| 191. |
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| 192. |
- Park, J, et al.
(author)
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Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:10
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Journal article (peer-reviewed)abstract
- In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
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| 193. |
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| 194. |
- Reddington, C. L., et al.
(author)
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THE GLOBAL AEROSOL SYNTHESIS AND SCIENCE PROJECT (GASSP) : Measurements and Modeling to Reduce Uncertainty
- 2017
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In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:9, s. 1857-1877
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Journal article (peer-reviewed)abstract
- The largest uncertainty in the historical radiative forcing of climate is caused by changes in aerosol particles due to anthropogenic activity. Sophisticated aerosol microphysics processes have been included in many climate models in an effort to reduce the uncertainty. However, the models are very challenging to evaluate and constrain because they require extensive in situ measurements of the particle size distribution, number concentration, and chemical composition that are not available from global satellite observations. The Global Aerosol Synthesis and Science Project (GASSP) aims to improve the robustness of global aerosol models by combining new methodologies for quantifying model uncertainty, to create an extensive global dataset of aerosol in situ microphysical and chemical measurements, and to develop new ways to assess the uncertainty associated with comparing sparse point measurements with low-resolution models. GASSP has assembled over 45,000 hours of measurements from ships and aircraft as well as data from over 350 ground stations. The measurements have been harmonized into a standardized format that is easily used by modelers and nonspecialist users. Available measurements are extensive, but they are biased to polluted regions of the Northern Hemisphere, leaving large pristine regions and many continental areas poorly sampled. The aerosol radiative forcing uncertainty can be reduced using a rigorous model-data synthesis approach. Nevertheless, our research highlights significant remaining challenges because of the difficulty of constraining many interwoven model uncertainties simultaneously. Although the physical realism of global aerosol models still needs to be improved, the uncertainty in aerosol radiative forcing will be reduced most effectively by systematically and rigorously constraining the models using extensive syntheses of measurements.
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| 195. |
- Reithmaier, Gloria M.S., et al.
(author)
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Carbonate chemistry and carbon sequestration driven by inorganic carbon outwelling from mangroves and saltmarshes
- 2023
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In: Nature Communications. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Mangroves and saltmarshes are biogeochemical hotspots storing carbon in sediments and in the ocean following lateral carbon export (outwelling). Coastal seawater pH is modified by both uptake of anthropogenic carbon dioxide and natural biogeochemical processes, e.g., wetland inputs. Here, we investigate how mangroves and saltmarshes influence coastal carbonate chemistry and quantify the contribution of alkalinity and dissolved inorganic carbon (DIC) outwelling to blue carbon budgets. Observations from 45 mangroves and 16 saltmarshes worldwide revealed that >70% of intertidal wetlands export more DIC than alkalinity, potentially decreasing thepH of coastal waters. Porewater-derived DIC outwelling (81 ± 47 mmol m−2 d−1 in mangroves and 57 ± 104 mmol m−2 d−1 in saltmarshes) was the major term in blue carbon budgets. However, substantial amounts of fixed carbon remain unaccounted for. Concurrently, alkalinity outwelling was similar or higher than sediment carbon burial and is therefore a significant but often overlooked carbon sequestration mechanism.
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| 196. |
- Rorth, R., et al.
(author)
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The prognostic value of troponin T and N-terminal pro B-type natriuretic peptide, alone and in combination, in heart failure patients with and without diabetes
- 2019
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 21:1, s. 40-49
-
Journal article (peer-reviewed)abstract
- Aims We examined the prognostic importance of N-terminal pro B-type natriuretic peptide (NT-proBNP) and troponin T (TnT) in heart failure patients with and without diabetes. Methods and results We measured NT-proBNP and TnT in the biomarker substudy of the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Of 1907 patients, 759 (40%) had diabetes. Median TnT in patients with diabetes was 18 (interquartile range 11-27) ng/L and 13 (9-21) ng/L in those without (P < 0.001). The TnT frequency-distribution curve was shifted to the right in patients with diabetes, compared to those without diabetes. By contrast, NT-proBNP did not differ between patients with and without diabetes. Diabetes and each biomarker were predictive of worse outcomes. Thus, patients with diabetes, an elevated TnT and a NT-proBNP level in the highest tertile (9% of all patients) had an absolute risk of cardiovascular death or heart failure hospitalization of 265 per 1000 person-years, compared to a rate of 42 per 1000 person-years in those without diabetes, a TnT < 18 ng/L and a NT-proBNP in the lowest tertile (16% of all patients). TnT remained an independent predictor of adverse outcomes in multivariable analyses including NT-proBNP. Conclusion TnT is elevated to a greater extent in heart failure patients with diabetes compared to those without (whereas NT-proBNP is not). TnT and NT-proBNP are additive in predicting risk and when combined help identify diabetes patients at extremely high absolute risk.
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| 197. |
- Rørth, R., et al.
(author)
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Comparison of BNP and NT-proBNP in Patients With Heart Failure and Reduced Ejection Fraction
- 2020
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In: Circulation. Heart failure. - 1941-3297. ; 13:2
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Journal article (peer-reviewed)abstract
- BACKGROUND: Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide) are widely used to aid diagnosis, assess the effect of therapy, and predict outcomes in heart failure and reduced ejection fraction. However, little is known about how these 2 peptides compare in heart failure and reduced ejection fraction, especially with contemporary assays. Both peptides were measured at screening in the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). METHODS: Eligibility criteria in PARADIGM-HF included New York Heart Association functional class II to IV, left ventricular ejection fraction ≤40%, and elevated natriuretic peptides: BNP ≥150 pg/mL or NT-proBNP ≥600 pg/mL (for patients with HF hospitalization within 12 months, BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL). BNP and NT-proBNP were measured simultaneously at screening and only patients who fulfilled entry criteria for both natriuretic peptides were included in the present analysis. The BNP/NT-proBNP criteria were not different for patients in atrial fibrillation. Estimated glomerular filtration rate <30 mL/min per 1.73 m2 was a key exclusion criterion. RESULTS: The median baseline concentration of NT-proBNP was 2067 (Q1, Q3: 1217-4003) and BNP 318 (Q1, Q3: 207-559), and the ratio, calculated from the raw data, was ≈6.25:1. This ratio varied considerably according to rhythm (atrial fibrillation 8.03:1; no atrial fibrillation 5.75:1) and with age, renal function, and body mass index but not with left ventricular ejection fraction. Each peptide was similarly predictive of death (all-cause, cardiovascular, sudden and pump failure) and heart failure hospitalization, for example, cardiovascular death: BNP hazard ratio, 1.41 (95% CI, 1.33-1.49) per 1 SD increase, P<0.0001; NT-proBNP, 1.45 (1.36-1.54); P<0.0001. CONCLUSIONS: The ratio of NT-proBNP to BNP in heart failure and reduced ejection fraction appears to be greater than generally appreciated, differs between patients with and without atrial fibrillation, and increases substantially with increasing age and decreasing renal function. These findings are important for comparison of natriuretic peptide concentrations in heart failure and reduced ejection fraction.
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| 198. |
- Schou, M. F., et al.
(author)
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Metabolic and functional characterization of effects of developmental temperature in Drosophila melanogaster
- 2017
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In: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 312:2
-
Journal article (peer-reviewed)abstract
- The ability of ectotherms to respond to changes in their thermal environment through plastic mechanisms is central to their adaptive capability. However, we still lack knowledge on the physiological and functional responses by which ectotherms acclimate to temperatures during development, and in particular, how physiological stress at extreme temperatures may counteract beneficial acclimation responses at benign temperatures. We exposed Drosophila melanogaster to 10 developmental temperatures covering their entire permissible temperature range. We obtained metabolic profiles and reaction norms for several functional traits: egg-to-adult viability, developmental time, and heat and cold tolerance. Females were more heat tolerant than males, whereas no sexual dimorphism was found in cold tolerance. A group of metabolites, mainly free amino acids, had linear reaction norms. Several energy-carrying molecules, as well as some sugars, showed distinct inverted U-shaped norms of reaction across the thermal range, resulting in a positive correlation between metabolite intensities and egg-to-adult viability. At extreme temperatures, low levels of these metabolites were interpreted as a response characteristic of costs of homeostatic perturbations. Our results provide novel insights into a range of metabolites reported to be central for the acclimation response and suggest several new candidate metabolites. Low and high temperatures result in different adaptive physiological responses, but they also have commonalities likely to be a result of the failure to compensate for the physiological stress. We suggest that the regulation of metabolites that are tightly connected to the performance curve is important for the ability of ectotherms to cope with variation in temperature.
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| 199. |
- Seidler, Y, et al.
(author)
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KNOWING WHAT TO DO WITH THE DATA - A QUALITATIVE STUDY ON CHALLENGES OF USING SMARTPHONE-BASED EPROS IN RHEUMATOID ARTHRITIS
- 2022
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1081-1081
-
Conference paper (other academic/artistic)abstract
- Using patient-reported outcomes (PROs) has a long tradition in rheumatology, and PRO measurement is included in many composite indices evaluating disease progression and treatment response [1]. However, little is known about patients´ and health professionals´ (HPs) perceptions of using digitally collected PROs, the so-called ePROs, with a personal smartphone app.ObjectivesTo identify main challenges in utilising ePROs for management and treatment of rheumatoid arthritis from patients’ and HPs’ perspectives.MethodsWe interviewed 25 people with rheumatoid arthritis (RA) and 17 HPs (nurses, rheumatologists, and physiotherapists) from Austria and Denmark. We used the RheumaBuddy app as a practical example to illustrate the digital data collection and the feedback that patients would get from entering their self-reported outcomes. Interviews were recorded and transcribed. We applied a qualitative thematic analysis to identify major themes using a procedure of rigorous coding. Analysis was done by two researchers, and conflicts were solved by consensus. Ethical approval was obtained in both countries.ResultsThree main themes emerged: 1) Being simple yet comprehensive; 2) Resources to interpret, use and act upon the collected data; and 3) Being reminded of the disease. Within the first theme, many valued the intuitiveness and simplicity of ePROs, especially when used as a monitoring tool in between clinical visits. HPs were concerned about not to overwhelm the patients with too many questions. On the other hand, the short ePROs asked in the app were not comprehensive enough to capture psychosocial and lifestyle aspects of the disease which were considered important both by patients and HPs. Within the second theme, patients and HPs expressed that ePROs could be the basis for shared decision making. Nevertheless, some patients had clearer ideas on making use of the feedback they could get from their self-reported data than the others. Participants from Denmark, who experienced a higher level of digital health maturity in official institutions, expressed more proactive use of the data than participants from Austria who were on average younger than their Danish counterparts. One patient in Austria even asserted having no idea what to do with the collected data but believed that the “doctor will make good use of it”. HPs in both countries, however, indicated that they needed more resources, skills, and time to make sense of the ePRO data and act accordingly. Under the third theme, patients considered the collection of ePROs to be very important when pain and disease activity were high. HPs, on the other hand, were more concerned that the regular collection of ePROs might constantly remind patients that they are living with the disease.ConclusionThe potential adoption of ePROs in practice depends on both patients and HPs’ motivations and ideas to use the feedback they would get from the collected data. This might be influenced by the level of digital health maturity of a country, as well as available resources. In addition, ePROs need to be intuitive and simple, but at the same time comprehensive and reliable enough so that they can be used for shared decision making. Challenges remain for the ePROs to be used as supporting and empowering tools, and not as reminders of the disease and pain.Table 1.Demographic data of the participants (N=42)DemographicAustriaDenmarkTotalDataPatientHPPatientHPPatientHPN14101172517Women (%)10(71)6(60)7(64)5(71)17(68)11(65)Men (%)4(29)4(40)4(36)2(29)8(32)6(35)AgeMean (Range)54(30-76)41(29-63)65(37-77)47(31-59)60(30-77)44(29-63)References[1]T Stamm, I Parodis, and P Studenic. Patient-reported outcomes with anifrolumab in patients with systemic lupus erythematosus, Lancet Rheumatol, (2022), in Press.AcknowledgementsWe would like to express our particular thank you to all those who have taken part in the interview study and for their valuable inputs.Disclosure of InterestsYuki Seidler: None declared, Tanja Schjødt Jørgensen Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Biogen and Eli Lilly., Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Biogen and Eli Lilly, Paul Studenic: None declared, Helga Radner Speakers bureau: Gilead, Merck Sharp, Pfizer, Abbvie, Consultant of: Gilead, Merck Sharp, Pfizer, Abbvie, Thomas Nygaard: None declared, Nadine Weibrecht: None declared, Nikolas Popper Speakers bureau: Roche, Consultant of: dwh GmbH (as CSO), Lars Erik Kristensen Speakers bureau: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Consultant of: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals, Grant/research support from: IIT research grants from Novo, UCB, Eli Lilly; Novartis and Abbvie, Tanita-Christina Wilhelmer: None declared, James Rickmann: None declared, Erika Mosor: None declared, Valentin Ritschl: None declared, Tanja Stamm Speakers bureau: AbbVie, Novartis, Roche, Sanofi, and Takeda., Consultant of: AbbVie and Sanofi Genzyme., Grant/research support from: AbbVie and Roche.
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| 200. |
- Shen, Li, et al.
(author)
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Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists : An Analysis of DAPA-HF.
- 2021
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In: JACC. Heart failure. - : Elsevier BV. - 2213-1779. ; 9:4, s. 254-264
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The purpose of this study was to assess the efficacy and safety of dapagliflozin in patients taking or not taking an mineralocorticoid receptor antagonist (MRA) at baseline in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. BACKGROUND: MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination. METHODS: A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes. RESULTS: A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m(2)), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction = 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo. CONCLUSIONS: Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).
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