintenance and also the optimisation of switches and crossings. Finally a discussion on technical, logistical and economical verifications of proposed solutions is presented. Many of the topics included in this overview paper are presented in detail in other contributions to the CM2009 conference.
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35.
  • Ploussard, Guillaume, et al. (author)
  • The Contemporary Concept of Significant Versus Insignificant Prostate Cancer
  • 2011
  • In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 60:2, s. 291-303
  • Research review (peer-reviewed)abstract
    • Context: The notion of insignificant prostate cancer (Ins-PCa) has progressively emerged in the past two decades. The clinical relevance of such a definition was based on the fact that low-grade, small-volume, and organ-confined prostate cancer (PCa) may be indolent and unlikely to progress to biologic significance in the absence of treatment. Objective: To review the definition of Ins-PCa, its incidence, and the clinical impact of Ins-PCa on the contemporary management of PCa. Evidence acquisition: A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction on language up to September 2010. The literature search used the following terms: insignificant, indolent, minute, microfocal, minimal, low volume, low risk, and prostate cancer. Evidence synthesis: The most commonly used criteria to define Ins-PCa are based on the pathologic assessment of the radical prostatectomy specimen: (1) Gleason score <= 6 without Gleason pattern 4 or 5, (2) organ-confined disease, and (3) tumour volume < 0.5 cm(3). Several preoperative criteria and prognostication tools for predicting Ins-PCa have been suggested. Nomograms are best placed to estimate the risk of progression on an individualised basis, but a substantial proportion of men with a high probability of harbouring Ins-PCa are at risk for pathologic understaging and/or undergrading. Thus, there is an ongoing need for identifying novel and more accurate predictors of Ins-PCa to improve the distinction between insignificant versus significant disease and thus to promote the adequate management of PCa patients at low risk for progression. Conclusions: The exciting challenge of obtaining the pretreatment diagnostic tools that can really distinguish insignificant from significant PCa should be one of the main objectives of urologists in the following years to decrease the risk of overtreatment of Ins-PCa. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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36.
  • Søgaard Jørgensen, Peter, et al. (author)
  • Antibiotic and pesticide susceptibility and the Anthropocene operating space
  • 2018
  • In: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 1:11, s. 632-641
  • Research review (peer-reviewed)abstract
    • Rising levels of antimicrobial and pesticide resistance increasingly undermine human health and systems for biomass production, and emphasize the sustainability challenge of preserving organisms susceptible to these biocides. In this Review, we introduce key concepts and examine dynamics of biocide susceptibility that must be governed to address this challenge. We focus on the impact of biocides on the capacity of susceptible organisms to prevent spread of resistance, and we then review how biocide use affects a broader suite of ecosystem services. Finally, we introduce and assess the state of what we term the Anthropocene operating space of biocide susceptibility, a framework for assessing the potential of antibiotic and pesticide resistance to undermine key functions of human society. Based on current trends in antibiotic, insecticide and herbicide resistance, we conclude that the states of all six assessed variables are beyond safe zones, with three variables surpassed regionally or globally.
  •  
37.
  • Søgaard Jørgensen, Peter, et al. (author)
  • Changing antibiotic resistance : sustainability transformation to a pro-microbial planet
  • 2017
  • In: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 25, s. 66-76
  • Research review (peer-reviewed)abstract
    • Decades of overuse, misuse, and environmental antibiotic pollution has increased the global pool of resistant bacteria. With estimates of hundreds of thousands of annual human deaths and a lack of new drugs to replace old ones, antimicrobial resistance probably constitutes one of the greatest human health and sustainability challenges of the 21st century. To safeguard treatable infections, a deliberate social-ecological transformation is needed toward stewardship of the global microbiome and long-term sustainable use of antibiotics. We review the foundation for such a transformation using recent insights from sustainability science, evolutionary biology and health, and the understanding of human interactions with microbes as two intertwined complex adaptive systems. A coherent strategy should acknowledge humans as the source of the world's strongest evolutionary force, reflect that antibiotics are building blocks of modern health systems, and strive to build social-ecological resilience to minimize levels of resistance and avoid over dependency on innovation of new drugs. Bottom up opportunities for seeding the transformation include participatory monitoring and stewardship of our personal and environmental microbiomes, as well as collective consumer action. Top down priorities include regular international institutions to coordinate multi-level action.
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38.
  • Søgaard Jørgensen, Peter, et al. (author)
  • Coevolutionary Governance of Antibiotic and Pesticide Resistance
  • 2020
  • In: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 35:6, s. 484-494
  • Research review (peer-reviewed)abstract
    • Development of new biocides has dominated human responses to evolution of antibiotic and pesticide resistance. Increasing and uniform biocide use, the spread of resistance genes, and the lack of new classes of compounds indicate the importance of navigating toward more sustainable coevolutionary dynamics between human culture and species that evolve resistance. To inform this challenge, we introduce the concept of coevolutionary governance and propose three priorities for its implementation: (i) new norms and mental models for lowering use, (ii) diversifying practices to reduce directional selection, and (iii) investment in collective action institutions to govern connectivity. We highlight the availability of solutions that facilitate broader sustainable development, which for antibiotic resistance include improved sanitation and hygiene, strong health systems, and decreased meat consumption.
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39.
  • Søgaard Jørgensen, Peter, et al. (author)
  • Evolution in the Anthropocene : Informing Governance and Policy
  • 2019
  • In: Annual Review of Ecology, Evolution and Systematics. - : Annual Reviews. - 1543-592X .- 1545-2069. ; 50, s. 527-546
  • Research review (peer-reviewed)abstract
    • The Anthropocene biosphere constitutes an unprecedented phase in the evolution of life on Earth with one species, humans, exerting extensive control. The increasing intensity of anthropogenic forces in the twenty-first century has widespread implications for attempts to govern both human-dominated ecosystems and the last remaining wild ecosystems. Here, we review how evolutionary biology can inform governance and policies in the Anthropocene, focusing on five governance challenges that span biodiversity, environmental management, food and other biomass production, and human health. The five challenges are: (a) evolutionary feedbacks, (b) maintaining resilience, (c) alleviating constraints, (d) coevolutionary disruption, and (e) biotechnology. Strategies for governing these dynamics will themselves have to be coevolutionary, as eco-evolutionary and social dynamics change in response to each other.
  •  
40.
  • Van Hemelrijck, Mieke, et al. (author)
  • Reasons for Discontinuing Active Surveillance : Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium
  • 2019
  • In: European Urology. - : Elsevier BV. - 0302-2838. ; 75:3, s. 523-531
  • Journal article (peer-reviewed)abstract
    • Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4–28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0–13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5–2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4–2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for <5 yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4–28.6%) at 5 yr and 38.2% (95% CI: 36.7–39.9%) at 10 yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up. Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. Patient summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5 yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS.
  •  
41.
  • Wang, Li-San, et al. (author)
  • Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
  • 2015
  • In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
  • Journal article (peer-reviewed)abstract
    • Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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42.
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43.
  • Wernli, Didier, et al. (author)
  • Mapping global policy discourse on antimicrobial resistance
  • 2017
  • In: BMJ Global Health. - : BMJ. - 2059-7908. ; 2:2
  • Journal article (peer-reviewed)abstract
    • The rising importance of antimicrobial resistance (AMR) to the global health agenda is associated with a growing number of parties voicing their concern about the issue. With more recommendations and policies appearing, understanding the policy process requires making sense of the views, values, interests and goals of each participant. Policy frame analysis provides a method to understand both the scientific view and the actions advocated by global health actors to tackle AMR. Here we review and refine policy frame analyses of AMR using a deductive approach. Among several policy frames previously defined in the field of global health, we identify 'AMR as healthcare', 'AMR as development', 'AMR as innovation' and 'AMR as security' as frequent frames used in dealing with AMR. In addition, we found that 'AMR as One Health' constitutes a recent framing of the topic that seeks to provide an integrated understanding between human and animal health. Each frame originates in distinct scientific fields, conceptualises the main causes of AMR and prioritises different interventions and measurements. Better understanding and integration of these frames into an overarching social and ecological framework will support policy progress in tackling AMR.
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