| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Liu, DJ, et al.
(författare)
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Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 369-
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.
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| 4. |
- Jacobsson, Jesper, 1984-, et al.
(författare)
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An open-access database and analysis tool for perovskite solar cells based on the FAIR data principles
- 2022
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Ingår i: Nature Energy. - : Springer Nature. - 2058-7546. ; 7:1, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- Large datasets are now ubiquitous as technology enables higher-throughput experiments, but rarely can a research field truly benefit from the research data generated due to inconsistent formatting, undocumented storage or improper dissemination. Here we extract all the meaningful device data from peer-reviewed papers on metal-halide perovskite solar cells published so far and make them available in a database. We collect data from over 42,400 photovoltaic devices with up to 100 parameters per device. We then develop open-source and accessible procedures to analyse the data, providing examples of insights that can be gleaned from the analysis of a large dataset. The database, graphics and analysis tools are made available to the community and will continue to evolve as an open-source initiative. This approach of extensively capturing the progress of an entire field, including sorting, interactive exploration and graphical representation of the data, will be applicable to many fields in materials science, engineering and biosciences.
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| 5. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 3635:312, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 6. |
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| 7. |
- Maes, S.L., et al.
(författare)
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Environmental drivers of increased ecosystem respiration in a warming tundra
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 629:8010, s. 105-113
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Tidskriftsartikel (refereegranskat)abstract
- Arctic and alpine tundra ecosystems are large reservoirs of organic carbon. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain. This hampers the accuracy of global land carbon–climate feedback projections. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9–2.0 °C] in air and 0.4 °C [CI 0.2–0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22–38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.
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| 8. |
- Parra, Esteban J., et al.
(författare)
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Genome-wide association study of warfarin maintenance dose in a Brazilian sample
- 2015
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Ingår i: Pharmacogenomics (London). - : Future Medicine Ltd. - 1462-2416 .- 1744-8042. ; 16:11, s. 1253-1263
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Extreme discordant phenotype and genome-wide association (GWA) approaches were combined to explore the role of genetic variants on warfarin dose requirement in Brazilians. Methods: Patients receiving low (<= 20 mg/week; n = 180) or high stable warfarin doses (>= 42.5 mg/week; n = 187) were genotyped with Affymetrix Axiom (R) Biobank arrays. Imputation was carried out using data from the combined 1000 Genomes project. Results: Genome-wide signals (p <= 5 x 10(-8)) were identified in the well-known VKORC1 (lead SNP, rs749671; OR: 20.4; p = 1.08 x 10(-33)) and CYP2C9 (lead SNP, rs9332238, OR: 6.8 and p = 4.4 x 10(-13)) regions. The rs9332238 polymorphism is in virtually perfect LD with CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910). No other genome-wide significant regions were identified in the study. Conclusion: We confirmed the important role of VKORC1 and CYP2C9 polymorphisms in warfarin dose.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Bengtsson, Fia, 1986-, et al.
(författare)
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Environmental drivers of Sphagnum growth in peatlands across the Holarctic region
- 2021
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Ingår i: Journal of Ecology. - : John Wiley & Sons. - 0022-0477 .- 1365-2745. ; 109:1, s. 417-431
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Tidskriftsartikel (refereegranskat)abstract
- The relative importance of global versus local environmental factors for growth and thus carbon uptake of the bryophyte genusSphagnum-the main peat-former and ecosystem engineer in northern peatlands-remains unclear. We measured length growth and net primary production (NPP) of two abundantSphagnumspecies across 99 Holarctic peatlands. We tested the importance of previously proposed abiotic and biotic drivers for peatland carbon uptake (climate, N deposition, water table depth and vascular plant cover) on these two responses. Employing structural equation models (SEMs), we explored both indirect and direct effects of drivers onSphagnumgrowth. Variation in growth was large, but similar within and between peatlands. Length growth showed a stronger response to predictors than NPP. Moreover, the smaller and denserSphagnum fuscumgrowing on hummocks had weaker responses to climatic variation than the larger and looserSphagnum magellanicumgrowing in the wetter conditions. Growth decreased with increasing vascular plant cover within a site. Between sites, precipitation and temperature increased growth forS. magellanicum. The SEMs indicate that indirect effects are important. For example, vascular plant cover increased with a deeper water table, increased nitrogen deposition, precipitation and temperature. These factors also influencedSphagnumgrowth indirectly by affecting moss shoot density. Synthesis. Our results imply that in a warmer climate,S. magellanicumwill increase length growth as long as precipitation is not reduced, whileS. fuscumis more resistant to decreased precipitation, but also less able to take advantage of increased precipitation and temperature. Such species-specific sensitivity to climate may affect competitive outcomes in a changing environment, and potentially the future carbon sink function of peatlands.
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| 13. |
- Cirulli, Elizabeth T., et al.
(författare)
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A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury
- 2019
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Ingår i: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 156:6, s. 1707-1716
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility.METHODS: We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings.RESULTS: We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.62; P = 1.2 x 10(-9) and replicated the finding in the validation set (OR 1.48; 95% CI 1.09-1.99; P =.01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32-1.98; P = 4.0 x 10(-6); allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21-1.56; P = 1.5 x 10(-6); allele frequency = 11.5%). Among amoxicillin-and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A* 02: 01 and DRB1* 15: 01.CONCLUSIONS: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.
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| 14. |
- Franke, James A., et al.
(författare)
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The GGCMI Phase 2 experiment : Global gridded crop model simulations under uniform changes in CO2, temperature, water, and nitrogen levels (protocol version 1.0)
- 2020
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 13:5, s. 2315-2336
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Tidskriftsartikel (refereegranskat)abstract
- Concerns about food security under climate change motivate efforts to better understand future changes in crop yields. Process-based crop models, which represent plant physiological and soil processes, are necessary tools for this purpose since they allow representing future climate and management conditions not sampled in the historical record and new locations to which cultivation may shift. However, process-based crop models differ in many critical details, and their responses to different interacting factors remain only poorly understood. The Global Gridded Crop Model Intercomparison (GGCMI) Phase 2 experiment, an activity of the Agricultural Model Intercomparison and Improvement Project (AgMIP), is designed to provide a systematic parameter sweep focused on climate change factors and their interaction with overall soil fertility, to allow both evaluating model behavior and emulating model responses in impact assessment tools. In this paper we describe the GGCMI Phase 2 experimental protocol and its simulation data archive. A total of 12 crop models simulate five crops with systematic uniform perturbations of historical climate, varying CO2, temperature, water supply, and applied nitrogen ("CTWN") for rainfed and irrigated agriculture, and a second set of simulations represents a type of adaptation by allowing the adjustment of growing season length. We present some crop yield results to illustrate general characteristics of the simulations and potential uses of the GGCMI Phase 2 archive. For example, in cases without adaptation, modeled yields show robust decreases to warmer temperatures in almost all regions, with a nonlinear dependence that means yields in warmer baseline locations have greater temperature sensitivity. Inter-model uncertainty is qualitatively similar across all the four input dimensions but is largest in high-latitude regions where crops may be grown in the future.
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| 15. |
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| 16. |
- Limdi, Nita A., et al.
(författare)
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Warfarin pharmacogenetics : a single VKORC1 polymorphism is predictive of dose across three racial groups
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:18, s. 3827-3834
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Tidskriftsartikel (refereegranskat)abstract
- Warfarin dosing algorithms incorporating CYP2C9 and VKORC1-1639G>A improve dose prediction compared to algorithms based solely on clinical and demographic factors. However these algorithms better capture dose variability among Whites compared to Asians or Blacks. Herein we evaluate whether other VKORC1 polymorphisms and haplotypes explain additional variation in warfarin dose beyond that explained by VKORC1-1639G>A among Asians (n=1103), Blacks (n=670) and Whites (n=3113). Participants were recruited from 11 countries as part of the International Warfarin Pharmacogenetics Consortium effort. Evaluation of the effects of individual VKORC1 SNPs and haplotypes on warfarin dose employed both univariate and multivariable linear regression. VKORC1-1639G>A and 1173C>T individually explained the greatest variance in dose in all three racial groups. Incorporation of additional VKORC1 SNPs or haplotypes did not further improve dose prediction. VKORC1 explained greater variability in dose among Whites as compared to Blacks and Asians. Differences in the percent variance in dose explained by VKORC1 across race was largely accounted for by the frequency of the -1639 A (or 1173 T) allele. Thus, clinicians should recognize that although at a population level, the contribution of VKORC1 towards dose requirements is higher in Whites compared to non-whites; genotype predicts similar dose requirements across racial groups.
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| 17. |
- Müller, Christoph, et al.
(författare)
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Substantial Differences in Crop Yield Sensitivities Between Models Call for Functionality-Based Model Evaluation
- 2024
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Ingår i: Earth's Future. - 2328-4277. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Crop models are often used to project future crop yield under climate and global change and typically show a broad range of outcomes. To understand differences in modeled responses, we analyzed modeled crop yield response types using impact response surfaces along four drivers of crop yield: carbon dioxide (C), temperature (T), water (W), and nitrogen (N). Crop yield response types help to understand differences in simulated responses per driver and their combinations rather than aggregated changes in yields as the result of simultaneous changes in various drivers. We find that models' sensitivities to the individual drivers are substantially different and often more different across models than across regions. There is some agreement across models with respect to the spatial patterns of response types but strong differences in the distribution of response types across models and their configurations suggests that models need to undergo further scrutiny. We suggest establishing standards in model evaluation based on emergent functionality not only against historical yield observations but also against dedicated experiments across different drivers to analyze emergent functional patterns of crop models.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Nicoletti, Paola, et al.
(författare)
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Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study
- 2017
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Ingår i: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 152:5, s. 1078-1089
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for druginduced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. RESULTS: We associated DILI with rs114577328 (a proxy for A* 33: 01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9 - 3.8; P = 2.4 x 10(-8)) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6 - 2.5; P = 9.7 x 10(-9)). The association with A* 33: 01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A* 33: 01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6 - 2.7; P = 4.8 x 10(-9)). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0 - 9.5; P = 7.1 x 10(-9)). We validated the association between A* 33: 01 terbinafine-and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS: In a GWAS of persons of European descent with DILI, we associated HLA-A* 33: 01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non-drug-specific risk factors.
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| 24. |
- Tanveer, M. K., et al.
(författare)
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Prevalence and chemo-therapeutical investigations of gastrointestinal nematodes in domestic pigeons in Lahore, Pakistan
- 2011
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Ingår i: Tropical Biomedicine. - 0127-5720. ; 28:1, s. 102-110
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of gastrointestinal nematodes was studied in 143 (80 male and 63 female) domestic pigeons. Faecal samples were collected to determine the gastrointestinal nematodes of domestic pigeons through qualitative and quantitative faecal examinations. A total of 48 (male 33 and 25 female) naturally infected domestic pigeons were divided into G(1) (albendzdole) and G(2) (fenbendazole) treatment-groups along with one control group (C). The overall prevalence of gastrointestinal nematodes was 40.5% (58/143) in domestic pigeons. Likewise, the prevalence of gastrointestinal nematodes in males and females was found 41.3% (33/58) and 39.7% (25/58) respectively. The overall prevalence of Capillaria obsignata and Ascaridia columbae was found to be 67.2% and 32.8%, respectively. The prevalence of C. obsignata and A. columbae in males was 72.7% (24/33) and 27.8% (9/33) and in females was 60% (15/25) and 40% (10/25), respectively. There was no significant sex related difference seen in the prevalence of C. obsignata (p>0.56) and A. columbae (p>0.40) in domestic pigeons, respectively. The overall efficacy of albendazole and fenbendazole was calculated to be 66% and 71%. A remarkable significant difference (p<0.05) was observed in eggs per gram before and after treatment in both G(1) and G(2) treated-groups. The efficacy of fenbendazole was found to be more significant (p<0.02) than albendazole.
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| 25. |
- Abdalla, Munir A, et al.
(författare)
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A CMOS APS for dental X-ray imaging using scintillating sensors
- 2001
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 460:1, s. 197-203
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we present an integrating CMOS Active Pixel Sensor (APS) circuit to be used with scintillator type X-ray sensors for intra oral dental X-ray imaging systems. Different pixel architectures were constructed to explore their performance characteristics and to study the feasibility of the development of such systems using the CMOS technology. A prototype 64 x 80 pixel array has been implemented in a CMOS 0.8 mum double poly n-well process with a pixel pitch of 50 mum. A spectral sensitivity measurement for the different pixels topologies, as well as measured X-ray direct absorption in the different APSs are presented. A measurement of the output signal showed a good linearity over a wide dynamic range. This chip showed that the very low sensitivity of the CMOS APSs to direct X-ray exposure adds a great advantage to the various CMOS advantages over CCD-based imaging systems,
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| 26. |
- Abdalla, Munir A, et al.
(författare)
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A new biasing method for CMOS preamplifier-shapers
- 2000
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Ingår i: ICECS 2000: 7TH IEEE INTERNATIONAL CONFERENCE ON ELECTRONICS, CIRCUITS & SYSTEMS, VOLS I AND II. ; , s. 15-18
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Konferensbidrag (refereegranskat)
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| 27. |
- Abdalla, Munir A, et al.
(författare)
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An integrating CMOS APS for X-ray imaging with an in-pixel preamplifier
- 2001
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 466:1, s. 232-236
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Tidskriftsartikel (refereegranskat)abstract
- We present in this paper an integrating CMOS Active Pixel Sensor (APS) circuit coated with scintillator type sensors for intra-oral dental X-ray imaging systems. The photosensing element in the pixel is formed by the p-diffusion on the n-well diode. The advantage of this photosensor is its very low direct absorption of X-rays compared to the other available photosensing elements in the CMOS pixel. The pixel features an integrating capacitor in the feedback loop of a preamplifier of a finite gain in order to increase the optical sensitivity. To verify the effectiveness of this in-pixel preamplification, a prototype 32 x 80 element CMOS active pixel array was implemented in a 0.8 mum CMOS double poly, n-well process with a pixel pitch of 50 mum. Measured results confirmed the improved optical sensitivity performance of the APS. Various measurements on device performance are presented.
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| 28. |
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| 29. |
- Brüggemann, Holger, et al.
(författare)
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Pan-genome analysis of the genus Finegoldia identifies two distinct clades, strain-specific heterogeneity, and putative virulence factors
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Finegoldia magna, a Gram-positive anaerobic coccus, is an opportunistic pathogen, associated with medical device-related infections. F. magna is the only described species of the genus Finegoldia. We report the analysis of 17 genomes of Finegoldia isolates. Phylogenomic analyses showed that the Finegoldia population can be divided into two distinct clades, with an average nucleotide identity of 90.7%. One clade contains strains of F. magna, whereas the other clade includes more heterogeneous strains, hereafter tentatively named "Finegoldia nericia". The latter species appears to be more abundant in the human microbiome. Surface structure differences between strains of F. magna and "F. nericia" were detected by microscopy. Strain-specific heterogeneity is high and previously identified host-interacting factors are present only in subsets of "F. nericia" and F. magna strains. However, all genomes encode multiple host factor-binding proteins such as albumin-, collagen-, and immunoglobulin-binding proteins, and two to four copies of CAMP (Christie-Atkins-Munch-Petersen) factors; in accordance, most strains show a positive CAMP reaction for co-hemolysis. Our work sheds new light of the genus Finegoldia and its ability to bind host components. Future research should explore if the genomic differences identified here affect the potential of different Finegoldia species and strains to cause opportunistic infections.
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| 30. |
- Brüggemann, Holger, et al.
(författare)
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Staphylococcus saccharolyticus Isolated From Blood Cultures and Prosthetic Joint Infections Exhibits Excessive Genome Decay
- 2019
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The slow-growing, anaerobic, coagulase-negative species Staphylococcus saccharolyticus is found on human skin and in clinical specimens but its pathogenic potential is unclear. Here, we investigated clinical isolates and sequenced the genomes of seven strains of S. saccharolyticus. Phylogenomic analyses showed that the closest relative of S. saccharolyticus is Staphylococcus capitis with an average nucleotide identity of 80%. Previously sequenced strains assigned to S. saccharoiyticus are misclassified and belong to S. capitis. Based on single nucleotide polymorphisms of the core genome, the population of S. saccharolyticus can be divided into two clades that also differ in a few larger genomic islands as part of the flexible genome. An unexpected feature of S. saccharolyticus is extensive genome decay, with over 300 pseudogenes, indicating ongoing reductive evolution. Many genes of the core metabolism are not functional, rendering the species auxotrophic for several amino acids, which could explain its slow growth and need for fastidious growth conditions. Secreted proteins of S. saccharolyticus were determined; they include stress response proteins such as heat and oxidative stress-related factors, as well as immunodominant staphylococcal surface antigens and enzymes that can degrade host tissue components. The strains secrete lipases and a hyaluronic acid lyase. Hyaluronidase as well as urease activities were detected in biochemical assays, with Glade-specific differences. Our study revealed that S. saccharolyticus has adapted its genome, possibly due to a recent change of habitat; moreover, the data imply that the species has tissue-invasive potential and might cause prosthetic joint infections.
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| 31. |
- Dagar, Janardan, et al.
(författare)
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Compositional and Interfacial Engineering Yield High-Performance and Stable p-i-n Perovskite Solar Cells and Mini-Modules
- 2021
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Ingår i: ACS applied materials & interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:11, s. 13022-13033
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Tidskriftsartikel (refereegranskat)abstract
- Through the optimization of the perovskite precursor composition and interfaces to selective contacts, we achieved a p-i-n-type perovskite solar cell (PSC) with a 22.3% power conversion efficiency (PCE). This is a new performance record for a PSC with an absorber bandgap of 1.63 eV. We demonstrate that the high device performance originates from a synergy between (1) an improved perovskite absorber quality when introducing formamidinium chloride (FACl) as an additive in the "triple cation" Cs0.05FA0.79MA0.16PbBr0.51I2.49 (Cs-MAFA) perovskite precursor ink, (2) an increased open-circuit voltage, VOC, due to reduced recombination losses when using a lithium fluoride (LiF) interfacial buffer layer, and (3) high-quality hole-selective contacts with a self-assembled monolayer (SAM) of [2-(9H-carbazol-9-yl)ethyl]phosphonic acid (2PACz) on ITO electrodes. While all devices exhibit a high performance after fabrication, as determined from current-density voltage, J-V, measurements, substantial differences in device performance become apparent when considering longer-term stability data. A reduced long-term stability of devices with the introduction of a LiF interlayer is compensated for by using FACl as an additive in the metal-halide perovskite thin-film deposition. Optimized devices maintained about 80% of the initial average PCE during maximum power point (MPP) tracking for >700 h. We scaled the optimized device architecture to larger areas and achieved fully laser patterned series-interconnected mini-modules with a PCE of 19.4% for a 2.2 cm2 active area. A robust device architecture and reproducible deposition methods are fundamental for high performance and stable large-area single junction and tandem modules based on PSCs.
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| 32. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Prevalence of Flp Pili-Encoding Plasmids in Cutibacterium acnes Isolates Obtained from Prostatic Tissue
- 2017
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is one of the hallmarks of prostate cancer. The origin of inflammation is unknown, but microbial infections are suspected to play a role. In previous studies, the Gram-positive, low virulent bacterium Cutibacterium (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue. It is unclear if the presence of the bacterium represents a true infection or a contamination. Here we investigated Cutibacterium acnes type II, also called subspecies defendens, which is the most prevalent type among prostatic C. acnes isolates. Genome sequencing of type II isolates identified large plasmids in several genomes. The plasmids are highly similar to previously identified linear plasmids of type I C. acnes strains associated with acne vulgaris. A PCR-based analysis revealed that 28.4% (21 out of 74) of all type II strains isolated from cancerous prostates carry a plasmid. The plasmid shows signatures for conjugative transfer. In addition, it contains a gene locus for tight adherence (tad) that is predicted to encode adhesive Flp (fimbrial low-molecular weight protein) pili. In subsequent experiments a tad locus-encoded putative pilin subunit was identified in the surface-exposed protein fraction of plasmid-positive C. acnes type II strains by mass spectrometry, indicating that the tad locus is functional. Additional plasmid-encoded proteins were detected in the secreted protein fraction, including two signal peptide-harboring proteins; the corresponding genes are specific for type II C. acnes, thus lacking from plasmid-positive type I C. acnes strains. Further support for the presence of Flp pili in C. acnes type II was provided by electron microscopy, revealing cell appendages in tad locus-positive strains. Our study provides new insight in the most prevalent prostatic subspecies of C. acnes, subsp. defendens, and indicates the existence of Flp pili in plasmid-positive strains. Such pili may support colonization and persistent infection of human prostates by C. acnes.
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| 33. |
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| 34. |
- Eger, Katrien, et al.
(författare)
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The effect of the COVID-19 pandemic on severe asthma care in Europe : will care change for good?
- 2022
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Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Background The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.
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| 35. |
- Fottrell, Edward, et al.
(författare)
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The effect of increased coverage of participatory women's groups on neonatal mortality in Bangladesh : A cluster randomized trial
- 2013
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Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6211 .- 2168-6203. ; 167:9, s. 816-25
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Community-based interventions can reduce neonatal mortality when health systems are weak. Population coverage of target groups may be an important determinant of their effect on behavior and mortality. A women's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality, despite a similar intervention having a significant effect on neonatal and maternal death in comparable settings.OBJECTIVE: To assess the effect of a participatory women's group intervention with higher population coverage on neonatal mortality in Bangladesh.DESIGN: A cluster randomized controlled trial in 9 intervention and 9 control clusters.SETTING: Rural Bangladesh.PARTICIPANTS: Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention.INTERVENTIONS: Women's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues.MAIN OUTCOMES AND MEASURES: Neonatal mortality rate.RESULTS: Analysis included 19 301 births during the final 24 months of the intervention. More than one-third of newly pregnant women joined the groups. The neonatal mortality rate was significantly lower in the intervention arm (21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas), a reduction in neonatal mortality of 38% (risk ratio, 0.62 [95% CI, 0.43-0.89]) when adjusted for socioeconomic factors. The cost-effectiveness was US $220 to $393 per year of life lost averted. Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight. Improvements were seen in hygienic home delivery practices, newborn thermal care, and breastfeeding practices.CONCLUSIONS AND RELEVANCE: Women's group community mobilization, delivered at adequate population coverage, is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh.TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN01805825.
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| 36. |
- Li, Jinzhao, et al.
(författare)
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20.8% Slot-Die Coated MAPbI3 Perovskite Solar Cells by Optimal DMSO-Content and Age of 2-ME Based Precursor Inks
- 2021
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Ingår i: Advanced Energy Materials. - : Wiley. - 1614-6832 .- 1614-6840. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Solar cells incorporating metal-halide perovskite (MHP) semiconductors are continuing to break efficiency records for solution-processed solar cell devices. Scaling MHP-based devices to larger area prototypes requires the development and optimization of scalable process technology and ink formulations that enable reproducible coating results. It is demonstrated that the power conversion efficiency (PCE) of small-area methylammonium lead iodide (MAPbI3) devices, slot-die coated from a 2-methoxy-ethanol (2-ME) based ink with dimethyl-sulfoxide (DMSO) used as an additive depends on the amount of DMSO and age of the ink formulation. When adding 12 mol% of DMSO, small-area devices of high performance (20.8%) are achieved. The effect of DMSO content and age on the thin film morphology and device performance through in situ X-ray diffraction and small-angle X-ray scattering experiments is rationalized. Adding a limited amount of DMSO prevents the formation of a crystalline intermediate phase related to MAPbI3 and 2-ME (MAPbI3-2-ME) and induces the formation of the MAPbI3 perovskite phase. Higher DMSO content leads to the precipitation of the (DMSO)2MA2Pb3I8 intermediate phase that negatively affects the thin-film morphology. These results demonstrate that rational insights into the ink composition and process control are critical to enable reproducible large-scale manufacturing of MHP-based devices for commercial applications.
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| 37. |
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| 38. |
- Marchal, J, et al.
(författare)
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Active pixel detector for ion beam profiling
- 2002
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 487:1-2, s. 224-231
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Tidskriftsartikel (refereegranskat)
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| 39. |
- Munir, M. Adeel, et al.
(författare)
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Blockchain Adoption for Sustainable Supply Chain Management : Economic, Environmental, and Social Perspectives
- 2022
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Ingår i: Frontiers in Energy Research. - : Frontiers Media S.A.. - 2296-598X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Due to the rapid increase in environmental degradation and depletion of natural resources, the focus of researchers is shifted from economic to socio-environmental problems. Blockchain is a disruptive technology that has the potential to restructure the entire supply chain for sustainable practices. Blockchain is a distributed ledger that provides a digital database for recording all the transactions of the supply chain. The main purpose of this research is to explore the literature relevant to blockchain for sustainable supply chain management. The focus of this review is on the sustainability of the blockchain-based supply chain concerning environmental conservation, social equality, and governance effectiveness. Using a systematic literature review, a total of 136 articles were evaluated and categorized according to the triple bottom-line aspects of sustainability. Challenges and barriers during blockchain adoption in different industrial sectors such as aviation, shipping, agriculture and food, manufacturing, automotive, pharmaceutical, and textile industries were critically examined. This study has not only explored the economic, environmental, and social impacts of blockchain but also highlighted the emerging trends in a circular supply chain with current developments of advanced technologies along with their critical success factors. Furthermore, research areas and gaps in the existing research are discussed, and future research directions are suggested. The findings of this study show that blockchain has the potential to revolutionize the entire supply chain from a sustainability perspective. Blockchain will not only improve the economic sustainability of the supply chain through effective traceability, enhanced visibility through information sharing, transparency in processes, and decentralization of the entire structure but also will help in achieving environmental and social sustainability through resource efficiency, accountability, smart contracts, trust development, and fraud prevention. The study will be helpful for managers and practitioners to understand the procedure of blockchain adoption and to increase the probability of its successful implementation to develop a sustainable supply chain network.
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| 40. |
- Shargaieva, Oleksandra, et al.
(författare)
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Hybrid perovskite crystallization from binary solvent mixtures: interplay of evaporation rate and binding strength of solvents
- 2020
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Ingår i: Materials Advances. - : Royal Society of Chemistry (RSC). - 2633-5409. ; 1:9, s. 3314-3321
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we rationalize the chemical pathways and kinetics of the crystallization of methylammonium lead iodide hybrid perovskite. Our approach includes a combination of analysis of solvent coordination, the structure of intermediate solvate phases, and modeling evaporation rates of precursor solutions. The evolution of solution species via intermediate solvate phases and into perovskite thin films during drying was monitored by in situ grazing-incidence wide-angle X-ray scattering (GIWAXS). All studied precursor solutions exhibited the formation of intermediate solvate phases including a previously unreported GBL phase. In single-solvent solutions, crystallization kinetics are determined by the solvent evaporation rate and saturation concentration required for nucleation. In binary solvent mixtures, the evaporation rate of solutions is dominated by the most volatile solvent which leads to unequal evaporation of the components of the mixture. The structure of the intermediate phases in such systems strongly depends on the coordination strength and the availability of solvents upon nucleation. The combined approach described in this work allows predicting the kinetics and the chemical pathways of crystallization of hybrid perovskites in complex solvent mixtures. This insight is of great importance for future perovskite ink design.
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| 41. |
- Siddiqui, Moneeza K., et al.
(författare)
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A common missense variant of LILRB5 is associated with statin intolerance and myalgia
- 2017
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:48, s. 3569-U31
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Tidskriftsartikel (refereegranskat)abstract
- Aims: A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels. Both biomarkers are released from injured muscle tissue, making this variant a potential candidate for susceptibility to muscle-related symptoms. We examined the association of this variant with statin intolerance ascertained from electronic medical records in the GoDARTS study.Methods and results: In the GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance (SI) phenotypes; one defined as having raised CK and being non-adherent to therapy [odds ratio (OR) 1.81; 95% confidence interval (CI): 1.34–2.45] and the other as being intolerant to the lowest approved dose of a statin before being switched to two or more other statins (OR 1.36; 95% CI: 1.07–1.73). Those homozygous for Asp247 had increased odds of developing both definitions of intolerance. Importantly the second definition did not rely on CK elevations. These results were replicated in adjudicated cases of statin-induced myopathy in the PREDICTION-ADR consortium (OR1.48; 95% CI: 1.05–2.10) and for the development of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35, 95% CI: 1.10–1.68). A meta-analysis across the studies showed a consistent association between Asp247Gly and outcomes associated with SI (OR1.34; 95% CI: 1.16–1.54).Conclusion: This study presents a novel immunogenetic factor associated with statin intolerance, an important risk factor for cardiovascular outcomes. The results suggest that true statin-induced myalgia and non-specific myalgia are distinct, with a potential role for the immune system in their development. We identify a genetic group that is more likely to be intolerant to their statins.
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| 42. |
- Siddiqui, Moneeza Kalhan, et al.
(författare)
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CKM Glu83Gly Is Associated With Blunted Creatine Kinase Variation, but Not With Myalgia
- 2017
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Ingår i: Circulation. - 1942-325X .- 1942-3268. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Glu83Gly (rs11559024) with constitutive creatine phosphokinase (CK) levels, CK variation, and inducibility. Given the diagnostic importance of CK in determining muscle damage, we tested the association of the variant with myalgia.METHODS AND RESULTS: ) lower for carriers of the variant, respectively. The variant was not associated with myalgia (odds ratio, 0.84; 95% confidence interval, 0.52-1.38).CONCLUSIONS: This study highlights that a genetic factor known to be associated with constitutive CK levels is also associated with CK variability and inducibility. This is discussed in the context of evidence to suggest that the variant has an impact on inducibility of CK by trauma through a previously reported case of a homozygous carrier. However, the lack of association between the variant and myalgia suggests that it cannot reliably be used as a biomarker for muscle symptoms.
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| 43. |
- Skokauskas, Norbert, et al.
(författare)
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The cost of child and adolescent mental health services
- 2018
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Ingår i: Lancet psychiatry. - 2215-0374 .- 2215-0366. ; 5, s. 299-300
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- More than 2·5 billion children and adolescents exist worldwide, with most individuals living in low-income and middle-income countries (LMICs).1 For these children and adolescents, mental health and neurodevelopmental disorders remain one of the leading causes of the global burden of disease and years lived with disability.2 Although the importance of child and adolescent mental health (CAMH) has been widely acknowledged by organisations such as the UN,3 the development of an inclusive cross-sectorial mental health system for children and adolescents has not gained adequate traction.
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| 44. |
- Verhoef, Talitha I, et al.
(författare)
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A systematic review of cost-effectiveness analyses of pharmacogenetic-guided dosing in treatment with coumarin derivatives.
- 2010
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Ingår i: Pharmacogenomics (London). - : Future Medicine Ltd. - 1462-2416 .- 1744-8042. ; 11:7, s. 989-1002
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Tidskriftsartikel (refereegranskat)abstract
- Anticoagulant therapy with coumarin derivatives is often sub- or supra-therapeutic, resulting in an increased risk of thromboembolic events or hemorrhage, respectively. Pharmacogenetic-guided dosing has been proposed as an effective way of reducing bleeding rates. Clinical trials to confirm the safety, efficacy and effectiveness of this strategy are ongoing, but in addition, it is also necessary to consider the cost-effectiveness of this strategy. This article describes the findings of a systematic review of published cost-effectiveness analyses of pharmacogenetic-guided dosing of coumarin derivatives. Similarities and differences in the approaches used were examined and the quality of the analyses was assessed. The results of the analyses are not sufficient to determine whether or not pharmacogenetic-guided dosing of coumarins is cost effective. More reliable cost-effectiveness estimates need to become available before it is possible to recommend whether or not this strategy should be applied in clinical practice.
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| 45. |
- Verhoef, Talitha I, et al.
(författare)
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Cost-effectiveness of pharmacogenetics in anticoagulation: international differences in healthcare systems and costs
- 2012
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Ingår i: Pharmacogenomics (London). - : Future Medicine. - 1462-2416 .- 1744-8042. ; 13:12, s. 1405-1417
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Forskningsöversikt (refereegranskat)abstract
- Genotyping patients for CYP2C9 and VKORC1 polymorphisms can improve the accuracy of dosing during the initiation of anticoagulation with vitamin K antagonists (coumarin derivatives). The anticipated degree of improvement in the safety of anticoagulation with coumarins through genotyping may vary depending on the quality of patient care, which varies both with and among countries. The management and the cost of anticoagulant care can therefore influence the cost effectiveness of genotyping within any given country. In this article, we provide an overview of the cost effectiveness of pharmacogenetics-guided dosing of coumarin derivatives. We describe the organization of anticoagulant care in the UK, Sweden, The Netherlands, Greece, Germany and Austria, where a genotype-guided dosing algorithm is currently being investigated as part of the EU-PACT trial. We also explore the costs of anticoagulant care for the treatment of atrial fibrillation in these countries.
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| 46. |
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| 47. |
- Zahra, Syeda Anum, et al.
(författare)
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Health inequalities in cardiopulmonary resuscitation and use of automated electrical defibrillators in out-of-hospital cardiac arrest
- 2024
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Ingår i: Current Problems in Cardiology. - 0146-2806. ; 49:5
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Forskningsöversikt (refereegranskat)abstract
- Out of hospital cardiac arrest (OHCA) outcomes can be improved by strengthening the chain of survival, namely prompt cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED). However, provision of bystander CPR and AED use remains low due to individual patient factors ranging from lack of education to socioeconomic barriers and due to lack of resources such as limited availability of AEDs in the community. Although the impact of health inequalities on survival from OHCA is documented, it is imperative that we identify and implement strategies to improve public health and outcomes from OHCA overall but with a simultaneous emphasis on making care more equitable. Disparities in CPR delivery and AED use in OHCA exist based on factors including sex, education level, socioeconomic status, race and ethnicity, all of which we discuss in this review. Most importantly, we discuss the barriers to AED use, and strategies on how these may be overcome.
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