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1.	Ahmad, T, et al. (author) Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries 2016 In: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 117:5, s. 601- 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.	Ahmad, T, et al. (author) Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries: a 7-day cohort study of elective surgery 2017 In: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 119:2, s. 258-266 Journal article (peer-reviewed)
4.	Fenstermacher, M.E., et al. (author) DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy 2022 In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4 Journal article (peer-reviewed)abstract DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
5.	2019 Journal article (peer-reviewed)
6.	Wang, Haidong, et al. (author) Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544 Journal article (peer-reviewed)abstract BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
7.	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.
8.	Poyatos, R., et al. (author) Global transpiration data from sap flow measurements: the SAPFLUXNET database 2021 In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:6, s. 2607-2649 Journal article (peer-reviewed)abstract Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land-atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets, while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes. SAPFLUXNET version 0.1.5 is freely available from the Zenodo repository (https://doi.org/10.5281/zenodo.3971689; Poyatos et al., 2020a). The "sapfluxnetr" R package - designed to access, visualize, and process SAPFLUXNET data - is available from CRAN.
9.	Mahajan, Anubha, et al. (author) Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation 2022 In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572 Journal article (peer-reviewed)abstract We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
10.	Weinstein, John N., et al. (author) The cancer genome atlas pan-cancer analysis project 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120 Research review (peer-reviewed)abstract The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
11.	Tiegs, Scott D., et al. (author) Global patterns and drivers of ecosystem functioning in rivers and riparian zones 2019 In: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1 Journal article (peer-reviewed)abstract River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
12.	Franz, D, et al. (author) Towards long-term standardised carbon and greenhouse gas observations for monitoring Europe´s terrestrial ecosystems: a review 2018 In: International Agrophysics. - : Walter de Gruyter GmbH. - 0236-8722 .- 2300-8725. ; 32, s. 439-455 Journal article (peer-reviewed)abstract Research infrastructures play a key role in launching a new generation of integrated long-term, geographically distributed observation programmes designed to monitor climate change, better understand its impacts on global ecosystems, and evaluate possible mitigation and adaptation strategies. The pan-European Integrated Carbon Observation System combines carbon and greenhouse gas (GHG; CO2, CH4, N2O, H2O) observations within the atmosphere, terrestrial ecosystems and oceans. High-precision measurements are obtained using standardised methodologies, are centrally processed and openly available in a traceable and verifiable fashion in combination with detailed metadata. The Integrated Carbon Observation System ecosystem station network aims to sample climate and land-cover variability across Europe. In addition to GHG flux measurements, a large set of complementary data (including management practices, vegetation and soil characteristics) is collected to support the interpretation, spatial upscaling and modelling of observed ecosystem carbon and GHG dynamics. The applied sampling design was developed and formulated in protocols by the scientific community, representing a trade-off between an ideal dataset and practical feasibility. The use of open-access, high-quality and multi-level data products by different user communities is crucial for the Integrated Carbon Observation System in order to achieve its scientific potential and societal value.
13.	Ralimanana, H., et al. (author) Madagascar’s extraordinary biodiversity: Threats and opportunities 2022 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 378:6623 Research review (peer-reviewed)abstract Madagascar’s unique biota is heavily affected by human activity and is under intense threat. Here, we review the current state of knowledge on the conservation status of Madagascar’s terrestrial and freshwater biodiversity by presenting data and analyses on documented and predicted species-level conservation statuses, the most prevalent and relevant threats, ex situ collections and programs, and the coverage and comprehensiveness of protected areas. The existing terrestrial protected area network in Madagascar covers 10.4% of its land area and includes at least part of the range of the majority of described native species of vertebrates with known distributions (97.1% of freshwater fishes, amphibians, reptiles, birds, and mammals combined) and plants (67.7%). The overall figures are higher for threatened species (97.7% of threatened vertebrates and 79.6% of threatened plants occurring within at least one protected area). International Union for Conservation of Nature (IUCN) Red List assessments and Bayesian neural network analyses for plants identify overexploitation of biological resources and unsustainable agriculture as the most prominent threats to biodiversity. We highlight five opportunities for action at multiple levels to ensure that conservation and ecological restoration objectives, programs, and activities take account of complex underlying and interacting factors and produce tangible benefits for the biodiversity and people of Madagascar.
14.	Pearce, Neil E, et al. (author) IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans 2015 In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514 Journal article (peer-reviewed)abstract BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
15.	Frankell, AM, et al. (author) The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic 2019 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 51:3, s. 506- Journal article (peer-reviewed)
16.	Mourikis, TP, et al. (author) Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma 2019 In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3101- Journal article (peer-reviewed)abstract The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.
17.	Young, WJ, et al. (author) Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease 2023 In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 1411- Journal article (peer-reviewed)abstract The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
18.	Abbas, S, et al. (author) Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma 2023 In: Nature communications. - 2041-1723. ; 14:1, s. 4239- Journal article (peer-reviewed)
19.	Potapov, Anton M., et al. (author) Global fine-resolution data on springtail abundance and community structure 2024 In: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1 Journal article (peer-reviewed)abstract Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
20.	Kehoe, Laura, et al. (author) Make EU trade with Brazil sustainable 2019 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341- Journal article (other academic/artistic)
21.	Razavi-Shearer, Devin M., et al. (author) Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories 2024 In: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242 Journal article (peer-reviewed)abstract Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
22.	Antonelli, Alexandre, 1978, et al. (author) Madagascar's extraordinary biodiversity : Evolution, distribution, and use 2022 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 378:6623, s. 962- Journal article (peer-reviewed)abstract Madagascar's biota is hyperdiverse and includes exceptional levels of endemicity. We review the current state of knowledge on Madagascar's past and current terrestrial and freshwater biodiversity by compiling and presenting comprehensive data on species diversity, endemism, and rates of species description and human uses, in addition to presenting an updated and simplified map of vegetation types. We report a substantial increase of records and species new to science in recent years; however, the diversity and evolution of many groups remain practically unknown (e.g., fungi and most invertebrates). Digitization efforts are increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge and identifying gaps in our understanding, particularly as species richness corresponds closely to collection effort. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. We highlight humid forests as centers of diversity and endemism because of their role as refugia and centers of recent and rapid radiations. However, the distinct endemism of other areas, such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest, is also biologically important despite lower species richness. The documented uses of Malagasy biodiversity are manifold, with much potential for the uncovering of new useful traits for food, medicine, and climate mitigation. The data presented here showcase Madagascar as a unique " living laboratory" for our understanding of evolution and the complex interactions between people and nature. The gathering and analysis of biodiversity data must continue and accelerate if we are to fully understand and safeguard this unique subset of Earth's biodiversity.
23.	Aragam, KG, et al. (author) Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants 2022 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:12, s. 1803-1815 Journal article (peer-reviewed)abstract The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.
24.	Aragam, KG, et al. (author) Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants 2022 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:12, s. 1803-1815 Journal article (peer-reviewed)abstract The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.
25.	Luyssaert, S., et al. (author) CO2 balance of boreal, temperate, and tropical forests derived from a global database 2007 In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 13:12, s. 2509-2537 Research review (peer-reviewed)abstract Terrestrial ecosystems sequester 2.1 Pg of atmospheric carbon annually. A large amount of the terrestrial sink is realized by forests. However, considerable uncertainties remain regarding the fate of this carbon over both short and long timescales. Relevant data to address these uncertainties are being collected at many sites around the world, but syntheses of these data are still sparse. To facilitate future synthesis activities, we have assembled a comprehensive global database for forest ecosystems, which includes carbon budget variables (fluxes and stocks), ecosystem traits (e.g. leaf area index, age), as well as ancillary site information such as management regime, climate, and soil characteristics. This publicly available database can be used to quantify global, regional or biome-specific carbon budgets; to re-examine established relationships; to test emerging hypotheses about ecosystem functioning [e.g. a constant net ecosystem production (NEP) to gross primary production (GPP) ratio]; and as benchmarks for model evaluations. In this paper, we present the first analysis of this database. We discuss the climatic influences on GPP, net primary production (NPP) and NEP and present the CO2 balances for boreal, temperate, and tropical forest biomes based on micrometeorological, ecophysiological, and biometric flux and inventory estimates. Globally, GPP of forests benefited from higher temperatures and precipitation whereas NPP saturated above either a threshold of 1500 mm precipitation or a mean annual temperature of 10 degrees C. The global pattern in NEP was insensitive to climate and is hypothesized to be mainly determined by nonclimatic conditions such as successional stage, management, site history, and site disturbance. In all biomes, closing the CO2 balance required the introduction of substantial biome-specific closure terms. Nonclosure was taken as an indication that respiratory processes, advection, and non-CO2 carbon fluxes are not presently being adequately accounted for.
26.	Maxwell, Tania L., et al. (author) Global dataset of soil organic carbon in tidal marshes 2023 In: Scientific Data. - : Springer Nature. - 2052-4463. ; 10:1 Journal article (peer-reviewed)abstract Tidal marshes store large amounts of organic carbon in their soils. Field data quantifying soil organic carbon (SOC) stocks provide an important resource for researchers, natural resource managers, and policy-makers working towards the protection, restoration, and valuation of these ecosystems. We collated a global dataset of tidal marsh soil organic carbon (MarSOC) from 99 studies that includes location, soil depth, site name, dry bulk density, SOC, and/or soil organic matter (SOM). The MarSOC dataset includes 17,454 data points from 2,329 unique locations, and 29 countries. We generated a general transfer function for the conversion of SOM to SOC. Using this data we estimated a median (± median absolute deviation) value of 79.2 ± 38.1 Mg SOC ha−1 in the top 30 cm and 231 ± 134 Mg SOC ha−1 in the top 1 m of tidal marsh soils globally. This data can serve as a basis for future work, and may contribute to incorporation of tidal marsh ecosystems into climate change mitigation and adaptation strategies and policies.
27.	Peters, CJ, et al. (author) A decade of the Oesophageal Cancer Clinical and Molecular Stratification Consortium 2023 In: Nature medicine. - 1546-170X. ; 30:1, s. 14-16 Journal article (other academic/artistic)
28.	Ruggeri, Kai, et al. (author) The globalizability of temporal discounting 2022 In: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 6:10, s. 1386-1397 Journal article (peer-reviewed)abstract Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns. Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.
29.	Wingate, L., et al. (author) Interpreting canopy development and physiology using a European phenology camera network at flux sites 2015 In: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 12:20, s. 5995-6015 Journal article (peer-reviewed)abstract Plant phenological development is orchestrated through subtle changes in photoperiod, temperature, soil moisture and nutrient availability. Presently, the exact timing of plant development stages and their response to climate and management practices are crudely represented in land surface models. As visual observations of phenology are laborious, there is a need to supplement long-term observations with automated techniques such as those provided by digital repeat photography at high temporal and spatial resolution. We present the first synthesis from a growing observational network of digital cameras installed on towers across Europe above deciduous and evergreen forests, grasslands and croplands, where vegetation and atmosphere CO2 fluxes are measured continuously. Using colour indices from digital images and using piecewise regression analysis of time series, we explored whether key changes in canopy phenology could be detected automatically across different land use types in the network. The piecewise regression approach could capture the start and end of the growing season, in addition to identifying striking changes in colour signals caused by flowering and management practices such as mowing. Exploring the dates of green-up and senescence of deciduous forests extracted by the piecewise regression approach against dates estimated from visual observations, we found that these phenological events could be detected adequately (RMSE < 8 and 11 days for leaf out and leaf fall, respectively). We also investigated whether the seasonal patterns of red, green and blue colour fractions derived from digital images could be modelled mechanistically using the PROSAIL model parameterised with information of seasonal changes in canopy leaf area and leaf chlorophyll and carotenoid concentrations. From a model sensitivity analysis we found that variations in colour fractions, and in particular the late spring 'green hump' observed repeatedly in deciduous broadleaf canopies across the network, are essentially dominated by changes in the respective pigment concentrations. Using the model we were able to explain why this spring maximum in green signal is often observed out of phase with the maximum period of canopy photosynthesis in ecosystems across Europe. Coupling such quasi-continuous digital records of canopy colours with co-located CO2 flux measurements will improve our understanding of how changes in growing season length are likely to shape the capacity of European ecosystems to sequester CO2 in the future.
30.	Abreu, A, et al. (author) Cardiac rehabilitation availability and delivery in Europe: How does it differ by region and compare with other high-income countries?: Endorsed by the European Association of Preventive Cardiology 2019 In: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 26:11, s. 1131-1146 Journal article (peer-reviewed)
31.	Ade, Peter, et al. (author) The Simons Observatory : science goals and forecasts 2019 In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2 Journal article (peer-reviewed)abstract The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
32.	Baturova, Maria A., et al. (author) Electrocardiographic and Echocardiographic predictors of paroxysmal atrial fibrillation detected after ischemic stroke 2016 In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 16:1 Journal article (peer-reviewed)abstract Background: Detection of atrial fibrillation after ischemic stroke is challenging due to its paroxysmal nature. We aimed to assess predictors of paroxysmal atrial fibrillation using non-invasive surface ECG and transthoracic echocardiography to select candidates for atrial fibrillation screening. Methods: Ischemic stroke patients without documented atrial fibrillation (n = 110, 67 ± 10 years, 40 female) and a control group of age- and gender-matched patients with history of paroxysmal atrial fibrillation prior to stroke (n = 55, 67 ± 10 years, 19 female) comprised the study sample. Using non-invasive ECG monitoring for three weeks, short episodes of paroxysmal atrial fibrillation were detected in 24 of 110 patients (22 %). The standard 12-lead ECG with sinus rhythm at stroke onset was digitally processed and analyzed. Transthoracic echocardiography data were reviewed for these patients. Results: Atrial fibrillation history was independently associated with P terminal force in lead V 1 > 40 mm*ms (OR 4.04 95 % CI 1.34-12.14, p = 0.013) and left atrial volume index (OR 1.08 95 % CI 1.03-1.13, p = 0.002; for LAVI > 40 mL/m2 OR 6.40 95 % CL 1.47-27.91, p = 0.013). Among patients without atrial fibrillation history, no ECG characteristics were predictive of atrial fibrillation detected after stroke. Left atrial volume index remained an independent predictor of atrial fibrillation detected after stroke (OR 1.09 95 % CI 1.02-1.16, p = 0.017). A cutoff of <40 mL/m2 had an 84 % negative predictive value for ruling out atrial fibrillation on ambulatory monitoring with a sensitivity of 50 % and a specificity of 86 %. Conclusion: In a post hoc analysis, left atrial dilatation assessed by left atrial volume index independently predicted atrial fibrillation after stroke in patients without prior atrial fibrillation history, while the other clinical or ECG markers were not predictive of atrial fibrillation detected early after ischemic stroke. Trial registration: This study is a post hoc analysis from the prospective case-control study registered in December 2011, ClinicalTrials.gov ID: NCT01325545.
33.	Nelson, CP, et al. (author) Association analyses based on false discovery rate implicate new loci for coronary artery disease 2017 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:9, s. 1385- Journal article (peer-reviewed)
34.	Rowland, L, et al. (author) Death from drought in tropical forests is triggered by hydraulics not carbon starvation. 2015 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 528:7580, s. 119-122 Journal article (peer-reviewed)abstract Drought threatens tropical rainforests over seasonal to decadal timescales, but the drivers of tree mortality following drought remain poorly understood. It has been suggested that reduced availability of non-structural carbohydrates (NSC) critically increases mortality risk through insufficient carbon supply to metabolism ('carbon starvation'). However, little is known about how NSC stores are affected by drought, especially over the long term, and whether they are more important than hydraulic processes in determining drought-induced mortality. Using data from the world's longest-running experimental drought study in tropical rainforest (in the Brazilian Amazon), we test whether carbon starvation or deterioration of the water-conducting pathways from soil to leaf trigger tree mortality. Biomass loss from mortality in the experimentally droughted forest increased substantially after >10 years of reduced soil moisture availability. The mortality signal was dominated by the death of large trees, which were at a much greater risk of hydraulic deterioration than smaller trees. However, we find no evidence that the droughted trees suffered carbon starvation, as their NSC concentrations were similar to those of non-droughted trees, and growth rates did not decline in either living or dying trees. Our results indicate that hydraulics, rather than carbon starvation, triggers tree death from drought in tropical rainforest.
35.	Supervia, M, et al. (author) Nature of Cardiac Rehabilitation Around the Globe 2019 In: EClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 13, s. 46-56 Journal article (peer-reviewed)
36.	Tschiderer, Lena, et al. (author) Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque : Individual Participant Data Meta-Analysis of 20 Prospective Studies 2023 In: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 12:12 Journal article (peer-reviewed)abstract Background: The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development.Methods and Results: We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I-2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I-2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I-2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques).Conclusions: Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.
37.	Turk-Adawi, K, et al. (author) Cardiac Rehabilitation Availability and Density around the Globe 2019 In: EClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 13, s. 31-45 Journal article (peer-reviewed)
38.	Wulf Hanson, Sarah, et al. (author) A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021 2022 Other publication (other academic/artistic)abstract Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery.Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms.Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.
39.	Wulf Hanson, Sarah, et al. (author) Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021 2022 In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 328:16, s. 1604-1615 Journal article (peer-reviewed)abstract IMPORTANCE: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).OBJECTIVE: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.DESIGN, SETTING, AND PARTICIPANTS: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022.EXPOSURES: Symptomatic SARS-CoV-2 infection.MAIN OUTCOMES AND MEASURES: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age.RESULTS: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months.CONCLUSIONS AND RELEVANCE: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.
40.	Bath, Jonathan, et al. (author) Contemporary outcomes after treatment of aberrant subclavian artery and Kommerell's diverticulum 2023 In: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 77:5, s. 1339-1348.e6 Journal article (peer-reviewed)abstract Objective: Aberrant subclavian artery (ASA) and Kommerell's diverticulum (KD) are rare vascular anomalies that may be associated with lifestyle-limiting and life-threatening complications. The aim of this study is to report contemporary outcomes after invasive treatment of ASA/KD using a large international dataset.Methods: Patients who underwent treatment for ASA/KD (2000-2020) were identified through the Vascular Low Frequency Disease Consortium, a multi-institutional collaboration to investigate uncommon vascular disorders. We report the early and mid-term clinical outcomes including stroke and mortality, technical success, and other operative outcomes including reintervention rates, patency, and endoleak.Results: Overall, 285 patients were identified during the study period. The mean patient age was 57 years; 47% were female and 68% presented with symptoms. A right-sided arch was present in 23%. The mean KD diameter was 47.4 mm (range, 13.0-108.0 mm). The most common indication for treatment was symptoms (59%), followed by aneurysm size (38%). The most common symptom reported was dysphagia (44%). A ruptured KD was treated in 4.2% of cases, with a mean diameter of 43.9 mm (range, 18.0-100.0 mm). An open procedure was performed in 101 cases (36%); the most common approach was ASA ligation with subclavian transposition. An endovascular or hybrid approach was performed in 184 patients (64%); the most common approach was thoracic endograft and carotid-subclavian bypass. A staged operative strategy was employed more often than single setting repair (55% vs 45%). Compared with endovascular or hybrid approach, those in the open procedure group were more likely to be younger (49 years vs 61 years; P < .0001), female (64% vs 36%; P < .0001), and symptomatic (85% vs 59%; P < .0001). Complete or partial symptomatic relief at 1 year after intervention was 82.6%. There was no association between modality of treatment and symptom relief (open 87.2% vs endovascular or hybrid approach 78.9%; P = .13). After the intervention, 11 subclavian occlusions (4.5%) occurred; 3 were successfully thrombectomized resulting in a primary and secondary patency of 95% and 96%, respectively, at a median follow-up of 39 months. Among the 33 reinterventions (12%), the majority were performed for endoleak (36%), and more reinterventions occurred in the endovascular or hybrid approach than open procedure group (15% vs 6%; P = .02). The overall survival rate was 87.3% at a median follow-up of 41 months. The 30-day stroke and death rates were 4.2% and 4.9%, respectively. Urgent or emergent presentation was independently associated with increased risk of 30-day mortality (odds ratio [OR], 19.8; 95% confidence interval [CI], 3.3-116.6), overall mortality (OR, 3.6; 95% CI, 1.2-11.2) and intraoperative complications (OR, 8.3; 95% CI, 2.8-25.1). Females had a higher risk of reintervention (OR, 2.6; 95% CI, 1.0-6.5). At an aneurysm size of 44.4 mm, receiver operator characteristic curve analysis suggested that 60% of patients would have symptoms.Conclusions: Treatment of ASA/KD can be performed safely with low rates of mortality, stroke and reintervention and high rates of symptomatic relief, regardless of the repair strategy. Symptomatic and urgent operations were associated with worse outcomes in general, and female gender was associated with a higher likelihood of reintervention. Given the worse overall outcomes when symptomatic and the inherent risk of rupture, consideration of repair at 40 mm is reasonable in most patients. ASA/KD can be repaired in asymptomatic patients with excellent outcomes and young healthy patients may be considered better candidates for open approaches versus endovascular or hybrid modalities, given the lower likelihood of reintervention and lower early mortality rate.
41.	Brown, Darron R., et al. (author) The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Generally HPV-Naive Women Aged 16-26 Years 2009 In: Journal Of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 199:7, s. 926-935 Conference paper (peer-reviewed)abstract Background. Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. Methods. We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of >= 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. Results. Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. Conclusions. HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for similar to 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type.
42.	Diaz, Ben P., et al. (author) Seasonal mixed layer depth shapes phytoplankton physiology, viral production, and accumulation in the North Atlantic 2021 In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1 Journal article (peer-reviewed)abstract Seasonal shifts in phytoplankton accumulation and loss largely follow changes in mixed layer depth, but the impact of mixed layer depth on cell physiology remains unexplored. Here, we investigate the physiological state of phytoplankton populations associated with distinct bloom phases and mixing regimes in the North Atlantic. Stratification and deep mixing alter community physiology and viral production, effectively shaping accumulation rates. Communities in relatively deep, early-spring mixed layers are characterized by low levels of stress and high accumulation rates, while those in the recently shallowed mixed layers in late-spring have high levels of oxidative stress. Prolonged stratification into early autumn manifests in negative accumulation rates, along with pronounced signatures of compromised membranes, death-related protease activity, virus production, nutrient drawdown, and lipid markers indicative of nutrient stress. Positive accumulation renews during mixed layer deepening with transition into winter, concomitant with enhanced nutrient supply and lessened viral pressure. Phytoplankton are important primary producers. Here the authors investigate phytoplankton physiological changes associated with bloom phases and mixing regimes in the North Atlantic, finding that stratification and deep mixing shape accumulation rates by altering physiology and viral production.
43.	Dillner, Joakim, et al. (author) Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial. 2010 In: BMJ: British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 341 Journal article (peer-reviewed)abstract OBJECTIVES: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). DESIGN: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. SETTING: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. PARTICIPANTS: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. INTERVENTION: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. MAIN OUTCOME MEASURES: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. RESULTS: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. CONCLUSIONS: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. TRIAL REGISTRATIONS: NCT00092521 and NCT00092534.
44.	Ebrahimi-Fakhari, Darius, et al. (author) Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia 2020 In: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944 Journal article (peer-reviewed)abstract Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
45.	Garratt, Michael P D, et al. (author) Opportunities to reduce pollination deficits and address production shortfalls in an important insect pollinated crop 2021 In: Ecological Applications. - : Wiley. - 1051-0761 .- 1939-5582. Journal article (peer-reviewed)abstract Pollinators face multiple pressures and there is evidence of populations in decline. As demand for insect-pollinated crops increases, crop production is threatened by shortfalls in pollination services. Understanding the extent of current yield deficits due to pollination and identifying opportunities to protect or improve crop yield and quality through pollination management is therefore of international importance. To explore the extent of 'pollination deficits', where maximum yield is not being achieved due to insufficient pollination, we use an extensive dataset on a globally important crop, apples. We quantified how these deficits vary between orchards and countries as well as compare 'pollinator dependence' across different apple varieties. We found evidence of pollination deficits and in some cases, risks of over-pollination were even apparent where fruit quality could be reduced by too much pollination. In almost all regions studied we found some orchards performing significantly better than others, in terms of avoiding a pollination deficit and crop yield shortfalls due to sub-optimal pollination. This represents an opportunity to improve production through better pollinator and crop management. Our findings also demonstrate that pollinator dependence varies considerably between apple varieties in terms of fruit number and fruit quality. We propose that assessments of pollination service and deficits in crops can be used to quantify supply and demand for pollinators and help target local management to address deficits although crop variety has a strong influence on the role of pollinators.
46.	Grace, O. M., et al. (author) Opinion Botanical Monography in the Anthropocene 2021 In: Trends in Plant Science. - : Elsevier BV. - 1360-1385. ; 26:5, s. 433-441 Journal article (peer-reviewed)abstract Unprecedented changes in the Earth?s biota are prompting urgent efforts to describe and conserve plant diversity. For centuries, botanical monographs ? comprehensive systematic treatments of a family or genus ? have been the gold standard for disseminating scientific information to accelerate research. The lack of a monograph compounds the risk that undiscovered species become extinct before they can be studied and conserved. Progress towards estimating the Tree of Life and digital information resources now bring even the most ambitious monographs within reach. Here, we recommend best practices to complete monographs urgently, especially for tropical plant groups under imminent threat or with expected socioeconomic benefits. We also highlight the renewed relevance and potential impact of monographies for the understanding, sustainable use, and conservation of biodiversity.
47.	Grace, O. M., et al. (author) Plant Power: Opportunities and challenges for meeting sustainable energy needs from the plant and fungal kingdoms 2020 In: Plants People Planet. - : Wiley. - 2572-2611. ; 2:5, s. 446-462 Journal article (peer-reviewed)abstract Societal Impact Statement Bioenergy is a major component of the global transition to renewable energy technologies. The plant and fungal kingdoms offer great potential but remain mostly untapped. Their increased use could contribute to the renewable energy transition and addressing the United Nations Sustainable Development Goal 7 "Ensure access to affordable, reliable, sustainable and modern energy for all." Current research focuses on species cultivated at scale in temperate regions, overlooking the wealth of potential new sources of small-scale energy where they are most urgently needed. A shift towards diversified, accessible bioenergy technologies will help to mitigate and adapt to the threats of climate change, decrease energy poverty, improve human health by reducing indoor pollution, increase energy resilience of communities, and decrease greenhouse gas emissions from fossil fuels. SummaryBioenergy derived from plants and fungi is a major component of the global transition to renewable energy technologies. There is rich untapped diversity in the plant and fungal kingdoms that offers potential to contribute to the shift away from fossil fuels and to address the United Nations Sustainable Development Goal 7 (SDG7) "Ensure access to affordable, reliable, sustainable and modern energy for all." Energy poverty-the lack of access to modern energy services-is most acute in the Global South where biodiversity is greatest and least investigated. Our systematic review of the literature over the last 5 years (2015-2020) indicates that research efforts have targeted a very small number of plant species cultivated at scale, mostly in temperate regions. The wealth of potential new sources of bioenergy in biodiverse regions, where the implementation of SDG7 is most urgently needed, has been largely overlooked. We recommend next steps for bioenergy stakeholders-research, industry, and government-to seize opportunities for innovation to alleviate energy poverty while protecting biodiversity. Small-scale energy production using native plant species in bioenergy landscapes overcomes many pitfalls associated with bioenergy crop monocultures, such as biodiversity loss and conflict with food production. Targeted trait-based screening of plant species and biological screening of fungi are required to characterize the potential of this resource. The benefits of diversified, accessible bioenergy go beyond the immediate urgency of energy poverty as more diverse agricultural landscapes are more resilient, store more carbon, and could also reduce the drivers of the climate and environmental emergencies.
48.	Joura, Elmar A., et al. (author) HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine 2008 In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 26:52, s. 6844-6851 Journal article (peer-reviewed)abstract The efficacy of the quadrivalent Human Papillomavirus (HPV) vaccine is thought to be mediated by humoral immunity. We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy. 17,622 women were vaccinated at day 1, and months 2 and 6. At day I and at 6-12 months intervals for up to 48 months, subjects underwent Papanicolaou and genital HPV testing. No immune correlate of protection could be found due to low number of cases. Although 40% of vaccine subjects were anti-HPV 18 seronegative at end-of-study, efficacy against HPV 18-related disease remained high (98.4%; 95% CI: 90.5-100.0) despite high attack rates in the placebo group. These results suggest vaccine-induced protection via immune memory, or lower than detectable HPV 18 antibody titers. (C) 2008 Elsevier Ltd. All rights reserved.
49.	Jucker, Tommaso, et al. (author) Tallo: A global tree allometry and crown architecture database 2022 In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:17, s. 5254-5268 Journal article (peer-reviewed)abstract Data capturing multiple axes of tree size and shape, such as a tree's stem diameter, height and crown size, underpin a wide range of ecological research—from developing and testing theory on forest structure and dynamics, to estimating forest carbon stocks and their uncertainties, and integrating remote sensing imagery into forest monitoring programmes. However, these data can be surprisingly hard to come by, particularly for certain regions of the world and for specific taxonomic groups, posing a real barrier to progress in these fields.To overcome this challenge, we developed the Tallo database, a collection of 498,838 georeferenced and taxonomically standardized records of individual trees for which stem diameter, height and/or crown radius have been measured. These data were collected at 61,856 globally distributed sites, spanning all major forested and non-forested biomes. The majority of trees in the database are identified to species (88%), and collectively Tallo includes data for 5163 species distributed across 1453 genera and 187 plant families. The database is publicly archived under a CC-BY 4.0 licence and can be access from: https://doi.org/10.5281/zenodo.6637599.To demonstrate its value, here we present three case studies that highlight how the Tallo database can be used to address a range of theoretical and applied questions in ecology—from testing the predictions of metabolic scaling theory, to exploring the limits of tree allometric plasticity along environmental gradients and modelling global variation in maximum attainable tree height. In doing so, we provide a key resource for field ecologists, remote sensing researchers and the modelling community working together to better understand the role that trees play in regulating the terrestrial carbon cycle.
50.	Kjaer, Susanne K., et al. (author) A Pooled Analysis of Continued Prophylactic Efficacy of Quadrivalent Human Papillomavirus (Types 6/11/16/18) Vaccine against High-grade Cervical and External Genital Lesions 2009 In: Cancer Prevention Research. - 1940-6207. ; 2:10, s. 868-878 Journal article (peer-reviewed)abstract Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18-related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18-related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination.

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