1. |
- Weinstein, John N., et al.
(author)
-
The cancer genome atlas pan-cancer analysis project
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 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.
|
|
2. |
- Beaty, D.W, et al.
(author)
-
The potential science and engineering value of samples delivered to Earth by Mars sample return : International MSR Objectives and Samples Team (iMOST)
- 2019
-
In: Meteoritics and Planetary Science. - : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 54:S1, s. 3-152
-
Journal article (peer-reviewed)abstract
- Executive Summary: Return of samples from the surface of Mars has been a goal of the international Mars science community for many years. Affirmation by NASA and ESA of the importance of Mars exploration led the agencies to establish the international MSR Objectives and Samples Team (iMOST). The purpose of the team is to re-evaluate and update the sample-related science and engineering objectives of a Mars Sample Return (MSR) campaign. The iMOST team has also undertaken to define the measurements and the types of samples that can best address the objectives. Seven objectives have been defined for MSR, traceable through two decades of previously published international priorities. The first two objectives are further divided into sub-objectives. Within the main part of the report, the importance to science and/or engineering of each objective is described, critical measurements that would address the objectives are specified, and the kinds of samples that would be most likely to carry key information are identified. These seven objectives provide a framework for demonstrating how the first set of returned Martian samples would impact future Martian science and exploration. They also have implications for how analogous investigations might be conducted for samples returned by future missions from other solar system bodies, especially those that may harbor biologically relevant or sensitive material, such as Ocean Worlds (Europa, Enceladus, Titan) and others. Summary of Objectives and Sub-Objectives for MSR Identified by iMOST: Objective 1 Interpret the primary geologic processes and history that formed the Martian geologic record, with an emphasis on the role of water. Intent To investigate the geologic environment(s) represented at the Mars 2020 landing site, provide definitive geologic context for collected samples, and detail any characteristics that might relate to past biologic processesThis objective is divided into five sub-objectives that would apply at different landing sites. 1.1 Characterize the essential stratigraphic, sedimentologic, and facies variations of a sequence of Martian sedimentary rocks. Intent To understand the preserved Martian sedimentary record. Samples A suite of sedimentary rocks that span the range of variation. Importance Basic inputs into the history of water, climate change, and the possibility of life 1.2 Understand an ancient Martian hydrothermal system through study of its mineralization products and morphological expression. Intent To evaluate at least one potentially life-bearing “habitable” environment Samples A suite of rocks formed and/or altered by hydrothermal fluids. Importance Identification of a potentially habitable geochemical environment with high preservation potential. 1.3 Understand the rocks and minerals representative of a deep subsurface groundwater environment. Intent To evaluate definitively the role of water in the subsurface. Samples Suites of rocks/veins representing water/rock interaction in the subsurface. Importance May constitute the longest-lived habitable environments and a key to the hydrologic cycle. 1.4 Understand water/rock/atmosphere interactions at the Martian surface and how they have changed with time. Intent To constrain time-variable factors necessary to preserve records of microbial life. Samples Regolith, paleosols, and evaporites. Importance Subaerial near-surface processes could support and preserve microbial life. 1.5 Determine the petrogenesis of Martian igneous rocks in time and space. Intent To provide definitive characterization of igneous rocks on Mars. Samples Diverse suites of ancient igneous rocks. Importance Thermochemical record of the planet and nature of the interior. Objective 2 Assess and interpret the potential biological history of Mars, including assaying returned samples for the evidence of life. Intent To investigate the nature and extent of Martian habitability, the conditions and processes that supported or challenged life, how different environments might have influenced the preservation of biosignatures and created nonbiological “mimics,” and to look for biosignatures of past or present life.This objective has three sub-objectives: 2.1 Assess and characterize carbon, including possible organic and pre-biotic chemistry. Samples All samples collected as part of Objective 1. Importance Any biologic molecular scaffolding on Mars would likely be carbon-based. 2.2 Assay for the presence of biosignatures of past life at sites that hosted habitable environments and could have preserved any biosignatures. Samples All samples collected as part of Objective 1. Importance Provides the means of discovering ancient life. 2.3 Assess the possibility that any life forms detected are alive, or were recently alive. Samples All samples collected as part of Objective 1. Importance Planetary protection, and arguably the most important scientific discovery possible. Objective 3 Quantitatively determine the evolutionary timeline of Mars. Intent To provide a radioisotope-based time scale for major events, including magmatic, tectonic, fluvial, and impact events, and the formation of major sedimentary deposits and geomorphological features. Samples Ancient igneous rocks that bound critical stratigraphic intervals or correlate with crater-dated surfaces. Importance Quantification of Martian geologic history. Objective 4 Constrain the inventory of Martian volatiles as a function of geologic time and determine the ways in which these volatiles have interacted with Mars as a geologic system. Intent To recognize and quantify the major roles that volatiles (in the atmosphere and in the hydrosphere) play in Martian geologic and possibly biologic evolution. Samples Current atmospheric gas, ancient atmospheric gas trapped in older rocks, and minerals that equilibrated with the ancient atmosphere. Importance Key to understanding climate and environmental evolution. Objective 5 Reconstruct the processes that have affected the origin and modification of the interior, including the crust, mantle, core and the evolution of the Martian dynamo. Intent To quantify processes that have shaped the planet's crust and underlying structure, including planetary differentiation, core segregation and state of the magnetic dynamo, and cratering. Samples Igneous, potentially magnetized rocks (both igneous and sedimentary) and impact-generated samples. Importance Elucidate fundamental processes for comparative planetology. Objective 6 Understand and quantify the potential Martian environmental hazards to future human exploration and the terrestrial biosphere. Intent To define and mitigate an array of health risks related to the Martian environment associated with the potential future human exploration of Mars. Samples Fine-grained dust and regolith samples. Importance Key input to planetary protection planning and astronaut health. Objective 7 Evaluate the type and distribution of in-situ resources to support potential future Mars exploration. Intent To quantify the potential for obtaining Martian resources, including use of Martian materials as a source of water for human consumption, fuel production, building fabrication, and agriculture. Samples Regolith. Importance Production of simulants that will facilitate long-term human presence on Mars. Summary of iMOST Findings: Several specific findings were identified during the iMOST study. While they are not explicit recommendations, we suggest that they should serve as guidelines for future decision making regarding planning of potential future MSR missions. The samples to be collected by the Mars 2020 (M-2020) rover will be of sufficient size and quality to address and solve a wide variety of scientific questions. Samples, by definition, are a statistical representation of a larger entity. Our ability to interpret the source geologic units and processes by studying sample sub sets is highly dependent on the quality of the sample context. In the case of the M-2020 samples, the context is expected to be excellent, and at multiple scales. (A) Regional and planetary context will be established by the on-going work of the multi-agency fleet of Mars orbiters. (B) Local context will be established at field area- to outcrop- to hand sample- to hand lens scale using the instruments carried by M-2020. A significant fraction of the value of the MSR sample collection would come from its organization into sample suites, which are small groupings of samples designed to represent key aspects of geologic or geochemical variation. If the Mars 2020 rover acquires a scientifically well-chosen set of samples, with sufficient geological diversity, and if those samples were returned to Earth, then major progress can be expected on all seven of the objectives proposed in this study, regardless of the final choice of landing site. The specifics of which parts of Objective 1 could be achieved would be different at each of the final three candidate landing sites, but some combination of critically important progress could be made at any of them. An aspect of the search for evidence of life is that we do not know in advance how evidence for Martian life would be preserved in the geologic record. In order for the returned samples to be most useful for both understanding geologic processes (Objective 1) and the search for life (Objective 2), the sample collection should contain BOTH typical and unusual samples from the rock units explored. This consideration should be incorporated into sample selection and the design of the suites. The retrieval missions of a MSR campaign should (1) minimize stray magnetic fields to which the samples would be exposed and carry a magnetic witness plate to record exposure, (2) collect and return atmospheric gas sample(s), and (3) collect additional dust and/or regolith sample mass if possible.
|
|
3. |
- Hillier, Ladeana W, et al.
(author)
-
Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
-
In: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
-
Journal article (peer-reviewed)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
|
|
4. |
- Hudson, Lawrence N, et al.
(author)
-
The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
-
In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
|
|
5. |
- Kõljalg, Urmas, et al.
(author)
-
Towards a unified paradigm for sequence-based identification of fungi.
- 2013
-
In: Molecular ecology. - : Wiley. - 1365-294X .- 0962-1083. ; 22:21, s. 5271-7
-
Journal article (peer-reviewed)abstract
- The nuclear ribosomal internal transcribed spacer (ITS) region is the formal fungal barcode and in most cases the marker of choice for the exploration of fungal diversity in environmental samples. Two problems are particularly acute in the pursuit of satisfactory taxonomic assignment of newly generated ITS sequences: (i) the lack of an inclusive, reliable public reference data set and (ii) the lack of means to refer to fungal species, for which no Latin name is available in a standardized stable way. Here, we report on progress in these regards through further development of the UNITE database (http://unite.ut.ee) for molecular identification of fungi. All fungal species represented by at least two ITS sequences in the international nucleotide sequence databases are now given a unique, stable name of the accession number type (e.g. Hymenoscyphus pseudoalbidus|GU586904|SH133781.05FU), and their taxonomic and ecological annotations were corrected as far as possible through a distributed, third-party annotation effort. We introduce the term 'species hypothesis' (SH) for the taxa discovered in clustering on different similarity thresholds (97-99%). An automatically or manually designated sequence is chosen to represent each such SH. These reference sequences are released (http://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and in the QIIME pipeline. The system and the data will be updated automatically as the number of public fungal ITS sequences grows. We invite everybody in the position to improve the annotation or metadata associated with their particular fungal lineages of expertise to do so through the new Web-based sequence management system in UNITE.
|
|
6. |
- Ademuyiwa, Adesoji O., et al.
(author)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
7. |
- Allanach, Benjamin C., et al.
(author)
-
Simple and statistically sound strategies for analysing physical theories
- 2022
-
In: Reports on progress in physics (Print). - : Institute of Physics Publishing (IOPP). - 0034-4885 .- 1361-6633. ; 85:5
-
Research review (peer-reviewed)abstract
- Physical theories that depend on many parameters or are tested against data from many different experiments pose unique challenges to statistical inference. Many models in particle physics, astrophysics and cosmology fall into one or both of these categories. These issues are often sidestepped with statistically unsound ad hoc methods, involving intersection of parameter intervals estimated by multiple experiments, and random or grid sampling of model parameters. Whilst these methods are easy to apply, they exhibit pathologies even in low-dimensional parameter spaces, and quickly become problematic to use and interpret in higher dimensions. In this article we give clear guidance for going beyond these procedures, suggesting where possible simple methods for performing statistically sound inference, and recommendations of readily-available software tools and standards that can assist in doing so. Our aim is to provide any physicists lacking comprehensive statistical training with recommendations for reaching correct scientific conclusions, with only a modest increase in analysis burden. Our examples can be reproduced with the code publicly available at Zenodo.
|
|
8. |
- Athron, Peter, et al.
(author)
-
A global fit of the MSSM with GAMBIT
- 2017
-
In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:12
-
Journal article (peer-reviewed)abstract
- We study the seven-dimensional Minimal Super-symmetric Standard Model (MSSM7) with the new GAMBIT software framework, with all parameters defined at the weak scale. Our analysis significantly extends previous weak-scale, phenomenological MSSM fits, by adding more and newer experimental analyses, improving the accuracy and detail of theoretical predictions, including dominant uncertainties from the Standard Model, the Galactic dark matter halo and the quark content of the nucleon, and employing novel and highly-efficient statistical sampling methods to scan the parameter space. We find regions of the MSSM7 that exhibit co-annihilation of neutralinos with charginos, stops and sbottoms, as well as models that undergo resonant annihilation via both light and heavy Higgs funnels. We find high-likelihood models with light charginos, stops and sbottoms that have the potential to be within the future reach of the LHC. Large parts of our preferred parameter regions will also be accessible to the next generation of direct and indirect dark matter searches, making prospects for discovery in the near future rather good.
|
|
9. |
- Athron, Peter, et al.
(author)
-
GAMBIT : the global and modular beyond-the-standard-model inference tool
- 2017
-
In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:11
-
Journal article (peer-reviewed)abstract
- We describe the open-source global fitting package GAMBIT: the Global And Modular Beyond-the-Standard-Model Inference Tool. GAMBIT combines extensive calculations of observables and likelihoods in particle and astroparticle physics with a hierarchical model database, advanced tools for automatically building analyses of essentially any model, a flexible and powerful system for interfacing to external codes, a suite of different statistical methods and parameter scanning algorithms, and a host of other utilities designed to make scans faster, safer and more easily-extendible than in the past. Here we give a detailed description of the framework, its design and motivation, and the current models and other specific components presently implemented in GAMBIT. Accompanying papers deal with individual modules and present flrst GAMBIT results. GAMBIT can be downloaded from gambit.hepforge.org.
|
|
10. |
- Athron, Peter, et al.
(author)
-
GAMBIT : the global and modular beyond-the-standard-model inference tool
- 2018
-
In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 78:2
-
Journal article (peer-reviewed)abstract
- In Ref. (GAMBIT Collaboration: Athron et. al., Eur. Phys. J. C. arXiv: 1705.07908, 2017) we introduced the global-fitting framework GAMBIT. In this addendum, we describe a new minor version increment of this package. GAMBIT 1.1 includes full support for Mathematica backends, which we describe in some detail here. As an example, we backend SUSYHD (Vega and Villadoro, JHEP 07: 159, 2015), which calculates the mass of the Higgs boson in the MSSM from effective field theory. We also describe updated likelihoods in PrecisionBit and DarkBit, and updated decay data included in DecayBit.
|
|
11. |
- Athron, Peter, et al.
(author)
-
Global fits of GUT-scale SUSY models with GAMBIT
- 2017
-
In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:12
-
Journal article (peer-reviewed)abstract
- We present the most comprehensive global fits to date of three supersymmetric models motivated by grand unification: the Constrained Minimal Supersymmetric Standard Model (CMSSM), and its Non-Universal Higgs Mass generalisations NUHM1 and NUHM2. We include likelihoods from a number of direct and indirect dark matter searches, a large collection of electroweak precision and flavour observables, direct searches for supersymmetry at LEP and Runs I and II of the LHC, and constraints from Higgs observables. Our analysis improves on existing results not only in terms of the number of included observables, but also in the level of detail with which we treat them, our sampling techniques for scanning the parameter space, and our treatment of nuisance parameters. We show that stau co-annihilation is now ruled out in the CMSSM at more than 95% confidence. Stop co-annihilation turns out to be one of the most promising mechanisms for achieving an appropriate relic density of darkmatter in all threemodels, whilst avoiding all other constraints. We find high-likelihood regions of parameter space featuring light stops and charginos, making them potentially detectable in the near future at the LHC. We also show that tonne-scale direct detection will play a largely complementary role, probing large parts of the remaining viable parameter space, including essentially all models with multi-TeV neutralinos.
|
|
12. |
- Athron, Peter, et al.
(author)
-
Status of the scalar singlet dark matter model
- 2017
-
In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:8
-
Journal article (peer-reviewed)abstract
- One of the simplest viable models for dark matter is an additional neutral scalar, stabilised by a symmetry. Using the GAMBIT package and combining results from four independent samplers, we present Bayesian and frequentist global fits of this model. We vary the singlet mass and coupling along with 13 nuisance parameters, including nuclear uncertainties relevant for direct detection, the local dark matter density, and selected quark masses and couplings. We include the dark matter relic density measured by Planck, direct searches with LUX, PandaX, SuperCDMS and XENON100, limits on invisible Higgs decays from the Large Hadron Collider, searches for high-energy neutrinos from dark matter annihilation in the Sun with IceCube, and searches for gamma rays from annihilation in dwarf galaxies with the Fermi-LAT. Viable solutions remain at couplings of order unity, for singlet masses between the Higgs mass and about 300 GeV, and at masses above 1 TeV. Only in the latter case can the scalar singlet constitute all of dark matter. Frequentist analysis shows that the low-mass resonance region, where the singlet is about half the mass of the Higgs, can also account for all of dark matter, and remains viable. However, Bayesian considerations show this region to be rather fine-tuned.
|
|
13. |
- Azevedo, Flavio, et al.
(author)
-
Social and moral psychology of COVID-19 across 69 countries
- 2023
-
In: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
-
Journal article (peer-reviewed)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
|
|
14. |
- Balázs, Csaba, et al.
(author)
-
ColliderBit : a GAMBIT module for the calculation of high-energy collider observables and likelihoods
- 2017
-
In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 77:11
-
Journal article (peer-reviewed)abstract
- We describe ColliderBit, a new code for the calculation of high energy collider observables in theories of physics beyond the Standard Model (BSM). ColliderBit features a generic interface to BSM models, a unique parallelised Monte Carlo event generation scheme suitable for large-scale supercomputer applications, and a number of LHC analyses, covering a reasonable range of the BSM signatures currently sought by ATLAS and CMS. ColliderBit also calculates likelihoods for Higgs sector observables, and LEP searches for BSM particles. These features are provided by a combination of new code unique to ColliderBit, and interfaces to existing state-of-the-art public codes. ColliderBit is both an important part of the GAMBIT framework for BSM inference, and a standalone tool for efficiently applying collider constraints to theories of new physics.
|
|
15. |
- Benjamin, Daniel J., et al.
(author)
-
Redefine statistical significance
- 2018
-
In: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 2:1, s. 6-10
-
Journal article (other academic/artistic)
|
|
16. |
- Cheng, Helen, et al.
(author)
-
Biomedical, psychological, environmental and behavioural factors associated with adult obesity in a nationally representative sample
- 2020
-
In: Journal of Public Health. - : Springer. - 1741-3842 .- 1741-3850. ; 42:3, s. 570-578
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To identify personality, biomedical and behavioural factors associated with adult obesity in a large longitudinal sample.METHOD: In total, 5360 participants with data on personality, neurological functioning, maternal smoking during pregnancy, education and occupation, physical exercise, adult self-reported BMI and obesity were included in the study. Obesity at 55 years was the outcome variable.RESULTS: The rates of obesity increased from 9.5 to 22.8% from age 33 to 55 years. Logistic regression analyses (adjusted estimates) showed that childhood neurological functioning (OR = 1.32: 1.07-1.63, P < 0.01), maternal smoking during pregnancy (OR = 1.42: 1.22-1.65, P < 0.001), educational qualifications (OR = 0.54: 0.37-0.79, P < 0.01), trait conscientiousness (OR = 0.80:0.74-0.86, P < 0.001) and physical exercise (OR = 0.87: 0.82-0.92, P < 0.001) were significant predictors of obesity at age 55 years for both men and women. Trait extraversion for men (OR = 1.16: 1.07-1.26, P < 0.001) and trait emotional stability for women (OR = 0.90: 0.82-0.99, P < 0.05) were also significant predictors of the outcome variable.CONCLUSION: Biomedical, psychological, environmental and behavioural factors were all associated with adult obesity.
|
|
17. |
- Cheng, Helen, et al.
(author)
-
Childhood heart problems, adulthood emotional stability, and sex associated with self-report heart conditions in adulthood
- 2021
-
In: Journal of Health Psychology. - : Sage Publications. - 1359-1053 .- 1461-7277. ; 26:4, s. 489-499
-
Journal article (peer-reviewed)abstract
- The present study investigated biomedical, social, and psychological factors associated with self-reported heart conditions in adulthood in a British cohort. In total, 5697 (50.7% males) participants with data on parental socioeconomic status, childhood cognitive ability, childhood heart problems, educational qualifications, current occupational levels, adulthood personality traits, and the prevalence of self-reported heart conditions in adulthood were included in the study. The prevalence of self-reported heart conditions measured at age 54 years was the outcome variable. Hierarchical logistic regression analysis showed that childhood heart problems identified by physicians (OR = 3.47:1.74-6.92, p < 0.001) and trait emotional stability (OR = 0.83:0.75-0.93, p < 0.001) were the significant and independent predictors of self-reported heart conditions in adulthood. There were also significant sex effects on the prevalence of the outcome variable (OR = 0.53:0.42-0.63, p < 0.001). Both a biomedical and a psychological factor were significantly associated with self-reported heart conditions in adulthood.
|
|
18. |
- Clark, Andrew G., et al.
(author)
-
Evolution of genes and genomes on the Drosophila phylogeny
- 2007
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
-
Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
|
|
19. |
- Edwards, Robert A., et al.
(author)
-
Global phylogeography and ancient evolution of the widespread human gut virus crAssphage
- 2019
-
In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:10, s. 1727-1736
-
Journal article (peer-reviewed)abstract
- Microbiomes are vast communities of microorganisms and viruses that populate all natural ecosystems. Viruses have been considered to be the most variable component of microbiomes, as supported by virome surveys and examples of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared with that of other environments. Here, we investigate the origin, evolution and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboration, we obtained DNA sequences of crAssphage from more than one-third of the world's countries and showed that the phylogeography of crAssphage is locally clustered within countries, cities and individuals. We also found fully colinear crAssphage-like genomes in both Old-World and New-World primates, suggesting that the association of crAssphage with primates may be millions of years old. Finally, by exploiting a large cohort of more than 1,000 individuals, we tested whether crAssphage is associated with bacterial taxonomic groups of the gut microbiome, diverse human health parameters and a wide range of dietary factors. We identified strong correlations with different clades of bacteria that are related to Bacteroidetes and weak associations with several diet categories, but no significant association with health or disease. We conclude that crAssphage is a benign cosmopolitan virus that may have coevolved with the human lineage and is an integral part of the normal human gut virome.
|
|
20. |
- Kilpeläinen, Tuomas O, et al.
(author)
-
Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.
- 2011
-
In: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 8:11
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) =0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio =1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio =1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
|
|
21. |
- Kirby, Robert C., et al.
(author)
-
Discrete Optimization of Finite Element Matrix Evaluation
- 2012
-
In: Automated Solution of Differential Equations by the Finite Element Method. Anders Logg, Kent-Andre Mardal, Garth Wells (Eds.). - Heidelberg : Springer. - 9783642230981 ; , s. 163-169
-
Book chapter (other academic/artistic)abstract
- The tensor contraction structure for the computation of the element tensor AT obtained in Chapter 8,enables not only the construction of a compiler for variational forms,but an optimizing compiler.For typical variational forms,the reference tensor A0 has significant structure that allows the element tensor AT to be computed on an arbitrary cell T at a lower computational cost.
|
|
22. |
- Lindblad-Toh, Kerstin, et al.
(author)
-
Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
-
Journal article (peer-reviewed)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
|
|
23. |
- Manni, Giovanni Li, et al.
(author)
-
The OpenMolcas Web : A Community-Driven Approach to Advancing Computational Chemistry
- 2023
-
In: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 19:20, s. 6933-6991
-
Journal article (peer-reviewed)abstract
- The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.
|
|
24. |
- Naidoo-Bagwell, Aaron A., et al.
(author)
-
A diatom extension to the cGEnIE Earth system model - EcoGEnIE 1.1
- 2024
-
In: Geoscientific Model Development. - 1991-959X. ; 17:4, s. 1729-1748
-
Journal article (peer-reviewed)abstract
- We extend the ecological component (ECOGEM) of the carbon-centric Grid-Enabled Integrated Earth system model (cGEnIE) to include a diatom functional group. ECOGEM represents plankton community dynamics via a spectrum of ecophysiological traits originally based on size and plankton food web (phyto- and zooplankton; EcoGEnIE 1.0), which we developed here to account for a diatom functional group (EcoGEnIE 1.1). We tuned EcoGEnIE 1.1, exploring a range of ecophysiological parameter values specific to phytoplankton, including diatom growth and survival (18 parameters over 550 runs) to achieve best fits to observations of diatom biogeography and size class distribution as well as to global ocean nutrient and dissolved oxygen distributions. This, in conjunction with a previously developed representation of opal dissolution and an updated representation of the ocean iron cycle in the water column, resulted in an improved distribution of dissolved oxygen in the water column relative to the previous EcoGEnIE 1.0, with global export production (7.4GtCyr-1) now closer to previous estimates. Simulated diatom biogeography is characterised by larger size classes dominating at high latitudes, notably in the Southern Ocean, and smaller size classes dominating at lower latitudes. Overall, diatom biological productivity accounts for ∼20% of global carbon biomass in the model, with diatoms outcompeting other phytoplankton functional groups when dissolved silica is available due to their faster maximum photosynthetic rates and reduced palatability to grazers. Adding a diatom functional group provides the cGEnIE Earth system model with an extended capability to explore ecological dynamics and their influence on ocean biogeochemistry.
|
|
25. |
|
|
26. |
- Schweinsberg, Martin, et al.
(author)
-
Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
-
In: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
-
Journal article (peer-reviewed)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
|
|
27. |
- Scott, Louis, 1987, et al.
(author)
-
Genetically Encoded Whole Cell Biosensor for Drug Discovery of HIF-1 Interaction Inhibitors
- 2022
-
In: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 11:10, s. 3182-3189
-
Journal article (peer-reviewed)abstract
- The heterodimeric transcription factor, hypoxia inducible factor-1 (HIF-1), is an important anticancer target as it supports the adaptation and response of tumors to hypoxia. Here, we optimized the repressed transactivator yeast two-hybrid system to further develop it as part of a versatile yeast-based drug discovery platform and validated it using HIF-1. We demonstrate both fluorescence-based and auxotrophy-based selections that could detect HIF-1α/HIF-1β dimerization inhibition. The engineered genetic selection is tunable and able to differentiate between strong and weak interactions, shows a large dynamic range, and is stable over different growth phases. Furthermore, we engineered mechanisms to control for cellular activity and off-target drug effects. We thoroughly characterized all parts of the biosensor system and argue this tool will be generally applicable to a wide array of protein-protein interaction targets. We anticipate this biosensor will be useful as part of a drug discovery platform, particularly when screening DNA-encoded new modality drugs.
|
|
28. |
- Strickson, Sam, et al.
(author)
-
Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex
- 2023
-
In: European Respiratory Journal. - 0903-1936. ; 62:3
-
Journal article (peer-reviewed)abstract
- Background Epithelial damage, repair and remodelling are critical features of chronic airway diseases including chronic obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged airway epithelia causes inflammation via its receptor, serum stimulation-2 (ST2). Oxidation of IL-33 to a non-ST2-binding form (IL-33ox) is thought to limit its activity. We investigated whether IL-33ox has functional activities that are independent of ST2 in the airway epithelium. Methods In vitro epithelial damage assays and three-dimensional, air–liquid interface (ALI) cell culture models of healthy and COPD epithelia were used to elucidate the functional role of IL-33ox. Transcriptomic changes occurring in healthy ALI cultures treated with IL-33ox and COPD ALI cultures treated with an IL-33-neutralising antibody were assessed with bulk and single-cell RNA sequencing analysis. Results We demonstrate that IL-33ox forms a complex with receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR) expressed on airway epithelium. Activation of this alternative, ST2-independent pathway impaired epithelial wound closure and induced airway epithelial remodelling in vitro. IL-33ox increased the proportion of mucus-producing cells and reduced epithelial defence functions, mimicking pathogenic traits of COPD. Neutralisation of the IL-33ox pathway reversed these deleterious traits in COPD epithelia. Gene signatures defining the pathogenic effects of IL-33ox were enriched in airway epithelia from patients with severe COPD. Conclusions Our study reveals for the first time that IL-33, RAGE and EGFR act together in an ST2-independent pathway in the airway epithelium and govern abnormal epithelial remodelling and mucoobstructive features in COPD.
|
|
29. |
- Van Bavel, Jay J., et al.
(author)
-
National identity predicts public health support during a global pandemic
- 2022
-
In: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
-
Journal article (peer-reviewed)abstract
- Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
|
|
30. |
-
- 2019
-
Journal article (peer-reviewed)
|
|