| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
- Callaghan, Terry V., et al.
(författare)
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Ecosystem change and stability over multiple decades in the Swedish subarctic : complex processes and multiple drivers
- 2013
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 368:1624
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Tidskriftsartikel (refereegranskat)abstract
- The subarctic environment of northernmost Sweden has changed over the past century, particularly elements of climate and cryosphere. This paper presents a unique geo-referenced record of environmental and ecosystem observations from the area since 1913. Abiotic changes have been substantial. Vegetation changes include not only increases in growth and range extension but also counterintuitive decreases, and stability: all three possible responses. Changes in species composition within the major plant communities have ranged between almost no changes to almost a 50 per cent increase in the number of species. Changes in plant species abundance also vary with particularly large increases in trees and shrubs (up to 600%). There has been an increase in abundance of aspen and large changes in other plant communities responding to wetland area increases resulting from permafrost thaw. Populations of herbivores have responded to varying management practices and climate regimes, particularly changing snow conditions. While it is difficult to generalize and scale-up the site-specific changes in ecosystems, this very site-specificity, combined with projections of change, is of immediate relevance to local stakeholders who need to adapt to new opportunities and to respond to challenges. Furthermore, the relatively small area and its unique datasets are a microcosm of the complexity of Arctic landscapes in transition that remains to be documented.
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| 4. |
- Cant, David J. H., et al.
(författare)
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Surface Properties of Nanocrystalline PbS Films Deposited at the Water-Oil Interface: A Study of Atmospheric Aging
- 2015
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 31:4, s. 1445-1453
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Tidskriftsartikel (refereegranskat)abstract
- Nanocrystalline thin films of PbS are obtained in a straightforward reaction by precipitation at the interface between toluene (containing a Pb precursor) and water (containing Na2S). Lead thiobiuret [Pb(SON(CN(i)Pr-2)(2))(2)] and lead diethyldithiocarbamate [Pb(S2CNEt2)(2)] precursors are used. The films are characterized by X-ray diffraction and electron microscopy, revealing typical particle sizes of 10-40 nm and preferred (200) orientation. Synchrotron-excited depth-profiling X-ray photoelectron spectroscopy (XPS) is used to determine the depth-dependent chemical composition as a function of surface aging in air for periods of up to 9 months. The as-synthesized films show a 1:1 Pb/S composition. Initial degradation occurs to form lead hydroxide and small quantities of surface-adsorbed -SH species. A lead-deficient Pb1-xS phase is produced as the aging proceeds. Oxidation of the sulfur occurs later to form sulfite and sulfate products that are highly localized at the surface layers of the nanocrystals. These species show logarithmic growth kinetics, demonstrating that the sulfite/sulfate layer acts to passivate the nanocrystals. Our results demonstrate that the initial reaction of the PbS nanocrystals (forming lead hydroxide) is incongruent. The results are discussed in the context of the use of PbS nanocrystals as light-harvesting elements in next-generation solar technology.
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| 5. |
- Chadburn, Sarah E., et al.
(författare)
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Modeled Microbial Dynamics Explain the Apparent Temperature Sensitivity of Wetland Methane Emissions
- 2020
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 34:11
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Tidskriftsartikel (refereegranskat)abstract
- Methane emissions from natural wetlands tend to increase with temperature and therefore may lead to a positive feedback under future climate change. However, their temperature response includes confounding factors and appears to differ on different time scales. Observed methane emissions depend strongly on temperature on a seasonal basis, but if the annual mean emissions are compared between sites, there is only a small temperature effect. We hypothesize that microbial dynamics are a major driver of the seasonal cycle and that they can explain this apparent discrepancy. We introduce a relatively simple model of methanogenic growth and dormancy into a wetland methane scheme that is used in an Earth system model. We show that this addition is sufficient to reproduce the observed seasonal dynamics of methane emissions in fully saturated wetland sites, at the same time as reproducing the annual mean emissions. We find that a more complex scheme used in recent Earth system models does not add predictive power. The sites used span a range of climatic conditions, with the majority in high latitudes. The difference in apparent temperature sensitivity seasonally versus spatially cannot be recreated by the non-microbial schemes tested. We therefore conclude that microbial dynamics are a strong candidate to be driving the seasonal cycle of wetland methane emissions. We quantify longer-term temperature sensitivity using this scheme and show that it gives approximately a 12% increase in emissions per degree of warming globally. This is in addition to any hydrological changes, which could also impact future methane emissions.
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| 6. |
- Dittrich, Christian, et al.
(författare)
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ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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| 7. |
- Donis, Daphne, et al.
(författare)
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Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
- 2021
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
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Tidskriftsartikel (refereegranskat)abstract
- To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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| 8. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 9. |
- FitzGerald, Edward A., 1991-
(författare)
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Fragment-based drug discovery : Novel methods and strategies for identifying and evolving fragment leads
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The need for new drugs became ever more apparent in the year 2020 when the world was faced with a viral pandemic. How drugs are discovered and their relevance to society became part of daily discussions in workplaces and homes throughout the world. Consequently, efficient strategies for preclinical drug discovery are clearly needed. The aim of this thesis has been to contribute to the drug discovery process by developing novel methods for fragment-based drug discovery (FBDD), a rapidly developing approach where success relies on access to sensitive and informative analytical methods as well as chemical compounds with suitable properties. This process is fundamentally dependent on the interplay between scientists and engineers across biology, chemistry and physics. This project is characterized by the development and implementation of novel biophysical methods over a series of studies, which are subdivided into: 1. Development of biosensor assays and approaches for challenging targets, 2. Discovery of fragments targeting dynamic proteins using biosensors, and 3. Reconstruction of ligands using fragment-based strategies.A selection of diverse targets was used as challenging prototypes for the target agnostic methodologies described herein. The targets in focus were: acetylcholine-binding protein (AChBP), a soluble homologue of ligand gated ion channels, and two complex multi-domain epigenetic enzymes lysine specific demethylase 1 (LSD1) and SET and MYND domain-containing protein 3 (SMYD3). Expression, purification, engineering of protein variants, and biochemical characterization were required before robust screening strategies could be established.Three types of biosensors, based on different time-resolved and very sensitive detection principles (SPR, SHG, GCI), were used to identify and characterize the kinetics of the interactions of novel fragments for the proteins. For SPR, a variety of multiplexed assays were designed for the screening of fragments against difficult targets. Notably, it led to the identification of an allosteric ligand and site in SMYD3, which was subsequently characterized kinetically and structurally using X-ray crystallography, and further evolved using computational approaches.An innovative SHG assay for the specific detection of ligands inducing conformational changes was developed and used for fragment screening against AChBP. It revealed that fragments with a potential to serve as functional regulators of ligand gated ion channels can be identified using this technique. The combined application of the novel biophysical and computational approaches enabled the identification of useful starting points for drug discovery projects.
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| 10. |
- FitzGerald, Edward A., et al.
(författare)
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Multiplexed experimental strategies for fragment library screening using SPR biosensors
- 2020
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Surface plasmon resonance biosensor technology (SPR) is ideally suited for fragment-based lead discovery. However, generally suitable experimental procedures or detailed protocols are lacking, especially for structurally or physico-chemically challenging targets or when tool compounds are lacking. Success depends on accounting for the features of both the target and the chemical library, purposely designing screening experiments for identification and validation of hits with desired specificity and mode-of-action, and availability of orthogonal methods capable of confirming fragment hits. By adopting a multiplexed strategy, the range of targets and libraries amenable to an SPR biosensor-based approach for identifying hits is considerably expanded. We here illustrate innovative strategies using five challenging targets and variants thereof. Two libraries of 90 and 1056 fragments were screened using two different flow-based SPR biosensor systems, allowing different experimental approaches. Practical considerations and procedures accounting for the characteristics of the proteins and libraries, and that increase robustness, sensitivity, throughput and versatility are highlighted.Competing Interest StatementAnna Moberg, Maria T. Lindgren and Claes Holmgren work for Cytiva, which produce Biacore systems.
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