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- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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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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| 8. |
- Beral, V, et al.
(författare)
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Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease
- 2002
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 87, s. 1234-45
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK.
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| 14. |
- Ek, Weronica E, et al.
(författare)
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Germline genetic contributions to risk for esophageal adenocarcinoma, barrett's esophagus, and gastroesophageal reflux
- 2013
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 105:22, s. 1711-1718
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Tidskriftsartikel (refereegranskat)abstract
- Background Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett's esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. Methods We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h2 g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were twosided, except in the case of variance-explained estimation where one-sided tests were used. Results We estimated a statistically significant genetic variance explained for BE (h2 g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10-9) and for EA (h2 g = 25 %; SE = 5%; one-sided P = 2 × 10-7). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10-6), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. Conclusions We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases. © The Author 2013.
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| 18. |
- Ek, Weronica E, et al.
(författare)
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Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma
- 2016
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 138:5, s. 1146-1152
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Tidskriftsartikel (refereegranskat)abstract
- The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p=0.002) and in males (p=0.003), but not in females separately (p=0.3). This association was found in tobacco smokers (p=0.003) and in BE patients without reflux (p=0.004), but not in nonsmokers (p=0.2) or those with reflux (p=0.036). SNPs within JMJD1C were associated with risk of EAC in females (p=0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.
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| 19. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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| 20. |
- Lee, Eunjung, et al.
(författare)
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Pleiotropic Analysis of Cancer Risk Loci on Esophageal Adenocarcinoma Risk.
- 2015
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus.METHODS: We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett's esophagus) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn.RESULTS: After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett's esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed.CONCLUSIONS: Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett's esophagus.IMPACT: To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett's esophagus. Cancer Epidemiol Biomarkers Prev; 24(11); 1801-3. ©2015 AACR.
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| 21. |
- Levine, David M, et al.
(författare)
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A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:12
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precancerous Barrett's esophagus (n = 3,175) with 10,120 controls in 2 phases. For the combined case group, we identified three new associations. The first is at 19p13 (rs10419226: P = 3.6 × 10(-10)) in CRTC1 (encoding CREB-regulated transcription coactivator), whose aberrant activation has been associated with oncogenic activity. A second is at 9q22 (rs11789015: P = 1.0 × 10(-9)) in BARX1, which encodes a transcription factor important in esophageal specification. A third is at 3p14 (rs2687201: P = 5.5 × 10(-9)) near the transcription factor FOXP1, which regulates esophageal development. We also refine a previously reported association with Barrett's esophagus near the putative tumor suppressor gene FOXF1 at 16q24 and extend our findings to now include esophageal adenocarcinoma.
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| 22. |
- Lynn Radlick, Rebecca, et al.
(författare)
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Digitally enhanced mentoring for immigrant youth social capital : Protocol for a mixed-methods pilot study and randomized controlled trial
- 2020
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Ingår i: JMIR Research Protocols. - Toronto : J M I R Publications, Inc.. - 1929-0748. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are large disparities between immigrants and native Norwegians in domains such as health, education, and employment. Reducing such disparities is essential for individual and societal well-being. Social capital is associated with positive effects on these domains, and mentoring programs have the potential to boost social capital. However, few studies have assessed mentoring as a social capital intervention among youth or the potential barriers and facilitators of implementing digitally augmented mentoring.Objective: The goal of this paper is to describe a protocol for assessing the implementation and effectiveness of a digitally augmented mentoring program for immigrant youth as a health intervention to promote social capital. The two-stage analytical framework for a pilot study followed by a randomized controlled trial (RCT) is presented. The pilot aims to assess program fidelity and make necessary intervention adjustments before the RCT. The RCT aims to assess the effects of the implemented intervention program on social capital and the relationship between program fidelity and effects.Methods: Both the pilot and RCT will use mixed methods with a process evaluation approach used to structure the intervention and a pre-post test survey component to measure social capital and fidelity of program implementation. Interviews will also be used to enrich the quantitative data from the survey.Results: The pilot study is scheduled to begin in fall 2019. Based on data analyses in spring 2020, potential adjustments will be made to the intervention, with findings used in preparation for the full-scale RCT study.Conclusions: Digitally enhanced mentoring programs may be a helpful intervention for providing immigrant youth with tools for increasing their social capital and indirectly improving health outcomes. This protocol provides new knowledge about the implementation and evaluation of such programs.
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| 23. |
- Nkambule, Comfort M., et al.
(författare)
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Efficient regioselective protection of myo-inositol via migration facile protecting group
- 2011
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 67:3, s. 618-623
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Tidskriftsartikel (refereegranskat)abstract
- A cis-1,2-cyclohexanediol, 1,4,5,6-tetra-O-benzyl-myo-inositol, was selectively protected at the axial C2-hydroxyl via acid-mediated rearrangement of the corresponding 1,2-orthoacetate, or via the base-induced migration of a protecting group that had previously been easily installed with complete regioselectivity at the adjacent equatorial hydroxyl. Esters 4a-6a were synthesized in high yields (75-82%) while sulfonate 7a and silyl ether 8a were obtained in 85 and 31% yields, respectively. The migration of the esters induced by DBU results in equilibrium between regioisomers favouring the C2 protected isomer, but NaH induced migration of sulfonyl and silyl groups results in complete migration from equatorial to axial hydroxyl groups.
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| 24. |
- Prateek, G. V, et al.
(författare)
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Modeling, Detecting, and Tracking Freezing of Gait in Parkinson Disease Using Inertial Sensors
- 2018
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Ingår i: IEEE Transactions on Biomedical Engineering. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0018-9294 .- 1558-2531. ; 65:10, s. 2152-2161
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Tidskriftsartikel (refereegranskat)abstract
- In this paper. we develop new methods to automatically detect the onset and duration of freezing of gait (FOG) in people with Parkinson disease (PD) in real time, using inertial sensors. We first build a physical model that describes the trembling motion during the FOG events. Then, we design a generalized likelihood ratio test framework to develop a two-stage detector for determining the zero-velocity and trembling events during gait. Thereafter, to filter out falsely detected FOG events, we develop a point-process filter that combines the output of the detectors with information about the speed of the foot, provided by a foot-mounted inertial navigation system. We computed the probability of FOG by using the point-process filter to determine the onset and duration of the FOG event. Finally, we validate the performance of the proposed system design using real data obtained from people with PD who performed a set of gait tasks. We compare our FOG detection results with an existing method that only uses accelerometer data. The results indicate that our method yields 81.03% accuracy in detecting FOG events and a threefold decrease in the false-alarm rate relative to the existing method.
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| 25. |
- Thrift, Aaron P, et al.
(författare)
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Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus : a Mendelian randomization study.
- 2014
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 106:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). However, the relationships may be affected by bias and confounding.METHODS: We used data from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided.RESULTS: The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m(2) increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses.CONCLUSIONS: People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses.
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| 26. |
- Varsi, Cecilie, et al.
(författare)
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Barriers Related To The Implementation Of An Informatics Intervention Into Regular Clinical Practice : A Leadership Perspective
- 2012
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Ingår i: Annals of Behavioral Medicine. - : Oxford University Press (OUP). - 0883-6612 .- 1532-4796. ; 43:S1, s. S197-S197
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Tidskriftsartikel (refereegranskat)abstract
- The importance of studying real world implementation of efficacious interventions and the roles of key players for implementation success, such as leadership, is highly recognized. This study explored clinical managers’ experiences and perceptions about the implementation of an informatics intervention called Choice into regular clinical practice. Choice is designed to support patient-provider communication and had shown to be efficacious in a previous RCT.6 nurses and 3 physicians in leadership positions at the 5 units in which Choice was implemented were interviewed post-implementation according to a structured interview guide. The following barriers emerged from the transcribed interviews: In spite of extensive preparation and training prior to implementation, more was needed; there was still resistance to change practice and a lack of motivation among some care providers. Also, time pressure and high turn-over rates required continuous re-training that hampered intervention use. Managers perceived sustained support from and collaboration with the interventionists as vital for the integration of Choice into routine practice.This study confirms that attitudes, established practices and clinical cultures are deeply rooted and hard to change. More research is needed to identify strategies for overcoming these barriers, and how leadership may be better supported to utilize the key role they play for implementation success.
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| 27. |
- Varsi, Cecilie, et al.
(författare)
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Middle managers' experiences and role in implementing an interactive tailored patient assessment eHealth intervention in clinical practice
- 2015
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Ingår i: Computers, Informatics, Nursing. - : Lippincott Williams & Wilkins. - 1538-2931 .- 1538-9774. ; 33:6, s. 249-257
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Tidskriftsartikel (refereegranskat)abstract
- The role of nurse and physician managers is considered crucial for implementing eHealth interventions inclinical practice, but fewstudieshaveexplored this. The aim of the current study was to examine the perceptions of nurse and physicianmanagers regarding facilitators, barriers, management role, responsibility, and action taken in the implementation of an eHealth intervention called Choice into clinical practice. Individual qualitative interviews were conducted with six nurses and three physicians in management positions at five hospital units. The findings revealed that nurse managers reported conscientiously supporting the implementation, but workloads prevented them from participating in the process as closely as they wanted. Physicianmanagers reported less contribution. The implementation process was influenced by facilitating factors such as perceptions of benefits from Choice and use of implementation strategies, along with barriers such as physician resistance, contextual factors and difficulties for front-line providers in learning a new way of communicating with the patients. The findings suggest that role descriptions for both nurse and physician managers should include implementation knowledge and implementation skills. Managers could benefit from an implementation toolkit. Implementation management should be included in management education for healthcare managers to prepare them for the constant need for implementation and improvement in clinical practice.
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| 28. |
- Varsi, Cecilie, et al.
(författare)
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Using the Consolidated Framework for Implementation Research to Identify Barriers and Facilitators for the Implementation of an Internet-Based Patient-Provider Communication Service in Five Settings : A Qualitative Study
- 2015
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although there is growing evidence of the positive effects of Internet-based patient-provider communication (IPPC) services for both patients and health care providers, their implementation into clinical practice continues to be a challenge.Objective: The 3 aims of this study were to (1) identify and compare barriers and facilitators influencing the implementation of an IPPC service in 5 hospital units using the Consolidated Framework for Implementation Research (CFIR), (2) assess the ability of the different constructs of CFIR to distinguish between high and low implementation success, and (3) compare our findings with those from other studies that used the CFIR to discriminate between high and low implementation success.Methods: This study was based on individual interviews with 10 nurses, 6 physicians, and 1 nutritionist who had used the IPPC to answer messages from patients.Results: Of the 36 CFIR constructs, 28 were addressed in the interviews, of which 12 distinguished between high and low implementation units. Most of the distinguishing constructs were related to the inner setting domain of CFIR, indicating that institutional factors were particularly important for successful implementation. Health care providers' beliefs in the intervention as useful for themselves and their patients as well as the implementation process itself were also important. A comparison of constructs across ours and 2 other studies that also used the CFIR to discriminate between high and low implementation success showed that 24 CFIR constructs distinguished between high and low implementation units in at least 1 study; 11 constructs distinguished in 2 studies. However, only 2 constructs (patient need and resources and available resources) distinguished consistently between high and low implementation units in all 3 studies.Conclusions: The CFIR is a helpful framework for illuminating barriers and facilitators influencing IPPC implementation. However, CFIR's strength of being broad and comprehensive also limits its usefulness as an implementation framework because it does not discriminate between the relative importance of its many constructs for implementation success. This is the first study to identify which CFIR constructs are the most promising to distinguish between high and low implementation success across settings and interventions. Findings from this study can contribute to the refinement of CFIR toward a more succinct and parsimonious framework for planning and evaluation of the implementation of clinical interventions.
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