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1.	2019 Journal article (peer-reviewed)
2.	Ahmad, T, et al. (author) In-hospital clinical outcomes after upper gastrointestinal surgery: Data from an international observational study 2017 In: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. - : Elsevier BV. - 1532-2157 .- 0748-7983. ; 43:12, s. 2324-2332 Journal article (peer-reviewed)
3.	Arndt, D. S., et al. (author) State of the Climate in 2016 2017 In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280 Journal article (peer-reviewed)abstract In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
4.	Beal, Jacob, et al. (author) Robust estimation of bacterial cell count from optical density 2020 In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1 Journal article (peer-reviewed)abstract Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
5.	Berger, Eloise, et al. (author) Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma : Findings from two prospective cohorts 2018 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1 Journal article (peer-reviewed)abstract Chronic inflammation may be involved in cancer development and progression. Using 28 inflammatory-related proteins collected from prospective blood samples from two case-control studies nested in the Italian component of the European Prospective Investigation into Cancer and nutrition (n = 261) and in the Northern Sweden Health and Disease Study (n = 402), we tested the hypothesis that an inflammatory score is associated with breast cancer (BC) and Β-cell Non-Hodgkin Lymphoma (B-cell NHL, including 68 multiple myeloma cases) onset. We modelled the relationship between this inflammatory score and the two cancers studied: (BC and B-cell NHL) using generalised linear models, and assessed, through adjustments the role of behaviours and lifestyle factors. Analyses were performed by cancer types pooling both populations, and stratified by cohorts, and time to diagnosis. Our results suggested a lower inflammatory score in B-cell NHL cases (β = -1.28, p = 0.012), and, to lesser, extent with BC (β = -0.96, p = 0.33) compared to controls, mainly driven by cancer cases diagnosed less than 6 years after enrolment. These associations were not affected by subsequent adjustments for potential intermediate confounders, notably behaviours. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated. These observations call for further studies involving larger populations, larger variety of cancer types and repeated measures of larger panel of inflammatory markers.
6.	Fullman, Nancy, et al. (author) Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016 2018 In: The Lancet. - : Lancet Publishing Group. - 1474-547X .- 0140-6736. ; 391:10136, s. 2236-2271 Journal article (peer-reviewed)
7.	Kattge, Jens, et al. (author) TRY plant trait database - enhanced coverage and open access 2020 In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188 Journal article (peer-reviewed)abstract Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
8.	Klionsky, Daniel J, et al. (author) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Journal article (peer-reviewed)
9.	Newby, Gretchen, et al. (author) Testing and treatment for malaria elimination : a systematic review 2023 In: Malaria Journal. - : BioMed Central (BMC). - 1475-2875. ; 22:1 Research review (peer-reviewed)abstract Background Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies.Methods A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission.Results A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively.Conclusion Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting.
10.	Stanaway, Jeffrey D., et al. (author) Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017 2018 In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994 Journal article (peer-reviewed)abstract Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
11.	Zuntini, Alexandre R., et al. (author) Phylogenomics and the rise of the angiosperms 2024 In: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850 Journal article (peer-reviewed)abstract Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
12.	Abbafati, Cristiana, et al. (author) 2020 Journal article (peer-reviewed)
13.	Abbott, Benjamin W., et al. (author) Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment 2016 In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3 Journal article (peer-reviewed)abstract As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
14.	Adrianto, Indra, et al. (author) Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus 2011 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:3, s. 253-258 Journal article (peer-reviewed)abstract Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 x 10(-8), odds ratio = 1.70) and Korean (P = 8.33 x 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-kappa B subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
15.	Blane, David, et al. (author) Social-biological transitions : how does the social become biological 2013 In: Longitudinal and Life Course Studies. - : Bristol University Press. - 1757-9597. ; 4:2 Journal article (peer-reviewed)abstract The present discussion paper sets forward a model within the life course perspective of how the social becomes biological. The model is intended to provide a framework for thinking about such questions as how does social class get into the molecules, cells and tissues of the body to produce social class differences in life expectancy and cause of death? A categorisation of social exposures and biological processes is suggested; and some principles governing their inter-relations proposed. The paper ends by suggesting two public health applications of this approach.
16.	Boud, David, et al. (author) Observing interprofessional simulation 2019 In: Interprofessional Simulation in Health Care. - Cham : Springer. - 9783030195410 - 9783030195427 ; , s. 115-137 Book chapter (peer-reviewed)abstract This chapter has a particular focus on the observers’ role in simulation-based learning activities. Simulation-based learning is often organised so that participants rotates between active participation in the scenario and participation as observers. The research examples provided show that the conditions for learning are related to the locations where and the ways the observers are situated, and to how the instructions to the observers are formulated. Arguments are put forward that the observers’ role in simulation has unexploited potential for developing skills of noticing.
17.	Bunnell, Sarah L., et al. (author) Science of Teaching Is Not Being Ignored 2022 In: The Chronicle of Higher Education. Journal article (other academic/artistic)
18.	Bø, Kari, et al. (author) Exercise and pregnancy in recreational and elite athletes : 2016/17 evidence summary from the IOC Expert Group Meeting, Lausanne. Part 3-exercise in the postpartum period. 2017 In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 51:21, s. 1516-1525 Journal article (peer-reviewed)
19.	Bø, Kari, et al. (author) Exercise and pregnancy in recreational and elite athletes : 2016/17 evidence summary from the IOC expert group meeting, Lausanne. Part 4-Recommendations for future research. 2017 In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 51, s. 1724-1726 Journal article (peer-reviewed)
20.	Bø, Kari, et al. (author) Exercise and pregnancy in recreational and elite athletes : 2016 evidence summary from the IOC expert group meeting, Lausanne. Part 2-the effect of exercise on the fetus, labour and birth. 2016 In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 50:21, s. 1297-1305 Journal article (peer-reviewed)abstract This is Part 2 of 5 in the series of evidence statements from the IOC expert committee on exercise and pregnancy in recreational and elite athletes. Part 1 focused on the effects of training during pregnancy and on the management of common pregnancy-related symptoms experienced by athletes. In Part 2, we focus on maternal and fetal perinatal outcomes.
21.	Bø, Kari, et al. (author) Exercise and pregnancy in recreational and elite athletes : 2016 evidence summary from the IOC expert group meeting, Lausanne. Part 1-exercise in women planning pregnancy and those who are pregnant 2016 In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 50:10, s. 571-589 Journal article (peer-reviewed)
22.	Bø, Kari, et al. (author) Exercise and pregnancy in recreational and elite athletes : 2016/2017 evidence summary from the IOC expert group meeting, Lausanne. Part 5. Recommendations for health professionals and active women. 2018 In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 52:17, s. 1080-1085 Journal article (peer-reviewed)
23.	Caudle, Kelly E, et al. (author) Incorporation of Pharmacogenomics into Routine Clinical Practice : the Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline Development Process 2014 In: Current drug metabolism. - : Bentham Science Publishers Ltd.. - 1389-2002 .- 1875-5453. ; 15:2, s. 209-217 Journal article (peer-reviewed)abstract The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes genotype-based drug guidelines to help clinicians understand how available genetic test results could be used to optimize drug therapy. CPIC has focused initially on well-known examples of pharmacogenomic associations that have been implemented in selected clinical settings, publishing nine to date. Each CPIC guideline adheres to a standardized format and includes a standard system for grading levels of evidence linking genotypes to phenotypes and assigning a level of strength to each prescribing recommendation. CPIC guidelines contain the necessary information to help clinicians translate patient-specific diplotypes for each gene into clinical phenotypes or drug dosing groups. This paper reviews the development process of the CPIC guidelines and compares this process to the Institute of Medicine's Standards for Developing Trustworthy Clinical Practice Guidelines.
24.	Chung, Sharon A, et al. (author) European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus 2009 In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:8, s. 2448-2456 Journal article (peer-reviewed)abstract OBJECTIVE: To determine whether genetic substructure in European-derived populations is associated with specific manifestations of systemic lupus erythematosus (SLE), including mucocutaneous phenotypes, autoantibody production, and renal disease. METHODS: SLE patients of European descent (n=1,754) from 8 case collections were genotyped for >1,400 ancestry informative markers that define a north-south gradient of European substructure. Using the Structure program, each SLE patient was characterized in terms of percent Northern (versus percent Southern) European ancestry based on these genetic markers. Nonparametric methods, including tests for trend, were used to identify associations between Northern European ancestry and specific SLE manifestations. RESULTS: In multivariate analyses, increasing levels of Northern European ancestry were significantly associated with photosensitivity (Ptrend=0.0021, odds ratio for highest quartile of Northern European ancestry versus lowest quartile [ORhigh-low] 1.64, 95% confidence interval [95% CI] 1.13-2.35) and discoid rash (Ptrend=0.014, ORhigh-low 1.93, 95% CI 0.98-3.83). In contrast, increasing levels of Northern European ancestry had a protective effect against the production of anticardiolipin autoantibodies (Ptrend=1.6x10(-4), ORhigh-low 0.46, 95% CI 0.30-0.69) and anti-double-stranded DNA autoantibodies (Ptrend=0.017, ORhigh-low 0.67, 95% CI 0.46-0.96). CONCLUSION: This study demonstrates that specific SLE manifestations vary according to Northern versus Southern European ancestry. Thus, genetic ancestry may contribute to the clinical heterogeneity and variation in disease outcomes among SLE patients of European descent. Moreover, these results suggest that genetic studies of SLE subphenotypes will need to carefully address issues of population substructure based on genetic ancestry.
25.	Cusack, Daniela Francis, et al. (author) Tradeoffs and Synergies in Tropical Forest Root Traits and Dynamics for Nutrient and Water Acquisition : Field and Modeling Advances 2021 In: Frontiers in Forests and Global Change. - : Frontiers Media S.A.. - 2624-893X. ; 4 Research review (peer-reviewed)abstract Vegetation processes are fundamentally limited by nutrient and water availability, the uptake of which is mediated by plant roots in terrestrial ecosystems. While tropical forests play a central role in global water, carbon, and nutrient cycling, we know very little about tradeoffs and synergies in root traits that respond to resource scarcity. Tropical trees face a unique set of resource limitations, with rock-derived nutrients and moisture seasonality governing many ecosystem functions, and nutrient versus water availability often separated spatially and temporally. Root traits that characterize biomass, depth distributions, production and phenology, morphology, physiology, chemistry, and symbiotic relationships can be predictive of plants’ capacities to access and acquire nutrients and water, with links to aboveground processes like transpiration, wood productivity, and leaf phenology. In this review, we identify an emerging trend in the literature that tropical fine root biomass and production in surface soils are greatest in infertile or sufficiently moist soils. We also identify interesting paradoxes in tropical forest root responses to changing resources that merit further exploration. For example, specific root length, which typically increases under resource scarcity to expand the volume of soil explored, instead can increase with greater base cation availability, both across natural tropical forest gradients and in fertilization experiments. Also, nutrient additions, rather than reducing mycorrhizal colonization of fine roots as might be expected, increased colonization rates under scenarios of water scarcity in some forests. Efforts to include fine root traits and functions in vegetation models have grown more sophisticated over time, yet there is a disconnect between the emphasis in models characterizing nutrient and water uptake rates and carbon costs versus the emphasis in field experiments on measuring root biomass, production, and morphology in response to changes in resource availability. Closer integration of field and modeling efforts could connect mechanistic investigation of fine-root dynamics to ecosystem-scale understanding of nutrient and water cycling, allowing us to better predict tropical forest-climate feedbacks.
26.	Davies, Neil, et al. (author) The founding charter of the Genomic Observatories Network 2014 In: GigaScience. - 2047-217X. ; 3:2 Journal article (peer-reviewed)abstract Abstract The co-authors of this paper hereby state their intention to work together to launch the Genomic Observatories Network (GOs Network) for which this document will serve as its Founding Charter. We define a Genomic Observatory as an ecosystem and/or site subject to long-term scientific research, including (but not limited to) the sustained study of genomic biodiversity from single-celled microbes to multicellular organisms.An international group of 64 scientists first published the call for a global network of Genomic Observatories in January 2012. The vision for such a network was expanded in a subsequent paper and developed over a series of meetings in Bremen (Germany), Shenzhen (China), Moorea (French Polynesia), Oxford (UK), Pacific Grove (California, USA), Washington (DC, USA), and London (UK). While this community-building process continues, here we express our mutual intent to establish the GOs Network formally, and to describe our shared vision for its future. The views expressed here are ours alone as individual scientists, and do not necessarily represent those of the institutions with which we are affiliated.
27.	De Jong, Wim H., et al. (author) Round robin study to evaluate the reconstructed human epidermis (RhE) model as an in vitro skin irritation test for detection of irritant activity in medical device extracts 2018 In: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 50, s. 439-449 Journal article (peer-reviewed)abstract Assessment of skin irritation is an essential component of the safety evaluation of medical devices. OECD Test Guideline 439 describes the use of reconstructed human epidermis (RhE) as an in vitro test system for classification of skin irritation by neat chemicals. An international round robin study was conducted to evaluate the RhE method for determination of skin irritant potential of medical device extracts. Four irritant polymers and three non-irritant controls were obtained or developed that had demonstrated their suitability to act as positive or negative test samples. The RhE tissues (EpiDerm™ and SkinEthic™ RHE) were dosed with 100 μL aliquots of either saline or sesame oil extract. Incubation times were 18 h (EpiDerm™) and 24 h (SkinEthic™ RHE). Cell viability reduction > 50% was indicative of skin irritation. Both the EpiDerm™ and SkinEthic™ RHE tissues were able to correctly identify virtually all of the irritant polymer samples either in the saline, sesame oil or both solvent extracts. Our results indicate that RhE tissue models can detect the presence of strong skin irritants at low levels in dilute medical device polymer extracts. Therefore, these models may be suitable replacements for the rabbit skin irritation test to support the biological evaluation of medical devices.
28.	Delpierre, Cyrille, et al. (author) Origins of heath inequalities : the case for Allostatic Load 2016 In: Longitudinal and Life Course Studies. - : Bristol University Press. - 1757-9597. ; 7:1, s. 79-103 Journal article (peer-reviewed)abstract In an opening paper Delpierre et al. explore the concept of allostatic load. The impact of the environment on our biological systems is summarised by the concept of embodiment. The biological embedding of social conditions could therefore be a relevant mechanism to partly explain the social gradient in health. A key issue is how to measure the 'physiological reality' the biological expression of embodiment at individual and population levels. Allostatic load (AL) has been proposed as a measure of the overall cost of adapting to the environment and may be a relevant tool or concept for measuring the way we have embodied our environment. Social inequalities in health may be partly explained by the embodiment of social environments, and AL may allow us to measure and compare embodiment between socioeconomic groups. However, before operationalising AL, a number of issues deserve further exploration. Among these, the choice of biological systems, and variables within each system, that should be included to remain 'loyal' to the theory of biological multisystem wastage underlying AL and the most appropriate methodological approach to be used to build an AL score, are particularly important. Moreover, studies analysing the link between adverse environments (physical, chemical, nutritional, psychosocial) across the life course and AL remain rare. Such studies require cohorts with data on socioeconomic and psychosocial environments over the life course, with multiple biological measures, made at various stages across the life span. The development and maintenance of these cohorts is essential to continue exploring the promising results that could enhance our understanding of the genesis of the social gradient in health by measuring embodiment. These points are then debated in commentaries by Linn Getz and Margret Olafia Tomasdottir, Tony Robertson and Per Gustafson. The commentaries are followed by a response from the authors of the opening paper.
29.	Do, Ron, et al. (author) Common variants associated with plasma triglycerides and risk for coronary artery disease 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345- Journal article (peer-reviewed)abstract Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
30.	Docherty, Anna R, et al. (author) GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors. 2023 In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738 Journal article (peer-reviewed)abstract Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
31.	Harley, Isaac T. W., et al. (author) The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus 2010 In: Journal of Biomedicine and Biotechnology. - : Hindawi Limited. - 1110-7243 .- 1110-7251. ; , s. 706825- Journal article (peer-reviewed)abstract Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated the IFNK locus in SLE susceptibility. We studied IFNK single nucleotide polymorphisms (SNPs) in 3982 SLE cases and 4275 controls, composed of European (EA), African-American (AA), and Asian ancestry. rs12553951C was associated with SLE in EA males (odds ratio = 1.93, P = 2.5 x 10(-4)), but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific. IFNK SNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association between IFNK SNPs and SLE and skin phenotypes. The serum IFN association suggests that IFNK variants could influence type I IFN producing plasmacytoid dendritic cells in affected skin.
32.	Harley, John B., et al. (author) Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci 2008 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:2, s. 204-10 Journal article (peer-reviewed)abstract Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.
33.	Hmelo, Laura R., et al. (author) Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange 2015 In: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 10:11, s. 1820-1841 Journal article (peer-reviewed)abstract Allelic exchange is an efficient method of bacterial genome engineering. This protocol describes the use of this technique to make gene knockouts and knock-ins, as well as single-nucleotide insertions, deletions and substitutions, in Pseudomonas aeruginosa. Unlike other approaches to allelic exchange, this protocol does not require heterologous recombinases to insert or excise selective markers from the target chromosome. Rather, positive and negative selections are enabled solely by suicide vector-encoded functions and host cell proteins. Here, mutant alleles, which are flanked by regions of homology to the recipient chromosome, are synthesized in vitro and then cloned into allelic exchange vectors using standard procedures. These suicide vectors are then introduced into recipient cells by conjugation. Homologous recombination then results in antibiotic-resistant single-crossover mutants in which the plasmid has integrated site-specifically into the chromosome. Subsequently, unmarked double-crossover mutants are isolated directly using sucrose-mediated counter-selection. This two-step process yields seamless mutations that are precise to a single base pair of DNANA. The entire procedure requires similar to 2 weeks.
34.	Hollestelle, Antoinette, et al. (author) No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer 2016 In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401 Journal article (peer-reviewed)abstract Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
35.	Holmfeldt, Linda, et al. (author) The genomic landscape of hypodiploid acute lymphoblastic leukemia 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252 Journal article (peer-reviewed)abstract The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
36.	Kassebaum, Nicholas J., et al. (author) Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658 Journal article (peer-reviewed)abstract Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
37.	Kato, Norihiro, et al. (author) Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation 2015 In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293 Journal article (peer-reviewed)abstract We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
38.	Kelly, Michelle, et al. (author) An unprecedented new genus and family of Tetractinellida (Porifera, Demospongiae) from New Zealand's Colville Ridge, with a new type of mitochondrial group I intron 2016 In: Zoological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4082 .- 1096-3642. ; 177:2, s. 335-352 Journal article (peer-reviewed)abstract A remarkable sponge with unprecedented megascleres and systematic affinities was collected recently from a previously unidentified volcano on Colville Ridge to the north-east of New Zealand. The sponge has the appearance of a tetillid sponge (family Tetillidae Sollas, 1886) with a perfectly spherical external form, radiating internal skeleton of huge oxeas and triaenes, and microspined sigmaspires as microscleres. The triaene megascleres, however, are unprecedented in their form and ornamentation; they are huge clubbed orthotriaenes the upper third of which is acanthose. Stupenda singularis gen. et sp. nov. is described here and the phylogenetic affinity and taxonomic position of this unique sponge is explored in relation to a broad range of tetractinellid sponges (order Tetractinellida Marshall, 1876) using the Folmer + Erpenbeck fragment of the cytochrome c oxidase subunit I (COI) gene and a nearly complete sequence of the 18S rDNA gene. Mitochondrial introns are rare in sponges but S. singularis gen. et sp. nov. possesses a mitochondrial group I intron at position 387 in COI; it hosts a putative LAGLIDADG endonuclease gene. This intron is the first of its kind in sponges: the self-splicing intron is homologous to a placozoan COI intron whereas the LAGLIDADG endonuclease gene may be related to Fungi LAGLIDADG endonuclease genes.
39.	Kelly, Michelle, et al. (author) Molecular study supports the position of the New Zealand endemic genus Lamellomorpha in the family Vulcanellidae (Porifera, Demospongiae, Tetractinellida), with the description of three new species 2019 In: European journal of taxonomy. - : Museum National D'Histoire Naturelle. - 2118-9773. ; 506, s. 1-25 Journal article (peer-reviewed)abstract Due to the possession of huge contort strongyles, and a lack of triaenes in an otherwise 'astrophorine' spicule complement, the phylogenetic position of the endemic, monospecific New Zealand sponge genus, Lamellomorpha Bergquist, 1968, has remained enigmatic. The genus was established within Jaspidae de Laubenfels, 1968 (in the abandoned order Epipolasida Sollas, 1888), but it was not until 2002 that the genus was transferred formally to Astrophorina Sollas, 1887, albeit incertae sedis, by Hooper & Maldonado (2002). In this study, we recognise specimens of Lamellomorpha from the Subantarctic New Zealand region and Chatham Rise, considered by Bergquist to be conspecific with the type species, L. strongylata Bergquist, 1968, first described from the Three Kings-Spirits Bay region of Northland, as the new species, L. australis Kelly & Cardenas sp. nov. These two species of Lamellomorpha have differences in external morphology and colour, skeletal architecture and spicules, natural products, geographical distribution, and depth ranges. Sequencing of the COI Folmer barcode/mini-barcode and of 28S (C1-C2 domains) of these two species suggests phylogenetic affinities of Lamellomorpha with the tetractinellid suborder Astrophorina and the family Vulcanellidae Cardenas et al., 2011. Two Subantarctic New Zealand species of the vulcanellid genus Poecillastra Sollas, 1888, P. ducitriaena Kelly & Cardenas sp. nov. and P. macquariensis Kelly & Cardenas sp. nov., provide further support for the close relationship of Lamellomorpha and Poecillastra.
40.	Kelly, Michelle, et al. (author) Preparing for Team Work Training in Simulation 2019 In: Interprofessional Simulation in Health Care. Abrandt Dahlgren M., Rystedt H., Felländer-Tsai L., Nyström S. (red.). - Cham : Springer. - 2210-5549 .- 2210-5557. - 9783030195427 ; , s. 59-89 Book chapter (peer-reviewed)abstract An important condition for serving the educational objectives of simulation-based team training is that the facilitator’s instructions during the briefing bridge the gap between the simulation and the clinical situation it is intended to represent. This chapter unpacks instructional challenges in briefings by focusing on how instructors make use of trainees’ exhibited understanding of tasks to demonstrate how procedures should be adapted to the specific conditions of the simulation. Further, the chapter addresses the interplay between the simulation scenario, the provision of manikin features and the instructor’s guidance in the scenario and the relation to team performance in the simulation. The chapter shows how additional information is conveyed to the participants during the scenario to overcome the shortcomings of the simulator and how the sequencing and timing of this information during the scenarios were crucial for furthering the participants’ activities.
41.	Kottyan, Leah C., et al. (author) The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. 2015 In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596 Journal article (peer-reviewed)abstract Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
42.	Langefeld, Carl D., et al. (author) Transancestral mapping and genetic load in systemic lupus erythematosus 2017 In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8 Journal article (peer-reviewed)abstract Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
43.	Lessard, Christopher J., et al. (author) Identification of a Systemic Lupus Erythematosus Susceptibility Locus at 11p13 between PDHX and CD44 in a Multiethnic Study 2011 In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 88:1, s. 83-91 Journal article (peer-reviewed)abstract Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 x 10(-8)) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 x 10(-8), OR = 0.83) and rs387619 (p = 7.7 x 10(-7), OR = 0.83) in the European samples with p(meta) = 1.82 x 10(-9) for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 x 10(-3), OR = 0.81 and p = 4.3 x 10(-4), OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p(meta) = 2.36 x 10(-13). This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.
44.	Lessard, Christopher J., et al. (author) Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in a Large-Scale Multiracial Replication Study 2012 In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 90:4, s. 648-660 Journal article (peer-reviewed)abstract Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p(meta-Euro) = 2.08 x 10(-10)), transmembrane protein 39A (TMEM39A; rs1132200; p(meta-all) 8.62 x 10(-9)), and 17q21 (rs1453560; p(meta-all) = 3.48 x 10(-10)) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 x 10(-8) < p(meta-Euro) < 9.99 x 10(-5)) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4 FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation.
45.	Lozano, Rafael, et al. (author) Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017 2018 In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138 Journal article (peer-reviewed)abstract Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
46.	McCormick, Stephen D, et al. (author) Taking it with you when you go: How perturbations to the freshwater environment, including temperature, dams, and contaminants, affect marine survival of salmon. 2009 In: American Fisheries Society Symposium. - 0892-2284. ; 69, s. 195-214 Research review (peer-reviewed)abstract Most anadromous fish undergo physiological and behavioral changes that are preparatory and adaptive for seawater entry. In anadromous salmonids, these preparatory changes are collectively known as smolting. Smolt development is regulated by environmental factors such as photoperiod and temperature and mediated by the neuroendocrine system. In this paper, we review evidence that a variety of anthropogenic factors can influence smolt development and affect marine survival. Hatchery rearing can affect the size of smolts and the extent and timing of smolt development. Smolt development is reversible, and the period of peak physiological preparedness in salmon smolts is limited by time and temperature. By influencing temperature and the duration of the migratory period, climate change and dams will have negative effects on smolt survival beyond direct lethal impacts. Contaminants acting on developmental physiology or underlying endocrine control mechanisms can also reduce marine survival. Exposure to estrogenic compounds prior to or during smolt development can reduce seawater tolerance and preference. Acid and aluminum exposure can reverse the development of seawater tolerance and reduce adult return rates. We conclude that environmental conditions in freshwater can affect physiological development, estuarine and ocean behavior, early seawater survival, and long-term seawater growth and homing, thus having influences on adult returns and long-term population sustainability of anadromous fishes.
47.	Menzies, Scott W, et al. (author) Dermoscopic Evaluation of Nodular Melanoma. 2013 In: JAMA dermatology (Chicago, Ill.). - : American Medical Association (AMA). - 2168-6084 .- 2168-6068. ; 149:6, s. 699-709 Journal article (peer-reviewed)abstract IMPORTANCE Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. OBJECTIVE To determine the dermoscopy features of NM. DESIGN Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. SETTING Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. RESULTS Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. CONCLUSIONS AND RELEVANCE When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.
48.	Mårtensson, Katarina, et al. (author) Expertise : How do we develop a career long engagement with teaching? 2020 In: Reflective Teaching in Higher Education. - 9781350084667 - 9781350084674 - 9781350084698 - 9781350084681 ; , s. 357-378 Book chapter (peer-reviewed)abstract In this chapter we examine how we can deepen our understanding and expertise as higher education teachers through ongoing personal and professional development, building on the notion in Chapter Three that ‘Our teaching is always in the process of developing’. The chapter begins with an overview of what it means to develop our ‘expertise’ in higher education teaching and puts this in relation to the notion of scholarship of teaching and learning. We look at the importance of informal learning and the influence of the collegial workplace in relation to our engagement and professional development. This chapter also considers some of the ways in which universities are trying to appraise and reward engagement with teaching through a variety of reward mechanisms and promotion policies that focus on recognising teaching excellence, scholarship of teaching and learning, and leadership in learning and teaching as key performance areas. Finally, we consider some of the milestones that might typically characterise an academic career and how we can engage with respect to our career trajectory and promotion opportunities, as well as what to consider when constructing a teaching portfolio.
49.	Namjou, Bahram, et al. (author) Evaluation of TRAF6 in a large multiancestral lupus cohort 2012 In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 64:6, s. 1960-1969 Journal article (peer-reviewed)abstract Objective Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development. Methods Fifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based casecontrol association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results Evidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 x 10(-5) and P = 4.73 x 10(-5), respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r2 = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 x 10(-4), OR 0.89 [95% CI 0.830.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 x 10(-6), OR 0.57 [95% CI 0.450.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model. Conclusion Our data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity.
50.	Namjou, Bahram, et al. (author) High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups 2009 In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1085-1095 Journal article (peer-reviewed)abstract OBJECTIVE: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility. METHODS: Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case-control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. RESULTS: We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 x 10(-25)). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4. CONCLUSION: Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.

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