| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
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.
|
|
| 2. |
- Gunnarsson, Ulrika
(författare)
-
Genetic Studies of Pigmentation in Chicken
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Domestic animals have been selected by humans for thousands of years, which have drastically altered their genetic constitution and phenotypes. In this thesis, several of the most important genes causing pigmentation differences between the wild red junglefowl (Gallus gallus) and domestic chickens have been identified. Pigmentation phenotypes are easily scored, and the genes underlying these phenotypes are valuable models to study gene function and gene interaction. Dominant white colour is widespread among domestic chickens. The Dominant white allele specifically inhibits the expression of black (eumelanin) pigment and we identified several insertion/deletion mutations in the PMEL17 gene causing the different phenotypes controlled by this locus. The Silver allele on the other hand inhibits the expression of red (pheomelanin) colour and is a genetic variant of the SLC45A2 gene. Silver is the first pheomelanin-specific mutation(s) reported for this gene. An 8 kb deletion, including a conserved enhancer element, 14 kb upstream of the transcription factor SOX10 is causing the Dark brown phenotype. This phenotype restricts the expression of eumelanin and enhances red pheomelanin in specific parts of the plumage. These three gene identifications have extended the knowledge about genes affecting melanocyte function. Carotenoid-based pigmentation is of utmost importance in birds and other animals. The yellow skin allele in chicken allows deposition of carotenoids in skin and explains why most domestic chickens have yellow legs. We demonstrated that the yellow skin phenotype is caused by a tissue specific regulatory mutation in the gene for the enzyme beta-caroten dioxygenase 2 (BCDO2). This was the first identification of a specific gene underlying carotenoid-based pigmentation. Interestingly, the yellow skin haplotype was shown to originate from the grey junglefowl (Gallus sonneratii) and not the red junglefowl as expected, thus presenting the first conclusive evidence for a hybrid origin of the domestic chicken.
|
|
| 3. |
- Hillier, Ladeana W, et al.
(författare)
-
Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
-
Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
|
|
| 4. |
- Jacobs, Kevin B, et al.
(författare)
-
Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
-
Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
-
Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
|
|
| 5. |
- Sampson, Joshua N., et al.
(författare)
-
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 6. |
- Torén, William, et al.
(författare)
-
Thymidylate synthase : A predictive biomarker in resected colorectal liver metastases receiving 5-FU treatment
- 2018
-
Ingår i: Future Oncology. - : Future Medicine Ltd. - 1479-6694 .- 1744-8301. ; 14:4, s. 343-351
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate the role of thymidylate synthase (TS) as a predictive biomarker in patients with resected colorectal liver metastases (CRLM). Materials & methods: PubMed, EMBASE and Cochrane Library were queried up to June 2017. Meta-analysis was performed using random-effects model. Risk of bias was assessed using funnel plots. Results: Six eligible studies were included, comprising a total of 542 patients. Meta-analysis demonstrated a trend to reduced overall survival in patients with resected CRLM with TS overexpression, with a hazard ratio of 1.13 (95% CI: 0.99-1.29; p = 0.08). In three studies where patients received systemic fluorouracil, the pooled hazard ratio was 2.25 (95% CI: 1.37-3.71; p = 0.001). Conclusion: TS appears to be a clinically relevant predictive biomarker in patients with resected CRLM receiving systemic 5-FU.
|
|
| 7. |
- Umans, Timurs, 1981-, et al.
(författare)
-
Top management teams’ shared leadership and ambidexterity : the role of management control systems
- 2020
-
Ingår i: International Review of Administrative Sciences. - : Sage Publications. - 0020-8523 .- 1461-7226. ; 86:3, s. 444-462
-
Tidskriftsartikel (refereegranskat)abstract
- The study explores how top management teams’ shared leadership is related to organizational ambidexterity in public-sector organizations, theoretically and empirically considering how this relationship is contingent on the management control system. Using a sample of 85 Swedish municipal housing corporations, we find that shared leadership has a positive relationship with organizational ambidexterity in public-sector organizations. Moreover, increasing use of new public management control systems, based on combined reward and performance controls, positively moderates this relationship. The study also finds that traditional public management control systems, based on combined planning and administrative controls, do not moderate the relationship between top management teams’ shared leadership and organizational ambidexterity. Accordingly, this article contributes to the public and strategic management literature, as well as to managerial practice.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Wang, Zhaoming, et al.
(författare)
-
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
|
|
