| 1. |
- Ruilope, LM, et al.
(author)
-
Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
-
In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
-
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.
|
|
| 2. |
-
- 2019
-
Journal article (peer-reviewed)
|
|
| 3. |
- Abbafati, Cristiana, et al.
(author)
-
- 2020
-
Journal article (peer-reviewed)
|
|
| 4. |
- Micah, Angela E., et al.
(author)
-
Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
-
In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
-
Research review (peer-reviewed)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
|
|
| 5. |
- Keable, Stephen M., et al.
(author)
-
Room temperature XFEL crystallography reveals asymmetry in the vicinity of the two phylloquinones in photosystem I
- 2021
-
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Photosystem I (PS I) has a symmetric structure with two highly similar branches of pigments at the center that are involved in electron transfer, but shows very different efficiency along the two branches. We have determined the structure of cyanobacterial PS I at room temperature (RT) using femtosecond X-ray pulses from an X-ray free electron laser (XFEL) that shows a clear expansion of the entire protein complex in the direction of the membrane plane, when compared to previous cryogenic structures. This trend was observed by complementary datasets taken at multiple XFEL beamlines. In the RT structure of PS I, we also observe conformational differences between the two branches in the reaction center around the secondary electron acceptors A1A and A1B. The π-stacked Phe residues are rotated with a more parallel orientation in the A-branch and an almost perpendicular confirmation in the B-branch, and the symmetry breaking PsaB-Trp673 is tilted and further away from A1A. These changes increase the asymmetry between the branches and may provide insights into the preferential directionality of electron transfer.
|
|
| 6. |
- Esteve-Codina, Anna, et al.
(author)
-
Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes
- 2021
-
In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.
|
|
| 7. |
- Andersson, Eva, et al.
(author)
-
Explorations of neighbourhood and educational outcomes for young Swedes
- 2006
-
In: Urban Studies. - : SAGE Publications. - 0042-0980 .- 1360-063X. ; 43:11, s. 2013-2025
-
Journal article (peer-reviewed)abstract
- The aim of this study is to estimate the impact of neighbourhoods on educational outcome for adolescents in Sweden. Using a multilevel statistical approach and the PLACE database that consists of a census of individuals in 1990-2000 in Sweden, the paper explores different domains of neighbourhood characteristics that predict educational outcomes in adolescents. Educational achievement in year 2000 was measured for three cohorts, geocoded to their neighbourhood environments. It was found that neighbourhood characteristics related to socioeconomic resources and demographic stability are predictors of individual educational outcomes. A strong association between neighbourhood socio-cultural capital variables and education were also observed. Despite national policies on availability and access to education in Sweden, there are substantial inequalities in educational outcomes that are not simply a result of differences in individual characteristics.
|
|
| 8. |
- Malmberg, Bo, et al.
(author)
-
Links between ill health and regional economic performance : Evidence from Swedish longitudinal data
- 2010
-
In: Environment and planning A. - : SAGE Publications. - 0308-518X .- 1472-3409. ; 42:5, s. 1210-1220
-
Journal article (peer-reviewed)abstract
- While poor health has been associated with economic outcomes at the national level, its effect on economic outcomes at the individual and local level remains less well known. Using nationally representative longitudinal data from Sweden, we examined the extent to which an individual’s poor health leads to poor economic outcomes for that individual. In order to understand the effects of poor health at a regional level, we also examined the spillover effects of the individual’s poor health on the economic outcomes of the people linked to the individual. We report an association between an individual’s poor health and both that individual’s subsequent adverse economic outcomes and adverse economic outcomes of the individual’s network. Our study highlights the importance of the association between health and economic well-being as well as potential adverse spillover effects of poor health on local economies.
|
|
| 9. |
- Merlo, Juan, et al.
(author)
-
General and specific contextual effects in multilevel regression analyses and their paradoxical relationship : A conceptual tutorial
- 2018
-
In: SSM - Population Health. - : Elsevier. - 2352-8273. ; 5, s. 33-37
-
Journal article (peer-reviewed)abstract
- To be relevant for public health, a context (e.g., neighborhood, school, hospital) should influence or affect the health status of the individuals included in it. The greater the influence of the shared context, the higher the correlation of subject outcomes within that context is likely to be. This intra-context or intra-class correlation is of substantive interest and has been used to quantify the magnitude of the general contextual effect (GCE). Furthermore, ignoring the intra-class correlation in a regression analysis results in spuriously narrow 95% confidence intervals around the estimated regression coefficients of the specific contextual variables entered as covariates and, thereby, overestimates the precision of the estimated specific contextual effects (SCEs). Multilevel regression analysis is an appropriate methodology for investigating both GCEs and SCEs. However, frequently researchers only report SCEs and disregard the study of the GCE, unaware that small GCEs lead to more precise estimates of SCEs so, paradoxically, the less relevant the context is, the easier it is to detect (and publish) small but "statistically significant" SCEs. We describe this paradoxical situation and encourage researchers performing multilevel regression analysis to consider simultaneously both the GCE and SCEs when interpreting contextual influences on individual health.
|
|
| 10. |
- Nicholls, Ian A., et al.
(author)
-
Rational design of biomimetic molecularly imprinted materials : theoretical and computational strategies for guiding nanoscale structured polymer development
- 2011
-
In: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 400:6, s. 1771-1786
-
Research review (peer-reviewed)abstract
- In principle, molecularly imprinted polymer science and technology provides a means for ready access to nano-structured polymeric materials of predetermined selectivity. The versatility of the technique has brought it to the attention of many working with the development of nanomaterials with biological or biomimetic properties for use as therapeutics or in medical devices. Nonetheless, the further evolution of the field necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. The rapid growth in computer power and software over the past decade has opened new possibilities for simulating aspects of the complex molecular imprinting process. We present here a survey of the current status of the use of in silico-based approaches to aspects of molecular imprinting. Finally, we highlight areas where ongoing and future efforts should yield information critical to our understanding of the underlying mechanisms sufficient to permit the rational design of molecularly imprinted polymers.
|
|
