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1.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Hudson, Lawrence N, et al. (author)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Journal article (peer-reviewed)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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4.
  • de Vries, Paul S., et al. (author)
  • Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
  • 2019
  • In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
  • Journal article (peer-reviewed)abstract
    • A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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5.
  • Ademuyiwa, Adesoji O., et al. (author)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Journal article (peer-reviewed)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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6.
  • Feitosa, Mary F., et al. (author)
  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
  • 2018
  • In: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
  • Journal article (peer-reviewed)abstract
    • Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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7.
  • Field, Christopher B., et al. (author)
  • Summary for Policymakers
  • 2014
  • In: Climate Change 2014: Impacts, Adaptation, and Vulnerability. Part A: Global and SectoralAspects.. - 9781107415379 ; , s. 1-32
  • Book chapter (peer-reviewed)
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8.
  • Nguyen, Thanh N, et al. (author)
  • Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
  • 2023
  • In: Neurology. - 1526-632X. ; 100:4
  • Journal article (peer-reviewed)abstract
    • Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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9.
  • Cruz, Raquel, et al. (author)
  • Novel genes and sex differences in COVID-19 severity
  • 2022
  • In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
  • Journal article (peer-reviewed)abstract
    • Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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10.
  • de las Fuentes, Lisa, et al. (author)
  • Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
  • 2021
  • In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
  • Journal article (peer-reviewed)abstract
    • Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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11.
  • Grande, Virginia, 1987-, et al. (author)
  • Making Visible and Modeling the Underrepresented : Teachers' Reflections on Their Role Modeling in Higher Education
  • 2022
  • In: ITiCSE '22. - New York, NY, USA : Association for Computing Machinery. ; , s. 566-567
  • Conference paper (peer-reviewed)abstract
    • This work contributes to a better understanding of computing teachers' perceptions of themselves as role models. Role models are described as important to address under-representation, yet there is little in-depth research on how role modeling works and what university teachers in computing can model to broaden participation in the discipline. We will analyze teachers' reflections on how they may, or want to, be perceived by their students, particularly in terms of professional competencies, emotions and attitudes towards well-being. We will use and further develop an already existing framework on role modeling in computing, and we will relate our findings to existing research on computing and science identities. Modeling aspects outside the computing norm can help provide students with a wider notion of what it means to be a computer scientist. Besides developing the theoretical understanding of computing teachers as role models , our work can support various ways of developing computing teachers' competences and departments' teaching culture. The results are one way to contribute to student diversity and equitable access, and more broadly increase the relevance of computing education for sustainability.
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12.
  • Hudson, Lawrence N., et al. (author)
  • The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
  • 2014
  • In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
  • Journal article (peer-reviewed)abstract
    • Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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13.
  • Johnston, Jennifer J., et al. (author)
  • Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations
  • 2010
  • In: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 31:10, s. 1142-1154
  • Journal article (peer-reviewed)abstract
    • A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc.
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14.
  • Lundgren, Jens D, et al. (author)
  • Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.
  • 2023
  • In: NEJM evidence. - : Massachusetts Medical Society. - 2766-5526. ; 2:3
  • Journal article (peer-reviewed)abstract
    • For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain.The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021.Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference).Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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15.
  • Mandarakas, N., et al. (author)
  • Zero-polarization candidate regions for the calibration of wide-field optical polarimeters
  • 2024
  • In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
  • Journal article (peer-reviewed)abstract
    • Context. The calibration of optical polarimeters relies on the use of stars with negligible polarization (i.e., unpolarized standard stars) for determining the instrumental polarization zero point. For wide-field polarimeters, calibration is often done by imaging the same star over multiple positions in the field of view (FoV), which is a time-consuming process. A more effective technique is to target fields containing multiple standard stars. While this method has been used for fields with highly polarized stars, there are no such sky regions with well measured unpolarized standard stars. Aims. We aim to identify sky regions with tens of stars exhibiting negligible polarization that are suitable for a zero-point calibration of wide-field polarimeters. Methods. We selected stars in regions with extremely low reddening, located at high Galactic latitudes. We targeted four ∼40′ × 40′ fields in the northern and eight in the southern equatorial hemispheres. Observations were carried out at the Skinakas Observatory and the South African Astronomical Observatory. Results. We found two fields in the north and seven in the south characterized by a mean polarization lower than p < 0.1%. Conclusions. At least 9 out of the 12 fields can be used for a zero-point calibration of wide-field polarimeters.
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16.
  • Micah, Angela E., et al. (author)
  • Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
  • 2021
  • In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
  • Research review (peer-reviewed)abstract
    • Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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17.
  • Pelgrims, V., et al. (author)
  • The first degree-scale starlight-polarization-based tomography map of the magnetized interstellar medium
  • 2024
  • In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
  • Journal article (peer-reviewed)abstract
    • We present the first degree-scale tomography map of the dusty magnetized interstellar medium (ISM) from stellar polarimetry and distance measurements. We used the RoboPol polarimeter at Skinakas Observatory to conduct a survey of the polarization of starlight in a region of the sky of about four square degrees. We propose a Bayesian method to decompose the stellar-polarization source field along the distance to invert the three-dimensional (3D) volume occupied by the observed stars. We used this method to obtain the first 3D map of the dusty magnetized ISM. Specifically, we produced a tomography map of the orientation of the plane-of-sky component of the magnetic field threading the diffuse, dusty regions responsible for the stellar polarization. For the targeted region centered on Galactic coordinates (l, b) (103.3, 22.3), we identified several ISM clouds. Most of the lines of sight intersect more than one cloud. A very nearby component was detected in the foreground of a dominant component from which most of the polarization signal comes and which we identified as being an intersection of the wall of the Local Bubble and the Cepheus Flare. Farther clouds, with a distance of up to 2 kpc, were similarly detected. Some of them likely correspond to intermediate-velocity clouds seen in H I spectra in this region of the sky. We found that the orientation of the plane-of-sky component of the magnetic field changes along distance for most of the lines of sight. Our study demonstrates that starlight polarization data coupled to distance measures have the power to reveal the great complexity of the dusty magnetized ISM in 3D and, in particular, to provide local measurements of the plane-of-sky component of the magnetic field in dusty regions. This demonstrates that the inversion of large data volumes, as expected from the PASIPHAE survey, will provide the necessary means to move forward in the modeling of the Galactic magnetic field and of the dusty magnetized ISM as a contaminant in observations of the cosmic microwave background polarization.
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18.
  • Sutton, Jill N., et al. (author)
  • A review of the stable isotope bio-geochemistry of the global silicon cycle and its associated trace elements
  • 2018
  • In: Frontiers in Earth Science. - : Frontiers Media SA. - 2296-6463. ; 5
  • Research review (peer-reviewed)abstract
    • Silicon (Si) is the second most abundant element in the Earth’s crust and is an important nutrient in the ocean. The global Si cycle plays a critical role in regulating primary productivity and carbon cycling on the continents and in the oceans. Development of the analytical tools used to study the sources, sinks, and fluxes of the global Si cycle (e.g., elemental and stable isotope ratio data for Ge, Si, Zn, etc.) have recently led to major advances in our understanding of the mechanisms and processes that constrain the cycling of Si in the modern environment and in the past. Here, we provide background on the geochemical tools that are available for studying the Si cycle and highlight our current understanding of the marine, freshwater and terrestrial systems. We place emphasis on the geochemistry (e.g., Al/Si, Ge/Si, Zn/Si, δ13 C, δ15 N, δ18 O, δ30 Si) of dissolved and biogenic Si, present case studies, such as the Silicic Acid Leakage Hypothesis, and discuss challenges associated with the development of these environmental proxies for the global Si cycle. We also discuss how each system within the global Si cycle might change over time (i.e., sources, sinks, and processes) and the potential technical and conceptual limitations that need to be considered for future studies.
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19.
  • Aglago, Elom K., et al. (author)
  • A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
  • 2023
  • In: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
  • Journal article (peer-reviewed)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.
  •  
20.
  • Block, Keith I., et al. (author)
  • Designing a broad-spectrum integrative approach for cancer prevention and treatment
  • 2015
  • In: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
  • Research review (peer-reviewed)abstract
    • Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
  •  
21.
  • Chen, Zhishan, et al. (author)
  • Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
  • 2024
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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22.
  • Cunningham, Virginia, et al. (author)
  • GRB 160625B : Evidence for a Gaussian-shaped Jet
  • 2020
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 904:2
  • Journal article (peer-reviewed)abstract
    • We present multiwavelength modeling of the afterglow from the long gamma-ray burst (GRB) 160625B using Markov Chain Monte Carlo techniques of the afterglowpy Python package. GRB 160625B is an extremely bright burst with a rich set of observations spanning from radio to gamma-ray frequencies. These observations range from similar to 0.1 days to >1000 days, thus making this event extremely well suited to such modeling. In this work we compare top-hat and Gaussian jet structure types in order to find best-fit values for the GRB jet collimation angle, viewing angle, and other physical parameters. We find that a Gaussian-shaped jet is preferred (2.7 sigma-5.3 sigma) over the traditional top-hat model. Our estimate for the opening angle of the burst ranges from 126 to 390, depending on jet-shape model. We also discuss the implications that assumptions on jet shape, viewing angle, and particularly the participation a fraction of electrons have on the final estimation of GRB intrinsic energy release and the resulting energy budget of the relativistic outflow. Most notably, allowing the participation fraction to vary results in an estimated total relativistic energy of similar to 10(53) erg. This is two orders of magnitude higher than when the total fraction is assumed to be unity; thus, this parameter has strong relevance for placing constraints on long GRB central engines, details of the circumburst media, and host environment.
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23.
  • de Schipper, Elles, et al. (author)
  • Ability and Disability in Autism Spectrum Disorder : A Systematic Literature Review Employing the International Classification of Functioning, Disability and Health-Children and Youth Version.
  • 2015
  • In: Autism Research. - : Wiley. - 1939-3792 .- 1939-3806. ; 8:6, s. 782-94
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: This study is the first in a series of four empirical investigations to develop International Classification of Functioning, Disability and Health (ICF) Core Sets for Autism Spectrum Disorder (ASD). The objective was to use a systematic review approach to identify, number, and link functional ability and disability concepts used in the scientific ASD literature to the nomenclature of the ICF-CY (Children and Youth version of the ICF, covering the life span).METHODS: Systematic searches on outcome studies of ASD were carried out in Medline/PubMed, PsycINFO, ERIC and Cinahl, and relevant functional ability and disability concepts extracted from the included studies. These concepts were then linked to the ICF-CY by two independent researchers using a standardized linking procedure. New concepts were extracted from the studies until saturation of identified ICF-CY categories was reached.RESULTS: Seventy-one studies were included in the final analysis and 2475 meaningful concepts contained in these studies were linked to 146 ICF-CY categories. Of these, 99 categories were considered most relevant to ASD (i.e., identified in at least 5% of the studies), of which 63 were related to Activities and Participation, 28 were related to Body functions, and 8 were related to Environmental factors. The five most frequently identified categories were basic interpersonal interactions (51%), emotional functions (49%), complex interpersonal interactions (48%), attention functions (44%), and mental functions of language (44%).CONCLUSION: The broad variety of ICF-CY categories identified in this study reflects the heterogeneity of functional differences found in ASD--both with respect to disability and exceptionality--and underlines the potential value of the ICF-CY as a framework to capture an individual's functioning in all dimensions of life. The current results in combination with three additional preparatory studies (expert survey, focus groups, and clinical study) will provide the scientific basis for defining the ICF Core Sets for ASD for multipurpose use in basic and applied research and every day clinical practice of ASD.
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24.
  • de Schipper, Elles, et al. (author)
  • Functioning and disability in autism spectrum disorder : A worldwide survey of experts
  • 2016
  • In: Autism Research. - : John Wiley & Sons. - 1939-3792 .- 1939-3806. ; 9:9, s. 959-969
  • Journal article (peer-reviewed)abstract
    • Objective: This study is the second of four to prepare International Classification of Functioning, Disability and Health (ICF; and Children and Youth version, ICF(-CY)) Core Sets for Autism Spectrum Disorder (ASD).The objective of this study was to survey the opinions and experiences of international experts on functioning and disability in ASD.Methods: Using a protocol stipulated by the World Health Organization (WHO) and monitored by the ICF Research Branch, an email-based questionnaire was circulated worldwide among ASD experts, and meaningful functional ability and disability concepts were extracted from their responses. These concepts were then linked to the ICF(-CY) by two independent researchers using a standardized linking procedure.Results: N  = 225 experts from 10 different disciplines and all six WHO-regions completed the survey. Meaningful concepts from the responses were linked to 210 ICF(-CY) categories. Of these, 103 categories were considered most relevant to ASD (i.e., identified by at least 5% of the experts), of which 37 were related toActivities and Participation, 35 to Body functions, 22 to Environmental factors, and 9 to Body structures. A variety of personal characteristics and ASD-related functioning skills were provided by experts, including honesty, loyalty, attention to detail and creative talents. Reported gender differences in ASD comprised more externalizing behaviors among males and more internalizing behaviors in females.Conclusion: The ICF(-CY) categories derived from international expert opinions indicate that the impact of ASD on functioning extends far beyond core symptom domains
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25.
  • Dutkiewicz, Stephanie, et al. (author)
  • Multiple biotic interactions establish phytoplankton community structure across environmental gradients
  • 2024
  • In: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590.
  • Journal article (peer-reviewed)abstract
    • The combination of taxa and size classes of phytoplankton that coexist at any location affects the structure of the marine food web and the magnitude of carbon fluxes to the deep ocean. But what controls the patterns of this community structure across environmental gradients remains unclear. Here, we focus on the North East Pacific Transition Zone, a similar to 10 degrees region of latitude straddling warm, nutrient-poor subtropical and cold, nutrient-rich subpolar gyres. Data from three cruises to the region revealed intricate patterns of phytoplankton community structure: poleward increases in the number of cell size classes; increasing biomass of picoeukaryotes and diatoms; decreases in diazotrophs and Prochlorococcus; and both increases and decreases in Synechococcus. These patterns can only be partially explained by existing theories. Using data, theory, and numerical simulations, we show that the patterns of plankton distributions across the transition zone are the result of gradients in nutrient supply rates, which control a range of complex biotic interactions. We examine how interactions such as size-specific grazing, multiple trophic strategies, shared grazing between several phytoplankton size classes and heterotrophic bacteria, and competition for multiple resources can individually explain aspects of the observed community structure. However, it is the combination of all these interactions together that is needed to explain the bulk compositional patterns in phytoplankton across the North East Pacific Transition Zone. The synthesis of multiple mechanisms is essential for us to begin to understand the shaping of community structure over large environmental gradients.
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26.
  • Emaus, Marleen J., et al. (author)
  • Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study
  • 2014
  • In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:12, s. 2887-2899
  • Journal article (peer-reviewed)abstract
    • Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3: 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3: 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.
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27.
  • Ferguson, Lynnette R., et al. (author)
  • Guide and Position of the International Society of Nutrigenetics/Nutrigenomics on Personalised Nutrition : Part 1 - Fields of Precision Nutrition
  • 2016
  • In: Journal of Nutrigenetics and Nutrigenomics. - : S. Karger AG. - 1661-6499. ; 9:1, s. 12-27
  • Journal article (peer-reviewed)abstract
    • Diversity in the genetic profile between individuals and specific ethnic groups affects nutrient requirements, metabolism and response to nutritional and dietary interventions. Indeed, individuals respond differently to lifestyle interventions (diet, physical activity, smoking, etc.). The sequencing of the human genome and subsequent increased knowledge regarding human genetic variation is contributing to the emergence of personalized nutrition. These advances in genetic science are raising numerous questions regarding the mode that precision nutrition can contribute solutions to emerging problems in public health, by reducing the risk and prevalence of nutrition-related diseases. Current views on personalized nutrition encompass omics technologies (nutrigenomics, transcriptomics, epigenomics, foodomics, metabolomics, metagenomics, etc.), functional food development and challenges related to legal and ethical aspects, application in clinical practice, and population scope, in terms of guidelines and epidemiological factors. In this context, precision nutrition can be considered as occurring at three levels: (1) conventional nutrition based on general guidelines for population groups by age, gender and social determinants; (2) individualized nutrition that adds phenotypic information about the person's current nutritional status (e.g. anthropometry, biochemical and metabolic analysis, physical activity, among others), and (3) genotype-directed nutrition based on rare or common gene variation. Research and appropriate translation into medical practice and dietary recommendations must be based on a solid foundation of knowledge derived from studies on nutrigenetics and nutrigenomics. A scientific society, such as the International Society of Nutrigenetics/Nutrigenomics (ISNN), internationally devoted to the study of nutrigenetics/nutrigenomics, can indeed serve the commendable roles of (1) promoting science and favoring scientific communication and (2) permanently working as a 'clearing house' to prevent disqualifying logical jumps, correct or stop unwarranted claims, and prevent the creation of unwarranted expectations in patients and in the general public. In this statement, we are focusing on the scientific aspects of disciplines covering nutrigenetics and nutrigenomics issues. Genetic screening and the ethical, legal, social and economic aspects will be dealt with in subsequent statements of the Society.
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28.
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29.
  • Freisling, Heinz, et al. (author)
  • Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases : a multinational cohort study
  • 2020
  • In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. METHODS: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. RESULTS: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. CONCLUSION: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
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30.
  • Grande, Virginia, 1987-, et al. (author)
  • Role Modeling as a Computing Educator in Higher Education : A Focus on Care, Emotions and Professional Competencies
  • 2022
  • In: ITiCSE-WGR '22. - New York, NY, USA : ACM Digital Library. ; , s. 37-63
  • Conference paper (peer-reviewed)abstract
    • This paper provides insights into role modeling by educators in computing that is beyond the technical, theoretical and rational perspectives which have historically been described as dominant in computing. Surveying 199 educators in higher education, we have built on frameworks of role modeling, care, emotions, and professional competencies as a lens to see different ways of engaging in computing.Our quantitative and qualitative findings show how educators model ways of caring (for oneself, other humans and living species, technology, and the planet), emotions, professional competencies and other types of role modeling. Examples of contexts within computing and reasons why an educator can(not) model these aspects bring new light to research on care and emotions being shown in computing.This work contributes to a better understanding of computing educators as potential role models, particularly in terms of displaying emotions and various types of care. Our work can support ways of developing the professional competences of computing educators and the teaching culture of computing departments. Our findings may inspire other educators to think about their own display of emotions and care, and what this transmits to their students. Thus, the work also contributes to the discussion of ways to increase diversity among students and equitable access to computing education.
  •  
31.
  • Grande, Virginia, et al. (author)
  • Role Modeling as a Computing Educator in Higher Education. A Focus on Care, Emotions and Professional Competencies
  • 2022
  • In: ITiCSE-WGR '22. - : ACM Digital Library. ; , s. 37-63
  • Conference paper (other academic/artistic)abstract
    • This paper provides insights into role modeling by educators in computing that is beyond the technical, theoretical and rational perspectives which have historically been described as dominant in computing. Surveying 199 educators in higher education, we have built on frameworks of role modeling, care, emotions, and professional competencies as a lens to see different ways of engaging in computing.Our quantitative and qualitative findings show how educators model ways of caring (for oneself, other humans and living species, technology, and the planet), emotions, professional competencies and other types of role modeling. Examples of contexts within computing and reasons why an educator can(not) model these aspects bring new light to research on care and emotions being shown in computing.This work contributes to a better understanding of computing educators as potential role models, particularly in terms of displaying emotions and various types of care. Our work can support ways of developing the professional competences of computing educators and the teaching culture of computing departments. Our findings may inspire other educators to think about their own display of emotions and care, and what this transmits to their students. Thus, the work also contributes to the discussion of ways to increase diversity among students and equitable access to computing education.  
  •  
32.
  • Harlid, Sophia, 1978-, et al. (author)
  • Soy formula and epigenetic modifications : analysis of vaginal epithelial cells from infant girls in the IFED study
  • 2017
  • In: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 125:3, s. 447-452
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Early-life exposure to estrogenic compounds affects the development of the reproductive system in rodent models and humans. Soy products, which contain phytoestrogens such as genistein, are one source of exposure in infants fed soy formula, and they result in high serum concentrations.OBJECTIVES: Our goal was to determine whether soy exposure is associated with differential DNA methylation in vaginal cells from soy-fed infant girls.METHODS: Using the Illumina HumanMethylation450 BeadChip, we evaluated epigenome-wide DNA methylation in vaginal cells from four soy formula-fed and six cow formula-fed girls from the Infant Feeding and Early Development (IFED) study. Using pyrosequencing we followed up the two most differentially methylated sites in 214 vaginal cell samples serially collected between birth and 9 months of age from 50 girls (28 soy formula-fed and 22 cow formula-fed). With a mouse model, we examined the effect of neonatal exposure to genistein on gene specific mRNA levels in vaginal tissue.RESULTS: The epigenome-wide scan suggested differences in methylation between soy formula-fed and cow formula-fed infants at three CpGs in the gene proline rich 5 like (PRR5L) (p < 10(4)). Pyrosequencing of the two feeding groups found that methylation levels progressively diverged with age, with pointwise differences becoming statistically significant after 126 days. Genistein-exposed mice showed a 50% decrease in vaginal Prr5l mRNA levels compared to controls.CONCLUSIONS: Girls fed soy formula have altered DNA methylation in vaginal cell DNA which may be associated with decreased expression of an estrogen-responsive gene.
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33.
  • Ho, Anna Y. Q., et al. (author)
  • Evidence for Late-stage Eruptive Mass Loss in the Progenitor to SN2018gep, a Broad-lined Ic Supernova : Pre-explosion Emission and a Rapidly Rising Luminous Transient
  • 2019
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 887:2
  • Journal article (peer-reviewed)abstract
    • We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.4 +/- 0.1 mag hr(-1)) and luminous (M-g,M- peak = -20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The high peak luminosity (L-bol greater than or similar to 3 x 10(44) erg s(-1)), the short rise time (t(rise) = 3 days in g band), and the blue colors at peak (g-r similar to -0.4) all resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T-eff greater than or similar to 40,000 K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M-g similar to M-r approximate to -14 mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E-gamma,E- iso < 4.9 x 10(48) erg, a limit on X-ray emission L-X < 10(40) erg s(-1), and a limit on radio emission nu L-v less than or similar to 10(37) erg s(-1). Taken together, we find that the early (< 10 days) data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M-circle dot) at large radii (3 x 10(14) cm) that was ejected in eruptive pre-explosion mass-loss episodes. The late-time (> 10 days) light curve requires an additional energy source, which could be the radioactive decay of Ni-56.
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34.
  • Hompland, Ivar, et al. (author)
  • Outcome in dedifferentiated chondrosarcoma for patients treated with multimodal therapy : Results from the EUROpean Bone Over 40 Sarcoma Study
  • 2021
  • In: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 151, s. 150-158
  • Journal article (peer-reviewed)abstract
    • Introduction: The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study. Materials and methods: The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models. Results: Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42–65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22–25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles. Conclusions: Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years.
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35.
  • Howick, Virginia M., et al. (author)
  • The Malaria Cell Atlas : Single parasite transcriptomes across the complete Plasmodium life cycle
  • 2019
  • In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6455
  • Journal article (peer-reviewed)abstract
    • Malaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. We profiled the single-cell transcriptomes of thousands of individual parasites, deriving the first high-resolution transcriptional atlas of the entire Plasmodium berghei life cycle. We then used our atlas to precisely define developmental stages of single cells from three different human malaria parasite species, including parasites isolated directly from infected individuals. The Malaria Cell Atlas provides both a comprehensive view of gene usage in a eukaryotic parasite and an open-access reference dataset for the study of malaria parasites.
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36.
  • Kamnitsas, Konstantinos, et al. (author)
  • Transductive Image Segmentation : Self-training and Effect of Uncertainty Estimation
  • 2021
  • In: Domain Adaptation and Representation Transfer, and Affordable Healthcare and AI for Resource Diverse Global Health - 3rd MICCAI Workshop, DART 2021, and 1st MICCAI Workshop, FAIR 2021, Held in Conjunction with MICCAI 2021, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783030877217 ; 12968 LNCS, s. 79-89
  • Conference paper (peer-reviewed)abstract
    • Semi-supervised learning (SSL) uses unlabeled data during training to learn better models. Previous studies on SSL for medical image segmentation focused mostly on improving model generalization to unseen data. In some applications, however, our primary interest is not generalization but to obtain optimal predictions on a specific unlabeled database that is fully available during model development. Examples include population studies for extracting imaging phenotypes. This work investigates an often overlooked aspect of SSL, transduction. It focuses on the quality of predictions made on the unlabeled data of interest when they are included for optimization during training, rather than improving generalization. We focus on the self-training framework and explore its potential for transduction. We analyze it through the lens of Information Gain and reveal that learning benefits from the use of calibrated or under-confident models. Our extensive experiments on a large MRI database for multi-class segmentation of traumatic brain lesions shows promising results when comparing transductive with inductive predictions. We believe this study will inspire further research on transductive learning, a well-suited paradigm for medical image analysis.
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37.
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38.
  • Kim, Haesook T., et al. (author)
  • Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients : Center for International Blood and Marrow Transplant Research Report
  • 2019
  • In: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 25:16, s. 5143-5155
  • Journal article (peer-reviewed)abstract
    • Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or >= 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
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39.
  • Klug, Stefanie J, et al. (author)
  • TP53 codon 72 polymorphism and cervical cancer : a pooled analysis of individual data from 49 studies
  • 2009
  • In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 10:8, s. 772-784
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.
  •  
40.
  • Lin, Crystal, et al. (author)
  • Pre-diagnostic circulating insulin-like growth factor-I and bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition
  • 2018
  • In: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 143:10, s. 2351-2358
  • Journal article (peer-reviewed)abstract
    • Previous in vitro and case–control studies have found an association between the insulin‐like growth factor (IGF)‐axis and bladder cancer risk. Circulating concentrations of IGF‐I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre‐diagnostic circulating IGF‐I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre‐diagnostic plasma concentrations of IGF‐I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow‐up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre‐diagnostic circulating IGF‐I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66–1.24, ptrend = 0.40) or UCC (n of cases = 776; 0.91, 0.65–1.26, ptrend = 0.40). There was no significant evidence of heterogeneity in the association of IGF‐I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (pheterogeneity > 0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF‐I concentrations and bladder cancer risk.
  •  
41.
  • Lujan-Barroso, Leila, et al. (author)
  • Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk : A Prospective Study in the EPIC Cohort
  • 2020
  • In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - Philadelphia : American Association of Cancer Research. - 1538-7755 .- 1055-9965. ; 29:8, s. 1654-1664
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. RESULTS: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25-0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed. CONCLUSIONS: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. IMPACT: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.
  •  
42.
  • Mathieu, François, et al. (author)
  • Impact of Antithrombotic Agents on Radiological Lesion Progression in Acute Traumatic Brain Injury : A CENTER-TBI Propensity-Matched Cohort Analysis
  • 2020
  • In: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:19, s. 2069-2080
  • Journal article (peer-reviewed)abstract
    • An increasing number of elderly patients are being affected by traumatic brain injury (TBI) and a significant proportion are on pre-hospital antithrombotic therapy for cardio- or cerebrovascular indications. We have quantified the impact of antiplatelet/anticoagulant (APAC) agents on radiological lesion progression in acute TBI, using a novel, semi-automated approach to volumetric lesion measurement, and explored the impact of use on clinical outcomes in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We used a 1:1 propensity-matched cohort design, matching controls to APAC users based on demographics, baseline clinical status, pre-injury comorbidities, and injury severity. Subjects were selected from a pool of patients enrolled in CENTER-TBI with computed tomography (CT) scan at admission and repeated within 7 days of injury. We calculated absolute changes in volume of intraparenchymal, extra-axial, intraventricular, and total intracranial hemorrhage (ICH) between scans, and compared volume of hemorrhagic progression, proportion of patients with significant degree of progression (>25% of initial volume), proportion with new ICH on follow-up CT, as well as clinical course and outcomes. A total of 316 patients were included (158 APAC users; 158 controls). The mean volume of progression was significantly higher in the APAC group for extra-axial (3.1 vs. 1.3 mL, p = 0.01), but not intraparenchymal (3.8 vs. 4.6 mL, p = 0.65), intraventricular (0.2 vs. 0.0 mL, p = 0.79), or total intracranial hemorrhage (ICH; 7.0 vs. 6.0 mL, p = 0.08). More patients had significant hemorrhage growth (54.1 vs. 37.0%, p = 0.003) and delayed ICH (4 of 18 vs. none; p = 0.04) in the APAC group compared with controls, but this was not associated with differences in length of stay (LOS), rates of neurosurgical intervention, mortality or Glasgow Outcome Scale Extended (GOS-E) score at 6 months. Pre-injury use of antithrombotic agents was associated with greater expansion of extra-axial lesions, higher rates of significant hemorrhagic progression, and higher risk of delayed traumatic ICH, but this was not associated with worse clinical course or functional outcomes.
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43.
  • Mobasheri, Ali, et al. (author)
  • Osteoarthritis Research Society International (OARSI) : Past, present and future
  • 2021
  • In: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 3:2
  • Research review (peer-reviewed)abstract
    • We provide a detailed account of the origin and establishment of the Osteoarthritis Research Society International (OARSI) and celebrate its history from inception to the current day. We discuss the mission, vision and strategic objectives of OARSI and how these have developed and evolved over the last 3 decades. We celebrate the achievements of the society as we approach its 30th birthday, honor the entire presidential line and respectfully pay tribute to the past presidents who are no longer with us. We reflect on the strong foundations of our society, OARSI's efforts to disseminate understanding of the health, disability and economic burdens of osteoarthritis (OA) to policymakers, and the exciting initiatives to make the society inclusive and international. We thank our corporate and industrial sponsors, who have supported us over many years, without whom our annual congresses would not have been possible. We celebrate our longstanding strategic partnership with our publisher, Elsevier, and the successful launch of our new journal Osteoarthritis and Cartilage Open, the most significant new development in our dissemination toolbox. For the first time in the history of the organization, our annual congress was cancelled in April 2020 and the 2021 meeting will be virtual. Despite the numerous challenges posed by the ongoing COVID-19 pandemic and the need to adapt quickly to a rapidly changing landscape, we must remain optimistic about the future. We will take advantage of new exciting opportunities to advance our mission and vision to enhance the quality of life of persons with OA.
  •  
44.
  • Montanier, Cedric, et al. (author)
  • The Active Site of a Carbohydrate Esterase Displays Divergent Catalytic and Noncatalytic Binding Functions
  • 2009
  • In: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 7:3, s. 687-697
  • Journal article (peer-reviewed)abstract
    • Multifunctional proteins, which play a critical role in many biological processes, have typically evolved through the recruitment of different domains that have the required functional diversity. Thus the different activities displayed by these proteins are mediated by spatially distinct domains, consistent with the specific chemical requirements of each activity. Indeed, current evolutionary theory argues that the colocalization of diverse activities within an enzyme is likely to be a rare event, because it would compromise the existing activity of the protein. In contrast to this view, a potential example of multifunctional recruitment into a single protein domain is provided by CtCel5C-CE2, which contains an N-terminal module that displays cellulase activity and a C-terminal module, CtCE2, which exhibits a noncatalytic cellulose-binding function but also shares sequence identity with the CE2 family of esterases. Here we show that, unlike other CE2 members, the CtCE2 domain displays divergent catalytic esterase and noncatalytic carbohydrate binding functions. Intriguingly, these diverse activities are housed within the same site on the protein. Thus, a critical component of the active site of CtCE2, the catalytic Ser-His dyad, in harness with inserted aromatic residues, confers noncatalytic binding to cellulose whilst the active site of the domain retains its esterase activity. CtCE2 catalyses deacetylation of noncellulosic plant structural polysaccharides to deprotect these substrates for attack by other enzymes. Yet it also acts as a cellulose-binding domain, which promotes the activity of the appended cellulase on recalcitrant substrates. The CE2 family encapsulates the requirement for multiple activities by biocatalysts that attack challenging macromolecular substrates, including the grafting of a second, powerful and discrete noncatalytic binding functionality into the active site of an enzyme. This article provides a rare example of "gene sharing,'' where the introduction of a second functionality into the active site of an enzyme does not compromise the original activity of the biocatalyst.
  •  
45.
  • Obon-Santacana, Mireia, et al. (author)
  • Acrylamide and Glycidamide Hemoglobin Adducts and Epithelial Ovarian Cancer : A Nested Case-Control Study in Nonsmoking Postmenopausal Women from the EPIC Cohort
  • 2016
  • In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 25:1, s. 127-134
  • Journal article (peer-reviewed)abstract
    • Background: Acrylamide was classified as “probably carcinogenic to humans (group 2A)” by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case–control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent.Methods: A nested case–control study in nonsmoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk.Results: No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but nonstatistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95% CI, 0.96–3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94–3.83, respectively); however, no linear dose–response trends were observed.Conclusion: This EPIC nested case–control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC.Impact: It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk.
  •  
46.
  • Obon-Santacana, Mireia, et al. (author)
  • Dietary Intake of Acrylamide and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort
  • 2015
  • In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:1, s. 291-297
  • Journal article (peer-reviewed)abstract
    • Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 mu g/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 mu g/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10 mu(g/d), 1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.
  •  
47.
  • Palmer, Elizabeth E., et al. (author)
  • Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition
  • 2023
  • In: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 28:2, s. 668-697
  • Journal article (peer-reviewed)abstract
    • Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.
  •  
48.
  • Pereira-Gurgel, Virginia M., et al. (author)
  • Abnormal vascular and neural retinal morphology in congenital lifetime isolated growth hormone deficiency
  • 2016
  • In: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 30-31, s. 11-15
  • Journal article (peer-reviewed)abstract
    • © 2016 Elsevier LtdObjective Experimental models demonstrate an important role of GH in retinal development. However, the interactions between GH and the neuro-vascularization of the human retina are still not clear. A model of untreated congenital isolated GH deficiency (IGHD) may clarify the actions of GH on the retina. The purpose of this work was to assess the retinal neuro-vascularization in untreated congenital IGHD (cIGHD). Design In a cross sectional study, we performed an endocrine and ophthalmological assessment of 25 adult cIGHD subjects, homozygous for a null mutation (c.57+1G>A) in the GHRH receptor gene and 28 matched controls. Intraocular pressure measurement, retinography (to assess the number of retinal vascular branching points and the optic disc and cup size), and optical coherence tomography (to assess the thickness of macula) were performed. Results cIGHD subjects presented a more significant reduction of vascular branching points in comparison to controls (91% vs. 53% [p=0.049]). The percentage of moderate reduction was higher in cIGHD than in controls (p=0.01). The percentage of individuals with increased optic disc was higher in cIGHD subjects in comparison to controls (92.9% vs. 57.1%). The same occurred for cup size (92.9% vs. 66.7%), p<0.0001 in both cases. There was no difference in macula thickness. Conclusions Most cIGHD individuals present moderate reduction of vascular branching points, increase of optic disc and cup size, but have similar thickness of the macula.
  •  
49.
  • Post, Eric, et al. (author)
  • The polar regions in a 2°C warmer world
  • 2019
  • In: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 5:12
  • Research review (peer-reviewed)abstract
    • Over the past decade, the Arctic has warmed by 0.75°C, far outpacing the global average, while Antarctic temperatures have remained comparatively stable. As Earth approaches 2°C warming, the Arctic and Antarctic may reach 4°C and 2°C mean annual warming, and 7°C and 3°C winter warming, respectively. Expected consequences of increased Arctic warming include ongoing loss of land and sea ice, threats to wildlife and traditional human livelihoods, increased methane emissions, and extreme weather at lower latitudes. With low biodiversity, Antarctic ecosystems may be vulnerable to state shifts and species invasions. Land ice loss in both regions will contribute substantially to global sea level rise, with up to 3 m rise possible if certain thresholds are crossed. Mitigation efforts can slow or reduce warming, but without them northern high latitude warming may accelerate in the next two to four decades. International cooperation will be crucial to foreseeing and adapting to expected changes.
  •  
50.
  • Richter, Sophie, et al. (author)
  • Serum biomarkers identify critically ill traumatic brain injury patients for MRI
  • 2022
  • In: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 26:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Magnetic resonance imaging (MRI) carries prognostic importance after traumatic brain injury (TBI), especially when computed tomography (CT) fails to fully explain the level of unconsciousness. However, in critically ill patients, the risk of deterioration during transfer needs to be balanced against the benefit of detecting prognostically relevant information on MRI. We therefore aimed to assess if day of injury serum protein biomarkers could identify critically ill TBI patients in whom the risks of transfer are compensated by the likelihood of detecting management-altering neuroimaging findings.METHODS: Data were obtained from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Eligibility criteria included: TBI patients aged ≥ 16 years, Glasgow Coma Score (GCS) < 13 or patient intubated with unrecorded pre-intubation GCS, CT with Marshall score < 3, serum biomarkers (GFAP, NFL, NSE, S100B, Tau, UCH-L1) sampled ≤ 24 h of injury, MRI < 30 days of injury. The degree of axonal injury on MRI was graded using the Adams-Gentry classification. The association between serum concentrations of biomarkers and Adams-Gentry stage was assessed and the optimum threshold concentration identified, assuming different minimum sensitivities for the detection of brainstem injury (Adams-Gentry stage 3). A cost-benefit analysis for the USA and UK health care settings was also performed. RESULTS: Among 65 included patients (30 moderate-severe, 35 unrecorded) axonal injury was detected in 54 (83%) and brainstem involvement in 33 (51%). In patients with moderate-severe TBI, brainstem injury was associated with higher concentrations of NSE, Tau, UCH-L1 and GFAP. If the clinician did not want to miss any brainstem injury, NSE could have avoided MRI transfers in up to 20% of patients. If a 94% sensitivity was accepted considering potential transfer-related complications, GFAP could have avoided 30% of transfers. There was no added net cost, with savings up to £99 (UK) or $612 (US). No associations between proteins and axonal injury were found in intubated patients without a recorded pre-intubation GCS.CONCLUSIONS: Serum protein biomarkers show potential to safely reduce the number of transfers to MRI in critically ill patients with moderate-severe TBI at no added cost.
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