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| 2. |
- Mduma, E., et al.
(författare)
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Etiology of severe invasive infections in young infants in rural settings in sub-Saharan Africa
- 2022
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Serious invasive infections in newborns are a major cause of death. Lack of data on etiological causes hampers progress towards reduction of mortality. This study aimed to identify pathogens responsible for such infections in young infants in sub-Saharan Africa and to describe their antibiotics resistance profile. METHODS: Between September 2016 and April 2018 we implemented an observational study in two rural sites in Burkina Faso and Tanzania enrolling young infants aged 0-59 days old with serious invasive infection. Blood samples underwent blood culture and molecular biology. RESULTS: In total 634 infants with clinical diagnosis of serious invasive infection were enrolled and 4.2% of the infants had a positive blood culture. The most frequent pathogens identified by blood culture were Klebsiella pneumonia and Staphylococcus aureus, followed by Escherichia coli. Gram-negative isolates were only partially susceptible to first line WHO recommended treatment for neonatal sepsis at community level. A total of 18.6% of the infants were PCR positive for at least one pathogen and Escherichia coli and Staphylococcus aureus were the most common bacteria detected. Among infants enrolled, 60/634 (9.5%) died. Positive blood culture but not positive PCR was associated with risk of death. For most deaths, no pathogen was identified either by blood culture or molecular testing, and hence a causal agent remained unclear. Mortality was associated with low body temperature, tachycardia, respiratory symptoms, convulsions, history of difficult feeding, movement only when stimulated or reduced level of consciousness, diarrhea and/or vomiting. CONCLUSION: While Klebsiella pneumonia and Staphylococcus aureus, as well as Escherichia coli were pathogens most frequently identified in infants with clinical suspicion of serious invasive infections, most cases remain without definite diagnosis, making more accurate diagnostic tools urgently needed. Antibiotics resistance to first line antibiotics is an increasing challenge even in rural Africa.
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| 3. |
- Andersson, E, et al.
(författare)
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Coronary angiography using laser plasma sources: X-ray source efficiency and optimization of a bent crystal monochromator
- 2001
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Ingår i: Applied Physics Reviews. - : AIP Publishing. - 1931-9401. ; 90:6, s. 3048-3056
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Tidskriftsartikel (refereegranskat)abstract
- A monochromator has been developed for coronary angiography, comprising a single bent crystal of silicon in Laue transmission geometry. K spectra of laser irradiated solid tin and tantalum (Z=50 and 73, respectively) targets were measured. The high resolution crystal spectrometer resolve the Sn and Ta K alpha doublets, allowing in a proof-of-principle experiment the absolute K alpha photon numbers emitted by the source to be determined. The Ta K alpha yield is measured as a function of the laser pulse energy, allowing an assessment to be made of the suitability of such sources for medical applications. (C) 2001 American Institute of Physics.
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| 5. |
- Gratz, Lukas, et al.
(författare)
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Pathway selectivity in Frizzleds is achieved by conserved micro-switches defining pathway-determining, active conformations
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The class Frizzled of G protein-coupled receptors (GPCRs), consisting of ten Frizzled (FZD(1-10)) paralogs and Smoothened, remains one of the most enigmatic GPCR families. This class mediates signaling predominantly through Disheveled (DVL) or heterotrimeric G proteins. However, the mechanisms underlying pathway selection are elusive. Here we employ a structure-driven mutagenesis approach in combination with an extensive panel of functional signaling readouts to investigate the importance of conserved state-stabilizing residues in FZD(5) for signal specification. Similar data were obtained for FZD(4) and FZD(10) suggesting that our findings can be extrapolated to other members of the FZD family. Comparative molecular dynamics simulations of wild type and selected FZD(5) mutants further support the concept that distinct conformational changes in FZDs specify the signal outcome. In conclusion, we find that FZD(5) and FZDs in general prefer coupling to DVL rather than heterotrimeric G proteins and that distinct active state micro-switches in the receptor are essential for pathway selection arguing for conformational changes in the receptor protein defining transducer selectivity. Signaling pathway selectivity downstream of GPCRs is not fully understood. Here, authors perform functional analysis of Frizzled mutants to uncover state-stabilizing residues or 'micro-switches' mediating selectivity towards Disheveled over G proteins.
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| 6. |
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| 7. |
- Gratz, M, et al.
(författare)
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Time-gated imaging in radiology: Theoretical and experimental studies
- 1996
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Ingår i: IEEE Journal of Selected Topics in Quantum Electronics. - : Institute of Electrical and Electronics Engineers (IEEE). - 1077-260X. ; 2:4, s. 1041-1048
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Tidskriftsartikel (refereegranskat)abstract
- Novel short-pulse X-ray sources, e.g., laser-produced plasmas, offer new approaches to the solution of the scatter-reduction problem in X-ray imaging, by the use of time-gated detection techniques. Monte Carlo simulations are used to estimate the scatter-reduction performance of time-gated imaging techniques within a range of X-ray energies, gating times and tissue parameters, Significant improvements can be achieved for thick tissues combined with high photon energies, Experimental studies on water phantoms are performed using a laser-produced plasma X-ray source. Problems arising on the technical realization are discussed.
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| 8. |
- Gratz, M, et al.
(författare)
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Time-gated x-ray tomography
- 1998
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 73:20, s. 2899-2901
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Tidskriftsartikel (refereegranskat)abstract
- Time-gated x-ray tomography with scatter reduction is demonstrated using a laser-produced plasma as an ultrashort-pulse x-ray source in combination with a time-resolving streak-camera detector. Backprojections of a phantom imbedded in 9 cm of water show an effective 50% increase in contrast when scattered x-ray quanta (being delayed in time) are suppressed by gating on the prompt, nonscattered photons. Implications for future volumetric tomography, in particular concerning possible dose reductions, are discussed. (C) 1998 American Institute of Physics. [S0003-6951(98)02846-0].
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| 9. |
- Gratz, M, et al.
(författare)
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X-ray generation for medical applications from a laser-produced plasma
- 1996
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Ingår i: Applied Surface Science. - : Elsevier BV. - 1873-5584 .- 0169-4332. ; 96-8, s. 443-447
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Tidskriftsartikel (refereegranskat)abstract
- We present investigations on the generation of X-ray radiation suitable for different types of medical imaging. Pulses from a 10 Hz terawatt laser system with a duration of 150 fs are focused onto a solid high-Z material target, with focal spot intensities reaching 10(18) W/cm(2). The produced plasma emits broadband X-ray radiation with photon energies up to the MeV region. The application of this X-ray radiation offers new features for medical radiography. Our source allows magnification imaging as well as ultrashort single-shot exposures. New contrast imaging techniques making use of an enhanced characteristic line emission are investigated. The experimental set-up also allows the study of ablation phenomena from sub-picosecond laser pulses by means of particle deposition on thin glass plates. Deposition patterns were studied dependent on different plasma-generation parameters.
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| 10. |
- Herrlin, K, et al.
(författare)
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Contrast-enhanced radiography by differential absorption, using a laser-produced X-ray source
- 1997
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Ingår i: Investigative Radiology. - 0020-9996. ; 32:5, s. 306-310
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE AND OBJECTIVES. The authors evaluate the feasibility of differential imaging of contrast media, with division of individual pixel values obtained from digital images generated by characteristic radiation from a laser-produced plasma, bridging the K-absorption edge of the contrast agent. METHODS. Laser pulses from an ultrashort-pulse terawatt laser system were focused onto gadolinium and tantalum targets, creating a plasma from which characteristic radiation and Bremsstrahlung was emitted. The elements of the target were selected so the characteristic emission lines of one of the elements were below the K edge of the contrast agent and the emission lines of the other element above. A phantom with gadolinium and other elements in various concentrations was examined. One radiographic exposure was made using a gadolinium target source and a subsequent exposure using a tantalum source. Both images were recorded digitally and the transmission ratios calculated by division of the individual pixel values. RESULTS. When viewed separately, the two images of the test phantom appeared similar. In the differential image, only the gadolinium solutions were bright, reflecting a difference in attenuation between the two exposures. CONCLUSIONS. Element-specific radiographs can be obtained by differential imaging. When fully explored, the technique may allow for contrast-enhanced radiography with increased sensitivity and decreased contrast dose.
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| 11. |
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| 12. |
- Schindler, L, et al.
(författare)
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Development of a Neurotensin-Derived 68Ga-Labeled PET Ligand with High In Vivo Stability for Imaging of NTS1 Receptor-Expressing Tumors
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:19
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of the neurotensin receptor type 1 (NTS1R), a peptide receptor located at the plasma membrane, has been reported for a variety of malignant tumors. Thus, targeting the NTS1R with 18F- or 68Ga-labeled ligands is considered a straightforward approach towards in vivo imaging of NTS1R-expressing tumors via positron emission tomography (PET). The development of suitable peptidic NTS1R PET ligands derived from neurotensin is challenging due to proteolytic degradation. In this study, we prepared a series of NTS1R PET ligands based on the C-terminal fragment of neurotensin (NT(8–13), Arg8-Arg9-Pro10-Tyr11-Ile12-Leu13) by attachment of the chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an Nω-carbamoylated arginine side chain. Insertion of Ga3+ in the DOTA chelator gave potential PET ligands that were evaluated concerning NTS1R affinity (range of Ki values: 1.2–21 nM) and plasma stability. Four candidates were labeled with 68Ga3+ and used for biodistribution studies in HT-29 tumor-bearing mice. [68Ga]UR-LS130 ([68Ga]56), containing an N-terminal methyl group and a β,β-dimethylated tyrosine instead of Tyr11, showed the highest in vivo stability and afforded a tumor-to-muscle ratio of 16 at 45 min p.i. Likewise, dynamic PET scans enabled a clear tumor visualization. The accumulation of [68Ga]56 in the tumor was NTS1R-mediated, as proven by blocking studies.
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| 13. |
- Svanberg, Sune, et al.
(författare)
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Generation, characterization, and medical utilization of laser-produced emission continua
- 2000
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Ingår i: Laser and Particle Beams. - 0263-0346. ; 18:3, s. 563-570
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Tidskriftsartikel (refereegranskat)abstract
- Intense continua of electromagnetic radiation of very brief duration are formed in the interaction of focused ultra-short terawatt laser pulses with matter. Two different kinds of experiments, which have been performed utilizing the Lund 10 Hz titanium-doped sapphire terawatt laser system are being described, where visible radiation and X-rays, respectively, have been generated. Focusing into water leads to the generation of a light continuum through self-phase modulation. The propagation of the light through tissue was studied addressing questions related to optical mammography and specific chromophore absorption. When terawatt laser pulses are focused onto a solid target with high nuclear charge Z, intense X-ray radiation of few ps duration and with energies exceeding hundreds of keV is emitted. Biomedical applications of this radiation are described, including differential absorption and gated-viewing imaging.
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