| 1. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 2. |
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| 3. |
- Aad, G, et al.
(author)
-
Determination of spin and parity of the Higgs boson in the [Formula: see text] decay channel with the ATLAS detector.
- 2015
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Journal article (peer-reviewed)abstract
- Studies of the spin and parity quantum numbers of the Higgs boson in the [Formula: see text] final state are presented, based on proton-proton collision data collected by the ATLAS detector at the Large Hadron Collider, corresponding to an integrated luminosity of 20.3 fb[Formula: see text] at a centre-of-mass energy of [Formula: see text] TeV. The Standard Model spin-parity [Formula: see text] hypothesis is compared with alternative hypotheses for both spin and CP. The case where the observed resonance is a mixture of the Standard-Model-like Higgs boson and CP-even ([Formula: see text]) or CP-odd ([Formula: see text]) Higgs boson in scenarios beyond the Standard Model is also studied. The data are found to be consistent with the Standard Model prediction and limits are placed on alternative spin and CP hypotheses, including CP mixing in different scenarios.
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| 4. |
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| 5. |
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| 6. |
- Aad, G, et al.
(author)
-
Measurements of the Higgs boson production and decay rates and coupling strengths using pp collision data at [Formula: see text] and 8 TeV in the ATLAS experiment.
- 2016
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
-
Journal article (peer-reviewed)abstract
- Combined analyses of the Higgs boson production and decay rates as well as its coupling strengths to vector bosons and fermions are presented. The combinations include the results of the analyses of the [Formula: see text] and [Formula: see text] decay modes, and the constraints on the associated production with a pair of top quarks and on the off-shell coupling strengths of the Higgs boson. The results are based on the LHC proton-proton collision datasets, with integrated luminosities of up to 4.7 [Formula: see text] at [Formula: see text] TeV and 20.3 [Formula: see text] at [Formula: see text] TeV, recorded by the ATLAS detector in 2011 and 2012. Combining all production modes and decay channels, the measured signal yield, normalised to the Standard Model expectation, is [Formula: see text]. The observed Higgs boson production and decay rates are interpreted in a leading-order coupling framework, exploring a wide range of benchmark coupling models both with and without assumptions on the Higgs boson width and on the Standard Model particle content in loop processes. The data are found to be compatible with the Standard Model expectations for a Higgs boson at a mass of 125.36 GeV for all models considered.
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| 7. |
- Aad, G, et al.
(author)
-
Observation and measurements of the production of prompt and non-prompt [Formula: see text] mesons in association with a [Formula: see text] boson in [Formula: see text] collisions at [Formula: see text] with the ATLAS detector.
- 2015
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Journal article (peer-reviewed)abstract
- The production of a [Formula: see text] boson in association with a [Formula: see text] meson in proton-proton collisions probes the production mechanisms of quarkonium and heavy flavour in association with vector bosons, and allows studies of multiple parton scattering. Using [Formula: see text] of data collected with the ATLAS experiment at the LHC in [Formula: see text] collisions at [Formula: see text], the first measurement of associated [Formula: see text] production is presented for both prompt and non-prompt [Formula: see text] production, with both signatures having a significance in excess of [Formula: see text]. The inclusive production cross-sections for [Formula: see text] boson production (analysed in [Formula: see text] or [Formula: see text] decay modes) in association with prompt and non-prompt [Formula: see text] are measured relative to the inclusive production rate of [Formula: see text] bosons in the same fiducial volume to be [Formula: see text] and [Formula: see text] respectively. Normalised differential production cross-section ratios are also determined as a function of the [Formula: see text] transverse momentum. The fraction of signal events arising from single and double parton scattering is estimated, and a lower limit of [Formula: see text] at [Formula: see text] confidence level is placed on the effective cross-section regulating double parton interactions.
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| 8. |
- Aad, G, et al.
(author)
-
Search for a new resonance decaying to a W or Z boson and a Higgs boson in the [Formula: see text] final states with the ATLAS detector.
- 2015
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:6
-
Journal article (peer-reviewed)abstract
- A search for a new resonance decaying to a W or Z boson and a Higgs boson in the [Formula: see text] final states is performed using 20.3 fb[Formula: see text] of pp collision data recorded at [Formula: see text] 8 TeV with the ATLAS detector at the Large Hadron Collider. The search is conducted by examining the WH / ZH invariant mass distribution for a localized excess. No significant deviation from the Standard Model background prediction is observed. The results are interpreted in terms of constraints on the Minimal Walking Technicolor model and on a simplified approach based on a phenomenological Lagrangian of Heavy Vector Triplets.
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| 9. |
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| 10. |
- Aad, G, et al.
(author)
-
Search for direct pair production of a chargino and a neutralino decaying to the 125 GeV Higgs boson in [Formula: see text] TeV [Formula: see text] collisions with the ATLAS detector.
- 2015
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Journal article (peer-reviewed)abstract
- A search is presented for the direct pair production of a chargino and a neutralino [Formula: see text], where the chargino decays to the lightest neutralino and the [Formula: see text] boson, [Formula: see text], while the neutralino decays to the lightest neutralino and the 125 GeV Higgs boson, [Formula: see text]. The final states considered for the search have large missing transverse momentum, an isolated electron or muon, and one of the following: either two jets identified as originating from bottom quarks, or two photons, or a second electron or muon with the same electric charge. The analysis is based on 20.3 [Formula: see text] of [Formula: see text] proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with the Standard Model expectations, and limits are set in the context of a simplified supersymmetric model.
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| 11. |
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| 12. |
- Aad, G, et al.
(author)
-
Search for heavy long-lived multi-charged particles in pp collisions at [Formula: see text] TeV using the ATLAS detector.
- 2015
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:8
-
Journal article (peer-reviewed)abstract
- A search for heavy long-lived multi-charged particles is performed using the ATLAS detector at the LHC. Data collected in 2012 at [Formula: see text] TeV from pp collisions corresponding to an integrated luminosity of 20.3 fb[Formula: see text]are examined. Particles producing anomalously high ionisation, consistent with long-lived massive particles with electric charges from [Formula: see text] to [Formula: see text] are searched for. No signal candidate events are observed, and 95 % confidence level cross-section upper limits are interpreted as lower mass limits for a Drell-Yan production model. The mass limits range between 660 and 785 GeV.
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| 13. |
- Aad, G, et al.
(author)
-
Search for Higgs boson pair production in the [Formula: see text] final state from pp collisions at [Formula: see text] TeVwith the ATLAS detector.
- 2015
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:9
-
Journal article (peer-reviewed)abstract
- A search for Higgs boson pair production [Formula: see text] is performed with 19.5 fb[Formula: see text] of proton-proton collision data at [Formula: see text] TeV, which were recorded by the ATLAS detector at the Large Hadron Collider in 2012. The decay products of each Higgs boson are reconstructed as a high-momentum [Formula: see text] system with either a pair of small-radius jets or a single large-radius jet, the latter exploiting jet substructure techniques and associated b-tagged track-jets. No evidence for resonant or non-resonant Higgs boson pair production is observed. The data are interpreted in the context of the Randall-Sundrum model with a warped extra dimension as well as the two-Higgs-doublet model. An upper limit on the cross-section for [Formula: see text] of 3.2 (2.3) fb is set for a Kaluza-Klein graviton [Formula: see text] mass of 1.0 (1.5) TeV, at the 95 % confidence level. The search for non-resonant Standard Model hh production sets an observed 95 % confidence level upper limit on the production cross-section [Formula: see text] of 202 fb, compared to a Standard Model prediction of [Formula: see text] fb.
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| 14. |
- Aad, G, et al.
(author)
-
Search for Higgs Boson Pair Production in the γγbb[over ¯] Final State Using pp Collision Data at sqrt[s]=8 TeV from the ATLAS Detector.
- 2015
-
In: Physical Review Letters. - 1079-7114. ; 114:8
-
Journal article (peer-reviewed)abstract
- Searches are performed for resonant and nonresonant Higgs boson pair production in the γγbb[over ¯] final state using 20 fb^{-1} of proton-proton collisions at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the CERN Large Hadron Collider. A 95% confidence level upper limit on the cross section times branching ratio of nonresonant production is set at 2.2 pb, while the expected limit is 1.0 pb. The difference derives from a modest excess of events, corresponding to 2.4 standard deviations from the background-only hypothesis. The limit observed in the search for a narrow X→hh resonance ranges between 0.7 and 3.5 pb as a function of the resonance mass.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Aad, G, et al.
(author)
-
Search for production of [Formula: see text] resonances decaying to a lepton, neutrino and jets in [Formula: see text] collisions at [Formula: see text] TeV with the ATLAS detector.
- 2015
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Journal article (peer-reviewed)abstract
- A search is presented for narrow diboson resonances decaying to [Formula: see text] or [Formula: see text] in the final state where one [Formula: see text] boson decays leptonically (to an electron or a muon plus a neutrino) and the other [Formula: see text] boson decays hadronically. The analysis is performed using an integrated luminosity of 20.3 fb[Formula: see text] of [Formula: see text] collisions at [Formula: see text] TeV collected by the ATLAS detector at the large hadron collider. No evidence for resonant diboson production is observed, and resonance masses below 700 and 1490 GeV are excluded at 95 % confidence level for the spin-2 Randall-Sundrum bulk graviton [Formula: see text] with coupling constant of 1.0 and the extended gauge model [Formula: see text] boson respectively.
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| 19. |
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| 20. |
- Aad, G, et al.
(author)
-
Study of the [Formula: see text] and [Formula: see text] decays with the ATLAS detector.
- 2016
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
-
Journal article (peer-reviewed)abstract
- The decays [Formula: see text] and [Formula: see text] are studied with the ATLAS detector at the LHC using a dataset corresponding to integrated luminosities of 4.9 and 20.6 fb[Formula: see text] of pp collisions collected at centre-of-mass energies [Formula: see text] TeV and 8 TeV, respectively. Signal candidates are identified through [Formula: see text] and [Formula: see text] decays. With a two-dimensional likelihood fit involving the [Formula: see text] reconstructed invariant mass and an angle between the [Formula: see text] and [Formula: see text] candidate momenta in the muon pair rest frame, the yields of [Formula: see text] and [Formula: see text], and the transverse polarisation fraction in [Formula: see text] decay are measured. The transverse polarisation fraction is determined to be [Formula: see text], and the derived ratio of the branching fractions of the two modes is [Formula: see text], where the first error is statistical and the second is systematic. Finally, a sample of [Formula: see text] decays is used to derive the ratios of branching fractions [Formula: see text] and [Formula: see text], where the third error corresponds to the uncertainty of the branching fraction of [Formula: see text] decay. The available theoretical predictions are generally consistent with the measurement.
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| 21. |
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| 22. |
- Aglago, Elom K., et al.
(author)
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A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
- 2023
-
In: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:15, s. 2572-2583
-
Journal article (peer-reviewed)abstract
- Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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| 23. |
- Armuand, Gabriela, et al.
(author)
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Characteristics of good contraceptive counselling : An interview study
- 2024
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In: Sexual & Reproductive HealthCare. - : Elsevier. - 1877-5756 .- 1877-5764. ; 39
-
Journal article (peer-reviewed)abstract
- ObjectiveOne key component in preventing unplanned pregnancies is to provide effective contraceptive counselling. This study aimed to investigate what characterises good contraceptive counselling from the woman's perspective.MethodsA qualitative study with a phenomenological approach. Twenty-four women aged 15–45 participated in semi-structured, individual, face-to-face interviews that lasted, on average, one hour. Data were analysed by latent content analysis.ResultsOne overall theme emerged, person-centred contraceptive counselling – an interactive process, with three main categories: (i) a trustworthy healthcare provider, (ii) creating a liaison and (iii) the right time and place.ConclusionsThe healthcare provider’s attributes as well as what happened between the healthcare provider and the woman, and the surrounding context, had a bearing on the women’s descriptions of good contraceptive counselling. The process of the counselling was described as more important than the actual outcome; thus, healthcare providers need to be aware that this seemingly straightforward consultation is rather multi-layered and has great health promoting potential.
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| 24. |
- Backhausen, Mette G., et al.
(author)
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Pregnancy planning and lifestyle prior to conception and during early pregnancy among Danish women
- 2014
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In: European journal of contraception & reproductive health care. - : Taylor & Francis. - 1362-5187 .- 1473-0782. ; 19:1, s. 57-65
-
Journal article (peer-reviewed)abstract
- Objective To investigate the extent to which Danish women attending antenatal care plan their pregnancies and to determine the association between pregnancy planning and the intake of folic acid, alcohol consumption and smoking habits prior to conception and before the 16th week of gestation. Methods A cross-sectional survey of 258 women. Main outcome measures: intake of folic acid, alcohol consumption and smoking. Pregnancy planning was assessed by the London Measure of Unplanned Pregnancy (LMUP) and the five graded Swedish Pregnancy Planning Scale. Results Most (77%) of the participants reported that their pregnancies were very or fairly well planned. Higher median LMUP scores were observed in women taking folic acid (p < 0.001), in those consuming less alcohol, and in women who stopped smoking prior to pregnancy (p = 0.043). However, 43% of the respondents with a high degree of pregnancy planning and 98% of those with a low degree of planning had not taken folic acid prior to pregnancy. Binge drinking during early pregnancy was reported by 20% of women with a high degree of planned pregnancy and 31% of those with a low degree (p = 0.1). Conclusion Pregnancy planning was associated with a healthier lifestyle but still many women could improve their lifestyle in connection to pregnancy. Their level of alcohol consumption is higher than that recommended for best pregnancy outcome.
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| 25. |
- Bodin, Maja, et al.
(author)
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Coherence of pregnancy planning within couples expecting a child
- 2015
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In: Midwifery. - : Elsevier BV. - 0266-6138 .- 1532-3099. ; 31:10, s. 973-978
-
Journal article (peer-reviewed)abstract
- Background: joint planning and decision-making within couples have evident effects on the well-being of the family. The purpose of this study was to investigate the level of pregnancy planning among pregnant women and their partners and to compare the coherence of pregnancy planning within the couples. Methods: pregnant women and their partners were recruited from 18 antenatal clinics in seven Swedish counties between October 2011 and April 2012. Participants, 232 pregnant women and 144 partners, filled out a questionnaire with questions about pregnancy planning, lifestyle and relationship satisfaction. 136 couples were identified and the women's and partners' answers were compared. Results: more than 75% of the pregnancies were very or rather planned and almost all participants had agreed with their partner to become pregnant There was no significant difference in level of pregnancy planning between women and partners, and coherence within couples was strong. Level of planning was not affected by individual socio-demographic variables. Furthermore, 98 % of women and 94 % of partners had non distressed relationships. Conclusion: one of the most interesting results was the strong coherence between partners concerning their pregnancy and relationship. Approaching these results from a social constructivist perspective brings to light an importance of togetherness and how a sense and impression of unity within a couple might be constructed in different ways. As implications for practice, midwives and other professionals counselling persons in fertile age should enquire about and emphasise the benefits of equality and mutual pregnancy planning for both women and men.
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| 26. |
- Bodin, Maja, et al.
(author)
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Exploring men's pregnancy-planning behaviour and fertility knowledge : a survey among fathers in Sweden
- 2017
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 122:2, s. 127-135
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: Research about pregnancy-planning behaviour mostly focuses on women, even though pregnancy planning usually also concerns men. The purpose of this study was to investigate how men plan for family, and to measure their fertility knowledge after having become fathers.MATERIAL AND METHODS: Data were collected in 2014 as part of a Swedish longitudinal pregnancy-planning study. Men were recruited through their female partner one year after childbirth. Participants were asked to fill out a questionnaire about pregnancy planning, lifestyles, and fertility.RESULTS: Of the 796 participants, 646 (81%) stated that the pregnancy had been very or fairly planned, and 17% (n = 128) had made a lifestyle adjustment before pregnancy to improve health and fertility. The most common adjustments were to reduce/quit the consumption of alcohol, cigarettes, or snuff, and to exercise more. First-time fathers and those who had used assisted reproductive technology to become pregnant were more likely to have made an adjustment. Fertility knowledge varied greatly. Men with university education had better fertility knowledge than men without university education.CONCLUSION: Our findings indicate that there is variation in how men plan and prepare for pregnancy. Most men did not adjust their lifestyle to improve health and fertility, while some made several changes. Both pregnancy-planning behaviour and fertility knowledge seem to be related to level of education and mode of conception. To gain deeper understanding of behaviour and underlying factors, more research is needed.
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| 27. |
- Bouras, Emmanouil, et al.
(author)
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Genome-wide interaction analysis of folate for colorectal cancer risk
- 2023
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In: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 118:5, s. 881-891
-
Journal article (peer-reviewed)abstract
- Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO).Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate.Conclusions: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.
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| 28. |
- Carreras-Torres, Robert, et al.
(author)
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Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation, and immune response
- 2023
-
In: Cancer Epidemiology, Biomarkers and Prevention. - : American association for cancer research. - 1055-9965 .- 1538-7755. ; 32:3, s. 315-328
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer.METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia.RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response.IMPACT: These findings can guide potential prevention treatments.
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| 29. |
- Conti, David, V, et al.
(author)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Journal article (peer-reviewed)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 30. |
- Delbaere, Ilse, et al.
(author)
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Fertility
- 2020. - 1
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In: Preconception health and care. - Cham : Springer. - 9783030317522 ; , s. 53-79
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Book chapter (other academic/artistic)
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| 31. |
- Drevin, Jennifer, et al.
(author)
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Adverse childhood experiences influence development of pain during pregnancy.
- 2015
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:8, s. 840-846
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the association between adverse childhood experiences (ACE) and pain with onset during pregnancy.DESIGN: Cross-sectional study.SETTING: Eighteen antenatal clinics in southern Mid-Sweden.SAMPLE: Of 293 women invited to participate, 232 (79%) women agreed to participate in early pregnancy and were assessed in late pregnancy.METHODS: Questionnaires were distributed in early and late pregnancy. The questionnaires sought information on socio-demography, ACE, pain location by pain drawing and pain intensity by visual analogue scales. Distribution of pain was coded in 41 predetermined areas.MAIN OUTCOME MEASURES: Pain in third trimester with onset during present pregnancy: intensity, location and number of pain locations.RESULTS: In late pregnancy, 62% of the women reported any ACE and 72% reported any pain location with onset during the present pregnancy. Among women reporting any ACE the median pain intensity was higher compared with women without such an experience (p = 0.01). The accumulated ACE displayed a positive association with the number of reported pain locations in late pregnancy (rs = 0.19, p = 0.02). This association remained significant after adjusting for background factors in multiple regression analysis (p = 0.01). When ACE was dichotomized the prevalence of pain did not differ between women with and without ACE. The subgroup of women reporting physical abuse as a child reported a higher prevalence of sacral and pelvic pain (p = 0.0003 and p = 0.02, respectively).CONCLUSIONS: Adverse childhood experiences were associated with higher pain intensities and larger pain distributions in late pregnancy, which are risk factors for transition to chronic pain postpartum.
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| 32. |
- Drevin, Jennifer, et al.
(author)
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Measuring pregnancy planning : A psychometric evaluation and comparison of two scales
- 2017
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In: Journal of Advanced Nursing. - : Wiley. - 0309-2402 .- 1365-2648. ; 73:11, s. 2765-2775
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Journal article (peer-reviewed)abstract
- AIMS: To psychometrically test the London Measure of Unplanned Pregnancy and compare it with the Swedish Pregnancy Planning Scale.BACKGROUND: The incidence of unplanned pregnancies is an important indicator of reproductive health. The London Measure of Unplanned Pregnancy measures pregnancy planning by taking contraceptive use, timing, intention to become pregnant, desire for pregnancy, partner agreement, and pre-conceptual preparations into account. It has, however, previously not been psychometrically evaluated using confirmatory factor analysis. The Likert-scored single-item Swedish Pregnancy Planning Scale has been developed to measure the woman's own view of pregnancy planning level.DESIGN: Cross-sectional design.METHODS: In 2012-2013, 5493 pregnant women living in Sweden were invited to participate in the Swedish Pregnancy Planning study, of whom 3327 (61%) agreed to participate and answered a questionnaire. A test-retest pilot study was conducted in 2011-2012. Thirty-two participants responded to the questionnaire on two occasions 14 days apart. Data were analysed using confirmatory factor analysis, Cohen's weighted kappa and Spearman's correlation.RESULTS: All items of the London Measure of Unplanned Pregnancy contributed to measuring pregnancy planning, but four items had low item-reliability. The London Measure of Unplanned Pregnancy and Swedish Pregnancy Planning Scale corresponded reasonably well with each other and both showed good test-retest reliability.CONCLUSION: The London Measure of Unplanned Pregnancy may benefit from item reduction and its usefulness may be questioned. The Swedish Pregnancy Planning Scale is time-efficient and shows acceptable reliability and construct validity, which makes it more useful for measuring pregnancy planning.
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| 33. |
- Drew, David A., et al.
(author)
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Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer
- 2024
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:22
-
Journal article (peer-reviewed)abstract
- Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
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| 34. |
- Ekstrand Ragnar, Maria, et al.
(author)
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Important but far away : adolescents' beliefs, awareness and experiences of fertility and preconception health
- 2018
-
In: European journal of contraception & reproductive health care. - : TAYLOR & FRANCIS LTD. - 1362-5187 .- 1473-0782. ; 23:4, s. 265-273
-
Journal article (peer-reviewed)abstract
- Objectives: The aim was to explore adolescents' beliefs and awareness regarding fertility and preconception health, as well as their views and experiences of information about fertility and preconception health directed at their age group. Methods: We performed seven semi-structured focus group interviews among upper secondary school students (n = 47) aged 16-18 years in two Swedish counties. Data were analysed by qualitative content analysis. Results: One theme ('important but far away') and five categories ('starting a family far down on the list'; 'high awareness but patchy knowledge of fertility and preconception health'; 'gender roles influence beliefs about fertility and preconception health'; 'wish to preserve fertility and preconception health in order to keep the door to procreation open'; 'no panacea - early and continuous education about fertility and preconception health') emerged from the interviews. Participants recognised the importance of preconception health and were highly aware of the overall importance of a healthy lifestyle. Their knowledge, however, was patchy and they had difficulties relating to fertility and preconception health on a personal and behavioural level. Participants wanted more information but had heterogeneous beliefs about when, where and how this information should be given. Conclusion: The adolescents wanted information on fertility and preconception health to be delivered repeatedly as well as through different sources.
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| 35. |
- Fernandez-Rozadilla, Ceres, et al.
(author)
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
-
Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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| 36. |
- Figueroa, Jonine D., et al.
(author)
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Genome-wide association study identifies multiple loci associated with bladder cancer risk
- 2014
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 23:5, s. 1387-1398
-
Journal article (peer-reviewed)abstract
- andidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10−5 was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10−9) and rs907611 on 11p15.5 (P = 4.11 × 10−8). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10−7) and rs4510656 on 6p22.3 (P = 6.98 × 10−7); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
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| 37. |
- Figueroa, Jonine D., et al.
(author)
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Genome-wide interaction study of smoking and bladder cancer risk
- 2014
-
In: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 35:8, s. 1737-1744
-
Journal article (peer-reviewed)abstract
- Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 x 10(-5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 x 10(-7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 x 10-7). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.
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| 38. |
- Figueroa, Jonine D., et al.
(author)
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Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry
- 2016
-
In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 25:6, s. 1203-1214
-
Journal article (peer-reviewed)abstract
- Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.
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| 39. |
- Fooladi, Ensieh, et al.
(author)
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Using reproductive life plan-based information in a primary health care center increased Iranian women's knowledge of fertility, but not their future fertility plan : A randomized, controlled trial
- 2018
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In: Midwifery. - : ELSEVIER SCI LTD. - 0266-6138 .- 1532-3099. ; 67, s. 77-86
-
Journal article (peer-reviewed)abstract
- Objectives: Reproductive Life Plan (RLP)-based information in counseling has been reported in the USA and Sweden to increase women's knowledge of fertility and informed decision making about future fertility plans. This study examined if utilizing the RLP tool would have the same impact on Iranian women.Design: A randomized, three-armed, controlled trial. 181 women were randomly allocated to the intervention group (IG, n = 61), control group 1 (CG1, n = 60) or control group 2 (CG2, n = 60).Setting: A primary health care center in the Sari city, the Provincial capital of Mazandaran, Iran.Participants: Women of reproductive age who were able to conceive.Interventions: The intervention group received oral and written information about fertility based on the RLP tool. Participants were contacted 2 months after the intervention. The primary outcome measure was the change in women's knowledge of fertility, particularly folic acid intake prior to pregnancy, over a 2 month period. The change in women's family planning intentions were also assessed. The participants in the IG shared their experiences at follow-up.Findings: At baseline, there was no difference between the groups regarding the mean knowledge of fertility score. At 2 months, after adjustment for age, history of pregnancy and baseline values, the between group difference in change from baseline was 5.8 (p < 0.001). While there was no significant difference between the IG and CG1 for folic acid intake prior to pregnancy at baseline, the group difference for folic acid intake prior to pregnancy post intervention was statistically significant (85% vs 25%, p < 0.001). At follow-up, women's desire to have more children, preferred age to conceive the last child and the desired age gap between children in the IG and CG1 did not significantly change over time. Women reported the RLP counseling tool used by midwives as useful.Key conclusions: Provision of RLP-based information for Iranian women with a clear pregnancy intention in the context of a stable relationship, increased knowledge of fertility without changing their future fertility plan. The RPL counseling tool was appreciated by study participants. The lack of improvement in women's fertility intentions over time may reflect the involvement of other factors influencing decision making about childbearing in Iran. Whether the RLP can change women's behavior is yet to be established.Implications for practice: The RLP can be used by health care professionals, especially midwives, as a tool to increase women's fertility knowledge, which may result in fertility behavior change.
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| 40. |
- Fu, Yi-Ping, et al.
(author)
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The 19q12 Bladder Cancer GWAS Signal : Association with Cyclin E Function and Aggressive Disease
- 2014
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:20, s. 5808-5818
-
Journal article (peer-reviewed)abstract
- A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) >= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P-trend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
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| 41. |
- Grandahl, Maria, et al.
(author)
-
In everybody's interest but no one's assigned responsibility : midwives' thoughts and experiences of preventive work for men's sexual and reproductive health and rights within primary care
- 2019
-
In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 19:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Sexual and reproductive health and rights (SRHR) have historically been regarded as a woman's issue. It is likely that these gender norms also hinder health care providers from perceiving boys and men as health care recipients, especially within the area of SRHR. The aim of this study was to explore midwives' thoughts and experiences regarding preventive work for men's sexual and reproductive health and rights in the primary care setting.METHODS: An exploratory qualitative study. Five focus group interviews, including 4-5 participants in each group, were conducted with 22 midwives aged 31-64, who worked with reproductive, perinatal and sexual health within primary care. Data were analysed by latent content analysis.RESULTS: One overall theme emerged, in everybody's interest, but no one's assigned responsibility, and three sub-themes: (i) organisational aspects create obstacles, (ii) mixed views on the midwife's role and responsibility, and (iii) beliefs about men and women: same, but different.CONCLUSIONS: Midwives believed that preventive work for men's sexual and reproductive health and rights was in everybody's interest, but no one's assigned responsibility. To improve men's access to sexual and reproductive health care, actions are needed from the state, the health care system and health care providers.
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| 42. |
- Grandahl, Maria, et al.
(author)
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Longer shared parental leave is associated with longer duration of breastfeeding : a cross-sectional study among Swedish mothers and their partners
- 2020
-
In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 20:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Breastfeeding is associated with health benefits for both the mother and infant and is therefore important to support; moreover, parental leave is a beneficial factor for breastfeeding. The Swedish parental leave is generous, allowing each parent to take 90 days; additionally, a further 300 days can be taken by either parent. Generally, mothers take 70% of the parental leave days, mainly during the first year. However, breastfeeding duration has declined in the last decade, and it is not known how shared parental leave is associated with the duration of breastfeeding.AIM: To investigate how parental leave is associated with the duration of exclusive and partial breastfeeding of the infant during the first 12 months after birth. An additional aim was to describe infants' and parents' characteristics and mode of birth in association with the duration of exclusive and partial breastfeeding.METHODS: This cross-sectional study was part of the Swedish Pregnancy Planning Study, conducted in Sweden in 2012-2015. The parents were recruited at 153 antenatal clinics in nine counties. In total, 813 couples completed a follow-up questionnaire 1 year after birth. Linear regression models were used to analyse the association between parental leave and the duration of breastfeeding.RESULTS: Infants were exclusively breastfed for, on average, 2.5 months (range 0-12 months) and partially breastfed, on average, 7 months (range 0-12 months). Most of the parental leave was taken by the mother (mean = 10.9 months) during the infant's first 12 months, while the partner took 3 months, on average. The parental leave (used and planned) during the infant's first 24 months were, on average, 21 months. In the multivariate linear regression analysis, mothers' and partners' high level of education (p < 0.001, p = 0.044, respectively), mothers' higher age (p = 0.049), non-instrumental vaginal birth (p = 0.004) and longer parental leave for the first 24 months (p < 0.001) were associated with longer duration of partial breastfeeding.CONCLUSION: The duration of partial breastfeeding was associated with higher parental educational level, higher age, non-instrumental vaginal birth and longer parental leave.
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| 43. |
- Jassinskaja, Maria, et al.
(author)
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A complex interplay of intra- and extracellular factors regulates the outcome of fetal- and adult-derived MLL-rearranged leukemia
-
In: Leukemia. - 0887-6924.
-
Journal article (peer-reviewed)abstract
- Infant and adult MLL1/KMT2A-rearranged (MLLr) leukemia represents a disease with a dismal prognosis. Here, we present a functional and proteomic characterization of in utero-initiated and adult-onset MLLr leukemia. We reveal that fetal MLL::ENL-expressing lymphomyeloid multipotent progenitors (LMPPs) are intrinsically programmed towards a lymphoid fate but give rise to myeloid leukemia in vivo, highlighting a complex interplay of intra- and extracellular factors in determining disease subtype. We characterize early proteomic events of MLL::ENL-mediated transformation in fetal and adult blood progenitors and reveal that whereas adult pre-leukemic cells are mainly characterized by retained myeloid features and downregulation of ribosomal and metabolic proteins, expression of MLL::ENL in fetal LMPPs leads to enrichment of translation-associated and histone deacetylases signaling proteins, and decreased expression of inflammation and myeloid differentiation proteins. Integrating the proteome of pre-leukemic cells with their secretome and the proteomic composition of the extracellular environment of normal progenitors highlights differential regulation of Igf2 bioavailability, as well as of VLA-4 dimer and its ligandome, upon initiation of fetal- and adult-origin leukemia, with implications for human MLLr leukemia cells’ ability to communicate with their environment through granule proteins. Our study has uncovered opportunities for targeting ontogeny-specific proteomic vulnerabilities in in utero-initiated and adult-onset MLLr leukemia.
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| 44. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 45. |
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| 46. |
- Mogilevkina, Iryna, et al.
(author)
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Ukrainian medical students’ attitudes to parenthood and knowledge of fertility
- 2016
-
In: European journal of contraception & reproductive health care. - : Informa UK Limited. - 1362-5187 .- 1473-0782. ; 21:2, s. 189-194
-
Journal article (peer-reviewed)abstract
- Objectives: The aim of our study was to investigate Ukrainian medical students’ intentions andattitudes in relation to future parenthood, and their knowledge about fertility. Methods: Aclassroom survey was carried out of randomly selected groups among 3568 Russian-speakingmedical students. The response rate was 88.8%; 858 were female and 407 were male; the mean agewas 20.6 (standard deviation [SD] 2.4) years. Results: One in four male and 16% of femalerespondents did not want to have children, 3.3% had children and 17% wanted one child only.Female respondents wished to have their first child when they were 24.4 (SD 2.4) years of age, andmale respondents when they were 26.8 (SD 3.4) years of age. Around 60% of respondents reportedthere was a pronounced decline in female fertility after the age of 45 years. Conclusions: The desireto have children in the future is not apparent among medical students, especially not among men.Gaps in students’ knowledge about fertility need to be addressed by sexual and reproductiveeducation.
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| 47. |
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| 48. |
- Salih Joelsson, Lana, 1969-, et al.
(author)
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Anxiety and depression symptoms among sub-fertile women, women pregnant after infertility treatment, and naturally pregnant women
- 2017
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In: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 45, s. 212-219
-
Journal article (peer-reviewed)abstract
- BackgroundInfertility has been associated with psychological distress, but whether these symptoms persist after achieving pregnancy via assisted reproductive technology (ART) remains unclear. We compared the prevalence of anxiety and depressive symptoms between women seeking for infertility treatment and women who conceived after ART or naturally.MethodsFour hundred and sixty-eight sub-fertile non-pregnant women, 2972 naturally pregnant women and 143 women pregnant after ART completed a questionnaire in this cross-sectional study. The Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A≥8) and Edinburgh Postnatal Depression Scale (EPDS≥12) were used for assessing anxiety and depressive symptoms, respectively. Multivariate Poisson regression models with robust variance were applied to explore associations with anxiety and depressive symptoms.ResultsThe prevalence of anxiety and depressive symptoms among sub-fertile, non-pregnant women (57.6% and 15.7%, respectively) were significantly higher compared to women pregnant after ART (21.1% and 8.5%, respectively) and naturally pregnant women (18.8% and 10.3%, respectively). History of psychiatric diagnosis was identified as an independent risk factor for both anxiety and depressive symptoms. The presence of at least one unhealthy lifestyle behavior (daily tobacco smoking, weekly alcohol consumption, BMI≥25, and regular physical exercise < 2 h/week) was also associated with anxiety (Prevalence Ratio, PR: 1.24; 95%CI: 1.09–1.40) and depressive symptoms (PR: 1.25; 95%CI: 1.04–1.49).ConclusionsWomen pregnant after ART showed no difference in anxiety and depressive symptoms compared to naturally pregnant women. However, early psychological counseling and management of unhealthy lifestyle behaviors for sub-fertile women may be advisable, particularly for women with a previous history of psychiatric diagnosis.
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| 49. |
- Schmit, Stephanie L, et al.
(author)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
-
Journal article (peer-reviewed)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 50. |
- Shawe, Jill, et al.
(author)
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Preconception care policy, guidelines, recommendations and services across six European countries : Belgium (Flanders), Denmark, Italy, the Netherlands, Sweden and the United Kingdom
- 2015
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In: European journal of contraception & reproductive health care. - : Taylor & Francis. - 1362-5187 .- 1473-0782. ; 20:2, s. 77-87
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Research review (peer-reviewed)abstract
- Objectives Preconception care is important for the screening, prevention and management of risk factors that affect pregnancy outcomes. We aimed to investigate pre-pregnancy care policies, guidelines, recommendations and services in six European countries. Methods In 2013, an electronic search and investigation was undertaken of preconception policy, guidelines, recommendations and services available to healthcare professionals and the general public in six European countries: Belgium (Flanders), Denmark, Italy, the Netherlands, Sweden and the United Kingdom. Findings were compared within five categories: Governmental policy and legislation; Professional bodies and organisations; Healthcare providers; Charitable organisations; Web-based public information and internet sites. Results All countries had preconception recommendations for women with chronic diseases, such as diabetes and epilepsy. Recommendations for healthy women and men were fragmented and inconsistent. Preconception guidance was often included in antenatal and pregnancy guidelines. Differences between countries were seen with regard to nutritional and lifestyle advice particularly in relation to fish, caffeine and alcohol consumption, and vitamin supplementation. Conclusions Current guidelines are heterogeneous. Collaborative research across Europe is required in order to develop evidence-based guidelines for preconception health and care. There is a need to establish a clear strategy for promoting advice and guidance within the European childbearing population.
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