| 1. |
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| 2. |
- Genet, Gwenaelle, 1980, et al.
(författare)
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Multi-input Markov chain equivalent fatigue loadings
- 2009
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Ingår i: Revue de Metallurgie. Cahiers DInformations Techniques. - : EDP Sciences. - 0035-1563. ; 106:5, s. 220-224
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Tidskriftsartikel (refereegranskat)abstract
- In the automotive industry, temporal, financial and human constraints impose to improve the design process of new vehicles. In order to reach the optimal design for mechanical components of cars, both the service loading and the component strength need to be considered. The equivalent fatigue approach, used at PSA Peugeot Citroën, is a method for transforming complicated loadings into simpler ones, equivalent in terms of damage, without information about the geometry of the structure. We use the equivalent fatigue approach for the design specifications of metallic structures, for the conditions of their tests trials, and finally for the characterization of customers and markets. The case of the one input equivalent fatigue approach has been thoroughly investigated at PSA. The current work treats the extension of the equivalent fatigue approach to the case of multi-input loadings. Especially the aim of this paper is to develop Markov chain models for the equivalent fatigue loadings.
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| 3. |
- Han, Lei, et al.
(författare)
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Two Isomeric Magnesium Metal-Organic Frameworks with [24-MC-6] Metallacrown Cluster
- 2013
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 13:5, s. 1807-1811
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Tidskriftsartikel (refereegranskat)abstract
- Two novel Mg-based metal-organic framework isomers with the formula [Mg-2(HCO2)(2)(NH2-BDC)-(DMF)(2)](n) (NH2-BDC = 2-amino-1,4-benzenedicarboxylate) have been synthesized based on a 6-connected [24-MC-6] metallacrown secondary building unit (SBU), which display a two-dimensional (2D) 3(6) net (1) and three-dimensional primitive rhombohedral net (2) derived from a different extended orientation of SBU, respectively. The 2D framework of 1 exhibits relevant thermal stability, solvents stability, high CO2 adsorption, and strong luminescent properties.
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| 4. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 5. |
- Huang, Joyce Y., et al.
(författare)
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Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:9, s. 2394-2405
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Tidskriftsartikel (refereegranskat)abstract
- Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p(trend) < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
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| 6. |
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| 7. |
- Li, Gui-Lan, et al.
(författare)
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Open-closed conformational change revealed by the crystal structures of 3-keto-L-gulonate 6-phosphate decarboxylase from Streptococcus mutans
- 2009
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 381:3, s. 33-429
-
Tidskriftsartikel (refereegranskat)abstract
- The 3-keto-L-gulonate 6-phosphate decarboxylase (KGPDC) catalyses the decarboxylation of 3-keto-L-gulonate 6-phosphate to L-xylulose in the presence of magnesium ions. The enzyme is involved in L-ascorbate metabolism and plays an essential role in the pathway of glucuronate interconversion. Crystal structures of Streptococcus mutans KGPDC were determined in the absence and presence of the product analog D-ribulose 5-phosphate. We have observed an 8 A alphaB-helix movement and other structural rearrangements around the active site between the apo-structures and product analog bound structure. These drastic conformational changes upon ligand binding are the first observation of this kind for the KGPDC family. The flexibilities of both the alpha-helix lid and the side chains of Arg144 and Arg197 are associated with substrate binding and product releasing. The open-closed conformational changes of the active site, through the movements of the alpha-helix lid and the arginine residues are important for substrate binding and catalysis.
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| 8. |
- Lin, Esther Ching-Lan, et al.
(författare)
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Factors influencing patient-perceived quality of care in psychiatric hospitals in Taiwan
- 2021
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Ingår i: Archives of Psychiatric Nursing. - : Elsevier. - 0883-9417 .- 1532-8228. ; 35:1, s. 9-16
-
Tidskriftsartikel (refereegranskat)abstract
- Patient-perceived quality of inpatient/outpatient psychiatric care remains under-researched. A cross-sectional survey with purposive sampling comprising 567 inpatients and 549 outpatients was conducted among eight psychiatric care facilities in Taiwan to examine the factors influencing patient-perceived care quality. Inpatients and outpatients perceived moderate quality of care, where "Encounter" was reported as the highest dimension. Inpatients perceived "Secure environment" as the lowest; outpatients rated "Discharge/Referring" as the lowest. Hospital region and customer loyalty were significantly associated with patient-perceived care quality. Other significant factors were also identified: inpatient employment, perceived mental health and treatment effects, understanding diagnosis, previous treatment, and visited by appointment.
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| 9. |
- Liu, Jin-ming, et al.
(författare)
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Mid-term effects of lung volume reduction surgery on pulmonary function in patients with chronic obstructive pulmonary disease
- 2007
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Ingår i: Chinese Medical Journal. - 0366-6999. ; 120:8, s. 658-662
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Tidskriftsartikel (refereegranskat)abstract
- Background Now lung volume reduction surgery (LVRS) has become one of the most effective methods for the management of some cases of severe chronic obstructive pulmonary disease (COPD). We evaluated the mid-term effects of LVRS on pulmonary function in patients with severe COPD. Methods Ten male patients with severe COPD aged 38-70 years underwent LVRS and their pulmonary function was assessed before, 3 months and 3 years after surgery. The spirometric and gas exchange parameters included residual volume, total lung capacity, inspiratory capacity, forced vital capacity, forced expiratory volume in one second, diffusion capacity for CO, and arterial blood gas. A 6-minute walk distance (6MWD) test was performed. Results As to preoperative assessment, most spirometric parameters and 6MWD were significantly improved after 3 months and slightly 3 years after LVRS. Gas exchange parameters were significantly improved 3 months after surgery, but returned to the preoperative levels after 3 years. Conclusions LVRS may significantly improve pulmonary function in patients with severe COPD indicating for LVRS. Mid-term pulmonary function 3 years after surgery can be decreased to the level at 3 months after surgery. Three years after LVRS, lung volume and pulmonary ventilation function can be significantly improved, but the improvement in gas exchange function was not significant.
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| 10. |
- 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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| 11. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 12. |
- Smith, Amber R., et al.
(författare)
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Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression
- 2015
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 6:14, s. 12558-12573
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Tidskriftsartikel (refereegranskat)abstract
- Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1.
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| 13. |
- 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
-
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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| 14. |
- Tegel, Hanna, et al.
(författare)
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High-throughput protein production--lessons from scaling up from 10 to 288 recombinant proteins per week
- 2009
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Ingår i: Biotechnology Journal. - : Wiley-VCH Verlagsgesellschaft. - 1860-6768 .- 1860-7314. ; 4:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- The demand for high-throughput recombinant protein production has markedly increased with the increased activity in the field of proteomics. Within the Human Protein Atlas project recombinantly produced human protein fragments are used for antibody production. Here we describe how the protein expression and purification protocol has been optimized in the project to allow for han- dling of nearly 300 different proteins per week. The number of manual handling steps has been significantly reduced (from 18 to 9) and the protein purification has been completely automated.
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| 15. |
- Uhlén, Mathias, et al.
(författare)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 16. |
- Wang, Meiyang, et al.
(författare)
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Alkali Metal Cations as Charge-Transfer Bridge for Polarization Promoted Solar-to-H2 Conversion
- 2023
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Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 33:9
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Tidskriftsartikel (refereegranskat)abstract
- Utilization of spontaneous polarization electric field of ferroelectric materials to realize the spatial separation and fast transfer of photogenerated charges has been regarded as a promising strategy to fabricate highly efficient photocatalysts. Herein, a novel heterostructure is constructed by coupling potassium poly(heptazine imide) (K-PHI) with ferroelectric BaxSr1-xTiO3 (BxST) through a facile electrostatic self-assembly strategy. The ionic species of K-PHI can neutralize the polarized charges in BxST to form intimate interfacial contact, substantially boosting the internal electric field. Notably, K+ cations intercalated into K-PHI act as charge-transfer bridge to promote migration and separation of photogenerated charge carriers. As a result, a significantly improved H2-evolution rate of 1087.4 µmol h−1 g−1 with an apparent quantum yield (AQY) of 8.05% at 420 nm is achieved over 5% K-PHI/B0.8ST, standing among the best polymeric carbon nitride-based photocatalysts reported up to date. Moreover, the extreme stability of the catalysts is evidenced by remaining outstanding catalytic performance even after storage for half a year. This strategy can be extended to other alkali metal (Na+ and Cs+) modified polymeric materials, highlighting the key role of the bridging ions in constructing polarized heterostructure, which sheds light on the design of ferroelectric-assisted photocatalysts.
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| 17. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 18. |
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| 19. |
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| 20. |
- Abercrombie, Daniel, et al.
(författare)
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Dark Matter benchmark models for early LHC Run-2 Searches : Report of the ATLAS/CMS Dark Matter Forum
- 2020
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Ingår i: Physics of the Dark Universe. - : Elsevier BV. - 2212-6864. ; 27
-
Tidskriftsartikel (refereegranskat)abstract
- This document is the final report of the ATLAS-CMS Dark Matter Forum, a forum organized by the ATLAS and CMS collaborations with the participation of experts on theories of Dark Matter, to select a minimal basis set of dark matter simplified models that should support the design of the early LHC Run-2 searches. A prioritized, compact set of benchmark models is proposed, accompanied by studies of the parameter space of these models and a repository of generator implementations. This report also addresses how to apply the Effective Field Theory formalism for collider searches and present the results of such interpretations.
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| 21. |
- Abidi, S, et al.
(författare)
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Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis
- 2020
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:3
-
Tidskriftsartikel (refereegranskat)abstract
- We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9–12 months (the “shorter regimen”) and individualised regimens of ≥20 months (“longer regimens”).We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD −0.15, 95% CI −0.17– −0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0–0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07–0.16), prothionamide/ethionamide (aRD 0.07, 95% CI −0.01–0.16) or ethambutol (aRD 0.09, 95% CI 0.04–0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
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| 22. |
- Ades, M., et al.
(författare)
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Global Climate : in State of the climate in 2019
- 2020
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
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Tidskriftsartikel (refereegranskat)
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| 23. |
- Ades, M., et al.
(författare)
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GLOBAL CLIMATE
- 2020
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
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Tidskriftsartikel (refereegranskat)
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| 24. |
- Adhikari, Deepak, et al.
(författare)
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Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles
- 2009
-
Ingår i: Molecular human reproduction. - : Oxford University Press. - 1360-9947 .- 1460-2407. ; 15:12, s. 765-770
-
Tidskriftsartikel (refereegranskat)abstract
- To maintain the length of reproductive life in a woman, it is essential that most of her ovarian primordial follicles are maintained in a quiescent state to provide a continuous supply of oocytes. However, our understanding of the molecular mechanisms that control the quiescence and activation of primordial follicles is still in its infancy. In this study, we provide some genetic evidence to show that the tumor suppressor tuberous sclerosis complex 2 (Tsc2), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the dormancy of primordial follicles. In mutant mice lacking the Tsc2 gene in oocytes, the pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in oocytes. This results in depletion of follicles in early adulthood, causing premature ovarian failure (POF). Our results suggest that the Tsc1-Tsc2 complex mediated suppression of mTORC1 activity is indispensable for maintenance of the dormancy of primordial follicles, thus preserving the follicular pool, and that mTORC1 activity in oocytes promotes follicular activation. Our results also indicate that deregulation of Tsc/mTOR signaling in oocytes may cause pathological conditions of the ovary such as infertility and POF.
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| 25. |
- Adhikari, Deepak, et al.
(författare)
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Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:3, s. 397-410
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Tidskriftsartikel (refereegranskat)abstract
- To maintain the female reproductive lifespan, the majority of ovarian primordial follicles are preserved in a quiescent state in order to provide ova for later reproductive life. However, the molecular mechanism that maintains the long quiescence of primordial follicles is poorly understood. Here we provide genetic evidence to show that the tumor suppressor tuberous sclerosis complex 1 (Tsc1), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the quiescence of primordial follicles. In mutant mice lacking the Tsc1 gene in oocytes, the entire pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in the oocyte, ending up with follicular depletion in early adulthood and causing premature ovarian failure (POF). We further show that maintenance of the quiescence of primordial follicles requires synergistic, collaborative functioning of both Tsc and PTEN (phosphatase and tensin homolog deleted on chromosome 10) and that these two molecules suppress follicular activation through distinct ways. Our results suggest that Tsc/mTORC1 signaling and PTEN/PI3K (phosphatidylinositol 3 kinase) signaling synergistically regulate the dormancy and activation of primordial follicles, and together ensure the proper length of female reproductive life. Deregulation of these signaling pathways in oocytes results in pathological conditions of the ovary, including POF and infertility.
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| 26. |
- Adie, Bailey Ashton, et al.
(författare)
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Careers, citations, bibliometrics, and impact : perspectives of new and emerging researchers
- 2024
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Ingår i: How to get published in the best tourism journals. - Cheltenham : Edward Elgar Publishing. - 9781035300600 - 9781035300594 ; , s. 211-238
-
Bokkapitel (refereegranskat)abstract
- This chapter brings together invited contributions from new and emerging academics with respect to their experiences and how publishing demands affect their careers and life, and vice versa. The provision of such experiences is important as it conveys the reality of publishing from a real-world context with respect to the pressures we face, especially when starting on the academic ladder. Authors were given a broad scope with respect to their contributions and the results are provided with only very minor editing. They have also been presented anonymously, or rather collectively, because although there are clearly different perspectives, emphasises, and interpretations, there are also commonalities in the contributors’ experiences. Nevertheless, as the reader will see, there are a number of common themes that emerge. Following the perspectives of the different contributions the chapter will discuss some of the main issues that emerge and their implications, including some of the darker aspects of the pressures of publishing.
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| 27. |
- Aguado, D. S., et al.
(författare)
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The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
- 2019
-
Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
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Tidskriftsartikel (refereegranskat)abstract
- Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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| 28. |
- Ahlström, Hanna, et al.
(författare)
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An Earth system law perspective on governing social-hydrological systems in the Anthropocene
- 2021
-
Ingår i: Earth System Governance. - : Elsevier BV. - 2589-8116. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- The global hydrological cycle is characterized by complex interdependencies and self-regulating feedbacks that keep water in an ever-evolving state of flux at local, regional, and global levels. Increasingly, the scale of human impacts in the Anthropocene is altering the dynamics of this cycle, which presents additional challenges for water governance. Earth system law provides an important approach for addressing gaps in governance that arise from the mismatch between the global hydrological cycle and dispersed regulatory architecture across institutions and geographic regions. In this article, we articulate the potential for Earth system law to account for core hydrological problems that complicate water governance, including delay, redistribution, intertwinements, permanence, and scale. Through merging concepts from Earth system law with existing policy and legal principles, we frame an approach for addressing hydrological problems in the Anthropocene and strengthening institutional fit between established governance systems and the global hydrological cycle. We discuss how such an approach can be applied, and the challenges and implications for governing water as a cycle and complex social-hydrological system, both in research and practice.
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| 29. |
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| 30. |
- Ahmed, M., et al.
(författare)
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Search for the lepton-family-number nonconserving decay μ +→e +γ
- 2002
-
Ingår i: Physical Review D. - : American Physical Society. - 1550-7998 .- 1550-2368. ; 65:11
-
Tidskriftsartikel (refereegranskat)abstract
- The MEGA experiment, which searched for the muon- and electron-number violating decay μ +→e + γ, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio, B(μ + →e + γ)<1.2×10 -11 with 90% confidence, is derived from a likelihood analysis.
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| 31. |
- Alikhani, Nyosha, et al.
(författare)
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Decreased proteolytic activity of the mitochondrial amyloid-β degrading enzyme, PreP peptidasome, in Alzheimer's disease brain mitochondria
- 2011
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 27:1, s. 75-87
-
Tidskriftsartikel (refereegranskat)abstract
- Accumulation of amyloid-β peptide (Aβ), the neurotoxic peptide implicated in the pathogenesis of Alzheimer's disease (AD), has been shown in brain mitochondria of AD patients and of AD transgenic mouse models. The presence of Aβ in mitochondria leads to free radical generation and neuronal stress. Recently, we identified the presequence protease, PreP, localized in the mitochondrial matrix in mammalian mitochondria as the novel mitochondrial Aβ-degrading enzyme. In the present study, we examined PreP activity in the mitochondrial matrix of the human brain's temporal lobe, an area of the brain highly susceptible to Aβ accumulation and reactive oxygen species (ROS) production. We found significantly lower hPreP activity in AD brains compared with non-AD age-matched controls. By contrast, in the cerebellum, a brain region typically spared from Aβ accumulation, there was no significant difference in hPreP activity when comparing AD samples to non-AD controls. We also found significantly reduced PreP activity in the mitochondrial matrix of AD transgenic mouse brains (Tg mAβPP and Tg mAβPP/ABAD) when compared to non-transgenic aged-matched mice. Furthermore, mitochondrial fractions isolated from AD brains and Tg mAβPP mice had higher levels of 4-hydroxynonenal, an oxidative product, as compared with those from non-AD and nonTg mice. Accordingly, activity of cytochrome c oxidase was significantly reduced in the AD mitochondria. These findings suggest that decreased PreP proteolytic activity, possibly due to enhanced ROS production, contributes to Aβ accumulation in mitochondria leading to the mitochondrial toxicity and neuronal death that is exacerbated in AD. Clearance of mitochondrial Aβ by PreP may thus be of importance in the pathology of AD.
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| 32. |
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| 33. |
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| 34. |
- Alstermark, Bror, et al.
(författare)
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Building a realistic neuronal model that simulates multi-joint arm and hand movements in 3D space
- 2007
-
Ingår i: HFSP Journal. - : Informa UK Limited. - 1955-2068. ; 1:4, s. 209-214
-
Tidskriftsartikel (refereegranskat)abstract
- The question as to how the brain controls voluntary movements of the arm and hand still remains largely unsolved despite much research focused on behavioral studies, neurophysiological investigations, and neuronal modeling in computer science. This is because behavioral studies are usually performed without detailed knowledge of the underlying neuronal networks, neurophysiological studies often lack an understanding of the function, and neuronal models are frequently focused on a particular control problem with restricted knowledge of the underlying neuronal networks involved. Therefore, it seems appropriate to start by trying to integrate knowledge of neuronal networks with known function and computer based neuronal models to seek more realistic models that can better control robots or artificial limbs and hands. We propose to combine knowledge of a behavioral model for reaching with the hand toward an object, which is based on detailed knowledge of the underlying neuronal network, and a neuronal model that includes several functional levels, from the planning level via intermediate levels to the final level of control of motoneurons and muscles.
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| 35. |
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| 36. |
- Alvarez, E. M., et al.
(författare)
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The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
-
Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 23:1, s. 27-52
-
Tidskriftsartikel (refereegranskat)abstract
- Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 37. |
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| 38. |
- Amann, F., et al.
(författare)
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A search for murarregamma at the level of 10-13
- 1991
-
Ingår i: Proceedings of the 25th International Conference on High Energy Physics. - 9810024347 ; , s. 1070-1071
-
Konferensbidrag (refereegranskat)abstract
- The MEGA experiment, which is a search for the decay murarregamma with a branching ratio sensitivity of about 10-13, employs highly modular, fast detectors, state-of-the-art electronics, and a staged trigger with on-line filters. The detectors are contained in a 1.5-T solenoidal field produced by a superconducting magnet. Positrons are confined to the central region and are measured by a set of thin MWPCs. Photons are measured by one of four layers of pair spectrometers in the outer region. Most aspects of the design have been validated in engineering runs; data taking will begin in 1990 with much of the electron arm and one pair spectrometer layer installed.
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| 39. |
- Amid, C., et al.
(författare)
-
Additive effects of the herbicide glyphosate and elevated temperature on the branched coral Acropora formosa in Nha Trang, Vietnam
- 2018
-
Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 25:14, s. 13360-13372
-
Tidskriftsartikel (refereegranskat)abstract
- The combined effects of the herbicide glyphosate and elevated temperature were studied on the tropical staghorn coral Acropora formosa, in Nha Trang bay, Vietnam. The corals were collected from two different reefs, one close to a polluted fish farm and one in a marine-protected area (MPA). In the laboratory, branches of the corals were exposed to the herbicide glyphosate at ambient (28 degrees C) and at 3 degrees C elevated water temperatures (31 degrees C). Effects of herbicide and elevated temperature were studied on coral bleaching using photography and digital image analysis (new colorimetric method developed here based on grayscale), chlorophyll a analysis, and symbiotic dinoflagellate (Symbiodinium, referred to as zooxanthellae) counts. All corals from the MPA started to bleach in the laboratory before they were exposed to the treatments, indicating that they were very sensitive, as opposed to the corals collected from the more polluted site, which were more tolerant and showed no bleaching response to temperature increase or herbicide alone. However, the combined exposure to the stressors resulted in significant loss of color, proportional to loss in chlorophyll a and zooxanthellae. The difference in sensitivity of the corals collected from the polluted site versus the MPA site could be explained by different symbiont types: the resilient type C3u and the stress-sensitive types C21 and C23, respectively. The additive effect of elevated temperatures and herbicides adds further weight to the notion that the bleaching of coral reefs is accelerated in the presence of multiple stressors. These results suggest that the corals in Nha Trang bay have adapted to the ongoing pollution to become more tolerant to anthropogenic stressors, and that multiple stressors hamper this resilience. The loss of color and decrease of chlorophyll a suggest that bleaching is related to concentration of chloro-pigments. The colorimetric method could be further fine-tuned and used as a precise, non-intrusive tool for monitoring coral bleaching in situ.
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| 40. |
- Andersson, J. C., et al.
(författare)
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Modeling the Äspö Pillar stability experiment
- 2010
-
Ingår i: Rock Mechanics in Civil and Environmental Engineering - Proceedings of the European Rock Mechanics Symposium, EUROCK 2010. - 9780415586542 ; , s. 787-790
-
Konferensbidrag (refereegranskat)abstract
- This paper presents results of the 1st stages ofTaskAof the Decovalex 2011 project, the numerical modeling of the Äspö Pillar Stability experiment performed by the Äspö Hard Rock Laboratory of the Swedish Nuclear Fuel and Waste Management Company (SKB). The objective is to perform back calculation of the Äspö pillar behavior using state of the art numerical modeling techniques for the material behavior. The work is divided into three stages and it is the first stage of thework that will be presented in this paper. Seven international teams from six different countries participated in the task and contributed to the results presented in this paper, concerning back calculation of uniaxial and triaxial compressive core testing and elastic back calculation of the stress path for excavation-induced stresses. The results are useful for understanding the occurrence of spalling in the upper part of the pillar during excavation and the stress path modeling gives the first approximation of the yielding strength of the pillar. The calculated results agree well with observations measured during experiment.
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| 41. |
- Anscombe, Elizabeth, et al.
(författare)
-
Identification and Characterization of an Irreversible Inhibitor of CDK2
- 2015
-
Ingår i: Chemistry and Biology. - : Elsevier BV. - 1074-5521 .- 1879-1301. ; 22:9, s. 1159-1164
-
Tidskriftsartikel (refereegranskat)abstract
- Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclo-hexylmethoxy)-9H-purin-2-yl) amino) benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl) phenyl)-9H- purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds.
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| 42. |
- Argirion, Ilona, et al.
(författare)
-
Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies
- 2023
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 32:5, s. 687-696
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Epstein-Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL).Methods: Anti-EBV IgG and IgA antibody responses target-ing 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case-control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their associ-ation with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies repre-senting the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models.Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glyco-protein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types.Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis.Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.
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| 43. |
- Arheimer, Berit, et al.
(författare)
-
The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
- 2024
-
Ingår i: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
-
Tidskriftsartikel (refereegranskat)abstract
- The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
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| 44. |
- Azoidou, Eva, et al.
(författare)
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Battery Lifetime Modeling and Validation of Wireless Building Automation Devices in Thread
- 2018
-
Ingår i: IEEE Transactions on Industrial Informatics. - : IEEE. - 1551-3203 .- 1941-0050. ; 14:7, s. 2869-2880
-
Tidskriftsartikel (refereegranskat)abstract
- The need for energy efficiency in wireless communication is prevalent in all areas, but to an even greater extent in low-power and lossy networks (LLN) that rely on resource constrained devices. This article seeks to address the problem of modeling the battery lifetime of a duty-cycled node, participating in a wireless sensor network that is typically used in smart home and building applications. Modeling in MATLAB and experimentation with prototype testing are employed to predict and validate. Various scenarios including sleepy end devices in a wireless sensor network are modeled and validated. They range from variable wake-up frequency and packet payload transmission to increasing network contention with the addition of network load. A comprehensive analysis of the main factors contributing to wasteful energy usage is provided. It can be concluded that the model can estimate the battery lifetime under different testing scenarios with an error rate less than 5 %.
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| 45. |
- Backström, Ellenor, 1980-, et al.
(författare)
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Adenovirus L4-22K stimulates major late transcription by a mechanism requiring the intragenic late-specific transcription factor-binding site
- 2010
-
Ingår i: Virus Research. - : Elsevier BV. - 0168-1702 .- 1872-7492. ; 151:2, s. 220-228
-
Tidskriftsartikel (refereegranskat)abstract
- The adenovirus major late promoter (MLP) generates a primary transcript that undergoes a complex pattern of regulated alternative RNA splicing and polyadenylation events. The late-specific activation of the MLP requires binding of two infected-cell specific transcription factor complexes, DEF-A and DEF-B, to the so-called DE sequence located downstream of the MLP start site. Previous studies have shown that DEF-B is a homodimer of the viral IVa2 protein and suggested that DEF-A is a heterodimer of IVa2 and an unknown protein. Here we have searched for a possible DEF-A candidate protein. The adenovirus L4-33K protein functions as a virus-encoded alternative RNA splicing factor, stimulating cytoplasmic accumulation of most late viral mRNAs. Interestingly, the L4 region also encodes for a second related protein, L4-22K, which share the 105 amino-terminal amino acids with L4-33K. Here we show that L4-22K both in vivo and in vitro stimulates transcription from the MLP in a DE sequence dependent manner. We also show that the viral pIX promoter is a natural target, activated by L4-22K. Interestingly, the position of the L4-22K DNA binding site in a promoter does not appear to be critical for function. Thus, tethering L4-22K, as a BPV E2 DNA binding domain fusion protein either to a position upstream or downstream of the MLP start site, or upstream of a minimal E1B promoter, resulted in an activation of transcription. Collectively, our results are compatible with the hypothesis that L4-22K may be the elusive component of DEF-A that partakes in activation of the MLP.
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| 46. |
- Balfors, Berit, et al.
(författare)
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Strategic Environmental Assessment of Energy Plans in Sweden
- 2012
-
Ingår i: Proceeding of the 32nd Annual Conference of the International Association for Impact Assessment. Energy Future The Role of Impact Assessment, Porto, Portugal, 27 May - 1 June 2012.
-
Konferensbidrag (refereegranskat)
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| 47. |
- Barber, R. M., et al.
(författare)
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Healthcare access and quality index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990-2015 : A novel analysis from the global burden of disease study 2015
- 2017
-
Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10091, s. 231-266
-
Tidskriftsartikel (refereegranskat)abstract
- Background National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015. Methods We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure-the Healthcare Quality and Access (HAQ) Index-on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r=0·88), an index of 11 universal health coverage interventions (r=0·83), and human resources for health per 1000 (r=0·77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time. Findings Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28·6 to 94·6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40·7 (95% uncertainty interval, 39·0-42·8) in 1990 to 53·7 (52·2-55·4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21·2 in 1990 to 20·1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73·8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015. Interpretation This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-system characteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world. Copyright © The Author(s). Published by Elsevier Ltd.
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| 48. |
- Barber, R. M., et al.
(författare)
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Healthcare Access and Quality Index based on mortality from causes amenable to personal health care in 195 countries and territories, 1990-2015: a novel analysis from the Global Burden of Disease Study 2015
- 2017
-
Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 390:10091, s. 231-266
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Tidskriftsartikel (refereegranskat)abstract
- Background National levels of personal health-care access and quality can be approximated by measuring mortality rates from causes that should not be fatal in the presence of effective medical care (ie, amenable mortality). Previous analyses of mortality amenable to health care only focused on high-income countries and faced several methodological challenges. In the present analysis, we use the highly standardised cause of death and risk factor estimates generated through the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015. Methods We mapped the most widely used list of causes amenable to personal health care developed by Nolte and McKee to 32 GBD causes. We accounted for variations in cause of death certification and misclassifications through the extensive data standardisation processes and redistribution algorithms developed for GBD. To isolate the effects of personal health-care access and quality, we risk-standardised cause-specific mortality rates for each geography-year by removing the joint effects of local environmental and behavioural risks, and adding back the global levels of risk exposure as estimated for GBD 2015. We employed principal component analysis to create a single, interpretable summary measure-the Healthcare Quality and Access (HAQ) Index-on a scale of 0 to 100. The HAQ Index showed strong convergence validity as compared with other health-system indicators, including health expenditure per capita (r= 0.88), an index of 11 universal health coverage interventions (r= 0.83), and human resources for health per 1000 (r= 0.77). We used free disposal hull analysis with bootstrapping to produce a frontier based on the relationship between the HAQ Index and the Socio-demographic Index (SDI), a measure of overall development consisting of income per capita, average years of education, and total fertility rates. This frontier allowed us to better quantify the maximum levels of personal health-care access and quality achieved across the development spectrum, and pinpoint geographies where gaps between observed and potential levels have narrowed or widened over time. Findings Between 1990 and 2015, nearly all countries and territories saw their HAQ Index values improve; nonetheless, the difference between the highest and lowest observed HAQ Index was larger in 2015 than in 1990, ranging from 28.6 to 94.6. Of 195 geographies, 167 had statistically significant increases in HAQ Index levels since 1990, with South Korea, Turkey, Peru, China, and the Maldives recording among the largest gains by 2015. Performance on the HAQ Index and individual causes showed distinct patterns by region and level of development, yet substantial heterogeneities emerged for several causes, including cancers in highest-SDI countries; chronic kidney disease, diabetes, diarrhoeal diseases, and lower respiratory infections among middle-SDI countries; and measles and tetanus among lowest-SDI countries. While the global HAQ Index average rose from 40.7 (95% uncertainty interval, 39.0-42.8) in 1990 to 53.7 (52.2-55.4) in 2015, far less progress occurred in narrowing the gap between observed HAQ Index values and maximum levels achieved; at the global level, the difference between the observed and frontier HAQ Index only decreased from 21.2 in 1990 to 20.1 in 2015. If every country and territory had achieved the highest observed HAQ Index by their corresponding level of SDI, the global average would have been 73.8 in 2015. Several countries, particularly in eastern and western sub-Saharan Africa, reached HAQ Index values similar to or beyond their development levels, whereas others, namely in southern sub-Saharan Africa, the Middle East, and south Asia, lagged behind what geographies of similar development attained between 1990 and 2015. Interpretation This novel extension of the GBD Study shows the untapped potential for personal health-care access and quality improvement across the development spectrum. Amid substantive advances in personal health care at the national level, heterogeneous patterns for individual causes in given countries or territories suggest that few places have consistently achieved optimal health-care access and quality across health-system functions and therapeutic areas. This is especially evident in middle-SDI countries, many of which have recently undergone or are currently experiencing epidemiological transitions. The HAQ Index, if paired with other measures of health-systemcharacteristics such as intervention coverage, could provide a robust avenue for tracking progress on universal health coverage and identifying local priorities for strengthening personal health-care quality and access throughout the world. Copyright (C) The Author(s). Published by Elsevier Ltd.
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| 49. |
- Becker-Dreps, Sylvia, et al.
(författare)
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Community Diarrhea Incidence Before and After Rotavirus Vaccine Introduction in Nicaragua
- 2013
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Ingår i: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 89:2, s. 246-250
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Tidskriftsartikel (refereegranskat)abstract
- We estimated the incidence of watery diarrhea in the community before and after introduction of the pentavalent rotavirus vaccine in Leon, Nicaragua. A random sample of households was selected before and after rotavirus vaccine introduction. All children < 5 years of age in selected households were eligible for inclusion. Children were followed every 2 weeks for watery diarrhea episodes. The incidence rate was estimated as numbers of episodes per 100 child-years of exposure time. A mixed effects Poisson regression model was fit to compare incidence rates in the pre-vaccine and vaccine periods. The pre-vaccine cohort (N = 726) experienced 36 episodes per 100 child-years, and the vaccine cohort (N = 826) experienced 25 episodes per 100 child-years. The adjusted incidence rate ratio was 0.60 (95% confidence interval [CI] 0.40, 0.91) during the vaccine period versus the pre-vaccine period, indicating a lower incidence of watery diarrhea in the community during the vaccine period.
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| 50. |
- Becker-Dreps, Sylvia, et al.
(författare)
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Etiology of Childhood Diarrhea After Rotavirus Vaccine Introduction A Prospective, Population-based Study in Nicaragua
- 2014
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Ingår i: The Pediatric Infectious Disease Journal. - : Lippincott, Williams andamp; Wilkins. - 0891-3668 .- 1532-0987. ; 33:11, s. 1156-1163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nicaragua was the first developing nation to implement routine immunization with the pentavalent rotavirus vaccine (RV5). In this RV5-immunized population, understanding infectious etiologies of childhood diarrhea is necessary to direct diarrhea treatment and prevention efforts. Methods: We followed a population-based sample of children less than5 years in Leon, Nicaragua for diarrhea episodes through household visits. Information was obtained on RV5 history and sociodemographics. Stool samples collected during diarrhea episodes and among healthy children underwent laboratory analysis for viral, bacterial and parasitic enteropathogens. Detection frequency and incidence of each enteropathogen was calculated. Results: The 826 children in the cohort experienced 677 diarrhea episodes during 607.5 child-years of exposure time (1.1 episodes per child-year). At least 1 enteropathogen was detected among 61.1% of the 337 diarrheal stools collected. The most common enteropathogens among diarrheal stools were: norovirus (20.4%), sapovirus (16.6%), enteropathogenic Escherichia coli (11.3%), Entamoeba histolytica/dispar (8.3%), Giardia lamblia (8.0%) and enterotoxigenic E. coli (7.7%), with rotavirus detected among 5.3% of diarrheal stools. Enteropathogenic Escherichia coli and enterotoxigenic E. coli were frequently detected among stools from healthy children. Among children with diarrhea, norovirus was more commonly detected among younger children (less than2 years) and G. lamblia was more commonly detected among older children (2-4 years). The mean age of rotavirus detection was 34.6 months. Conclusions: In this Central American community after RV5 introduction, rotavirus was not commonly detected among children with diarrhea. Prevention and appropriate management of norovirus and sapovirus should be considered to further reduce the burden of diarrheal disease.
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