| 1. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
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| 7. |
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- 2019
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Journal article (peer-reviewed)
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| 12. |
- Arndt, D. S., et al.
(author)
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STATE OF THE CLIMATE IN 2017
- 2018
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In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Research review (peer-reviewed)
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| 13. |
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| 14. |
- Hollestelle, Antoinette, et al.
(author)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Journal article (peer-reviewed)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 15. |
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| 16. |
- Arndt, D. S., et al.
(author)
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State of the Climate in 2016
- 2017
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In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Journal article (peer-reviewed)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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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Shu, Xiang, et al.
(author)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Journal article (peer-reviewed)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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| 21. |
- Tsiantoulas, D., et al.
(author)
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APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 597, s. 92-96
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Journal article (peer-reviewed)abstract
- Atherosclerotic cardiovascular disease causes heart attacks and strokes, which are the leading causes of mortality worldwide(1). The formation of atherosclerotic plaques is initiated when low-density lipoproteins bind to heparan-sulfate proteoglycans (HSPGs)(2) and become trapped in the subendothelial space of large and medium size arteries, which leads to chronic inflammation and remodelling of the artery wall(2). A proliferation-inducing ligand (APRIL) is a cytokine that binds to HSPGs(3), but the physiology of this interaction is largely unknown. Here we show that genetic ablation or antibody-mediated depletion of APRIL aggravates atherosclerosis in mice. Mechanistically, we demonstrate that APRIL confers atheroprotection by binding to heparan sulfate chains of heparan-sulfate proteoglycan 2 (HSPG2), which limits the retention of low-density lipoproteins, accumulation of macrophages and formation of necrotic cores. Indeed, antibody-mediated depletion of APRIL in mice expressing heparan sulfate-deficient HSPG2 had no effect on the development of atherosclerosis. Treatment with a specific anti-APRIL antibody that promotes the binding of APRIL to HSPGs reduced experimental atherosclerosis. Furthermore, the serum levels of a form of human APRIL protein that binds to HSPGs, which we termed non-canonical APRIL (nc-APRIL), are associated independently of traditional risk factors with long-term cardiovascular mortality in patients with atherosclerosis. Our data reveal properties of APRIL that have broad pathophysiological implications for vascular homeostasis.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Middha, Pooja K., et al.
(author)
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A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- 2023
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In: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
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Journal article (peer-reviewed)abstract
- Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
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| 26. |
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| 27. |
- Saliba-Gustafsson, P., et al.
(author)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Journal article (peer-reviewed)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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| 28. |
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| 29. |
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| 30. |
- Bonomi, A, et al.
(author)
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Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
- 2020
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In: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 21:2, s. 100-108
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Journal article (peer-reviewed)abstract
- The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–maxβ = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.
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| 31. |
- El Kharraz, S., et al.
(author)
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The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation
- 2021
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In: Embo Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 22:12
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Journal article (peer-reviewed)abstract
- Whereas dimerization of the DNA-binding domain of the androgen receptor (AR) plays an evident role in recognizing bipartite response elements, the contribution of the dimerization of the ligand-binding domain (LBD) to the correct functioning of the AR remains unclear. Here, we describe a mouse model with disrupted dimerization of the AR LBD (AR(Lmon/Y)). The disruptive effect of the mutation is demonstrated by the feminized phenotype, absence of male accessory sex glands, and strongly affected spermatogenesis, despite high circulating levels of testosterone. Testosterone replacement studies in orchidectomized mice demonstrate that androgen-regulated transcriptomes in AR(Lmon/Y) mice are completely lost. The mutated AR still translocates to the nucleus and binds chromatin, but does not bind to specific AR binding sites. In vitro studies reveal that the mutation in the LBD dimer interface also affects other AR functions such as DNA binding, ligand binding, and co-regulator binding. In conclusion, LBD dimerization is crucial for the development of AR-dependent tissues through its role in transcriptional regulation in vivo. Our findings identify AR LBD dimerization as a possible target for AR inhibition.
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| 32. |
- Kapoor, Pooja Middha, et al.
(author)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
-
Journal article (peer-reviewed)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 33. |
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| 34. |
- Shraim, M. A., et al.
(author)
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Features and methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system: a Delphi expert consensus study
- 2022
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In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 163:9, s. 1812-1828
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Journal article (peer-reviewed)abstract
- Classification of musculoskeletal pain based on underlying pain mechanisms (nociceptive, neuropathic, and nociplastic pain) is challenging. In the absence of a gold standard, verification of features that could aid in discrimination between these mechanisms in clinical practice and research depends on expert consensus. This Delphi expert consensus study aimed to: (1) identify features and assessment findings that are unique to a pain mechanism category or shared between no more than 2 categories and (2) develop a ranked list of candidate features that could potentially discriminate between pain mechanisms. A group of international experts were recruited based on their expertise in the field of pain. The Delphi process involved 2 rounds: round 1 assessed expert opinion on features that are unique to a pain mechanism category or shared between 2 (based on a 40% agreement threshold); and round 2 reviewed features that failed to reach consensus, evaluated additional features, and considered wording changes. Forty-nine international experts representing a wide range of disciplines participated. Consensus was reached for 196 of 292 features presented to the panel (clinical examination-134 features, quantitative sensory testing-34, imaging and diagnostic testing-14, and pain-type questionnaires-14). From the 196 features, consensus was reached for 76 features as unique to nociceptive (17), neuropathic (37), or nociplastic (22) pain mechanisms and 120 features as shared between pairs of pain mechanism categories (78 for neuropathic and nociplastic pain). This consensus study generated a list of potential candidate features that are likely to aid in discrimination between types of musculoskeletal pain.
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| 35. |
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| 36. |
- Askmyr, Maria, et al.
(author)
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Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure.
- 2015
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Journal article (peer-reviewed)abstract
- The gp130 receptor and its binding partners play a central role in cytokine signalling. Ciliary neurotrophic factor (CNTF) is one of the cytokines that signals through the gp130 receptor complex. CNTF has previously been shown to be a negative regulator of trabecular bone remodelling and important for motor neuron development. Since haematopoietic cell maintenance and differentiation is dependent on the bone marrow (BM) microenvironment, where cells of the osteoblastic lineage are important regulators, we hypothesised that CNTF may also have important roles in regulating haematopoiesis. Analysis of haematopoietic parameters in male and female Cntf(-/-) mice at 12 and 24 weeks of age revealed altered B lymphopoiesis. Strikingly, the B lymphocyte phenotype differed based on sex, age and also the BM microenvironment in which the B cells develop. When BM cells from wildtype mice were transplanted into Cntf(-/-) mice, there were minimal effects on B lymphopoiesis or bone parameters. However, when Cntf(-/-) BM cells were transplanted into a wildtype BM microenvironment, there were changes in both haematopoiesis and bone parameters. Our data reveal that haematopoietic cell-derived CNTF has roles in regulating BM B cell lymphopoiesis and both trabecular and cortical bone, the latter in a sex-dependent manner.
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| 37. |
- Bosman, M., et al.
(author)
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Placebo response in pharmacological trials in patients with functional dyspepsia-A systematic review and meta-analysis
- 2023
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:2
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Research review (peer-reviewed)abstract
- Background Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response. Methods We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined. Key Results We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1-50.0) using the symptom responder definition, 20.5% (12.8-31.0) using the symptom-free responder definition, 38.5% (33.8-43.6) using the adequate relief responder definition, and 35.5% (31.6-39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms. Conclusions and Inferences The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.
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| 38. |
- de Man, F., et al.
(author)
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Towards optimal nutritional care for all : A multi-disciplinary patient centred approach to a complex challenge
- 2020
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In: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 39:5, s. 1309-1314
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Journal article (peer-reviewed)abstract
- Ten years ago, European health care professional societies, health associations and members of the European Parliament convened in Brussels to discuss the necessary and urgent actions needed to improve access, initiation and follow up nutritional care for European citizens. As a response to this, in 2014 the Optimal Nutritional Care for All (ONCA) campaign was launched under the leadership of the European Nutritional for Health Alliance and its members. As of today this campaign has been rolled out in 18 European countries, whereby national multi-disciplinary platforms including patient groups work together to implement national nutritional care programs and develop good practices in care, research, education in order to increase awareness on malnutrition and improve nutritional care. This article describes the making of and evolution of the ONCA campaign, the outcomes and impact created, as well as opportunities to accelerate implementation of personalized nutritional care for all European citizens.
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| 39. |
- Dees, M., et al.
(author)
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Status and Future of Biomass Assessment for Energetic Use in Europe
- 2012
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In: 20th European Biomass Conference and Exhibition. - 9788889407547 ; , s. 23-24
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Conference paper (peer-reviewed)abstract
- Results from biomass potential assessments vary considerably, both on global and European level. On the other hand reliable figures on biomass potentials are an important basis for energy policy and for strategies that aim at an increase of use of biomass for energy both on EU-Level as well as e. g. on national level in the National Renewable Energy Action Plans (NREAPs) by the 27 member states. This paper is based on the findings of two projects, BEE and CEUBIOM. It presents an overview of the findings of these projects and includes an analysis of biomass potential aspects within the NREAPs. It presents how, based on an analysis of the status quo of potential studies, the projects developed proposals for a harmonisation of the methodologies and it presents the key areas they identified for future work in the field.
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| 40. |
- den Hoed, M, et al.
(author)
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SNP analyses of postprandial responses in (an)orexigenic hormones and feelings of hunger reveal long-term physiological adaptations to facilitate homeostasis.
- 2008
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 32:12
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Journal article (peer-reviewed)abstract
- BACKGROUND: The postprandial responses in (an)orexigenic hormones and feelings of hunger are characterized by large inter-individual differences. Food intake regulation was shown earlier to be partly under genetic control.OBJECTIVE: This study aimed to determine whether the postprandial responses in (an)orexigenic hormones and parameters of food intake regulation are associated with single nucleotide polymorphisms (SNPs) in genes encoding for satiety hormones and their receptors.DESIGN: Peptide YY (PYY), glucagon-like peptide 1 and ghrelin levels, as well as feelings of hunger and satiety, were determined pre- and postprandially in 62 women and 41 men (age 31+/-14 years; body mass index 25.0+/-3.1 kg/m(2)). Dietary restraint, disinhibition and perceived hunger were determined using the three-factor eating questionnaire. SNPs were determined in the GHRL, GHSR, LEP, LEPR, PYY, NPY, NPY2R and CART genes.RESULTS: The postprandial response in plasma ghrelin levels was associated with SNPs in PYY (215G>C, P<0.01) and LEPR (326A>G and 688A>G, P<0.01), and in plasma PYY levels with SNPs in GHRL (-501A>C, P<0.05) and GHSR (477G>A, P<0.05). The postprandial response in feelings of hunger was characterized by an SNP-SNP interaction involving SNPs in LEPR and NPY2R (668A>G and 585T>C, P<0.05). Dietary restraint and disinhibition were associated with an SNP in GHSR (477G>A, P<0.05), and perceived hunger with SNPs in GHSR and NPY (477G>A and 204T>C, P<0.05).CONCLUSIONS: Part of the inter-individual variability in postprandial responses in (an)orexigenic hormones can be explained by genetic variation. These postprandial responses represent either long-term physiological adaptations to facilitate homeostasis or reinforce direct genetic effects.
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| 41. |
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| 42. |
- Evers, AWM, et al.
(author)
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What Should Clinicians Tell Patients about Placebo and Nocebo Effects? Practical Considerations Based on Expert Consensus
- 2020
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In: Psychotherapy and psychosomatics. - : S. Karger AG. - 1423-0348 .- 0033-3190. ; 90:1, s. 49-56
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Journal article (peer-reviewed)abstract
- <b><i>Introduction:</i></b> Clinical and laboratory studies demonstrate that placebo and nocebo effects influence various symptoms and conditions after the administration of both inert and active treatments. <b><i>Objective:</i></b> There is an increasing need for up-to-date recommendations on how to inform patients about placebo and nocebo effects in clinical practice and train clinicians how to disclose this information. <b><i>Methods:</i></b> Based on previous clinical recommendations concerning placebo and nocebo effects, a 3-step, invitation-only Delphi study was conducted among an interdisciplinary group of internationally recognized experts. The study consisted of open- and closed-ended survey questions followed by a final expert meeting. The surveys were subdivided into 3 parts: (1) informing patients about placebo effects, (2) informing patients about nocebo effects, and (3) training clinicians how to communicate this information to the patients. <b><i>Results:</i></b> There was consensus that communicating general information about placebo and nocebo effects to patients (e.g., explaining their role in treatment) could be beneficial, but that such information needs to be adjusted to match the specific clinical context (e.g., condition and treatment). Experts also agreed that training clinicians to communicate about placebo and nocebo effects should be a regular and integrated part of medical education that makes use of multiple formats, including face-to-face and online modalities. <b><i>Conclusions:</i></b> The current 3-step Delphi study provides consensus-based recommendations and practical considerations for disclosures about placebo and nocebo effects in clinical practice. Future research is needed on how to optimally tailor information to specific clinical conditions and patients’ needs, and on developing standardized disclosure training modules for clinicians.
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| 43. |
- Haugen, Ida K., et al.
(author)
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Development of radiographic classification criteria for hand osteoarthritis : a methodological report (Phase 2)
- 2022
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In: RMD Open. - : BMJ. - 2056-5933. ; 8:1
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Journal article (peer-reviewed)abstract
- ObjectivesIn Phase 1 of developing new hand osteoarthritis (OA) classification criteria, features associated with hand OA were identified in a population with hand complaints. Radiographic findings could better discriminate patients with hand OA and controls than clinical examination findings. The objective of Phase 2 was to achieve consensus on the features and their weights to be included in three radiographic criteria sets of overall hand OA, interphalangeal OA and thumb base OA.MethodsMultidisciplinary, international expert panels were convened. Patient vignettes were used to identify important features consistent with hand OA. A consensus-based decision analysis approach implemented using 1000minds software was applied to identify the most important features and their relative importance influencing the likelihood of symptoms being due to hand OA. Analyses were repeated for interphalangeal and thumb base OA. The reliability and validity of the proposed criteria sets were tested.ResultsThe experts agreed that the criteria sets should be applied in a population with pain, aching or stiffness in hand joint(s) not explained by another disease or acute injury. In this setting, five additional criteria were considered important: age, morning stiffness, radiographic osteophytes, radiographic joint space narrowing and concordance between symptoms and radiographic findings. The reliability and validity were very good.ConclusionRadiographic features were considered critical when determining whether a patient had symptoms due to hand OA. The consensus-based decision analysis approach in Phase 2 complemented the data-driven results from Phase 1, which will form the basis of the final classification criteria sets.
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| 44. |
- Hayden, JA, et al.
(author)
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Exercise treatment effect modifiers in persistent low back pain: an individual participant data meta-analysis of 3514 participants from 27 randomised controlled trials
- 2020
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In: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 54:21, s. 1277-
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Journal article (peer-reviewed)abstract
- Low back pain is one of the leading causes of disability worldwide. Exercise therapy is widely recommended to treat persistent non-specific low back pain. While evidence suggests exercise is, on average, moderately effective, there remains uncertainty about which individuals might benefit the most from exercise.MethodsIn parallel with a Cochrane review update, we requested individual participant data (IPD) from high-quality randomised clinical trials of adults with our two primary outcomes of interest, pain and functional limitations, and calculated global recovery. We compiled a master data set including baseline participant characteristics, exercise and comparison characteristics, and outcomes at short-term, moderate-term and long-term follow-up. We conducted descriptive analyses and one-stage IPD meta-analysis using multilevel mixed-effects regression of the overall treatment effect and prespecified potential treatment effect modifiers.ResultsWe received IPD for 27 trials (3514 participants). For studies included in this analysis, compared with no treatment/usual care, exercise therapy on average reduced pain (mean effect/100 (95% CI) −10.7 (−14.1 to –7.4)), a result compatible with a clinically important 20% smallest worthwhile effect. Exercise therapy reduced functional limitations with a clinically important 23% improvement (mean effect/100 (95% CI) −10.2 (−13.2 to –7.3)) at short-term follow-up. Not having heavy physical demands at work and medication use for low back pain were potential treatment effect modifiers—these were associated with superior exercise outcomes relative to non-exercise comparisons. Lower body mass index was also associated with better outcomes in exercise compared with no treatment/usual care. This study was limited by inconsistent availability and measurement of participant characteristics.ConclusionsThis study provides potentially useful information to help treat patients and design future studies of exercise interventions that are better matched to specific subgroups.Protocol publicationhttps://doi.org/10.1186/2046-4053-1-64
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| 46. |
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| 47. |
- Jais, JP, et al.
(author)
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X-linked Alport syndrome: Natural history and genotype-phenotype correlations in girls and women belonging to 195 families: A "European community Alport syndrome concerted action" study
- 2003
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In: Journal of the American Society of Nephrology. - 1046-6673. ; 14:10, s. 2603-2610
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Journal article (peer-reviewed)abstract
- Alport syndrome (AS) is a type IV collagen hereditary disease characterized by progressive hematuric nephritis, hearing loss, and ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease characterized by much less severe disease in girls and women. A "European Community Alport Syndrome Concerted Action" (ECASCA) group was established to delineate the Alport syndrome phenotype in each gender and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of heterozygous girls and women belonging to the 195 families with proven COL4A5 mutation are compared with those of hemizygous boys and men. Hematuria was observed in 95% of carriers and consistently absent in the others. Proteinuria, hearing loss, and ocular defects developed in 75%, 28%, and 15%, respectively. The probability of developing end-stage renal disease or deafness before the age of 40 yr was 12% and 10%, respectively, in girls and women versus 90 and 80%, respectively, in boys and men. The risk of progression to end-stage renal disease appears to increase after the age of 60 yr in women. Because of the absence of genotype-phenotype correlation and the large intrafamilial phenotypic heterogeneity, early prognosis of the disease in X-linked Alport syndrome carriers remains moot. Risk factors for developing renal failure have been identified: the occurrence and progressive increase in proteinuria, and the development of a hearing defect.
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| 48. |
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| 49. |
- Klaassen, T., et al.
(author)
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Psychometric evaluation of an experience sampling method-based patient-reported outcome measure in functional dyspepsia
- 2021
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:9
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Journal article (peer-reviewed)abstract
- Background Due to important biases, conventional end-of-day and end-of-week assessment methods of gastrointestinal symptoms in functional dyspepsia (FD) are considered suboptimal. Real-time symptom assessment based on the experience sampling method (ESM) could be a more accurate measurement method. This study aimed to evaluate validity and reliability of an ESM-based patient-reported outcome measure (PROM) for symptom assessment in FD. Methods Thirty-five patients with FD (25 female, mean age 44.7 years) completed the ESM-based PROM (a maximum of 10 random moments per day) and an end-of-day symptom diary for 7 consecutive days. On day 7, end-of-week questionnaires were completed including the Nepean Dyspepsia Index (NDI) and Patient Assessment of Gastrointestinal Symptom Severity Index (PAGI-SYM). Key Results Experience sampling method and corresponding end-of-day scores for gastrointestinal symptoms were significantly associated (ICCs range 0.770-0.917). However, end-of-day scores were significantly higher (Delta 0.329-1.031) than mean ESM scores (p < 0.05). Comparing ESM with NDI and PAGI-SYM scores, correlations were weaker (Pearson's r range 0.467-0.846). Cronbach's alpha coefficient was good for upper gastrointestinal symptoms (alpha = 0.842). First half-week and second half-week scores showed very good consistency (ICCs range 0.913-0.975). Conclusion and Inferences Good validity and reliability of a novel ESM-based PROM for assessing gastrointestinal symptoms in FD patients was demonstrated. Moreover, this novel PROM allows to evaluate individual symptom patterns and can evaluate interactions between symptoms and environmental/contextual factors. ESM has the potential to increase patients' disease insight, provide tools for self-management, and improve shared decision making. Hence, this novel tool may aid in the transition toward personalized health care for FD patients.
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