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| 2. |
- Lozano, Rafael, et al.
(författare)
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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
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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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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| 3. |
- Liu, Yong, et al.
(författare)
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Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity
- 2017
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Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889 .- 2041-4889. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.
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| 4. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 5. |
- Xu, Bing, et al.
(författare)
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Clinicopathological significance of caspase-8 and caspase-10 expression in rectal cancer
- 2008
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Ingår i: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 74:3-4, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the expression of caspase-8 and -10 in rectal adenoma, adenocarcinoma and the corresponding normal mucosa tissue, and to clarify the relationship between their expression and clinicopathological parameters of rectal cancer. Methods: The expression of caspase-8 and -10 was determined by real-time RT-PCR and immunohistochemistry in 36 rectal adenomas, 93 rectal cancers and 93 corresponding normal rectal mucosa samples. Results: Compared with normal mucosa, the mRNA expression of caspase-8 was higher in adenomas (p = 0.003), while that of caspase-10 was lower in adenomas (p = 0.035) and cancers (p = 0.001). Immunohistochemical results showed caspase-8 up-regulation in adenomas (p = 0.014), and caspase-10 down-regulation in adenomas (p = 0.034) and cancers (p < 0.001) compared with normal mucosa samples. Cancers with poor differentiation had lower caspase-10 mRNA and protein levels than those with better differentiation (p = 0.041 and p = 0.046, respectively). The protein expression of caspase-8 and -10 was in accordance with the mRNA expression (p = 0.043 and p = 0.018, respectively). Conclusions: Caspase-8 expression was up-regulated in rectal adenomas. Caspase-10 expression was down-regulated in both rectal adenomas and cancers, and was further related to differentiation. Caspase-8 and -10 may be involved in the pathogenesis of rectal cancer. Copyright © 2008 S. Karger AG.
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| 6. |
- Yuan, Shuai, et al.
(författare)
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[Ti8Zr2O12(COO)(16)] Cluster : An Ideal Inorganic Building Unit for Photoactive Metal-Organic Frameworks
- 2018
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Ingår i: Acs Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 4:1, s. 105-111
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Tidskriftsartikel (refereegranskat)abstract
- Metal-organic frameworks (MOFs) based on Ti-oxo clusters (Ti-MOFs) represent a naturally self-assembled superlattice of TiO2 nanoparticles separated by designable organic linkers as antenna chromophores, epitomizing a promising platform for solar energy conversion. However, despite the vast, diverse, and well-developed Ti-cluster chemistry, only a scarce number of Ti-MOFs have been documented. The synthetic conditions of most Ti-based clusters are incompatible with those required for MOF crystallization, which has severely limited the development of Ti-MOFs. This challenge has been met herein by the discovery of the [Ti8Zr2O12(COO)(16)] cluster as a nearly ideal building unit for photoactive MOFs. A family of isoreticular photoactive MOFs were assembled, and their orbital alignments were fine-tuned by rational functionalization of organic linkers under computational guidance. These MOFs demonstrate high porosity, excellent chemical stability, tunable photoresponse, and good activity toward photocatalytic hydrogen evolution reactions. The discovery of the [Ti8Zr2O12(COO)(16)] cluster and the facile construction of photoactive MOFs from this cluster shall pave the way for the development of future Ti-MOF-based photocatalysts. GRAPHICS
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| 7. |
- Aurell, Erik, 1961-, et al.
(författare)
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The bulk and the tail of minimal absent words in genome sequences
- 2016
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Ingår i: Physical Biology. - : Institute of Physics (IOP). - 1478-3967 .- 1478-3975. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Minimal absent words (MAW) of a genomic sequence are subsequences that are absent themselves but the subwords of which are all present in the sequence. The characteristic distribution of genomic MAWs as a function of their length has been observed to be qualitatively similar for all living organisms, the bulk being rather short, and only relatively few being long. It has been an open issue whether the reason behind this phenomenon is statistical or reflects a biological mechanism, and what biological information is contained in absent words. % In this work we demonstrate that the bulk can be described by a probabilistic model of sampling words from random sequences, while the tail of long MAWs is of biological origin. We introduce the novel concept of a core of a minimal absent word, which are sequences present in the genome and closest to a given MAW. We show that in bacteria and yeast the cores of the longest MAWs, which exist in two or more copies, are located in highly conserved regions the most prominent example being ribosomal RNAs (rRNAs). We also show that while the distribution of the cores of long MAWs is roughly uniform over these genomes on a coarse-grained level, on a more detailed level it is strongly enhanced in 3' untranslated regions (UTRs) and, to a lesser extent, also in 5' UTRs. This indicates that MAWs and associated MAW cores correspond to fine-tuned evolutionary relationships, and suggest that they can be more widely used as markers for genomic complexity.
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| 8. |
- Del Ferraro, Gino, 1983-, et al.
(författare)
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On one-step replica symmetry breaking in the Edwards-Anderson spin glass model
- 2016
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Ingår i: Journal of statistical physics. - : Institute of Physics (IOP). - 0022-4715 .- 1572-9613.
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Tidskriftsartikel (refereegranskat)abstract
- We consider a one-step replica symmetry breaking description of the Edwards–Anderson spin glass model in 2D. The ingredients of this description are a Kikuchi approximation to the free energy and a second-level statistical model built on the extremal points of the Kikuchi approximation, which are also fixed points of a generalized belief propagation (GBP) scheme. We show that a generalized free energy can be constructed where these extremal points are exponentially weighted by their Kikuchi free energy and a Parisi parameter y, and that the Kikuchi approximation of this generalized free energy leads to second-level, one-step replica symmetry breaking (1RSB), GBP equations. We then proceed analogously to the Bethe approximation case for tree-like graphs, where it has been shown that 1RSB belief propagation equations admit a survey propagation solution. We discuss when and how the one-step-replica symmetry breaking GBP equations that we obtain also allow a simpler class of solutions which can be interpreted as a class of generalized survey propagation equations for the single instance graph case.
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| 9. |
- Gao, Chen-Yi, et al.
(författare)
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Correlation-compressed direct-coupling analysis
- 2018
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Ingår i: Physical review. E. - : American Physical Society. - 2470-0045 .- 2470-0053. ; 98:3
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Tidskriftsartikel (refereegranskat)abstract
- Learning Ising or Potts models from data has become an important topic in statistical physics and computational biology, with applications to predictions of structural contacts in proteins and other areas of biological data analysis. The corresponding inference problems are challenging since the normalization constant (partition function) of the Ising or Potts distribution cannot be computed efficiently on large instances. Different ways to address this issue have resulted in a substantial amount of methodological literature. In this paper we investigate how these methods could be used on much larger data sets than studied previously. We focus on a central aspect, that in practice these inference problems are almost always severely under-sampled, and the operational result is almost always a small set of leading predictions. We therefore explore an approach where the data are prefiltered based on empirical correlations, which can be computed directly even for very large problems. Inference is only used on the much smaller instance in a subsequent step of the analysis. We show that in several relevant model classes such a combined approach gives results of almost the same quality as inference on the whole data set. It can therefore provide a potentially very large computational speedup at the price of only marginal decrease in prediction quality. We also show that the results on whole-genome epistatic couplings that were obtained in a recent computation-intensive study can be retrieved by our approach. The method of this paper hence opens up the possibility to learn parameters describing pairwise dependences among whole genomes in a computationally feasible and expedient manner.
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| 10. |
- Gao, Chen-Yi, et al.
(författare)
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DCA for genome-wide epistasis analysis : the statistical genetics perspective
- 2019
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Ingår i: Physical Biology. - : IOP PUBLISHING LTD. - 1478-3967 .- 1478-3975. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Direct coupling analysis (DCA) is a now widely used method to leverage statistical information from many similar biological systems to draw meaningful conclusions on each system separately. DCA has been applied with great success to sequences of homologous proteins, and also more recently to whole-genome population-wide sequencing data. We here argue that the use of DCA on the genome scale is contingent on fundamental issues of population genetics. DCA can be expected to yield meaningful results when a population is in the quasi-linkage equilibrium (QLE) phase studied by Kimura and others, but not, for instance, in a phase of clonal competition. We discuss how the exponential (Potts model) distributions emerge in QLE, and compare couplings to correlations obtained in a study of about 3000 genomes of the human pathogen Streptococcus pneumoniae.
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