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Sökning: WFRF:(Madhu B)

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1.
  • Lozano, Rafael, et al. (författare)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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2.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
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3.
  • Murray, Christopher J. L., et al. (författare)
  • Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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4.
  • Lin, Yen-Hung, et al. (författare)
  • A piperidinium salt stabilizes efficient metal-halide perovskite solar cells
  • 2020
  • Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 369:6499, s. 96-
  • Tidskriftsartikel (refereegranskat)abstract
    • Longevity has been a long-standing concern for hybrid perovskite photovoltaics. We demonstrate high-resilience positive-intrinsic-negative perovskite solar cells by incorporating a piperidinium-based ionic compound into the formamidinium-cesium lead-trihalide perovskite absorber. With the bandgap tuned to be well suited for perovskite-on-silicon tandem cells, this piperidinium additive enhances the open-circuit voltage and cell efficiency. This additive also retards compositional segregation into impurity phases and pinhole formation in the perovskite absorber layer during aggressive aging. Under full-spectrum simulated sunlight in ambient atmosphere, our unencapsulated and encapsulated cells retain 80 and 95% of their peak and post-burn-in efficiencies for 1010 and 1200 hours at 60 degrees and 85 degrees C, respectively. Our analysis reveals detailed degradation routes that contribute to the failure of aged cells.
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5.
  • Bollano, Entela, 1970, et al. (författare)
  • Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene.
  • 2000
  • Ingår i: Endocrinology. - 0013-7227. ; 141:6, s. 2229-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.
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6.
  • Gorji Bahri, Gilar, et al. (författare)
  • Stromal cartilage oligomeric matrix protein as a tumorigenic driver in ovarian cancer via Notch3 signaling and epithelial-to-mesenchymal transition
  • 2024
  • Ingår i: Journal of Translational Medicine. - 1479-5876. ; 22:351, s. 1-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cartilage oligomeric matrix protein (COMP), an extracellular matrix glycoprotein, is vital in preserving cartilage integrity. Further, its overexpression is associated with the aggressiveness of several types of solid cancers. This study investigated COMP's role in ovarian cancer, exploring clinicopathological links and mechanistic insights.Methods: To study the association of COMP expression in cancer cells and stroma with clinicopathological features of ovarian tumor patients, we analyzed an epithelial ovarian tumor cohort by immunohistochemical analysis. Subsequently, to study the functional mechanisms played by COMP, an in vivo xenograft mouse model and several molecular biology techniques such as transwell migration and invasion assay, tumorsphere formation assay, proximity ligation assay, and RT-qPCR array were performed.Results: Based on immunohistochemical analysis of epithelial ovarian tumor tissues, COMP expression in the stroma, but not in cancer cells, was linked to worse overall survival (OS) of ovarian cancer patients. A xenograft mouse model showed that carcinoma-associated fibroblasts (CAFs) expressing COMP stimulate the growth and metastasis of ovarian tumors through the secretion of COMP. The expression of COMP was upregulated in CAFs stimulated with TGF-β. Functionally, secreted COMP by CAFs enhanced the migratory capacity of ovarian cancer cells. Mechanistically, COMP activated the Notch3 receptor by enhancing the Notch3-Jagged1 interaction. The dependency of the COMP effect on Notch was confirmed when the migration and tumorsphere formation of COMP-treated ovarian cancer cells were inhibited upon incubation with Notch inhibitors. Moreover, COMP treatment induced epithelial-to-mesenchymal transition and upregulation of active β-catenin in ovarian cancer cells.Conclusion: This study suggests that COMP secretion by CAFs drives ovarian cancer progression through the induction of the Notch pathway and epithelial-to-mesenchymal transition.
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8.
  • Myers, William K., et al. (författare)
  • Double Electron-Electron Resonance Probes Ca2+-Induced Conformational Changes and Dimerization of Recoverin
  • 2013
  • Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 52:34, s. 5800-5808
  • Tidskriftsartikel (refereegranskat)abstract
    • Recoverin a member of the neuronal calcium sensor (NCS) branch of the calmodulin superfamily, is expressed in retinal photoreceptor cells and serves as a calcium sensor in vision. Ca2+-induced conformational changes in recoverin cause extrusion of its covalently attached myristate (termed Ca2+-myristoyl switch) that promotes translocation of recoverin to disk membranes during phototransduction in retinal rod cells. Here we report double electron electron resonance (DEER) experiments on recoverin that probe Ca2+-induced changes in distance as measured by the dipolar coupling between spin-labels strategically positioned at engineered cysteine residues on the protein surface. The DEER distance between nitroxide spin-labels attached at C39 and N120C is 2.5 +/- 0.1 nm for Ca2+-free recoverin and 3.7 +/- 0.1 nm for Ca2+-bound recoverin. An additional DEER distance (5-6 nm) observed for Ca2+-bound recoverin may represent an intermolecular distance between C39 and N120. N-15 NMR relaxation analysis and CW-EPR experiments both confirm that Ca2+-bound recoverin forms a dimer at protein concentrations above 100 mu M, whereas Ca2+-free recoverin is monomeric We propose that Ca2+-induced dimerization of recoverin at the disk membrane surface may play a role in regulating Ca2+-dependent phosphorylation of dimeric rhodopsin. The DEER approach will be useful for elucidating dimeric structures of NCS proteins in general for which Ca2+-induced dimerization is functionally important but not well understood.
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9.
  • Nygaard, Eva B., et al. (författare)
  • Structural Modeling and Electron Paramagnetic Resonance Spectroscopy of the Human Na+/H+ Exchanger Isoform 1, NHE1
  • 2011
  • Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 286:1, s. 634-648
  • Tidskriftsartikel (refereegranskat)abstract
    • We previously presented evidence that transmembrane domain (TM) IV and TM X-XI are important for inhibitor binding and ion transport by the human Na+/H+ exchanger, hNHE1 (Pedersen, S. F., King, S. A., Nygaard, E. B., Rigor, R. R., and Cala, P. M. (2007) J. Biol. Chem. 282, 19716-19727). Here, we present a structural model of the transmembrane part of hNHE1 that further supports this conclusion. The hNHE1 model was based on the crystal structure of the Escherichia coli Na+/H+ antiporter, NhaA, and previous cysteine scanning accessibility studies of hNHE1 and was validated by EPR spectroscopy of spin labels in TM IV and TM XI, as well as by functional analysis of hNHE1 mutants. Removal of all endogenous cysteines in hNHE1, introduction of the mutations A173C (TM IV) and/or I461C (TM XI), and expression of the constructs in mammalian cells resulted in functional hNHE1 proteins. The distance between these spin labels was similar to 15 A, confirming that TM IV and TM XI are in close proximity. This distance was decreased both at pH 5.1 and in the presence of the NHE1 inhibitor cariporide. A similar TM IV.TM XI distance and a similar change upon a pH shift were found for the cariporide-insensitive Pleuronectes americanus (pa) NHE1; however, in paNHE1, cariporide had no effect on TM IV.TM XI distance. The central role of the TM IV.TM XI arrangement was confirmed by the partial loss of function upon mutation of Arg(425), which the model predicts stabilizes this arrangement. The data are consistent with a role for TM IV and TM XI rearrangements coincident with ion translocation and inhibitor binding by hNHE1.
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10.
  • Omerovic, Elmir, 1968, et al. (författare)
  • Growth hormone improves bioenergetics and decreases catecholamines in postinfarct rat hearts.
  • 2000
  • Ingår i: Endocrinology. - 0013-7227. ; 141:12, s. 4592-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The aims of this study were to examine, in vivo, the effects of GH treatment on myocardial energy metabolism, function, morphology, and neurohormonal status in rats during the early postinfarct remodeling phase. Myocardial infarction (MI) was induced in male Sprague Dawley rats. Three different groups were studied: MI rats treated with saline (n = 7), MI rats treated with GH (MI + GH; n = 11; 3 mg/kg x day), and sham-operated rats (sham; n = 8). All rats were investigated with 31P magnetic resonance spectroscopy and echocardiography at 3 days after MI and 3 weeks later. After 3 weeks treatment with GH, the phosphocreatine/ATP ratio increased significantly, compared with the control group (MI = 1.69 +/- 0.09 vs. MI + GH = 2.42 +/- 0.05, P < 0.001; sham = 2.34 +/- 0.08). Treatment with GH significantly attenuated an increase in left ventricular end systolic volume and end diastolic volume. A decrease in ejection fraction was prevented in GH-treated rats (P < 0.05 vs. MI). Myocardial and plasma noradrenaline levels were significantly lower in MI rats treated with GH. These effects were accompanied by normalization of plasma brain natriuretic peptide levels (sham = 124.1 +/- 8.4; MI = 203.9 +/- 34.7; MI + GH = 118.3 +/- 8.4 ng/ml; P < 0.05 vs. MI). In conclusion, GH improves myocardial energy reserve, preserves left ventricular function, and attenuates pathologic postinfarct remodeling in the absence of induction of left ventricular hypertrophy in postinfarct rats. The marked decrease in myocardial content of noradrenaline, after GH treatment, may protect myocardium from adverse effects of catecholamines during postinfarct remodeling.
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11.
  • Pascual, Unai, et al. (författare)
  • Valuing nature's contributions to people : the IPBES approach
  • 2017
  • Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435. ; 26-27, s. 7-16
  • Forskningsöversikt (refereegranskat)abstract
    • Nature is perceived and valued in starkly different and often conflicting ways. This paper presents the rationale for the inclusive valuation of nature's contributions to people (NCP) in decision making, as well as broad methodological steps for doing so. While developed within the context of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES), this approach is more widely applicable to initiatives at the knowledge–policy interface, which require a pluralistic approach to recognizing the diversity of values. We argue that transformative practices aiming at sustainable futures would benefit from embracing such diversity, which require recognizing and addressing power relationships across stakeholder groups that hold different values on human nature-relations and NCP.
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