| 1. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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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.
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| 2. |
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| 3. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 4. |
- 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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| 5. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 6. |
- Ho, Joshua W. K., et al.
(författare)
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Comparative analysis of metazoan chromatin organization
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Tidskriftsartikel (refereegranskat)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 7. |
- Johnson, Stacey, et al.
(författare)
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French validation of the e-PROSCeSS questionnaire : stakeholder perceptions of the health promoting sports club
- 2023
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Ingår i: Health Promotion International. - : Oxford University Press. - 0957-4824 .- 1460-2245. ; 38:3
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Tidskriftsartikel (refereegranskat)abstract
- The health promoting sports club describes the development of the settings-based approach in sports clubs. Based on this model, a questionnaire was developed to measure health promotion perceptions in sports clubs (e-PROSCeSS). The objective of this study was to assess the psychometric properties of a French version of the e-PROSCeSS measurement tool. The questionnaire includes three scales measuring stakeholder's perceptions of club (macro), managers (meso) and coaches (micro) activities toward promoting health. Five steps were undertaken to assess perceptions. First, scales were translated into French. Second, each item's content clarity was tested in three populations: managers, coaches, sports participants. Third, descriptive statistics were analyzed for each scale. Fourth, confirmatory factorial analysis was used to select items for each level. Predictive validity found positive relationships between health promotion perceptions and managing/coaching positions, and negative relationships with drop-out intentions. Positive relationships were found between sports participants' perceptions of health promotion and their self-rated performance and quality of life, while negative relationships were detected with drop-out intentions. The French e-PROSCeSS subscales showed good psychometric properties in measuring health determinants at multiple levels. However, the tool did not measure health promotion as an overarching concept that questions its applicability in the sports club setting.
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| 8. |
- Johnson, Stacey, et al.
(författare)
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Measuring Health Promotion in Sports Club Settings : A Modified Delphi Study
- 2019
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Ingår i: Health Education & Behavior. - : SAGE Publications Inc. - 1090-1981 .- 1552-6127. ; 47:1, s. 78-90
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Tidskriftsartikel (refereegranskat)abstract
- Settings-based approaches have become an increasing health promotion focus since the World Health Organization's 1986 Ottawa Charter. While schools, cities, and prisons have implemented this approach, its development within sports environments is recent. Sports are a popular leisure-time activity, requiring validated tools to measure health promotion activity. This study's aim was to develop a measurement tool based on international consensus that measures perceptions of health promotion within sports clubs. It is grounded in the settings-based approach and builds on theory from previous works expanding their context and knowledge. An online, three-round international Delphi study was conducted, inviting experts in sports and health fields to participate in designing the tool. Round 1 created a collaborative list of items; Round 2 validated items based on relevance, importance, and feasibility; and the final round classified items into one determinant category-social, cultural, environmental, or economic. Panelists (69 experts) from 13 countries participated, creating a final list of 62 items at 3 organizational levels; the sports club level included 23 items, the officials level retained 20 items, and the coaching level contained 19 items. This study provides several innovations: (1) applying the settings-based approach to health promotion within sports clubs, (2) defining each club level (sports club, official, coaching) and determinants (social, cultural, environmental, economic) within 3-levels, (3) creating a tool that measures perceptions of health-promotion activities per level and determinant, and (4) obtaining expert consensus on included items. These advancements allow further research on promoting health within sports clubs.
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| 9. |
- Kolaas, Karoline, et al.
(författare)
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Feasibility of a video-delivered mental health course for primary care patients : a single-group prospective cohort study
- 2023
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Ingår i: BMC Primary Care. - : BioMed Central (BMC). - 2731-4553. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In many health care systems, primary care is tasked with offering psychological treatment for common mental disorders. Resources are often limited, which complicates widespread dissemination of traditional psychological treatments. Stepped care models where the less resource-intensive interventions are delivered first, can be employed, but often do not eliminate the need for a thorough diagnostic assessment, which can be time-consuming, has the potential to bottleneck patient intake, and can add to waiting times. Novel low-threshold formats are needed to improve access to mental health care in the primary care setting.METHODS: This was a single-group prospective cohort study (N = 91). We assessed the feasibility of a video-delivered course as a first-line intervention for patients seeking help for mental health problems at a primary care center. The course had a transdiagnostic approach, suitable for both depression and anxiety disorders, and was based on cognitive behavioral techniques. Patients in need of psychosocial assessment, which usually entailed a four- to six-week wait, were referred by physicians or triage nurses. Study participants could start within a week, without the need for conventional diagnostic assessment, and were informed that they would be offered assessment after the course if needed. Key feasibility outcomes included participant satisfaction, attendance rates, the proportion of participants in need of additional clinical intervention after the course, and the rate of clinically significant improvement in anxiety and depression symptoms.RESULTS: Participants scored a mean of 21.8 (SD = 4.0, 9-32, n = 86) on the Client Satisfaction Questionnaire-8; just below our target of 22. The mean attendance rate was 5.0/6 lectures (SD = 1.6, range: 0-6, n = 91). Forty-six percent (37/81) reported experiencing no need of further clinical intervention after the course. The rate of clinically significant improvement was 59% (27/46) for anxiety and 48% (22/46) for depression. No serious adverse event was reported.CONCLUSIONS: Delivering a low-threshold online video-delivered mental health course in primary care appears to be feasible. Adjustments to further improve patient satisfaction are warranted, such as offering the choice of participating online or face-to-face.TRIAL REGISTRATION: (ClinicalTrials.gov NCT04522713) August 21, 2020.
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| 10. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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