| 1. |
- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
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- 2019
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Journal article (peer-reviewed)
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| 4. |
- Cheung, K. H., et al.
(author)
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Extending gene ontology in the context of extracellular RNA and vesicle communication
- 2016
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In: Journal of Biomedical Semantics. - : Springer Science and Business Media LLC. - 2041-1480. ; 7
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Journal article (peer-reviewed)abstract
- Background: To address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research. Methods: By following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO. In addition, we have initiated an ongoing process of extractions of gene product annotations associated with these terms from Vesiclepedia and ExoCarta, conversion of the extracted annotations to Gene Association File (GAF) format for batch submission to GO, and curation of the submitted annotations by the GO Consortium. As a use case, we have incorporated some of the GO terms into annotations of samples from the exRNA Atlas and implemented a faceted search interface based on such annotations. Results: We have added 7 new terms and modified 9 existing terms (along with their synonyms and relationships) to GO. Additionally, 18,695 unique coding gene products (mRNAs and proteins) and 963 unique non-coding gene products (ncRNAs) which are associated with the terms: "extracellular vesicle", "extracellular exosome", "apoptotic body", and "microvesicle" were extracted from ExoCarta and Vesiclepedia. These annotations are currently being processed for submission to GO. Conclusions: As an inter-community effort, we have made a substantial update to GO in the exRNA context. We have also demonstrated the utility of some of the new GO terms for sample annotation and metadata search.
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| 5. |
- Stenholm, S., et al.
(author)
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Patterns of weight gain in middle-aged and older US adults from 1992-2010
- 2015
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In: Epidemiology. - 1044-3983 .- 1531-5487. ; 26:2, s. 165-168
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Journal article (peer-reviewed)abstract
- Background: Cross-sectional analyses of national data have found that persons with high baseline body mass index (BMI) gain weight faster than persons at the median and that those whose weight was below the median gain very little weight. However, it is not clear whether these population-level changes reflect patterns at the individual level. Methods: We examined longitudinal changes in BMI in initially underweight, normal-weight, overweight, and obese US men and women using individual-level repeat data from the Health and Retirement Study (n = 15,895; age range, 40-69 years at baseline). Linear mixed-effect regression was used to model 6-year change in self-reported BMI during 4 study periods (1992/1994-1998/2000, 1996/1998-2002/2004, 2000/2002-2006/2008, and 2004-2010). Results: In the first 6-year period, the mean increase in BMI was greatest among persons who were initially normal weight (0.3 kg/m(2) [95% confidence interval = 0.2 to 0.4]) and overweight (0.2 kg/m(2) [0.1 to 0.3]). Weight gain accelerated in these groups with each subsequent period. Weight gain was less for initially class-I obese participants, and a net decrease in BMI was observed for class-II obese participants. Conclusion: These analyses suggest that the change in mean BMI among middle-aged and older US adults between 1992 and 2010 resulted mainly from accelerated weight gain among persons who were initially normal weight and overweight.
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| 6. |
- van den Besselaar, A. M. H. P., et al.
(author)
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International collaborative study for the calibration of proposed International Standards for thromboplastin, rabbit, plain, and for thromboplastin, recombinant, human, plain
- 2018
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In: Journal of Thrombosis and Haemostasis. - : WILEY. - 1538-7933 .- 1538-7836. ; 16:1, s. 142-149
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Journal article (peer-reviewed)abstract
- Background: The availability of International Standards for thromboplastin is essential for the calibration of routine reagents and hence the calculation of the International Normalized Ratio (INR). Stocks of the current Fourth International Standards are running low. Candidate replacement materials have been prepared. This article describes the calibration of the proposed Fifth International Standards for thromboplastin, rabbit, plain (coded RBT/16) and for thromboplastin, recombinant, human, plain (coded rTF/16). Methods: An international collaborative study was carried out for the assignment of International Sensitivity Indexes (ISIs) to the candidate materials, according to the World Health Organization (WHO) guidelines for thromboplastins and plasma used to control oral anticoagulant therapy with vitamin K antagonists. Results: Results were obtained from 20 laboratories. In several cases, deviations from the ISI calibration model were observed, but the average INR deviation attributabled to the model was not greater than 10%. Only valid ISI assessments were used to calculate the mean ISI for each candidate. The mean ISI for RBT/16 was 1.21 (between-laboratory coefficient of variation [CV]: 4.6%), and the mean ISI for rTF/16 was 1.11 (between-laboratory CV: 5.7%). Conclusions: The between-laboratory variation of the ISI for candidate material RBT/16 was similar to that of the Fourth International Standard (RBT/05), and the between-laboratory variation of the ISI for candidate material rTF/16 was slightly higher than that of the Fourth International Standard (rTF/09). The candidate materials have been accepted by WHO as the Fifth International Standards for thromboplastin, rabbit plain, and thromboplastin, recombinant, human, plain.
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| 7. |
- De Neve, Jan-Walter, et al.
(author)
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Antiretroviral therapy coverage associated with increased co-residence between older and working-age adults in Africa
- 2018
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In: AIDS. - 1473-5571. ; 32:14, s. 2051-2057
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To determine whether national antiretroviral therapy (ART) coverage is associated with changes in the living arrangements of older adults.DESIGN: Retrospective analysis using 103 nationally representative surveys from 28 African countries between 1991 and 2015.METHODS: The sample consisted of individuals aged at least 60 years. We investigated how three measures of living arrangements of older adults have changed with ART coverage: the number of older individuals living without working-age adults, the number of older individuals living with only dependent children (i.e. 'missing generation' households), and the number of working-age adults per household where an older individual lives.RESULTS: Our sample consisted of 297 331 older adults. An increase in ART coverage of 1% was associated with a 0.7 percentage point reduction (P < 0.001) in the probability of an older adult living without working-age adult and a 0.2 percentage point reduction (P = 0.005) in the probability of an older adult living in a 'missing generation' household. Increases in ART coverage were also associated with more working-age adults in households with at least one older adult. In our study countries, representing 75% (749 million) of the sub-Saharan population, an additional 103 000-358 000 older adults could be living with working-age adults as a result of increased ART coverage (1%).CONCLUSION: The scale-up of ART has likely led to substantial increases in co-residence between older and working-age adults in Africa. Returns to investments in HIV treatment will be too low, if the social benefits from these changes in living arrangements of older adults are not taken into account.
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| 8. |
- Diaz, Sandra, et al.
(author)
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Pervasive human-driven decline of life on Earth points to the need for transformative change
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 366:6471
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Research review (peer-reviewed)abstract
- The human impact on life on Earth has increased sharply since the 1970s, driven by the demands of a growing population with rising average per capita income. Nature is currently supplying more materials than ever before, but this has come at the high cost of unprecedented global declines in the extent and integrity of ecosystems, distinctness of local ecological communities, abundance and number of wild species, and the number of local domesticated varieties. Such changes reduce vital benefits that people receive from nature and threaten the quality of life of future generations. Both the benefits of an expanding economy and the costs of reducing nature's benefits are unequally distributed. The fabric of life on which we all depend-nature and its contributions to people-is unravelling rapidly. Despite the severity of the threats and lack of enough progress in tackling them to date, opportunities exist to change future trajectories through transformative action. Such action must begin immediately, however, and address the root economic, social, and technological causes of nature's deterioration.
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| 10. |
- Juratli, Tareq A., et al.
(author)
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Targeted treatment of papillary craniopharyngiomas harboring BRAF V600E mutations
- 2019
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In: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 125:17, s. 2910-2914
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Journal article (other academic/artistic)abstract
- Papillary craniopharyngiomas (PCPs) are characterized by the presence of BRAF V600E mutations, which are emerging as a useful guide for diagnosis and treatment decision making. The ongoing multicenter phase 2 Alliance A071601 trial is evaluating the efficacy of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors for patients with PCPs. With continued successful responses, it is proposed that BRAF (and MEK) inhibitors be evaluated for the neoadjuvant treatment of patients with PCPs.
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