| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
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| 3. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 4. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 5. |
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| 6. |
- Andres, E., et al.
(författare)
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Selected recent results from AMANDA
- 2001
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Ingår i: ICHEP 2000. Proceedings of the 30th International Conference on High Energy Physics. - : World Scientific. ; , s. 965-968
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Konferensbidrag (refereegranskat)abstract
- We present a selection of results based on data taken in 1997 with the 302-PMT Antarctic Muon and Neutrino Detector Array-B10 ("AMANDA-B10") array. Atmospheric neutrinos created in the northern hemisphere are observed indirectly through their charged current interactions which produce relativistic, Cherenkov-light-emitting upgoing muons in the South Pole ice cap. The reconstructed angular distribution of these events is in good agreement with expectation and demonstrates the viability of this ice-based device as a neutrino telescope. Studies of nearly vertical upgoing muons limit the available parameter space for WIMP dark matter under the assumption that WIMPS are trapped in the earth's gravitational potential well and annihilate with one another near the earth's center.
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| 7. |
- Karle, A., et al.
(författare)
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Observation of high energy atmospheric neutrinos with AMANDA
- 2000
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Ingår i: AIP Conference Proceedings. - : American Institute of Physics (AIP). ; , s. 823-827
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Konferensbidrag (refereegranskat)abstract
- In 1997 the Antarctic Muon and Neutrino Detector Array (AMANDA) started operating with 10 strings. In an analysis of data taken during the first year of operation 188 atmospheric neutrino candidates were found. Their zenith angle distribution agrees with expectations based on Monte Carlo simulations. A preliminary upper limit is given on a diffuse flux of high energy neutrinos of astrophysical origin.
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| 8. |
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| 9. |
- Thomas, B., et al.
(författare)
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Global Cardiovascular and Renal Outcomes of Reduced GFR
- 2017
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 28:7, s. 2167-2179
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Tidskriftsartikel (refereegranskat)abstract
- The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.
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| 10. |
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| 11. |
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| 12. |
- Halzen, F., et al.
(författare)
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From the first neutrino telescope, the antarctic muon and neutrino detector array AMANDA, to the IceCube observatory
- 1999
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Ingår i: Proceedings of the 26th International Cosmic Ray Conference, August 17-25, 1999, Salt Lake City : Invited, Rapporteur, and Highlight Papers. - : American Institute of Physics (AIP). ; , s. 428-431
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Konferensbidrag (refereegranskat)
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| 13. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Barwick, S. W., et al.
(författare)
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Initial results from the AMANDA high-energy neutrino detector
- 1998
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Ingår i: High-energy physics. Proceedings, 29th International Conference, ICHEP'98, Vancouver, Canada, July 23-29, 1998. Vol. 1, 2. ; , s. 1447-1452
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Konferensbidrag (refereegranskat)
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| 22. |
- Gilbert, M. R., et al.
(författare)
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Perspectives on multiscale modelling and experiments to accelerate materials development for fusion
- 2021
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 554
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Forskningsöversikt (refereegranskat)abstract
- Prediction of material performance in fusion reactor environments relies on computational modelling, and will continue to do so until the first generation of fusion power plants come on line and allow long-term behaviour to be observed. In the meantime, the modelling is supported by experiments that attempt to replicate some aspects of the eventual operational conditions. In 2019, a group of leading experts met under the umbrella of the IEA to discuss the current position and ongoing challenges in modelling of fusion materials and how advanced experimental characterisation is aiding model improvement. This review draws from the discussions held during that workshop. Topics covering modelling of irradiation-induced defect production and fundamental properties, gas behaviour, clustering and segregation, defect evolution and interactions are discussed, as well as new and novel multiscale simulation approaches, and the latest effort s to link modelling to experiments through advanced observation and characterisation techniques.
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| 23. |
- Kupers, LK, et al.
(författare)
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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
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Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
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| 24. |
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| 25. |
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| 26. |
- Winkler, M., et al.
(författare)
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The rich sides of mountain summits - a pan-European view on aspect preferences of alpine plants
- 2016
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270. ; 43:11, s. 2261-2273
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Tidskriftsartikel (refereegranskat)abstract
- Aim In the alpine life zone, plant diversity is strongly determined by local topography and microclimate. We assessed the extent to which aspect and its relatedness to temperature affect plant species diversity, and the colonization and disappearance of species on alpine summits on a pan-European scale. Methods Vascular plant species and their percentage cover were recorded in permanent plots in each cardinal direction on 123 summits in 32 regions across Europe. For a subset from 17 regions, resurvey data and 6-year soil temperature series were available. Differences in temperature sum and Shannon index as well as species richness, colonization and disappearance of species among cardinal directions were analysed using linear mixed-effects and generalised mixed-effects models, respectively. Results Temperature sums were higher in east-and south-facing aspects than in the north-facing ones, while the west-facing ones were intermediate; differences were smallest in northern Europe. The patterns of temperature sums among aspects were consistent among years. In temperate regions, thermal differences were reflected by plant diversity, whereas this relationship was weaker or absent on Mediterranean and boreal mountains. Colonization of species was positively related to temperature on Mediterranean and temperate mountains, whereas disappearance of species was not related to temperature. Main conclusions Thermal differences caused by solar radiation determine plant species diversity on temperate mountains. Advantages for plants on eastern slopes may result from the combined effects of a longer diurnal period of radiation due to convection cloud effects in the afternoon and the sheltered position against the prevailing westerly winds. In northern Europe, long summer days and low sun angles can even out differences among aspects. On Mediterranean summits, summer drought may limit species numbers on the warmer slopes. Warmer aspects support a higher number of colonization events. Hence, aspect can be a principal determinant of the pace of climate-induced migration processes.
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| 27. |
- Akimov, D., et al.
(författare)
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Physics with WASA and PROMICE
- 1994
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Ingår i: Physics with GeV-particle beams, Juelich 1994. ; , s. 519-530
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Konferensbidrag (refereegranskat)
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| 28. |
- Andres, E, et al.
(författare)
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Observation of high-energy neutrinos using Cerenkov detectors embedded deep in Antarctic ice
- 2001
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Ingår i: NATURE. - : MACMILLAN PUBLISHERS LTD. - 0028-0836. ; 410:6827, s. 441-443
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Tidskriftsartikel (refereegranskat)abstract
- Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical info
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| 29. |
- Bergstrom, K, et al.
(författare)
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Core 1- and 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice.
- 2017
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Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 10, s. 91-103
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Tidskriftsartikel (refereegranskat)abstract
- Core 1- and 3-derived mucin-type O-glycans are primary components of the mucus layer in the colon. Reduced mucus thickness and impaired O-glycosylation are observed in human ulcerative colitis. However, how both types of O-glycans maintain mucus barrier function in the colon is unclear. We found that C1galt1 expression, which synthesizes core 1 O-glycans, was detected throughout the colon, whereas C3GnT, which controls core 3 O-glycan formation, was most highly expressed in the proximal colon. Consistent with this, mice lacking intestinal core 1-derived O-glycans (IEC C1galt1(-/-)) developed spontaneous colitis primarily in the distal colon, whereas mice lacking both intestinal core 1- and 3-derived O-glycans (DKO) developed spontaneous colitis in both the distal and proximal colon. DKO mice showed an early onset and more severe colitis than IEC C1galt1(-/-) mice. Antibiotic treatment restored the mucus layer and attenuated colitis in DKO mice. Mucins from DKO mice were more susceptible to proteolysis than wild-type mucins. This study indicates that core 1- and 3-derived O-glycans collectively contribute to the mucus barrier by protecting it from bacterial protease degradation and suggests new therapeutic targets to promote mucus barrier function in colitis patients.Mucosal Immunology advance online publication, 4 May 2016; doi:10.1038/mi.2016.45.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Heggebo, L. C., et al.
(författare)
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Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden
- 2023
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
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| 34. |
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| 35. |
- Miller, T. C., et al.
(författare)
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Particle astrophysics in antarctica
- 1996
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Ingår i: International School of Cosmic Ray Astrophysics: 10th Course: Toward the Millennium in Astrophysics: Problems and Prospects 16-26 Jun 1996. Erice, Italy. ; , s. 157-166
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Konferensbidrag (refereegranskat)
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| 36. |
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| 37. |
- Raghavan, Maanasa, et al.
(författare)
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Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
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Tidskriftsartikel (refereegranskat)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 38. |
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| 39. |
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| 40. |
- Andres, E, et al.
(författare)
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Results from the AMANDA high energy neutrino detector
- 2001
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Ingår i: NUCLEAR PHYSICS B-PROCEEDINGS SUPPLEMENTS. - : ELSEVIER SCIENCE BV. - 0920-5632. ; 91, s. 423-430
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Tidskriftsartikel (refereegranskat)abstract
- This paper briefly summarizes the search for astronomical sources of high-energy neutrinos using the AMANDA-B10 detector. The complete data set from 1997 was analyzed. Far E-mu > 10 TeV, the detector exceeds 10,000 m(2) in effective area between declinati
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| 41. |
- Andres, EC, et al.
(författare)
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The AMANDA neutrino telescope
- 1999
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Ingår i: NUCLEAR PHYSICS B-PROCEEDINGS SUPPLEMENTS. - : ELSEVIER SCIENCE BV. - 0920-5632. ; 77, s. 474-485
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- With an effective telescope area of order 10(4) m(2) for TeV neutrinos, a threshold near similar to 50 GeV and a pointing accuracy of 2.5 degrees per muon track, the AMANDA detector represents the first of a new generation of high energy neutrino telescop
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| 42. |
- Axelsson, A, et al.
(författare)
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Excited superdeformed band in Eu-143
- 1999
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 6:2, s. 175-183
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Tidskriftsartikel (refereegranskat)abstract
- A new superdeformed band has been discovered in a EUROBALL experiment and assigned to Eu-143. It has a maximum intensity of 35% of the Eu-143 yrast superdeformed band and the transition energies of the two bands are very similar. Based on comparison with cranked shell model calculations the new band is tentatively assigned the high-N intruder configuration pi 6(2)nu 7(0) and the parity and signature quantum numbers (pi, alpha) = (-1, +1/2). In addition to the already known high-energy transition at 3361 keV another discrete line at 2715 keV was found to be in coincidence with the yrast superdeformed band. However, it was not possible to connect the decay out of either of the superdeformed bands to, known normally deformed states.
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| 49. |
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| 50. |
- Hohmann, C, et al.
(författare)
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Sex-specific incidence of asthma, rhinitis and respiratory multimorbidity before and after puberty onset: individual participant meta-analysis of five birth cohorts collaborating in MeDALL
- 2019
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Ingår i: BMJ open respiratory research. - : BMJ. - 2052-4439. ; 6:1, s. e000460-
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Tidskriftsartikel (refereegranskat)abstract
- To understand the puberty-related sex shift in the prevalence of asthma and rhinitis as single entities and as respiratory multimorbidities, we investigated if there is also a sex-specific and puberty-related pattern of their incidences.MethodsWe used harmonised questionnaire data from 18 451 participants in five prospective observational European birth cohorts within the collaborative MeDALL (Mechanisms of the Development of Allergy) project. Outcome definitions for IgE-associated and non-IgE-associated asthma, rhinitis and respiratory multimorbidity (first occurrence of coexisting asthma and rhinitis) were based on questionnaires and the presence of specific antibodies (IgE) against common allergens in serum. For each outcome, we used proportional hazard models with sex–puberty interaction terms and conducted a one-stage individual participant data meta-analysis.ResultsGirls had a lower risk of incident asthma (adjusted HR 0.67, 95% CI 0.61 to 0.74), rhinitis (0.73, 0.69 to 0.78) and respiratory multimorbidity (0.58, 0.51 to 0.66) before puberty compared with boys. After puberty onset, these incidences became more balanced across the sexes (asthma 0.84, 0.64 to 1.10; rhinitis 0.90, 0.80 to 1.02; respiratory multimorbidity 0.84, 0.63 to 1.13). The incidence sex shift was slightly more distinct for non-IgE-associated respiratory diseases (asthma 0.74, 0.63 to 0.87 before vs 1.23, 0.75 to 2.00 after puberty onset; rhinitis 0.88, 0.79 to 0.98 vs 1.20, 0.98 to 1.47; respiratory multimorbidity 0.66, 0.49 to 0.88 vs 0.96, 0.54 to 1.71) than for IgE-associated respiratory diseases.DiscussionWe found an incidence ‘sex shift’ in chronic respiratory diseases from a male predominance before puberty to a more sex-balanced incidence after puberty onset, which may partly explain the previously reported sex shift in prevalence. These differences need to be considered in public health to enable effective diagnoses and timely treatment in adolescent girls.
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