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- Ikuta, K. S., et al.
(författare)
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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
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Tidskriftsartikel (refereegranskat)abstract
- Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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- Karmaker, Palash Chandra, et al.
(författare)
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Characterization of Nd(Tb)-Fe-B-based exchange-spring nanocomposite magnets
- 2019
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Ingår i: Emerging Materials Research. - : ICE PUBLISHING. - 2046-0147 .- 2046-0155. ; 8:2, s. 153-165
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Tidskriftsartikel (refereegranskat)abstract
- The authors attempt to optimize for performance the composition of R2Fe14B/Fe3B-based hard nanocomposite alloys with R = neodymium (Nd) and terbium (Tb) by optimizing phases in order to develop hysteresis parameters such as maximum magnetization, coercivity and maximum energy product through variation in composition and heat treatment. The samples were prepared from arc-melted ingots of different compositions. The crystallization temperatures were obtained from the differential scanning calorimeter traces of the samples with the composition Nd(4-x)TbxFe(71)Co(5)Cu(0.5)Nb(1)B(18.5) (x = 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0). Depending on their crystallization temperatures, the samples were annealed at 600, 625, 650, 675 and 700 degrees C for 10 min. Amorphosity and crystallization behavior were studied by X-ray diffraction using copper (Cu) K-alpha radiation (1.5418 angstrom). The Mossbauer spectra of all the samples were recorded at room temperature by using iron-57 (Fe-57) Mossbauer spectrometry in transmission geometry with a constant-acceleration spectrometer. Magnetic properties were determined by a vibrating-sample magnetometer in the as-cast and annealed conditions. Although the highest values of coercivity and remanent ratio were found to be 4.18 kOe and 0.72, respectively, for the sample of composition Nd3Tb1Fe71Co5Cu0.5Nb1B18.5 annealed at 650 degrees C with a higher concentration of terbium, the highest maximum energy product was determined to be 12.67 MGOe for the sample of Nd3.8Tb0.2Fe71Co5Cu0.5Nb1B18.5.
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- Lindhe, Örjan, et al.
(författare)
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[(18)F]Fluoroacetate is not a functional analogue of [(11)C]acetate in normal physiology
- 2009
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 36:9, s. 1453-1459
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: [(11)C]Acetate (C-AC) is a general PET tracer of cellular carbon flux and useful for clinical imaging in heart disease as well as prostate cancer and other tumours. C-AC has a high (70%) whole-body extraction fraction, proportional to blood flow in many organs. Trapping is related to organ-specific enzymatic activation and formation of [(11)C]-acetyl-CoA, the fate of which has been well characterized. Due to the logistic challenges with C-AC, 2-[(18)F]fluoroacetate (F-AC) has been proposed as a marker for prostate cancer imaging. METHOD: We evaluated the potential of F-AC as a tracer for imaging blood flow and early enzymatic steps in the intermediary metabolism. C-AC and F-AC were injected serially in three cynomolgus monkeys and one domestic pig and scanned using PET/CT. A dynamic scan covering heart and liver was followed by repeated whole-body imaging. Kinetic patterns were compared for the myocardium, liver, blood and other organs. RESULTS: C-AC kinetics and organ distribution in both species were similar to those previously established in man. In contrast, F-AC showed prolonged blood retention, no detectable trapping in myocardium or salivary glands, rapid clearance from liver and extensive excretion to bile and urine. Massive defluorination was seen in the pig, resulting in intense skeletal activity. CONCLUSION: 2-[(18)F]Fluoroacetate cannot be regarded as a functional analogue of 1-[(11)C]acetate in normal physiology and appears to be of little use for studies of organ blood flow, intermediary metabolism or lipid synthesis.
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- Långström, Bengt, et al.
(författare)
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[11C]Carbon monoxide, a versatile and useful precursor in labelling chemistry for PET-ligand development
- 2007
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Ingår i: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 50:9-10, s. 794-810
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Forskningsöversikt (refereegranskat)abstract
- In this review the recent progress in the development of suitable precursors for 11C-labelling is discussed. Especially the last few years' advancement of the use of [11C] carbon monoxide as a versatile and useful precursor in labelling chemistry is presented. The development is set in perspective of its potential in applying molecular imaging tools in drug and tracer development.The possibility of exploring small tracer libraries utilizing the microdosing concept is explored.
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- Obaidur, Rahman, 1963-, et al.
(författare)
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Automated synthesis of 18F-labelled analogues of etomidate, vorozole and harmine using commercial synthesizer TRACERLab FXFN
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- 18F-Labelled analogues of three biologically interesting compounds, ethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (ETO), 6-[(S)-(4-chlorophenyl)-(1H)-1,2,4-triazol-1-yl)methyl]-1-methyl-1H-benzotriazole (VOZ) and 7-methoxy-1-methyl-9H-β-carboline (HAR) were synthesized by one-step nucleophilic fluorination. The 18F-labelled products were obtained with 20–30% isolated decay-corrected radiochemical yields and the radiochemical purities were over 99% in all cases. The labelling syntheses were performed using fully automated commercial synthesizer TRACERLab FXFN. The automation of the syntheses of these three promising PET tracers using a commercial synthesizer will make them accessible for clinical applications.
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- Rahman, Obaidur, 1963-
(författare)
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[11C]Carbon Monoxide and Aryl Triflates in Palladium-Mediated Carbonylation Reactions : Synthetic approaches to [11C]Carbonyl Compounds and [11C]Amines
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The usefulness of low concentrations (typically 10 to 100 µM) of [11C]carbon monoxide and aryl triflates as substrates in 11C-carbonylation using different nucleophiles in the presence of lithium bromide was investigated. The reactions were performed in a micro autoclave of 200 µL volume and catalysed (mediated) by palladium(0). A peripheral type benzodiazepine receptor (PBR) ligand, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxamide (PK11195) and its structural analogues including an irreversible ligand for PBR, some other amides, ketones and carboxylic acids, were all labelled with 11C using this approach. The [carbonyl-11C]PK11195, analogues and other amides were prepared from aryl triflates and amines, and the [carbonyl-11C]ketones were prepared from aryl triflates and organoboranes. In the synthesis of [carboxyl-11C]carboxylic acids, water was utilised as nucleophile. The decay-corrected radiochemical yields were 10 to 55% for [11C]PK11195 and analogues, 2 to 63% for other [11C]amides, 10 to 75% for [11C]ketones and 25 to 65% for [11C]carboxylic acids. The specific radioactivity of the labelled compounds was in the range of 150 to 900 GBq/µmol. Some [11C]amines were prepared by a reductive amination of the corresponding [carbonyl-11C]ketones. These reactions were performed using different amines in the presence of TiCl4 and NaBH3CN. The radiochemical yields of the [11C]amines varied from 2 to 78% (determined by analytical HPLC). In order to confirm the labelling position, synthesis of selected 13C-substituted compounds were performed. For each substance group/ synthesis method, a selected compound was synthesised using (13C)carbon monoxide and the 13C-substituted compound was then analysed by 13C NMR.A synthetic route was developed for the preparation of 1-(2-chloro-phenyl)-isoquinolin-3-yl trifluoromethanesulfonate used as the precursor in the synthesis of [carbonyl-11C]PK11195 and analogues.
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