| 1. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 2. |
- Almeida, Nuno A.F., et al.
(författare)
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Pressure dependent luminescence in titanium dioxide particles modified with europium ions
- 2016
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier BV. - 0925-4005 .- 1873-3077. ; 234, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- Particles of titanium dioxide were prepared in the presence of europium ions (TiO2:Eu) by a solvothermal method and thermal annealed in air at 500 °C. The spectroscopic properties of TiO2:Eu particles were analyzed indicating that the Eu3+ ions are likely distributed at the surface or near the surface of the titanium dioxide particles. The photoluminescence analysis showed that the intraionic emission was strongly sensitive to reduced pressure conditions, as seen by its absence under vacuum conditions. The ion emission was re-established as soon as the atmosphere was restored. Additionally, the ion integrated emission intensity follows a linearly dependence with pressure in the range of 150 to 800 mbar revealing a high sensitivity to small variations in pressure, which is an unprecedented result. This innovation will allow the study of new technologies in the area of low vacuum sensors where TiO2:Eu may act as the active element of an optical sensor for a pressure device.
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| 3. |
- Baptista, Antonio M. G., et al.
(författare)
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Causes of Vision Impairment in Portugal : A hospital based study
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Causes of vision impairment (VI) are influenced by factors such as race or socio-economic circumstances. Because of this collecting national information is important for planning reduction of vision loss. The aim of this study was to determine causes of vision impairment in a population visiting ophthalmology departments in public hospitals in Portugal.Methods This study was designed according with the guidelines of the Vancouver Economic Burden of Vision Loss Group (IOVS, 2010, V51/4/1801). Recommendations are to collect hospital data during 1 year to determine causes of VI. We selected four public hospitals that are expected to have over 120-140K appointments per year. Files are analysed weekly to detect patients with vision impairment. Inclusion criteria are: visual acuity with the current refractive correction equal or less than 0.5 (20/40) in the better-seeing eye and/or a visual field of less than 20 degrees. Patients were selected by trained hospital staff (medics and orthoptists) and inserted in a database. Diagnoses were classified according the ICD9. Data collected included fundamental demographic information, main diagnosis, secondary diagnosis and comorbidities.Results We have now 2462 patients selected that correspond to 4 to 33 weeks of data collection. The number of weeks is variable because we did not start all hospitals simultaneously. From the current number of cases detected, 58% are female, 1.9% are under 20, 8.2% are between 20 and 50 and 89.9% are 50 years or older. The leading causes of vision impairment among these patients are diabetic retinopathy (DR), cataract (C), glaucoma (GC) and age-related macular degeneration (AMD). Using the North American definition of VI the proportions are 26.8% for DR, 25.5% for C, 10.4% for GC and 8.2% for AMD. The remaining causes of VI have percentages below 5% and in total they correspond to approximately 29% of the cases detected.Conclusions Our results show that the most common causes of vision impairment are eye diseases related with systemic conditions and aging of the population. Vision impairment was relatively low under the age of 20 and the causes were mostly inherited diseases. Numbers reported now will be more accurate at the end of the study but they already highlight the importance of targeting conditions such as diabetes.
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| 4. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 5. |
- Marques, Ana Patricia, et al.
(författare)
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Estimating the cost of visual impairment : initial results
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Vision loss can have a substantial human and economic impact on individuals and society that include disability, loss of productivity and reduction in quality of life. The purpose of this study was to estimate economic burden of visual impairment in Portugal.Methods: A prevalence-based cost of illness approach was adopted to estimate costs of vision impairment. We estimated direct medical costs and indirect economic costs. Direct medical hospital costs were determined using a bottom up approach. For those meeting the inclusion criteria (visual acuity of 20/40 or 0.5decimal or worse in the better eye and/or visual field of less than 20deg) we estimated direct costs by collecting information from administrative records that included: physician’s office visits, emergency and outpatient visits. We developed a survey based in parts of the annotated cost questionnaire-HERU Discussion Paper N.03/01 (UK Working Party on Patient Costs) and the Service Receipt Inventory-European Version. Using the questionnaire that we developed, in face-to-face interviews, we collect direct medical expenditures supported by patients that included: costs with medical prescriptions, low vision aids and devices. With the same questionnaire we collected information for indirect costs calculations. Indirect costs were calculated by estimating the value of productivity losses including employment participation, absenteeism and caregiver costs.Results: Results presented here correspond to 442 patients that met the inclusion criteria. The four main causes of visual impairment in this sample were Diabetic Retinopathy, Cataract, Glaucoma and Age-related macular degeneration. Direct medical hospital costs were accountable for 12% of total costs calculated. Patient expenditures represented 25% of expenses with visual impairment and indirect costs corresponded to 63% of the total. From this data we estimated that the average annual direct cost per patient with VI was 958 euro and average annual indirect cost was 1655 euro.Conclusions: With the instruments and methodology that was adopted we were able quantify direct medical hospital costs as well as indirect costs of visual impairment. Results of this study show that more than half of the costs with VI are indirect. This highlights that particular attention should be given to costs that arise for individuals with vision loss.
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| 6. |
- Yang, Yaohua, et al.
(författare)
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Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk
- 2019
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:3, s. 505-517
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
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| 7. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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