Browsing by Subject "ORIGIN"

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  • Duggan, Ana T.; Perdomo , Maria F.; Piombino-Mascali, Dario; Marciniak, Stephanie; Poinar, Debi; Emery, Matthew V.; Buchmann, Jan P.; Duchene, Sebastian; Jankauskas, Rimantas; Humphreys, Margaret; Golding, G. Brian; Southon, John; Devault, Alison; Rouillard, Jean-Marie; Sahl, Jason W.; Dutour, Olivier; Hedman, Klaus; Sajantila, Antti; Smith, Geoffrey L.; Holmes, Edward C.; Poinar, Hendrik N. (2016)
    Smallpox holds a unique position in the history of medicine. It was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. Although there have been claims of smallpox in Egypt, India, and China dating back millennia [1-4], the timescale of emergence of the causative agent, variola virus (VARV), and how it evolved in the context of increasingly widespread immunization, have proven controversial [4-9]. In particular, some molecular-clock-based studies have suggested that key events in VARV evolution only occurred during the last two centuries [4-6] and hence in apparent conflict with anecdotal historical reports, although it is difficult to distinguish smallpox from other pustular rashes by description alone. To address these issues, we captured, sequenced, and reconstructed a draft genome of an ancient strain of VARV, sampled from a Lithuanian child mummy dating between 1643 and 1665 and close to the time of several documented European epidemics [1, 2, 10]. When compared to vaccinia virus, this archival strain contained the same pattern of gene degradation as 20th century VARVs, indicating that such loss of gene function had occurred before ca. 1650. Strikingly, the mummy sequence fell basal to all currently sequenced strains of VARV on phylogenetic trees. Molecular-clock analyses revealed a strong clock-like structure and that the timescale of smallpox evolution is more recent than often supposed, with the diversification of major viral lineages only occurring within the 18th and 19th centuries, concomitant with the development of modern vaccination.
  • Ala-Lahti, Matti; Kilpua, Emilia K. J.; Soucek, Jan; Pulkkinen, Tuija; Dimmock, Andrew P. (2019)
    We report on a statistical analysis of the occurrence and properties of Alfven ion cyclotron (AIC) waves in sheath regions driven by interplanetary coronal mass ejections (ICMEs). We have developed an automated algorithm to identify AIC wave events from magnetic field data and apply it to investigate 91 ICME sheath regions recorded by the Wind spacecraft. Our analysis focuses on waves generated by the ion cyclotron instability. AIC waves are observed to be frequent structures in ICME-driven sheaths, and their occurrence is the highest in the vicinity of the shock. Together with previous studies, our results imply that the shock compression has a crucial role in generating wave activity in ICME sheaths. AIC waves tend to have their frequency below the ion cyclotron frequency, and, in general, occur in plasma that is stable with respect to the ion cyclotron instability and has lower ion beta(parallel to) than mirror modes. The results suggest that the ion beta anisotropy beta(perpendicular to)/beta(parallel to) > 1 appearing in ICME sheaths is regulated by both ion cyclotron and mirror instabilities.
  • Kerr, Shona M.; Klaric, Lucija; Halachev, Mihail; Hayward, Caroline; Boutin, Thibaud S.; Meynert, Alison M.; Semple, Colin A.; Tuiskula, Annukka M.; Swan, Heikki; Santoyo-Lopez, Javier; Vitart, Veronique; Haley, Chris; Dean, John; Miedzybrodzka, Zosia; Aitman, Timothy J.; Wilson, James F. (2019)
    The Viking Health Study Shetland is a population-based research cohort of 2,122 volunteer participants with ancestry from the Shetland Isles in northern Scotland. The high kinship and detailed phenotype data support a range of approaches for associating rare genetic variants, enriched in this isolate population, with quantitative traits and diseases. As an exemplar, the c.1750G > A; p.Gly584Ser variant within the coding sequence of the KCNH2 gene implicated in Long QT Syndrome (LQTS), which occurred once in 500 whole genome sequences from this population, was investigated. Targeted sequencing of the KCNH2 gene in family members of the initial participant confirmed the presence of the sequence variant and identified two further members of the same family pedigree who shared the variant. Investigation of these three related participants for whom single nucleotide polymorphism (SNP) array genotypes were available allowed a unique shared haplotype of 1.22 Mb to be defined around this locus. Searching across the full cohort for this haplotype uncovered two additional apparently unrelated individuals with no known genealogical connection to the original kindred. All five participants with the defined haplotype were shown to share the rare variant by targeted Sanger sequencing. If this result were verified in a healthcare setting, it would be considered clinically actionable, and has been actioned in relatives ascertained independently through clinical presentation. The General Practitioners of four study participants with the rare variant were alerted to the research findings by letters outlining the phenotype (prolonged electrocardiographic QTc interval). A lack of detectable haplotype sharing between c.1750G > A; p.Gly584Ser chromosomes from previously reported individuals from Finland and those in this study from Shetland suggests that this mutation has arisen more than once in human history. This study showcases the potential value of isolate population-based research resources for genomic medicine. It also illustrates some challenges around communication of actionable findings in research participants in this context.
  • Majander, Kerttu; Pfrengle, Saskia; Kocher, Arthur; Neukamm, Judith; du Plessis, Louis; Pla-Diaz, Marta; Arora, Natasha; Akgul, Gulfirde; Salo, Kati; Schats, Rachel; Inskip, Sarah; Oinonen, Markku; Valk, Heiki; Malve, Martin; Kriiska, Aivar; Onkamo, Paivi; Gonzalez-Candelas, Fernando; Kuehnert, Denise; Krause, Johannes; Schuenemann, Verena J. (2020)
    Syphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15th century. Together with non-venereal treponemal diseases, like bejel and yaws, which are found today in subtropical and tropical regions, it currently poses a substantial health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis' potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a high diversity of Treponema pallidumin early modern Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and yaws-causing T. pallidum subspecies were already present in Northern Europe in the early modern period. We also discovered a previously unknown T. pallidum lineage recovered as a sister group to yaws- and bejel-causing lineages. These findings imply a more complex pattern of geographical distribution and etiology of early treponemal epidemics than previously understood.
  • Arju, Georg; Taivosalo, Anastassia; Pismennoi, Dmitri; Lints, Taivo; Vilu, Raivo; Daneberga, Zanda; Vorslova, Svetlana; Renkonen, Risto; Joenvaara, Sakari (2020)
    Until now, cheese peptidomics approaches have been criticised for their lower throughput. Namely, analytical gradients that are most commonly used for mass spectrometric detection are usually over 60 or even 120 min. We developed a cheese peptide mapping method using nano ultra-high-performance chromatography data-independent acquisition high-resolution mass spectrometry (nanoUHPLC-DIA-HRMS) with a chromatographic gradient of 40 min. The 40 min gradient did not show any sign of compromise in milk protein coverage compared to 60 and 120 min methods, providing the next step towards achieving higher-throughput analysis. Top 150 most abundant peptides passing selection criteria across all samples were cross-referenced with work from other publications and a good correlation between the results was found. To achieve even faster sample turnaround enhanced DIA methods should be considered for future peptidomics applications.
  • Smith, Drew H.; Grewal, Jaskaran; Mehboob, Saba; Mohan, Shiva; Pombo, Luisa F.; Rodriguez, Pura; Gonzalez, Juan Carlos; Zevallos, Juan; Barengo, Noel C. (2022)
    Background Studies in the United States have shown a genetic predisposition to hypertension in individuals of African descent. However, studies on the associations between ethnic groups and hypertension in Latin America are lacking and the limited results have been inconsistent. The objective of this study is to determine whether Afro-Colombian ethnicity increases the risk of hypertension. Methods This study is a secondary data analysis of a cross sectional study from five provinces in Northern Colombia. Randomly selected individuals (N = 2613; age-range 18-74 years) enrolled in a health care insurance company underwent physical examinations and completed questionnaires regarding ethnicity, lifestyle, and other risk factors. Hypertension in these patients was determined. Unadjusted and adjusted logistic regression analysis were calculated to determine the association between ethnicity and hypertension. Results No association between Afro-Colombian ethnicity and hypertension was found (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.66-1.09). As expected, people with a body mass index (BMI) of 30 or higher were at a greater risk of having hypertension (OR, 3.12; 95% CI, 2.35-4.16) compared with those with a normal BMI. Conclusions Findings from this study suggest no independent association between Afro-Colombian ethnicity and hypertension. Further research should focus on genotyping or socioeconomic factors such as income level.
  • Lutfullahoglu-Bal, Guleycan; Keskin, Abdurrahman; Seferoglu, Ayse Bengisu; Dunn, Cory D. (2017)
    Background: During the generation and evolution of the eukaryotic cell, a proteobacterial endosymbiont was re-fashioned into the mitochondrion, an organelle that appears to have been present in the ancestor of all present-day eukaryotes. Mitochondria harbor proteomes derived from coding information located both inside and outside the organelle, and the rate-limiting step toward the formation of eukaryotic cells may have been development of an import apparatus allowing protein entry to mitochondria. Currently, a widely conserved translocon allows proteins to pass from the cytosol into mitochondria, but how proteins encoded outside of mitochondria were first directed to these organelles at the dawn of eukaryogenesis is not clear. Because several proteins targeted by a carboxyl-terminal tail anchor (TA) appear to have the ability to insert spontaneously into the mitochondrial outer membrane (OM), it is possible that self-inserting, tail-anchored polypeptides obtained from bacteria might have formed the first gate allowing proteins to access mitochondria from the cytosol. Results: Here, we tested whether bacterial TAs are capable of targeting to mitochondria. In a survey of proteins encoded by the proteobacterium Escherichia coli, predicted TA sequences were directed to specific subcellular locations within the yeast Saccharomyces cerevisiae. Importantly, TAs obtained from DUF883 family members ElaB and YqjD were abundantly localized to and inserted at the mitochondrial OM. Conclusions: Our results support the notion that eukaryotic cells are able to utilize membrane-targeting signals present in bacterial proteins obtained by lateral gene transfer, and our findings make plausible a model in which mitochondrial protein translocation was first driven by tail-anchored proteins.
  • Moreau, Juulia-Gabrielle; Joeleht, Argo; Aruvali, Jaan; Heikkila, Mikko J.; Stojic, Aleksandra N.; Thomberg, Thomas; Plado, Juri; Hietala, Satu (2022)
    Stoichiometric troilite (FeS) is a common phase in differentiated and undifferentiated meteorites. It is the endmember of the iron sulfide system. Troilite is important for investigating shock metamorphism in meteorites and studying spectral properties and space weathering of planetary bodies. Thus, obtaining coarse-grained meteoritic troilite in quantities is beneficial for these fields. The previous synthesis of troilite was achieved by pyrite or pyrrhotite heating treatments or chemical syntheses. However, most of these works lacked a visual characterization of the step by step process and the final product, the production of large quantities, and they were not readily advertised to planetary scientists or the meteoritical research community. Here, we illustrate a two-step heat treatment of pyrite to synthesize troilite. Pyrite powder was decomposed to pyrrhotite at 1023-1073 K for 4-6 h in Ar; the run product was then retrieved and reheated for 1 h at 1498-1598 K in N-2 (gas). The minerals were analyzed with a scanning electron microscope, X-ray diffraction (XRD) at room temperature, and in situ high-temperature XRD. The primary observation of synthesis from pyrrhotite to troilite is the shift of a major diffraction peak from similar to 43.2 degrees 2 theta to similar to 43.8 degrees 2 theta. Troilite spectra matched an XRD analysis of natural meteoritic troilite. Slight contamination of Fe was observed during cooling to troilite, and alumina crucibles locally reacted with troilite. The habitus and size of troilite crystals allowed us to store it as large grains rather than powder; 27 g of pyrite yielded 17 g of stochiometric troilite.
  • Güzel, Murat Erdem; Kilian, Norbert; Sennikov, Alexander N.; Coşkunçelebi, Kamil; Makbul, Serdar; Gültepe, Mutlu (2022)
    A new genus, Caucasoseris, is established to accommodate Prenanthes abietina, a species of hitherto uncertain systematic position distributed in the western Caucasus and northeasternmost Turkey in montane conifer and mixed forests. Agreement has existed that the species belongs somewhere in the Crepidinae or Lactucinae but its morphological features do not match any genus and previous molecular phylogenetic analyses could not establish its sister group. This study provides additional micro- and macromorphological, palynological and anatomical data, and used a molecular phylogenetic sampling designed to ascertain its relationship. A sister group relationship with the Chondrillinae is inferred from the phylogenetic tree based on nrITS. In the plastid DNA tree, where the Chondrillinae are resolved as a clade nested inside the Crepidinae, the species is resolved further remote from the Chondrillinae clade and in a rather early diverging position of the Crepidinae. In agreement also with the anatomical and microand macromorphological findings, it is considered an orphan lineage with affinities to the Chondrillinae, best treated as a genus of its own. A key to the genera of the Chondrillinae including Caucasoseris is provided.
  • Riihimaki, Matias; Hemminki, Akseli; Sundquist, Kristina; Hemminki, Kari (2014)
  • Stanczuk, Lukas; Martinez-Corral, Ines; Ulvmar, Maria H.; Zhang, Yang; Lavina, Barbbara; Fruttiger, Marcus; Adams, Ralf H.; Saur, Dieter; Betsholtz, Christer; Ortega, Sagrario; Alitalo, Kari; Graupera, Mariona; Makinen, Taija (2015)
  • Good, S. W.; Kilpua, E. K. J.; Ala-Lahti, M.; Osmane, A.; Bale, S. D.; Zhao, L. -L. (2020)
    Magnetic clouds are large-scale transient structures in the solar wind with low plasma-beta, low-amplitude magnetic field fluctuations, and twisted field lines with both ends often connected to the Sun. Their inertial-range turbulent properties have not been examined in detail. In this Letter, we analyze the normalized cross helicity, sigma(c), and residual energy, sigma(r), of plasma fluctuations in the 2018 November magnetic cloud observed at 0.25.au by the Parker Solar Probe. A low value of |sigma(c)| was present in the cloud core, indicating that wave power parallel and antiparallel to the mean field was approximately balanced, while the cloud's outer layers displayed larger amplitude Alfvenic fluctuations with high |sigma(c)| values and sigma(r) similar to 0. These properties are discussed in terms of the cloud's solar connectivity and local interaction with the solar wind. We suggest that low |sigma(c)| is likely a common feature of magnetic clouds given their typically closed field structure. Antisunward fluctuations propagating immediately upstream of the cloud had strongly negative sigma(r) values.
  • Liu, Yun; Liao, Shihong; Liu, Xiangkun; Zhang, Jiajun; An, Rui; Fan, Zuhui (2022)
    The interacting dark energy (IDE) model, which considers the interaction between dark energy and dark matter, provides a natural mechanism to alleviate the coincidence problem and can also relieve the observational tensions under the ?CDM model. Previous studies have put constraints on IDE models by observations of cosmic expansion history, cosmic microwave background, and large-scale structures. However, these data are not yet enough to distinguish IDE models from ?CDM effectively. Because the non-linear structure formation contains rich cosmological information, it can provide additional means to differentiate alternative models. In this paper, based on a set of N-body simulations for IDE models, we investigate the formation histories and properties of dark matter haloes and compare with their ?CDM counterparts. For the model with dark matter decaying into dark energy and the parameters being the best-fitting values from previous constraints, the structure formation is markedly slowed down, and the haloes have systematically lower mass, looser internal structure, higher spin, and anisotropy. This is inconsistent with the observed structure formation, and thus this model can be safely ruled out from the perspective of non-linear structure formation. Moreover, we find that the ratio of halo concentrations between IDE and ?CDM counterparts depends sensitively on the interaction parameter and is independent of halo mass. This can act as a powerful probe to constrain IDE models. Our results concretely demonstrate that the interaction of the two dark components can affect the halo formation considerably, and therefore the constraints from non-linear structures are indispensable.
  • Kieseppä, Valentina; Holm, Minna; Jokela, Markus; Suvisaari, Jaana; Gissler, Mika; Lehti, Venla (2021)
    Background: The aims of this study were to (1) compare differences in psychiatric comorbidity of depression and anxiety disorders between immigrants and native Finns and to (2) compare differences in the intensity of psychiatric care received by different immigrant groups and Finnish-born controls with depression and/or anxiety disorders. Methods: The study uses registered-based data, which includes all immigrants living in Finland at the end of 2010 and matched Finnish-born controls. For this study, we selected individuals who had received a diagnosis of depression and/or an anxiety disorder during the follow-up (2011?2015) (immigrants n = 6542, Finnish-born controls n = 9281). We compared differences in comorbidity between the immigrants and the Finnish-born controls using chi-squared tests. Multinomial logistic regression was used to predict psychiatric treatment intensity by immigrant status, region of origin, and other background factors. Results: In both diagnosis groups, Finnish-born participants exhibited greater comorbidity of other psychiatric disorders. Immigrants more often received lower intensity treatment and less often higher intensity treatment. These differences were most striking among those from Eastern Europe, the Middle East, and Africa. Limitations: We did not have the information on the perceived need for the services, which limits us from drawing further conclusions about the mechanisms behind the observed patterns. Conclusions: Immigrants in Finland receive less intensive treatment for depression and anxiety disorders compared to the Finnish-born population. Since lower symptom levels can unlikely alone explain these differences, they could reflect a need for improvement in the psychiatric services for immigrants.
  • Cascone, Annunziata; Bruelle, Celine; Lindholm, Dan; Bernardi, Paolo; Eriksson-Rosenberg, Ove (2012)
  • Nikbakhsh, S.; Tanskanen, E. I.; Käpylä, M. J.; Hackman, T. (2019)
    Aims. Our aim is to examine the solar cycle variability of magnetically simple and complex active region. Methods. We studied simple (alpha and beta) and complex (beta gamma and beta gamma delta) active regions based on the Mount Wilson magnetic classification by applying our newly developed daily approach. We analyzed the daily number of the simple active regions (SARs) and compared that to the abundance of the complex active regions (CARs) over the entire solar cycle 23 and cycle 24 until December 2018. Results. We show that CARs evolve differently over the solar cycle from SARs. The time evolution of SARs and CARs on different hemispheres also shows differences, even though on average their latitudinal distributions are shown to be similar. The time evolution of SARs closely follows that of the sunspot number, and their maximum abundance was observed to occur during the early maximum phase, while that of the CARs was seen roughly two years later. We furthermore found that the peak of CARs was reached before the latitudinal width of the activity band starts to decease. Conclusion. Our results suggest that the active region formation process is a competition between the large-scale dynamo (LSD) and the small-scale dynamo (SSD) near the surface, the former varying cyclically and the latter being independent of the solar cycle. During solar maximum, LSD is dominant, giving a preference to SARs, while during the declining phase the relative role of SSD increases. Therefore, a preference for CARs is seen due to the influence of the SSD on the emerging flux.
  • Mac Lennan, Eric Michael; Toliou, Athanasia; Granvik, Mikael (2021)
    The near-Earth objects (NEOs) (3200) Phaethon and (155140) 2005 UD are thought to share a common origin, with the former exhibiting dust activity at perihelion that is thought to directly supply the Geminid meteor stream. Both of these objects currently have very small perihelion distances (0.140 au and 0.163 au for Phaethon and 2005 UD, respectively), which results in them having perihelion temperatures around 1000 K. A comparison between NEO population models to discovery statistics suggests that low-perihelion objects are destroyed over time by a, possibly temperature-dependent, mechanism that is efficient at heliocentric distances less than 0.3 au. By implication, the current activity from Phaethon is linked to the destruction mechanism of NEOs close to the Sun. We model the past thermal characteristics of Phaethon and 2005 UD using a combination of a thermophysical model (TPM) and orbital integrations of each object. Temperature characteristics such as maximum daily temperature, maximum thermal gradient, and temperature at different depths are extracted from the model, which is run for a predefined set of semi-major axis and eccentricity values. Next, dynamical integrations of orbital clones of Phaethon and 2005 UD are used to estimate the past orbital elements of each object. These dynamical results are then combined with the temperature characteristics to model the past evolution of thermal characteristics such as maximum (and minimum) surface temperature and thermal gradient. The orbital histories of Phaethon and 2005 UD are characterized by cyclic changes in.., resulting in perihelia values periodically shifting between present-day values and 0.3 au. Currently, Phaethon is experiencing relatively large degrees of heating when compared to the recent 20, 000 yr. We find that the subsurface temperatures are too large over this timescale for water ice to be stable, unless actively supplied somehow. The near-surface thermal gradients strongly suggest that thermal fracturing may be very effective at breaking down and ejecting dust particles. Observations by the DESTINY+ flyby mission will provide important constraints on the mechanics of dust-loss from Phaethon and, potentially, reveal signs of activity from 2005 UD. In addition to simulating the recent dynamical evolution of these objects, we use orbital integrations that start from the Main Belt to assess their early dynamical evolution (origin and delivery mechanism). We find that dwarf planet (2) Pallas is unlikely to be the parent body for Phaethon and 2005 UD, and it is more likely that the source is in the inner part of the asteroid belt in the families of, e.g., (329) Svea or (142) Polana.
  • Pohle, Alexander; Kröger, Björn; Warnock, Rachel C. M.; King, Andy H.; Evans, David H.; Aubrechtová, Martina; Cichowolski, Marcela; Fang, Xiang; Klug, Christian (2022)
    Background: Despite the excellent fossil record of cephalopods, their early evolution is poorly understood. Different, partly incompatible phylogenetic hypotheses have been proposed in the past, which reflected individual author's opinions on the importance of certain characters but were not based on thorough cladistic analyses. At the same time, methods of phylogenetic inference have undergone substantial improvements. For fossil datasets, which typically only include morphological data, Bayesian inference and in particular the introduction of the fossilized birth-death model have opened new possibilities. Nevertheless, many tree topologies recovered from these new methods reflect large uncertainties, which have led to discussions on how to best summarize the information contained in the posterior set of trees. Results: We present a large, newly compiled morphological character matrix of Cambrian and Ordovician cephalopods to conduct a comprehensive phylogenetic analysis and resolve existing controversies. Our results recover three major monophyletic groups, which correspond to the previously recognized Endoceratoidea, Multiceratoidea, and Orthoceratoidea, though comprising slightly different taxa. In addition, many Cambrian and Early Ordovician representatives of the Ellesmerocerida and Plectronocerida were recovered near the root. The Ellesmerocerida is para- and polyphyletic, with some of its members recovered among the Multiceratoidea and early Endoceratoidea. These relationships are robust against modifications of the dataset. While our trees initially seem to reflect large uncertainties, these are mainly a consequence of the way clade support is measured. We show that clade posterior probabilities and tree similarity metrics often underestimate congruence between trees, especially if wildcard taxa are involved. Conclusions: Our results provide important insights into the earliest evolution of cephalopods and clarify evolutionary pathways. We provide a classification scheme that is based on a robust phylogenetic analysis. Moreover, we provide some general insights on the application of Bayesian phylogenetic inference on morphological datasets. We support earlier findings that quartet similarity metrics should be preferred over the Robinson-Foulds distance when higher-level phylogenetic relationships are of interest and propose that using a posteriori pruned maximum clade credibility trees help in assessing support for phylogenetic relationships among a set of relevant taxa, because they provide clade support values that better reflect the phylogenetic signal.
  • Joensuu, Heikki; Wardelmann, Eva; Sihto, Harri; Eriksson, Mikael; Hall, Kirsten Sundby; Reichardt, Annette; Hartmann, Joerg T.; Pink, Daniel; Cameron, Silke; Hohenberger, Peter; Al-Batran, Salah-Eddin; Schlemmer, Marcus; Bauer, Sebastian; Nilsson, Bengt; Kallio, Raija; Junnila, Jouni; Vehtari, Aki; Reichardt, Peter (2017)
    IMPORTANCE Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations. OBJECTIVE To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib. DESIGN, SETTING, AND PARTICIPANTS This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial. Between February 4, 2004, and September 29, 2008, 400 patients who had undergone surgery for GISTs with a high risk of recurrence were randomized to receive adjuvant imatinib for 1 or 3 years. Of the 397 patients who provided consent, 341 (85.9%) had centrally confirmed, localized GISTs with mutation analysis for KIT and PDGFRA performed centrally using conventional sequencing. During a median follow-up of 88 months (completed December 31, 2013), 142 patients had GIST recurrence. Data of the evaluable population were analyzed February 4, 2004, through December 31, 2013. MAIN OUTCOMES AND MEASURES The main outcome was RFS. Mutations were grouped by the gene and exon. KIT exon 11 mutations were further grouped as deletion or insertion-deletion mutations, substitution mutations, insertion or duplication mutations, and mutations that involved codons 557 and/or 558. RESULTS Of the 341 patients (175 men and 166women; median age at study entry, 62 years) in the 1-year group and 60 years in the 3-year group), 274 (80.4%) had GISTs with a KIT mutation, 43 (12.6%) had GISTs that harbored a PDGFRA mutation, and 24 (7.0%) had GISTs thatwere wild type for these genes. PDGFRA mutations and KIT exon 11 insertion or duplication mutations were associated with favorable RFS, whereas KIT exon 9 mutations were associated with unfavorable outcome. Patients with KIT exon 11 deletion or insertion-deletion mutation had better RFS when allocated to the 3-year group compared with the 1-year group (5-year RFS, 71.0% vs 41.3%; P CONCLUSIONS AND RELEVANCE Patients with KIT exon 11 deletion mutations benefit most from the longer duration of adjuvant imatinib. The duration of adjuvant imatinib modifies the risk of GIST recurrence associated with some KIT mutations, including deletions that affect exon 11 codons 557 and/or 558.