| 1. |
- 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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| 2. |
- Blunden, Jessica, et al.
(författare)
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State of the Climate in 2012
- 2013
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
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Tidskriftsartikel (refereegranskat)abstract
- For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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| 3. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 4. |
- Abrahamson, Josefin, et al.
(författare)
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Adolescent elite skiers with and without cam morphology did change their hip joint range of motion with 2 years follow-up
- 2019
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 27:10, s. 3149-3157
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate how range of motion of the hips and the lumbar spine are affected by continued elite, alpine skiing in young subjects, with and without a magnetic resonance imaging verified cam morphology, in a 2-year follow-up study. The hypothesis is that skiers with cam morphology will show a decrease in hip joint range of motion as compared with skiers without cam, after a 2-year follow-up. Method: Thirty adolescent elite alpine skiers were examined at the baseline (mean age 17.3 ± 0.7 years) and after 2 years. All skiers were examined for the presence of cam morphology (α-angle > 55°) using magnetic resonance imaging at the baseline. Clinical examinations of range of motion in standing lumbar flexion and extension, supine hip flexion, internal rotation, FABER test and sitting internal rotation and external rotation were performed both at the baseline and after 2 years. Results: Skiers with and without cam morphology showed a significant decrease from baseline to follow-up in both hips for supine internal rotation (right: mean − 13.3° and − 10.9° [P < 0.001]; left: mean − 7.6° [P = 0.004] and − 7.9° [P = 0.02]), sitting internal rotation (right: mean − 9.6° and − 6.3° [P < 0.001]; left: mean − 7.6° [P = 0.02] and − 3.3° [P = 0.008]) and sitting external rotation (right: mean − 16.9° and − 11.4° and left: mean − 17.9° and − 14.5° [P < 0.001]) and were shown to have an increased left hip flexion (mean + 8.4° and + 4.6° [P = 0.004]). Skiers with cam were also shown to have an increased right hip flexion (mean + 6.4° [P = 0.037]). Differences were found between cam and no-cam skiers from baseline to follow-up in the sitting internal rotation in both hips (right: mean 3.25°, left: mean 4.27° [P < 0.001]), the right hip flexion (mean 6.02° [P = 0.045]) and lumbar flexion (mean − 1.21°, [P = 0.009]). Conclusion: Young, elite alpine skiers with cam morphology decreased their internal rotation in sitting position as compared with skiers without the cam morphology after 2 years of continued elite skiing. Level of evidence: II.
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| 5. |
- Abrahamson, Josefin, et al.
(författare)
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Hip pain and its correlation with cam morphology in young skiers-a minimum of 5 years follow-up
- 2020
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Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThere is conflicting evidence regarding the association between cam morphological changes and hip pain, and it remains unclear who with cam morphology will develop hip pain and who will not. This study aimed to investigate the correlation between cam morphology, hip pain, and activity level at a 5-year follow-up in young Alpine and Mogul skiers.MethodAll students (n = 76) at angstrom re Ski National Sports High School were invited and accepted participation in this prospective study at baseline. Magnetic resonance imaging (MRI) of both hips was conducted to evaluate the presence of cam morphology (alpha -angle >= 55 degrees) and its size alongside the reporting of hip pain, type, and frequency of training by the Back and hip questionnaire, at baseline. After 5 years, the skiers were invited to complete a shortened version of the same questionnaire.ResultsA total of 60 skiers (80%) completed the follow-up questionnaire, of which 53 had concomitant MRI data. Cam morphology was present in 25 skiers (47.2%, 39 hips). Hip pain at baseline and at follow-up was reported in 17 (28.3%) and 22 (36.7%) skiers, respectively. No correlations were found between the activity level, the frequency, and the size of cam morphology and hip pain, except for the right hip alpha -angle at 1 o'clock and hip pain in skiers with cam morphology at baseline (r(s) = 0.49; P = 0.03) and at follow-up (r(s) = 0.47; P = 0.04). A total of 73.3% skiers had retired, of which 48% reported this was due to injuries.ConclusionHip pain was not shown to be correlated, or had a low correlation, with activity level and the presence and size of cam morphology in young skiers on a 5-year follow-up. Based on these results, cam morphology or activity level did not affect hip pain to develop during 5 years of follow-up in young skiers. Furthermore, this study highlights that almost 75% of young elite skiers had retired from their elite career with almost 50% reporting that this was due to injuries sustained from skiing.
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| 6. |
- Aminoff, Amina Swärd, et al.
(författare)
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The effect of pelvic tilt and cam on hip range of motion in young elite skiers and nonathletes
- 2018
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Ingår i: Open Access Journal of Sports Medicine. - : Informa UK Limited. - 1179-1543. ; 9, s. 147-156
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Tidskriftsartikel (refereegranskat)abstract
- Background: Current knowledge of the effect of changes in posture and the way cam morphology of the hip joint may affect hip range of motion (ROM) is limited. Purpose: To determine the effect of changes in pelvic tilt (PT) on hip ROM and with/without the presence of cam. Materials and methods: The hip ROM of 87 subjects (n=61 young elite skiers, n=26 nonathletes) was examined using a goniometer, in three different seated postures (flexed, neutral, and extended). The hips of the subjects were further subgrouped into cam and no-cam morphology, based on the magnetic resonance imaging findings in the hips. Results: There was a significant correlation between the hip ROM and the seated posture in both extended and flexed postures compared with the neutral posture. There was a significant decrease in internal hip rotation when the subjects sat with an extended posture with maximum anterior PT (p<0.0001). There was a significant increase in internal hip rotation when the subjects sat with a flexed posture with maximum posterior PT (p<0.001). External rotation was significantly decreased in an extended posture with maximum anterior PT (p<0.0001), but there was no difference in flexed posture with maximum posterior PT. The hips with cam morphology had reduced internal hip rotation in all three positions, but they responded to the changes in position in a similar manner to hips without cam morphology. Conclusion: Dynamic changes in PT significantly influence hip ROM in young people, independent of cam or no-cam morphology.
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| 7. |
- Aminoff, Anna Swärd, et al.
(författare)
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Young elite Alpine and Mogul skiers have a higher prevalence of cam morphology than non-athletes
- 2020
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 28:4, s. 1262-1269
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To investigate the prevalence of cam morphology in (1) a group of young elite Mogul and Alpine skiers compared with non-athletes and (2) between the sexes. Method The hip joints of 87 subjects [n = 61 young elite skiers (29 females and 32 males) and n = 26 non-athletes (17 females and 9 males)] were examined using MRI, for measurements of the presence of cam morphology (alpha-angle >= 55). Results The skiers had a significantly higher prevalence of cam morphology compared with the non-athletes (49% vs 19%, p = 0.009). A significant difference (p < 0.001) was also found between females and males, where 22% of the females and 61% of the males had cam morphology. Among the skiers, there was also a significant difference (p < 0.001) between the sexes, where 28% of the females and 68% of the males had cam morphology. This difference between the sexes was not found in the non-athletic group. No significant differences were found between Mogul and Alpine skiers. Conclusion Young male elite skiers have a higher prevalence of cam morphology of the hips compared with non-athletes.
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| 8. |
- Edling, Silvia, 1974-
(författare)
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Ruptured narratives : An analysis of the contradictions within young people's responses to issues of personal responsibility and social violence within an educational context
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis addresses the problems of social violence which are based on stereotyped prejudices, and directed towards people who differ from the norm, and asks how education aiming at counteracting social violence can be understood. Within education, the aspiration to contest social violence is generally motivated by a democratic framework stressing distributive justice and everyone’s equal value. The promotion of justice has recently become linked to the development of individuals’ moral responsibility in ways which overlook relational complexities. In contrast to a developmental approach, the intention with this thesis is to explore how education can be understood by using nine young people’s responses and sense of responsibility(-ies) in relation to others’ life circumstances as a starting-point for analysis. Hence, the investigation delves into the relationship between moral action and justice/injustice within the unpredictable field of culture, outside the notion of a democratic (moral) foundation. Using an ethics of alterity, which advocates a respect for difference, it is possible to claim that young people already are (unconditionally and unlimitedly) responsible as seen in their everyday responses to others’ life circumstances. The question at stake is rather what they choose to do with their responsibility. An ethics of dissensus, on the other hand, is used to acknowledge the embodiedness of human relations which now and then can be accompanied by unintended reactions, power relations, and contradictions – all of which necessary to pay attention to when social violence is discussed. An ethics of dissensus creates a link to Julia Kristeva’s subject-in-process, and to ruptured narratives, which has been used as an analytical lens in this investigation. The results of the thesis indicate that the youths already are forced to face other people’s more or less harsh life circumstances. Furthermore, all of the young people portray themselves as persons who do not want to expose people to harm and at times even as persons who want to promote others’ well-being. These ideal self images, however, collide with other forces which place these ideals on trial. A comparison between the young people’s narratives indicates two things. Firstly, although they sometimes use the same word when they describe their sense of responsibility, the meaning they assign the word differs along with their possibilities of action. Secondly, there is a notable distinction between young people who in concordance to the educational discourse position their sense of responsibility in the future and within knowledge acquisition, and those who chiefly position their sense of responsibility in their everyday interactions by using the resources available. Another result of the analysis is the evidence of a gap between the concept of democracy and young people’s everyday responses. Overall, the young people’s ruptured narratives shed light on how they contribute to the creation of social violence as well as to how they promote others’ well-being in ways, which challenge the foundation in democracy as an educational possibility to contest social violence on several points.
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| 9. |
- Franke, Andre, et al.
(författare)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
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Tidskriftsartikel (refereegranskat)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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| 10. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 11. |
- Green, Richard E., et al.
(författare)
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Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1335-
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Tidskriftsartikel (refereegranskat)abstract
- To provide context for the diversification of archosaurs-the group that includes crocodilians, dinosaurs, and birds-we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.
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| 12. |
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| 13. |
- Kelsen, Jesper, et al.
(författare)
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Copenhagen Head Injury Ciclosporin Study : A Phase IIa Safety, Pharmacokinetics, and Biomarker Study of Ciclosporin in Severe Traumatic Brain Injury Patients
- 2019
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 36:23, s. 3253-3263
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. Exploratory pharmacodynamic study measures included microdialysis in brain parenchyma and protein biomarkers of brain injury in the cerebrospinal fluid (CSF). Sixteen adult patients with severe TBI (Glasgow Coma Scale 4-8) were included, and all patients received an initial loading dose of 2.5 mg/kg followed by a continuous infusion for 5 days. The first 10 patients received an infusion dosage of 5 mg/kg/day whereas the subsequent 6 patients received 10 mg/kg/day. No mortality was registered within the study duration, and the distribution of adverse events was similar between the two treatment groups. Pharmacokinetic analysis of CSF confirmed dose-dependent brain exposure. Between- and within-patient variability in blood concentrations was limited, whereas CSF concentrations were more variable. The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood-brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy.
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| 14. |
- Leebens-Mack, James H., et al.
(författare)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 15. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 16. |
- Schlegel, Todd T., et al.
(författare)
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Accuracy of advanced versus strictly conventional 12-lead ECG for detection and screening of coronary artery disease, left ventricular hypertrophy and left ventricular systolic dysfunction
- 2010
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD) and left ventricular hypertrophy (LVH) and low positive predictive value (PPV) for prediction of left ventricular systolic dysfunction (LVSD). We hypothesized that a similar to 5-min resting 12-lead advanced ECG test ("A-ECG") that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG. Methods: Results from nearly every conventional and advanced resting ECG parameter known from the literature to have diagnostic or predictive value were first retrospectively evaluated in 418 healthy controls and 290 patients with imaging-proven CAD, LVH and/or LVSD. Each ECG parameter was examined for potential inclusion within multi-parameter A-ECG scores derived from multivariate regression models that were designed to optimally screen for disease in general or LVSD in particular. The performance of the best retrospectively-validated A-ECG scores was then compared against that of optimized pooled criteria from the strictly conventional ECG in a test set of 315 additional individuals. Results: Compared to optimized pooled criteria from the strictly conventional ECG, a 7-parameter A-ECG score validated in the training set increased the sensitivity of resting ECG for identifying disease in the test set from 78% (72-84%) to 92% (88-96%) (P < 0.0001) while also increasing specificity from 85% (77-91%) to 94% (88-98%) (P < 0.05). In diseased patients, another 5-parameter A-ECG score increased the PPV of ECG for LVSD from 53% (41-65%) to 92% (78-98%) (P < 0.0001) without compromising related negative predictive value. Conclusion: Resting 12-lead A-ECG scoring is more accurate than strictly conventional ECG in screening for CAD, LVH and LVSD.
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| 19. |
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| 20. |
- Thoreson, Olof, 1981, et al.
(författare)
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Back pain and MRI changes in the thoraco-lumbar spine of youngelite Mogul skiers.
- 2017
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Ingår i: Scandinavian journal of medicine & science in sports. - : Wiley. - 1600-0838 .- 0905-7188. ; 27:9, s. 983-989
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Tidskriftsartikel (refereegranskat)abstract
- Athletes have a higher prevalence of LBP and spinal abnormalities on Magnetic Resonance Imaging (MRI) compared to non-athletes. The objective of this study was to investigate the amount of spinal MRI abnormalities and the lifetime prevalence of low back pain (LBP) in 16 young elite Mogul skiers compared to 28 non-athletes in the corresponding age in a cross-sectional design. LBP was assessed by a questionnaire consisting of a part regarding previous or present back pain, the Oswestry disability index, and the EuroQol questionnaire. MRI examinations from Th5 to sacrum were conducted to evaluate spinal pathologies. The Mogul skiers had significantly more MRI abnormalities (like disc degeneration) in mean (7.25 vs 3.78, P<0.023) compared to the controls. No significant difference was seen regarding the lifetime LBP prevalence between the groups (50% vs 42%, P=0.555). No correlation could be found between disc degeneration and back pain in this study. Young elite Mogul skiers, compared to an age-matched control group of non-athletes, have an increased risk of developing spinal abnormalities potentially due to the different high loads that they are subjected to in their sport. Future relationship between the MRI abnormalities and LBP cannot be verified by this study design.
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| 24. |
- Todd, Carl, et al.
(författare)
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No difference in prevalence of spine and hip pain in young Elite skiers
- 2018
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:7, s. 1959-1965
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the prevalence between back and hip pain in young Elite skiers. Sample group (n = 102), consisted of young Elite skiers (n = 75) and age-matched non-athletes (n = 27), all completed a three-part back and hip pain questionnaire, Oswestry Disability Index and EuroQoL to evaluate general health, activity level, back and hip pain prevalence. No significant differences were shown for lifetime prevalence of back pain in the skiers (50%) compared with controls (44%) (n.s.). Duration of back pain for the skiers showed (30%) > 1 year, whilst (46%) > 5 years. A significant difference was shown with increased Visual Analogue Scale back pain levels for skiers 5.3 (SD 3.1) compared with controls 2.4 (SD 1.9, p = 0.025). No significant differences were shown for lifetime prevalence of hip pain in skiers (21%) compared with controls (8%) (n.s.). Young Elite skiers are shown not to have increased lifetime prevalence for back and hip pain compared with a non-athletic control group.
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| 25. |
- Todd, Carl, et al.
(författare)
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Pelvic Retroversion is Associated with Flat Back and Cam Type Femoro-Acetabular Impingement in Young Elite Skiers
- 2016
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Ingår i: Journal of spine. - : OMICS Publishing Group. - 2165-7939. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The spino-pelvic complex in humans helps to maintain an upright posture, by balancing the spinal sagittal alignment with the hip joints and pelvic girdle. The extent of how the hip joint may influence the spino-pelvic alignment is not fully understood. Hip joint cam femoro-acetabular impingement is a common source of hip and groin disability in young athletes and has been linked to abnormal joint morphology from repetitive loading of the proximal femoral head abutting against the acetabulum. The aim of this study was to compare the radiological parameters of spino-pelvic sagittal alignment and spinal types according to Roussouly’s classification in relation to hip joint cam femoro-acetabular impingement. Methods: The sample group (n=102), mean age (17.7 ± 1.4) years, consisted of elite skiers (n=75) and nonathletes (n=27). Hip joints were examined for increased morphological cam deformity, (alpha angle greater than 55o) with Magnetic Resonance Imaging and standing lateral plain radiographs were taken for measurements of the spinopelvic sagittal alignment. Results: A significant difference was shown in a mixed population (skiers and non-athletes) for an increased Pelvic Tilt angle (13°, SD 10.2) in the presence of morphological hip joint cam deformity compared with participants without cam deformity (8.5°, SD 7.1, P=0.036). Type II Roussouly spines occurred more frequently in skiers in the presence of increased cam (67%) compared with no cam (33%), however, this was not significant (P=0.19). Secondary findings highlighted significant differences shown for the prevalence of cam in a mixed-population for gender; males 60% (n=26) shown to have significantly more cam deformity compared with females 22% (n=10, P=0.001). Similar for height, with taller participants being shown to have significantly more cam deformity >177cm (SD 7.6) compared with no cam deformity <170 cm (SD 7.5, P=0.001). Conclusion: A significant difference was shown with an increased Pelvic Tilt angle for an age-matched mixedgroup of elite skiers and non-athletes in the presence of increased morphological hip joint cam type femoro-acetabular impingement. Moreover, Elite skiers were shown to have an increased distribution of spinal Type II classification according to Roussouly in the presence of an increased frequency of cam femoro-acetabular impingement.
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| 26. |
- Todd, Carl, et al.
(författare)
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Resolving anterior hip pain in a young male footballer following arthroscopic surgery for Femoroacetabular Impingement Syndrome: A case report
- 2020
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Ingår i: Journal of Bodywork and Movement Therapies. - : Elsevier BV. - 1360-8592. ; 24:1, s. 63-68
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Tidskriftsartikel (refereegranskat)abstract
- Background: There appear to be limited studies available regarding the conservative management of patients following hip joint arthroscopic surgery, or investigating reasons for which patients still report hip and groin pain post surgery. Objectives: Treatment was applied to restore spino-pelvic mechanics and to reduce soft tissue restrictions in hip joint motion. Neuromuscular movement control and work capacity exercises were encouraged to support the integrity of the hip joint and spino-pelvic complex. Clinical features: A 22-year-old male footballer, (height 190cm and weight 82kg) presented reporting an eighteen-month history of hip and groin pain, having previously undergone bilateral arthroscopic surgery twelve months earlier for Femoroacetabular Impingement Syndrome. Strength measurements were recorded using the MicroFET 2 Wireless Digital Handheld Dynamometer. Trunk muscular endurance was evaluated with Sorenson test. Results: Five treatment consultations over a five-week period resulted in pain reduction, (Visual Analogue Scale 8/10 to 0/10). Improvement in range of motion, right hip flexion (70–100°) and left (80–100°), right internal rotation (30–45°) and left (40–45°). Improvement in strength, specifically right hip flexion (0.29–0.43Nm/kg, 48%) and right hip abduction (0.35–0.46Nm/kg, 31%). Improvement in trunk muscular endurance increased 41% from 170 seconds to 240 seconds. Conclusion: This case report supports the rationale that the post arthroscopic management of Femoroacetabular Impingement Syndrome, should include both treatment to address spino-pelvic restrictions, if appropriate, combined with exercises that specifically target hip flexor strength. However, a larger randomized study would provide a clearer understanding for the management of this particular subset of patients. © 2019 Elsevier Ltd
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| 27. |
- Todd, Carl, et al.
(författare)
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Validation of spinal sagittal alignment with plain radiographs and the Debrunner Kyphometer
- 2015
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Ingår i: Medical research archives. - : Knowledge Enterprise Journals. - 2375-1916 .- 2375-1924. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Validation of the Debrunner Kyphometer as a clinical non-radiological method for investigating spinal sagittal alignment was compared with standing lateral radiographs. The sample group (n=102) consisted of elite Alpine skiers (n=75) and a non-athletic population (n=27), mean age 17.7 (±1.4) years. Non-radiological and radiological measurements of the spinal sagittal kyphosis and lordosis range of motion were carried out in the erect standing position. Thoracic kyphosis measurements comparing the Debrunner Kyphometer with a radiological standard, showed a good level of agreement and a statistical significance (ICC 0.67, 95% CI: 0.26 to 0.83, p<0.001). Lumbar lordosis measurements showed poor levels of agreement in spite of being statistically significant (ICC 0.33, 95% CI: 0.13 to 0.50, p=0.001). There was no significant difference reported in the spinal alignment between skiers and controls using both radiological and non-radiological methods. Therefore, we conclude that due to the large variation in ranges between both methods, there is a limited value in using the Debrunner Kyphometer as a non-invasive method for the evaluation of spinal sagittal alignment.
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| 28. |
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| 30. |
- Voight, Benjamin F., et al.
(författare)
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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
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Tidskriftsartikel (refereegranskat)abstract
- By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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| 31. |
- Witwit, Wisam, et al.
(författare)
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Disc degeneration on MRI is more prevalent in young elite skiers compared to controls.
- 2018
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Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 26:1, s. 325-332
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Tidskriftsartikel (refereegranskat)abstract
- Evidence-based facts regarding spine abnormalities and back pain are needed in order to develop rehabilitation programs and prevent spine injuries in young skiers. The aim therefore is to identify MRI changes in the thoraco-lumbar spine and the lifetime prevalence of back pain, as well as the association between them, in young skiers compared to non-athletes.Seventy-five young elite alpine and mogul skiers, age range 16-20years, were compared with 27 non-athletic controls. All subjects underwent spinal MRI and answered back pain questionnaires.Fifty-six percent of skiers had at least one disc Pfirrmann grade ≥3 compared to 30% of controls (p=0.027). Schmorl's nodes (46%) and disc height reduction (37%) were significantly more prevalent in skiers compared to controls (0%) (p<0.001). When all parameters were combined together, skiers had significantly higher rate of radiological changes than controls, 82% compared to 54% (p=0.007). The mean number of discs with Pfirrmann grade ≥3 was 1.1 per individual in skiers (median 1, range 0-6) versus 0.6 in controls (median 0, range 0-3). There was no significant difference in lifetime prevalence of back pain between skiers (50%) and controls (44%) (n.s.). MRI abnormalities in skiers did not correlate with lifetime prevalence of back pain. Skiers had a better health perception than controls (p=0.026).Alpine skiers have more degenerative disc changes compared to non-athletes, but these changes do not correlate with the lifetime prevalence of back pain. Lifetime prevalence of back pain is not significantly different between the groups; however, skiers report more severe pain on VAS score.II.
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| 32. |
- Witwit, Wisam, et al.
(författare)
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No Significant Change in MRI Abnormalities or Back Pain Prevalence in the Thoraco-Lumbar Spine of Young Elite Skiers Over a 2-Year Follow-Up
- 2022
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Ingår i: Open Access Journal of Sports Medicine. - 1179-1543. ; 13, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- Background: Young athletes are at increasing risk for spinal column injuries due to overloading the spine with excessive sports activities, with potential development of complications later in life.Purpose: The purpose of this 2-year follow-up study of young elite skiers and non-athletes was to investigate any potential change in the thoraco-lumbar findings on MIRI and to outline any change in back pain prevalence with continuing sporting activity and age. Study Design: Longitudinal cross-sectional study.Methods: MIRI of the thoraco-lumbar spine was performed on 30 skiers (mean age 20 years, female 43%) and 16 non-athletes (mean age 19, female 75%), available for the 2-year follow-up. The intervertebral discs were evaluated for signal, height, bulge/herniation, and additionally according to Pfirrmann classification, and the endplates were graded according to endplate defect score. Any of the following disc findings was defined as disc degenerative change: reduced signal, reduced height, bulge, or herniation. All participants answered a specific back pain questionnaire.Results: No significant difference in spinal column abnormalities, nor back pain, was found between baseline and 2-year follow-up in neither skiers nor controls. There was significantly higher prevalence of disc degenerative changes in skiers (73%) than in non-athletes (44%, p=0.05). Skiers (63%) had significantly more Pfirrmann grade >= 3 discs compared to non-athletes (25%) (p=0.03). There was no significant difference in number of endplates with score >= 4 between skiers and non-athletes (50% vs 38%, p=0.40) nor in lifetime prevalence of back pain between skiers (46%) and non-athletes (40%).Conclusion: There was no significant change over time of the spinal column MIRI abnormalities, nor back pain prevalence, during a 2-year follow-up of skiers and non-athletes. Young skiers had significantly higher prevalence of spine abnormalities compared with non-athletes. There was no significant difference of the back pain lifetime prevalence in skiers compared with non-athletes.
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| 33. |
- Witwit, Wisam, et al.
(författare)
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Young soccer players have significantly more spinal changes on MRI compared to non-athletes.
- 2020
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Ingår i: Translational Sports Medicine. - : Hindawi Limited. - 2573-8488. ; 3:4, s. 288-295
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Evidence-based facts regarding spinal abnormalities and back pain in young athletes are needed in order to be able to adapt rehabilitation programs and preventive measures accordingly. The aim of this study was therefore to identify MRI changes in the thoracolumbar spine and the lifetime prevalence of back pain in young football players compared to non-athletes. Methods Young elite football players (n = 27) and non-athletes (n = 26) completed MRI examinations of the thoracolumbar spine. MRI images were evaluated for disk signal, height, bulging, herniation, Schmorl's nodes, spondylolisthesis, and vertebral wedging. All participants answered questionnaires regarding training hours and back pain. Results Disk degenerative changes were more commonly displayed by 89% of the football players compared to 54% of the controls (P = .006). Schmorl's nodes (22%), disk herniation (30%), and reduced disk height (37%) were more prevalent in football players compared to controls (0%) (P = .023 and P = .001, respectively). The lifetime prevalence of back pain was reported by 52% of football players and 44% of controls, a difference that was not statistically significant. Conclusion Young male football (soccer) players have more degenerative disk changes compared to non-athletes. Both groups displayed high lifetime prevalence of back pain.
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| 34. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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