| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 3. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 4. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 5. |
- Barretina, Jordi, et al.
(författare)
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Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 715-21
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Tidskriftsartikel (refereegranskat)abstract
- Soft-tissue sarcomas, which result in approximately 10,700 diagnoses and 3,800 deaths per year in the United States, show remarkable histologic diversity, with more than 50 recognized subtypes. However, knowledge of their genomic alterations is limited. We describe an integrative analysis of DNA sequence, copy number and mRNA expression in 207 samples encompassing seven major subtypes. Frequently mutated genes included TP53 (17% of pleomorphic liposarcomas), NF1 (10.5% of myxofibrosarcomas and 8% of pleomorphic liposarcomas) and PIK3CA (18% of myxoid/round-cell liposarcomas, or MRCs). PIK3CA mutations in MRCs were associated with Akt activation and poor clinical outcomes. In myxofibrosarcomas and pleomorphic liposarcomas, we found both point mutations and genomic deletions affecting the tumor suppressor NF1. Finally, we found that short hairpin RNA (shRNA)-based knockdown of several genes amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields a detailed map of molecular alterations across diverse sarcoma subtypes and suggests potential subtype-specific targets for therapy.
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| 6. |
- Cosma, Alina, et al.
(författare)
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Gender Differences in Bullying Reflect Societal Gender Inequality : A Multilevel Study With Adolescents in 46 Countries
- 2022
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Ingår i: Journal of Adolescent Health. - : Elsevier. - 1054-139X .- 1879-1972. ; 71:5, s. 601-608
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Social patterns in bullying show consistent gender differences in adolescent perpetration and victimization with large cross-national variations. Previous research shows associations between societal gender inequality and gender differences in some violent behaviors in adolescents. Therefore, there is a need to go beyond individual associations and use a more social ecological perspective when examining gender differences in bullying behaviors. The aim of the present study was twofold: (1) to explore cross-national gender differences in bullying behaviors and (2) to examine whether national-level gender inequality relates to gender differences in adolescent bullying behaviors.Methods: Traditional bullying and cyberbullying were measured in 11-year-olds to 15-year-olds in the 2017/18 Health Behaviour in School-aged Children study (n = 200,423). We linked individual data to national gender inequality (Gender Inequality Index, 2018) in 46 countries and tested their association using mixed-effects (multilevel) logistic regression models.Results: Large cross-national variations were observed in gender differences in bullying. Boys had higher odds of perpetrating both traditional and cyberbullying and victimization by traditional bullying than girls. Greater gender inequality at country level was associated with heightened gender differences in traditional bullying. In contrast, lower gender inequality was associated with larger gender differences for cyber victimization.Discussion: Societal gender inequality relates to adolescents' involvement in bullying and gendered patterns in bullying. Public health policy should target societal factors that have an impact on young people's behavior.
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| 7. |
- Craig, Wendy, et al.
(författare)
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Social Media Use and Cyber-Bullying: A Cross-National Analysis of Young People in 42 Countries
- 2020
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Ingår i: Journal of Adolescent Health. - : ELSEVIER SCIENCE INC. - 1054-139X .- 1879-1972. ; 66:6, s. S100-S108
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Social media use (SMU) has become an intrinsic part of adolescent life. Negative consequences of SMU for adolescent health could include exposures to online forms of aggression. We explored age, gender, and cross-national differences in adolescents engagement in SMU, then relationships between SMU and victimization and the perpetration of cyber-bullying. Methods: We used data on young people aged 11-15 years (weighted n = 180,919 in 42 countries) who participated in the 2017-2018 Health Behaviour in School-aged Children study to describe engagement in the three types of SMU (intense, problematic, and talking with strangers online) by age and gender and then in the perpetration and victimization of cyber-bullying. Relationships between SMU and cyber-bullying outcomes were estimated using Poisson regression (weighted n = 166,647 from 42 countries). Results: Variations in SMU and cyber-bullying follow developmental and gender-based patterns across countries. In pooled analyses, engagement in SMU related to cyber-bullying victimization (adjusted relative risks = 1.14 [95% confidence interval (CI): 1.10-1.19] to 1.48 [95% CI: 1.42-1.55]) and perpetration (adjusted relative risk = 1.31 [95% CI: 1.26-1.36] to 1.84 [95% CI: 1.74-1.95]). These associations were stronger for cyber-perpetration versus cyber-victimization and for girls versus boys. Problematic SMU was most strongly and consistently associated with cyber-bullying, both for victimization and perpetration. Stratified analyses showed that SMU related to cyber-victimization in 19%-45% of countries and to cyber-perpetration in 38%-86% of countries. Conclusions: Accessibility to social media and its pervasive use has led to new opportunities for online aggression. The time adolescents spend on social media, engage in problematic use, and talk to strangers online each relate to cyber-bullying and merit public health intervention. Problematic use of social media poses the strongest and most consistent risk. (C) 2020 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.
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| 8. |
- Craig, Wendy, et al.
(författare)
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Social Media Use and Cyber-Bullying: A Cross-National Analysis of Young People in 42 Countries
- 2020
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Ingår i: Journal of Adolescent Health. - : Elsevier BV. - 1054-139X .- 1879-1972. ; 66:6
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Social media use (SMU) has become an intrinsic part of adolescent life. Negative consequences of SMU for adolescent health could include exposures to online forms of aggression. We explored age, gender, and cross-national differences in adolescents' engagement in SMU, then relationships between SMU and victimization and the perpetration of cyber-bullying. Methods: We used data on young people aged 11–15 years (weighted n = 180,919 in 42 countries) who participated in the 2017–2018 Health Behaviour in School-aged Children study to describe engagement in the three types of SMU (intense, problematic, and talking with strangers online) by age and gender and then in the perpetration and victimization of cyber-bullying. Relationships between SMU and cyber-bullying outcomes were estimated using Poisson regression (weighted n = 166,647 from 42 countries). Results: Variations in SMU and cyber-bullying follow developmental and gender-based patterns across countries. In pooled analyses, engagement in SMU related to cyber-bullying victimization (adjusted relative risks = 1.14 [95% confidence interval (CI): 1.10–1.19] to 1.48 [95% CI: 1.42–1.55]) and perpetration (adjusted relative risk = 1.31 [95% CI: 1.26–1.36] to 1.84 [95% CI: 1.74–1.95]). These associations were stronger for cyber-perpetration versus cyber-victimization and for girls versus boys. Problematic SMU was most strongly and consistently associated with cyber-bullying, both for victimization and perpetration. Stratified analyses showed that SMU related to cyber-victimization in 19%–45% of countries and to cyber-perpetration in 38%–86% of countries. Conclusions: Accessibility to social media and its pervasive use has led to new opportunities for online aggression. The time adolescents spend on social media, engage in problematic use, and talk to strangers online each relate to cyber-bullying and merit public health intervention. Problematic use of social media poses the strongest and most consistent risk.
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| 9. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 10. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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