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1.	Radivoyevitch, Tomas, et al. (författare) Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma 2018 Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 74, s. 130-136 Tidskriftsartikel (refereegranskat)abstract Background: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Methods: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n=916), non-Hodgkin lymphoma (NHL; n=3546) and plasma cell myeloma (PCM; n=4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS.Results: 335 MDS/ AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR=4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR=2.5 [1.1, 2.5]); (2) >= 3 versus 1 line of chemotherapy for NHL (HR=1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR=2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/ MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort.Conclusions: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
2.	Berner, Logan T., et al. (författare) The Arctic plant aboveground biomass synthesis dataset 2024 Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.
3.	Birney, Ewan, et al. (författare) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project 2007 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816 Tidskriftsartikel (refereegranskat)abstract We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
4.	Bjugård Nyberg, Henrik, 1984-, et al. (författare) Population Pharmacokinetics and Dosing of Ethionamide in Children with Tuberculosis 2020 Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 64:3 Tidskriftsartikel (refereegranskat)abstract Ethionamide has proven efficacy against both drug-susceptible and some drug-resistant strains of Mycobacterium tuberculosis. Limited information on its pharmacokinetics in children is available, and current doses are extrapolated from weight-based adult doses. Pediatric doses based on more robust evidence are expected to improve antituberculosis treatment, especially in small children. In this analysis, ethionamide concentrations in children from 2 observational clinical studies conducted in Cape Town, South Africa, were pooled. All children received ethionamide once daily at a weight-based dose of approximately 20 mg/kg of body weight (range, 10.4 to 25.3 mg/kg) in combination with other first- or second-line antituberculosis medications and with antiretroviral therapy in cases of HIV coinfection. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. The MDR-PK1 study contributed data for 110 children on treatment for multidrug-resistant tuberculosis, while the DATiC study contributed data for 9 children treated for drug-susceptible tuberculosis. The median age of the children in the studies combined was 2.6 years (range, 0.23 to 15 years), and the median weight was 12.5 kg (range, 2.5 to 66 kg). A one-compartment, transit absorption model with first-order elimination best described ethionamide pharmacokinetics in children. Allometric scaling of clearance (typical value, 8.88 liters/h), the volume of distribution (typical value, 21.4 liters), and maturation of clearance and absorption improved the model fit. HIV coinfection decreased the ethionamide bioavailability by 22%, rifampin coadministration increased clearance by 16%, and ethionamide administration by use of a nasogastric tube increased the rate, but the not extent, of absorption. The developed model was used to predict pediatric doses achieving the same drug exposure achieved in 50- to 70-kg adults receiving 750-mg once-daily dosing. Based on model predictions, we recommend a weight-banded pediatric dosing scheme using scored 125-mg tablets.
5.	Escala-Garcia, Maria, et al. (författare) A network analysis to identify mediators of germline-driven differences in breast cancer prognosis 2020 Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
6.	Exner-Pirot, Heather, et al. (författare) Form and Function: The Future of the Arctic Council 2019 Annan publikation (refereegranskat)
7.	Flannick, Jason, et al. (författare) Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls 2017 Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4 Tidskriftsartikel (refereegranskat)abstract To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
8.	Fuchsberger, Christian, et al. (författare) The genetic architecture of type 2 diabetes 2016 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47 Tidskriftsartikel (refereegranskat)abstract The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
9.	Gaudet, Mia M., et al. (författare) Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium 2016 Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 155:3, s. 531-540 Tidskriftsartikel (refereegranskat)abstract Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case-control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values < 1.5 x 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P (interaction) = 1.2 x 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.
10.	Jones, Benedict C, et al. (författare) To which world regions does the valence-dominance model of social perception apply? 2021 Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169 Tidskriftsartikel (refereegranskat)abstract Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
11.	Justice, Anne E., et al. (författare) Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution 2019 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469 Tidskriftsartikel (refereegranskat)abstract Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
12.	Locke, Adam E, et al. (författare) Genetic studies of body mass index yield new insights for obesity biology. 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401 Tidskriftsartikel (refereegranskat)abstract Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
13.	Mahajan, Anubha, et al. (författare) Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus. 2015 Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.
14.	Manning, Alisa, et al. (författare) A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk 2017 Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032 Tidskriftsartikel (refereegranskat)abstract To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
15.	Marouli, Eirini, et al. (författare) Rare and low-frequency coding variants alter human adult height 2017 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190 Tidskriftsartikel (refereegranskat)abstract Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
16.	Pettersen, Trond Røed, et al. (författare) Discharge Information About Adverse Drug Reactions Indicates Lower Self-Reported Adverse Drug Reactions and Fewer Concerns in Patients After Percutaneous Coronary Intervention 2024 Ingår i: Heart, Lung and Circulation. - : Elsevier. - 1443-9506 .- 1444-2892. ; 33:3, s. 350-361 Tidskriftsartikel (refereegranskat)abstract AimThere are discrepancies between the information patients desire about adverse drug reactions (ADRs) and the information they receive from healthcare providers; this is an impediment to shared decision-making. This study aimed to establish whether patients received information about ADRs resulting from prescribed pharmacotherapy, before hospital discharge, after percutaneous coronary intervention (PCI) and to determine whether receiving information about ADRs was associated with incidence of self-reported ADRs or concerns related to prescribed pharmacotherapy.MethodsCONCARDPCI, a prospective multicentre cohort study including 3,417 consecutive patients after PCI, was conducted at seven high-volume referral PCI centres in two Nordic countries. Clinical data were collected from patients’ medical records and national quality registries. Patient-reported outcome measures were registered 2 months (T1), 6 months (T2), and 12 months (T3) after discharge. Covariate-adjusted logistic regression yielded adjusted odds ratios (aORs) with 95% confidence intervals (CIs).ResultsAt discharge, 38% of participants had been informed about potential ADRs. For these patients, the incidence of self-reported ADRs was significantly lower at T1 (aOR 0.61, 95% CI 0.50–0.74; p<0.001), T2 (aOR 0.60, 95% CI 0.49–0.74; p<0.001), and T3 (aOR 0.57, 95% CI 0.46–0.71; p<0.001). Those who were not informed reported higher levels of concern about prescribed pharmacotherapy at all measuring points (p<0.001 for all comparisons). Those living alone (aOR 0.73, 95% CI 0.57–0.92; p=0.008), who were female (aOR 0.57, 95% CI 0.44–0.72; p<0.001), and with three or more versus no comorbidities (aOR 0.61, 95% CI 0.44–0.84; p=0.002) were less likely to receive information.ConclusionA substantial proportion of patients were not informed about potential ADRs from prescribed pharmacotherapy after PCI. Patients informed about ADRs had lower incidences of self-reported ADRs and fewer concerns about prescribed pharmacotherapy.
17.	Surendran, Praveen, et al. (författare) Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension 2016 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161 Tidskriftsartikel (refereegranskat)abstract High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
18.	Turcot, Valerie, et al. (författare) Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity 2018 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41 Tidskriftsartikel (refereegranskat)abstract Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
19.	Walker, Emily V., et al. (författare) Malignant primary brain and other central nervous system tumors diagnosed in Canada from 2009 to 2013 2019 Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 21:3, s. 360-369 Tidskriftsartikel (refereegranskat)abstract Background: We present a national surveillance report on malignant primary brain and other central nervous system (CNS) tumors diagnosed in the Canadian population in 2009–2013.Methods: Patients were identified through the Canadian Cancer Registry, an administrative dataset that includes cancer incidence data from all provinces/territories in Canada. Tumor types were classified by site and histology using the definitions from the Central Brain Tumor Registry of the United States (CBTRUS). Incidence rates (IRs) and 95% confidence intervals (CIs) were calculated per 100000 person-years (py) and age-standardized to the 2011 Canadian population for comparisons within Canada and to the 2000 United States population for comparisons with the US.Results: Overall, 12515 malignant brain and other CNS tumors were diagnosed in the Canadian population in 2009–2013 (IR: 8.71/100000 py; 95% CI: 8.56, 8.86); 7085 were among males (IR: 10.06/100000 py; 95% CI: 9.82, 10.29) and 5430 among females (IR: 7.41/100000 py; 95% CI: 7.22, 7.61). Of these, 12115 were classifiable according to histological subgroups defined by CBTRUS. The most common histology was glioblastoma (IR: 4.06/100000 py; 95% CI: 3.95, 4.16). Among those aged 0–19 years, 1130 malignant brain and CNS tumors were diagnosed in 2009–2013 (IR: 3.36/100000 py; 95% CI: 3.16, 3.56). The most common histology among the pediatric population was embryonal tumor (IR: 0.74/100000 py; 95% CI: 0.65, 0.84).Conclusions: These data represent an initial detailed report on the frequency and distribution of primary malignant brain and other CNS tumors diagnosed in the Canadian population in 2009–2013. The reported distributions of tumor diagnoses by sex and age reflected expected patterns based on the literature from similar populations. A report incorporating data on nonmalignant primary brain tumors is forthcoming.
20.	Abazajian, Kevork, et al. (författare) CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves 2022 Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1 Tidskriftsartikel (refereegranskat)abstract CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
21.	Abbey, Susan E., et al. (författare) Qualitative interviews versus standardised self-report questionnaires in assessing qualityb of life in heart transplant recipients 2011 Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier. - 1053-2498 .- 1557-3117. ; 30:8, s. 963-966 Tidskriftsartikel (refereegranskat)abstract Quality of life (QoL) studies in heart transplant recipients (HTRs) using validated, quantitative, self-report questionnaires have reported poor QoL in approximately 20% of patients. This consecutive mixed methods study compared self-report questionnaires, the Medical Outcomes Study 36-item Short Form Health Survey (MOS SF-36) and the Atkinson Life Satisfaction Scale, with phenomenologically informed audiovisual (AV) qualitative interview data in 27 medically stable HTRs (70% male; age 53 ± 13.77 years; time since transplant 4.06 ± 2.42 years). Self-report questionnaire data reported poor QoL and more distress compared with previous studies and normative population samples; in contrast, 52% of HTRs displayed pervasive distress according to visual methodology. Using qualitative methods to assess QoL yields information that would otherwise remain unobserved by the exclusive use of quantitative QOL questionnaires.
22.	Abbott, Benjamin W., et al. (författare) Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment 2016 Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3 Tidskriftsartikel (refereegranskat)abstract As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
23.	Abolfathi, Bela, et al. (författare) The LSST DESC DC2 Simulated Sky Survey 2021 Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 253:31 Tidskriftsartikel (refereegranskat)abstract We describe the simulated sky survey underlying the second data challenge (DC2) carried out in preparation for analysis of the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) by the LSST Dark Energy Science Collaboration (LSST DESC). Significant connections across multiple science domains will be a hallmark of LSST; the DC2 program represents a unique modeling effort that stresses this interconnectivity in a way that has not been attempted before. This effort encompasses a full end-to-end approach: starting from a large N-body simulation, through setting up LSST-like observations including realistic cadences, through image simulations, and finally processing with Rubin's LSST Science Pipelines. This last step ensures that we generate data products resembling those to be delivered by the Rubin Observatory as closely as is currently possible. The simulated DC2 sky survey covers six optical bands in a wide-fast-deep area of approximately 300 deg2, as well as a deep drilling field of approximately 1 deg2. We simulate 5 yr of the planned 10 yr survey. The DC2 sky survey has multiple purposes. First, the LSST DESC working groups can use the data set to develop a range of DESC analysis pipelines to prepare for the advent of actual data. Second, it serves as a realistic test bed for the image processing software under development for LSST by the Rubin Observatory. In particular, simulated data provide a controlled way to investigate certain image-level systematic effects. Finally, the DC2 sky survey enables the exploration of new scientific ideas in both static and time domain cosmology.
24.	Abraham, Vojtech, et al. (författare) Patterns in recent and Holocene pollen accumulation rates across Europe - the Pollen Monitoring Programme Database as a tool for vegetation reconstruction 2021 Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 18:15, s. 4511-4534 Tidskriftsartikel (refereegranskat)abstract The collection of modern, spatially extensive pollen data is important for the interpretation of fossil pollen assemblages and the reconstruction of past vegetation communities in space and time. Modern datasets are readily available for percentage data but lacking for pollen accumulation rates (PARs). Filling this gap has been the motivation of the pollen monitoring network, whose contributors monitored pollen deposition in modified Tauber traps for several years or decades across Europe. Here we present this monitoring dataset consisting of 351 trap locations with a total of 2742 annual samples covering the period from 1981 to 2017. This dataset shows that total PAR is influenced by forest cover and climate parameters, which determine pollen productivity and correlate with latitude. Treeless vegetation produced PAR values of at least 140 grains cm(-2) yr(-1). Tree PAR increased by at least 400 grains cm(-2) yr(-1) with each 10% increase in forest cover. Pollen traps situated beyond 200 km of the distribution of a given tree species still collect occasional pollen grains of that species. The threshold of this long-distance transport differs for individual species and is generally below 60 grains cm(-2) yr(-1). Comparisons between modern and fossil PAR from the same regions show similar values. For temperate taxa, modern analogues for fossil PARs are generally found downslope or southward of the fossil sites. While we do not find modern situations comparable to fossil PAR values of some taxa (e.g. Corylus), CO2 fertilization and land use may cause high modern PARs that are not documented in the fossil record. The modern data are now publicly available in the Neotoma Paleoecology Database and aid interpretations of fossil PAR data.
25.	Adams, Marc A., et al. (författare) Patterns of neighborhood environment attributes related to physical activity across 11 countries : a latent class analysis 2013 Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 10 Tidskriftsartikel (refereegranskat)abstract Background: Neighborhood environment studies of physical activity (PA) have been mainly single-country focused. The International Prevalence Study (IPS) presented a rare opportunity to examine neighborhood features across countries. The purpose of this analysis was to: 1) detect international neighborhood typologies based on participants' response patterns to an environment survey and 2) to estimate associations between neighborhood environment patterns and PA. Methods: A Latent Class Analysis (LCA) was conducted on pooled IPS adults (N=11,541) aged 18 to 64 years old (mean=37.5 +/- 12.8 yrs; 55.6% women) from 11 countries including Belgium, Brazil, Canada, Colombia, Hong Kong, Japan, Lithuania, New Zealand, Norway, Sweden, and the U. S. This subset used the Physical Activity Neighborhood Environment Survey (PANES) that briefly assessed 7 attributes within 10-15 minutes walk of participants' residences, including residential density, access to shops/services, recreational facilities, public transit facilities, presence of sidewalks and bike paths, and personal safety. LCA derived meaningful subgroups from participants' response patterns to PANES items, and participants were assigned to neighborhood types. The validated short-form International Physical Activity Questionnaire (IPAQ) measured likelihood of meeting the 150 minutes/week PA guideline. To validate derived classes, meeting the guideline either by walking or total PA was regressed on neighborhood types using a weighted generalized linear regression model, adjusting for gender, age and country. Results: A 5-subgroup solution fitted the dataset and was interpretable. Neighborhood types were labeled, "Overall Activity Supportive (52% of sample)", "High Walkable and Unsafe with Few Recreation Facilities (16%)", "Safe with Active Transport Facilities (12%)", "Transit and Shops Dense with Few Amenities (15%)", and "Safe but Activity Unsupportive (5%)". Country representation differed by type (e. g., U. S. disproportionally represented "Safe but Activity Unsupportive"). Compared to the Safe but Activity Unsupportive, two types showed greater odds of meeting PA guideline for walking outcome (High Walkable and Unsafe with Few Recreation Facilities, OR=2.26 (95% CI 1.18-4.31); Overall Activity Supportive, OR=1.90 (95% CI 1.13-3.21). Significant but smaller odds ratios were also found for total PA. Conclusions: Meaningful neighborhood patterns generalized across countries and explained practical differences in PA. These observational results support WHO/UN recommendations for programs and policies targeted to improve features of the neighborhood environment for PA.
26.	af Bjerkén, Sara, et al. (författare) Effects of glial cell line-derived neurotrophic factor deletion on ventral mesencephalic organotypic tissue cultures. 2007 Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1133:1, s. 10-9 Tidskriftsartikel (refereegranskat)abstract Glial cell line-derived neurotrophic factor (GDNF) is potent for survival and promotion of nerve fibers from midbrain dopamine neurons. It is also known to exert different effects on specific subpopulations of dopamine neurons. In organotypic tissue cultures, dopamine neurons form two diverse nerve fiber growth patterns, targeting the striatum differently. The aim of this study was to investigate the effect of GDNF on the formation of dopamine nerve fibers. Organotypic tissue cultures of ventral mesencephalon of gdnf gene-deleted mice were studied. The results revealed that dopamine neurons survive in the absence of GDNF. Tyrosine hydroxylase immunoreactivity demonstrated, in gdnf knockout and wildtype cultures, nerve fiber formation with two separate morphologies occurring either in the absence or the presence of astrocytes. The outgrowth that occurred in the absence of astrocytes was unaffected by gdnf deletion, whereas nerve fibers guided by the presence of astrocytes were affected in that they reached significantly shorter distances from the gdnf gene-deleted tissue slice, compared to those measured in wildtype cultures. Treatment with GDNF reversed this effect and increased nerve fiber density independent of genotype. Furthermore, migration of astrocytes reached significantly shorter distances from the tissue slice in GDNF knockout compared to wildtype cultures. Exogenous GDNF increased astrocytic migration in gdnf gene-deleted tissue cultures, comparable to lengths observed in wildtype tissue cultures. In conclusion, cultured midbrain dopamine neurons survive in the absence of GDNF, and the addition of GDNF improved dopamine nerve fiber formation - possibly as an indirect effect of astrocytic stimulation.
27.	Aglago, Elom K., et al. (författare) A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk 2023 Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583 Tidskriftsartikel (refereegranskat)abstract Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
28.	Aglago, Elom K., et al. (författare) Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort 2020 Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:3, s. 6-666 Tidskriftsartikel (refereegranskat)abstract Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
29.	Agrell, Wilhelm, et al. (författare) Intelligence and Espionage (Sweden) 2017 Ingår i: 1914-1918 online. International Encyclopedia of the First World War. Bokkapitel (refereegranskat)
30.	Agugiaro, G., et al. (författare) A web-based interactive tool for multi-resolution 3d models of a maya archaeological site 2011 Ingår i: 4TH ISPRS INTERNATIONAL WORKSHOP 3D-ARCH 2011. ; , s. 23-30 Konferensbidrag (refereegranskat)abstract Continuous technological advances in surveying, computing and digital-content delivery are strongly contributing to a change in the way Cultural Heritage is "perceived": new tools and methodologies for documentation, reconstruction and research are being created to assist not only scholars, but also to reach more potential users (e.g. students and tourists) willing to access more detailed information about art history and archaeology. 3D computer-simulated models, sometimes set in virtual landscapes, offer for example the chance to explore possible hypothetical reconstructions, while on-line GIS resources can help interactive analyses of relationships and change over space and time. While for some research purposes a traditional 2D approach may suffice, this is not the case for more complex analyses concerning spatial and temporal features of architecture, like for example the relationship of architecture and landscape, visibility studies etc. The project aims therefore at creating a tool, called "QueryArch3D" tool, which enables the web-based visualisation and queries of an interactive, multi-resolution 3D model in the framework of Cultural Heritage. More specifically, a complete Maya archaeological site, located in Copan (Honduras), has been chosen as case study to test and demonstrate the platform's capabilities. Much of the site has been surveyed and modelled at different levels of detail (LoD) and the geometric model has been semantically segmented and integrated with attribute data gathered from several external data sources. The paper describes the characteristics of the research work, along with its implementation issues and the initial results of the developed prototype. [GRAPHICS] .
31.	Ahmad, T, et al. (författare) Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries 2016 Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 117:5, s. 601- Tidskriftsartikel (refereegranskat)
32.	Ahmad, T, et al. (författare) In-hospital clinical outcomes after upper gastrointestinal surgery: Data from an international observational study 2017 Ingår i: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. - : Elsevier BV. - 1532-2157 .- 0748-7983. ; 43:12, s. 2324-2332 Tidskriftsartikel (refereegranskat)
33.	Ahmad, T, et al. (författare) Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries: a 7-day cohort study of elective surgery 2017 Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 119:2, s. 258-266 Tidskriftsartikel (refereegranskat)
34.	Ahmed, Fozia Z., et al. (författare) Use of healthcare claims to validate the Prevention of Arrhythmia Device Infection Trial cardiac implantable electronic device infection risk score 2021 Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:9, s. 1446-1455 Tidskriftsartikel (refereegranskat)abstract AIM: The Prevention of Arrhythmia Device Infection Trial (PADIT) infection risk score, developed based on a large prospectively collected data set, identified five independent predictors of cardiac implantable electronic device (CIED) infection. We performed an independent validation of the risk score in a data set extracted from U.S. healthcare claims.METHODS AND RESULTS: Retrospective identification of index CIED procedures among patients aged ≥18 years with at least one record of a CIED procedure between January 2011 and September 2014 in a U.S health claims database. PADIT risk factors and major CIED infections (with system removal, invasive procedure without system removal, or infection-attributable death) were identified through diagnosis and procedure codes. The data set was randomized by PADIT score into Data Set A (60%) and Data Set B (40%). A frailty model allowing multiple procedures per patient was fit using Data Set A, with PADIT score as the only predictor, excluding patients with prior CIED infection. A data set of 54 042 index procedures among 51 623 patients with 574 infections was extracted. Among patients with no history of prior CIED infection, a 1 unit increase in the PADIT score was associated with a relative 28% increase in infection risk. Prior CIED infection was associated with significant incremental predictive value (HR 5.66, P < 0.0001) after adjusting for PADIT score. A Harrell's C-statistic for the PADIT score and history of prior CIED infection was 0.76.CONCLUSION: The PADIT risk score predicts increased CIED infection risk, identifying higher risk patients that could potentially benefit from targeted interventions to reduce the risk of CIED infection. Prior CIED infection confers incremental predictive value to the PADIT score.
35.	Ahn, Jiyoung, et al. (författare) Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3). 2009 Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 18:19, s. 3749-57 Tidskriftsartikel (refereegranskat)abstract Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3 alpha-androstanediol-glucuronide (N = 4767) and 17beta-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 x 10(-21)), consistent with previous studies, and testosterone (P = 7.54 x 10(-15)), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10(-6)) and SRD5A2 with 3 alpha-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.
36.	Akre, Olof, et al. (författare) Maternal and gestational risk factors for hypospadias 2008 Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:8, s. 1071-1076 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. OBJECTIVES: Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors. METHODS: We conducted a case-control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls. The response rate was 88% and 81% among mothers of cases and controls, respectively. The analyses included 292 cases and 427 controls. RESULTS: A diet during pregnancy lacking both fish and meat was associated with a more than 4-fold increased risk of hypospadias [odds ratio (OR) 4.6, 95% confidence interval (CI), 1.6-13.3]. Boys born to obese [body mass index (BMI) > ;= 30] women had a more than 2-fold increased risk of hypospadias (OR = 2.6, 95% CI, 1.2-5.7) compared with boys born to mothers with a normal weight (BMI = 20-24). Maternal hypertension during pregnancy and absence of maternal nausea increased a boy's risk of hypospadias 2.0-fold (95% CI, 1.1-3.7) and 1.8-fold (95% CI, 1.2-2.8), respectively. Nausea in late pregnancy also appeared to be positively associated with hypospadias risk (OR = 7.6, 95% CI, 1.1-53). CONCLUSIONS: A pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring. Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.
37.	Al-Adili, Lina (författare) The evaluation process of nutrition interventions for patients at risk of malnutrition : From a person-centred perspective 2023 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract This thesis is aimed at exploring the process of evaluating nutrition interventions for patients at risk of malnutrition from a person-centred perspective. An explorative cross-sectional study was conducted based on data from the International Nutrition Care Process and Terminology Implementation Survey (INIS). Associations between the reported documentation of goals and outcomes and the reported implementation of the nutrition care process and its terminology, demographic factors, and factors associated with the workplace were explored. Responses were received from 347 Scandinavian dietitians. Strong associations were found between the implementation of nutrition monitoring and evaluation terminology and the documentation of goals and outcomes. Standardisation may support the documentation of goals and outcomes, and improve nutrition monitoring and evaluation. Focus group interviews were held with Swedish dietitians working in hospital and primary healthcare settings. The dietitians’ reflections on the process of nutrition monitoring and evaluation (Paper II) and the goal-setting process (Paper III) with patients at risk of malnutrition in nutrition intervention were explored. A lack of routine and structure in the process of evaluation and a lack of shared decision-making (SDM) in goal-setting was found. Dietitians described qualitative subjective outcomes as being most important to patients but that these are only implied in the nutrition intervention. They highlighted discrepancies between their clinically oriented goals and the patients’ own goals. The clarification of patients’ perspectives in the evaluation process is necessary to promote person-centredness, improve communication, and support the evidence-informed practice of nutrition intervention.An interview study with patients at risk of malnutrition was conducted. Patients’ experiences, perspectives and needs concerning goals in nutrition intervention were explored. Patients rarely reflected on goals in nutrition interventions, instead they described striving towards increased strength and energy. Goal-setting is part of the dietitian’s structured way of working, while the patient’s life-world is complex and unstructured. Elucidating patients’ goals may counteract the discrepancies between the dietitians’ clinically oriented goals and patients’ perspectives.In summary, this thesis highlights the need for tools and strategies for the improvement of the evaluation process in nutrition intervention. The person-centred practice of the evaluation process is described in this thesis as key to improving this process. This can be achieved through exploring what matters to patients in terms of perspectives, goals, and priorities, creating partnerships through involving patients in goal-setting and communicating feedback, and documenting and evaluating outcomes that are meaningful to patients.
38.	Al Khabour, Anas, et al. (författare) Raqqa : A History of the Destruction of Cultural Heritage 2021 Ingår i: Heritage in Conflict. - 9789042943179 - 9789042943186 ; 57, s. 183-195 Bokkapitel (refereegranskat)abstract In the present paper I will demonstrate the history of Raqqa’s cultural heritage, its floruit and its destruction, from its resettlement in the 19th century until the “Islamic State” period. I will also discuss the recent situation and the challenges to heritage associated with post-war construction in Raqqa. Raqqa was the summer capital of the caliph Harun Al Rashid and the centre of government for the Islamic world for 13 years. After the Mongols’ invasion in 1258 the city was abandoned for six centuries. The Ottoman Empire encouraged people to settle in the city by building the police station in 1863. After that date, many changes occurred to the city’s cultural heritage, but the most destructive challenge was the arrival of a new ideology and new people who targeted both the inhabitants and their heritage. This was the so-called “Islamic State” in Iraq and Syria, which settled in Raqqa, making it the capital de facto of the state; this period is known to the local population as “the dark plague”.
39.	Alami, Ilias, et al. (författare) Making space for the new state capitalism, part II : Relationality, spatiotemporality and uneven development 2023 Ingår i: Environment and planning A. - : Sage Publications. - 0308-518X .- 1472-3409. ; 55:3, s. 621-635 Tidskriftsartikel (refereegranskat)abstract The theme issue ‘Making Space for the New State Capitalism’ brings together insights from critical economic geography and heterodox political economy through a series of papers published in three installments, each accompanied by an introductory essay written by the guest editors. In this, the second of these introductory commentaries, we explore the consequences of embracing relationality, spatiotemporality and uneven development, together with the second group of papers. Introducing a final group of papers, the third installment will address the challenges and opportunities of thinking conjuncturally.
40.	Alarcon, Sonia, et al. (författare) Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2 ',3,4,4 ',5,5 '-heptachlorobiphenyl (PCB 180) : A postnatal follow-up study in rats 2021 Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 102, s. 109-127 Tidskriftsartikel (refereegranskat)abstract PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions.
41.	Albrecht, Matthias, et al. (författare) The effectiveness of flower strips and hedgerows on pest control, pollination services and crop yield : a quantitative synthesis 2020 Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 23:10, s. 1488-1498 Tidskriftsartikel (refereegranskat)abstract Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control (18 studies) and pollination services (17 studies) in adjacent crops in North America, Europe and New Zealand. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimise floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.
42.	Aleksandrova, Krasimira, et al. (författare) Combined impact of healthy lifestyle factors on colorectal cancer : a large European cohort study 2014 Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 12:1, s. 168- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.
43.	Aleksandrova, Krasimira, et al. (författare) Physical activity, mediating factors and risk of colon cancer : insights into adiposity and circulating biomarkers from the EPIC cohort 2017 Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 46:6, s. 1823-1835 Tidskriftsartikel (refereegranskat)abstract There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer. We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline. High physical activity was associated with a lower risk of colon cancer: relative risk a parts per thousand91 MET-h/week vs < 91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively. Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.
44.	Alentorn-Geli, Eduard, et al. (författare) Correction to: Factors associated with poorer outcomes in the surgical treatment of multiligament knee injuries. 2019 Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 27:2 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract The author would like to correct the following errors in the publication of the original article.
45.	Alentorn-Geli, Eduard, et al. (författare) Factors predictive of poorer outcomes in the surgical repair of multiligament knee injuries. 2019 Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 27:2, s. 445-459 Tidskriftsartikel (refereegranskat)abstract To investigate the influence of injury and treatment factors on clinical/functional outcomes in multiligament knee injuries (MLKI).Thirty-nine consecutive patients with confirmed and surgically treated MLKI who met inclusion criteria were scheduled for a follow-up visit to obtain: SF-12 and subjective feeling of normalcy between the operated and healthy knee, and IKDC, active range of motion (ROM), and stability exam (Lachman test, posterior drawer, and dial test at 30°). A chart review was used to obtain data on injury and treatment factors.The postoperative mean (SD) outcomes were: IKDC score 62.7 (25.9), flexion-extension ROM 125° (29°), and percentage of normalcy 74% (20%). The postoperative normal/nearly normal stability exam was: Lachman test 36 (95%) patients, posterior drawer at 90° 38 (97%) patients, and dial test of 39 (100%) patients. There were 24 (61.5%) and 23 (59%) patients with complications and reoperations, respectively. The presence of bicruciate injuries was associated with worse Lachman (p=0.03) and posterior drawer tests (p=0.03). Presence of injury to meniscal structures was associated with worse Lachman test (p=0.03), lower percentage of normalcy (p=0.02) and extension lag (p=0.04). Injury to cartilage structures was associated with worse IKDC scores (p=0.04). IKDC was lower in cases of posterolateral corner reconstruction (p=0.03) and use of allograft tendons for reconstruction (p=0.02); ROM was lower in allograft reconstruction (p=0.02) and need for meniscal repair (p = 0.01). Bicruciate reconstruction led to worst posterior drawer test (p=0.006).The outcomes of MLKI might be negatively influenced by bicruciate ligament, meniscal, and cartilage injuries; with regards to treatment characteristics, need for posterolateral corner or bicruciate ligament reconstruction, use of allografts, or need for meniscal repair may similarly diminish outcomes. While surgical treatment provides good overall function, ROM and stability, it rarely results in a "normal" knee and the chances of complications and reoperations are high.Cross-sectional comparative study, Level III.
46.	Alexander, Steven M., et al. (författare) Qualitative data sharing and synthesis for sustainability science 2020 Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 3:2, s. 81-88 Tidskriftsartikel (refereegranskat)abstract Opportunities, challenges and recommended targeted actions to accelerate qualitative data sharing to address complex socio-environmental problems Socio-environmental synthesis as a research approach contributes to broader sustainability policy and practice by reusing data from disparate disciplines in innovative ways. Synthesizing diverse data sources and types of evidence can help to better conceptualize, investigate and address increasingly complex socio-environmental problems. However, sharing qualitative data for re-use remains uncommon when compared to sharing quantitative data. We argue that qualitative data present untapped opportunities for sustainability science, and discuss practical pathways to facilitate and realize the benefits from sharing and reusing qualitative data. However, these opportunities and benefits are also hindered by practical, ethical and epistemological challenges. To address these challenges and accelerate qualitative data sharing, we outline enabling conditions and suggest actions for researchers, institutions, funders, data repository managers and publishers.
47.	Alexandridis, Nikolaos, et al. (författare) Archetype models upscale understanding of natural pest control response to land-use change 2022 Ingår i: Ecological Applications. - : Wiley. - 1051-0761 .- 1939-5582. ; 32:8 Tidskriftsartikel (refereegranskat)abstract Control of crop pests by shifting host plant availability and natural enemy activity at landscape scales has great potential to enhance the sustainability of agriculture. However, mainstreaming natural pest control requires improved understanding of how its benefits can be realized across a variety of agroecological contexts. Empirical studies suggest significant but highly variable responses of natural pest control to land-use change. Current ecological models are either too specific to provide insight across agroecosystems, or too generic to guide management with actionable predictions. We suggest getting the full benefit of available empirical, theoretical and methodological knowledge, by combining trait-mediated understanding from correlative studies with the explicit representation of causal relationships achieved by mechanistic modeling. To link these frameworks, we adapt the concept of archetypes, or context-specific generalizations, from sustainability science. Similar responses of natural pest control to land-use gradients across cases that share key attributes, such as functional traits of focal organisms, indicate general processes that drive system behavior in a context-sensitive manner. Based on such observations of natural pest control, a systematic definition of archetypes can provide the basis for mechanistic models of intermediate generality that cover all major agroecosystems worldwide. Example applications demonstrate the potential for upscaling understanding and improving prediction of natural pest control, based on knowledge transfer and scientific synthesis. A broader application of this mechanistic archetype approach promises to enhance ecology's contribution to natural resource management across diverse regions and social-ecological contexts.
48.	Alexandridis, Nikolaos, et al. (författare) Models of natural pest control : Towards predictions across agricultural landscapes 2021 Ingår i: Biological Control. - : Elsevier BV. - 1049-9644. ; 163 Forskningsöversikt (refereegranskat)abstract Natural control of invertebrate crop pests has the potential to complement or replace conventional insecticide-based practices, but its mainstream application is hampered by predictive unreliability across agroecosystems. Inconsistent responses of natural pest control to changes in landscape characteristics have been attributed to ecological complexity and system-specific conditions. Here, we review agroecological models and their potential to provide predictions of natural pest control across agricultural landscapes. Existing models have used a multitude of techniques to represent specific crop-pest-enemy systems at various spatiotemporal scales, but less wealthy regions of the world are underrepresented. A realistic representation of natural pest control across systems appears to be hindered by a practical trade-off between generality and realism. Nonetheless, observations of context-sensitive, trait-mediated responses of natural pest control to land-use gradients indicate the potential of ecological models that explicitly represent the underlying mechanisms. We conclude that modelling natural pest control across agroecosystems should exploit existing mechanistic techniques towards a framework of contextually bound generalizations. Observed similarities in causal relationships can inform the functional grouping of diverse agroecosystems worldwide and the development of the respective models based on general, but context-sensitive, ecological mechanisms. The combined use of qualitative and quantitative techniques should allow the flexible integration of empirical evidence and ecological theory for robust predictions of natural pest control across a wide range of agroecological contexts and levels of knowledge availability. We highlight challenges and promising directions towards developing such a general modelling framework.
49.	Ali, Md Ashim, et al. (författare) Prediction of Propeller Tip Vortex Using OpenFOAM 2017 Ingår i: Proceedings of the International Conference on Offshore Mechanics and Arctic Engineering - OMAE. - 9780791857731 ; 7A-2017 Konferensbidrag (refereegranskat)abstract It is important to predict the propeller tip vortex flow and its effect on hull vibration and noise. In our previous work, the tip vortex flow of the David Taylor Model Basin (DTMB) 5168 propeller model has been studied based on the Reynolds Averaged Navier-Stokes equation (RANS) solution using various eddy viscosity and Reynolds Stress turbulence models. A set of structural grids were used, however, large Jacobian values of the structural grids around the propeller tip region led to the convergence problem and inaccurate solutions. In the present work, the numerical prediction of the same propeller model was improved by using a steady-state RANS solver simpleFoam in OpenFOAM with locally refined unstructured grid along the tip vortex trajectory. The computed thrust and torque coefficients and the velocity components across the vortex core are compared with experimental data and results in the previous studies. Improvement in the prediction of velocity components across the tip vortex core were achieved.
50.	Alimena, Juliette, et al. (författare) Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider 2020 Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9 Tidskriftsartikel (refereegranskat)abstract Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.

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