| 1. |
- Block, Keith I., et al.
(author)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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In: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Research review (peer-reviewed)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 2. |
- Pantazis, N, et al.
(author)
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Determining the likely place of HIV acquisition for migrants in Europe combining subject-specific information and biomarkers data
- 2019
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In: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 28:7, s. 1979-1997
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Journal article (peer-reviewed)abstract
- In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( n = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.
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| 3. |
- Chalmers, J. R., et al.
(author)
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Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)
- 2016
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In: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 175:1, s. 69-79
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Journal article (peer-reviewed)abstract
- This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmo, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [ including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.
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| 4. |
- Harcourt, R., et al.
(author)
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Animal-borne telemetry: An integral component of the ocean observing toolkit
- 2019
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:JUN
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Journal article (peer-reviewed)abstract
- Animal telemetry is a powerful tool for observing marine animals and the physical environments that they inhabit, from coastal and continental shelf ecosystems to polar seas and open oceans. Satellite-linked biologgers and networks of acoustic receivers allow animals to be reliably monitored over scales of tens of meters to thousands of kilometers, giving insight into their habitat use, home range size, the phenology of migratory patterns and the biotic and abiotic factors that drive their distributions. Furthermore, physical environmental variables can be collected using animals as autonomous sampling platforms, increasing spatial and temporal coverage of global oceanographic observation systems. The use of animal telemetry, therefore, has the capacity to provide measures from a suite of essential ocean variables (EOVs) for improved monitoring of Earth's oceans. Here we outline the design features of animal telemetry systems, describe current applications and their benefits and challenges, and discuss future directions. We describe new analytical techniques that improve our ability to not only quantify animal movements but to also provide a powerful framework for comparative studies across taxa. We discuss the application of animal telemetry and its capacity to collect biotic and abiotic data, how the data collected can be incorporated into ocean observing systems, and the role these data can play in improved ocean management. © 2019 Harcourt, Sequeira, Zhang, Roquet, Komatsu, Heupel, McMahon, Whoriskey, Meekan, Carroll, Brodie, Simpfendorfer, Hindell, Jonsen, Costa, Block, Muelbert, Woodward, Weise, Aarestrup, Biuw, Boehme, Bograd, Cazau, Charrassin, Cooke, Cowley, de Bruyn, Jeanniard du Dot, Duarte, Eguíluz, Ferreira, Fernández-Gracia, Goetz, Goto, Guinet, Hammill, Hays, Hazen, Hückstädt, Huveneers, Iverson, Jaaman, Kittiwattanawong, Kovacs, Lydersen, Moltmann, Naruoka, Phillips, Picard, Queiroz, Reverdin, Sato, Sims, Thorstad, Thums, Treasure, Trites, Williams, Yonehara and Fedak.
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| 5. |
- Khuyagbaatar, J., et al.
(author)
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Fusion reaction 48Ca + 249Bk leading to formation of the element Ts (Z=117)
- 2019
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In: Physical Review C. - 2469-9985. ; 99:5
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Journal article (peer-reviewed)abstract
- The heaviest currently known nuclei, which have up to 118 protons, have been produced in 48Ca induced reactions with actinide targets. Among them, the element tennessine (Ts), which has 117 protons, has been synthesized by fusing 48Ca with the radioactive target 249Bk, which has a half-life of 327 d. The experiment was performed at the gas-filled recoil separator TASCA. Two long and two short α decay chains were observed. The long chains were attributed to the decay of 294Ts. The possible origin of the short-decay chains is discussed in comparison with the known experimental data. They are found to fit with the decay chain patterns attributed to 293Ts. The present experimental results confirm the previous findings at the Dubna Gas-Filled Recoil Separator on the decay chains originating from the nuclei assigned to Ts.
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| 6. |
- Di Nitto, A., et al.
(author)
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Study of Non-fusion Products in the 50Ti+249Cf Reaction
- 2018
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In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 784, s. 199-205
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Journal article (peer-reviewed)abstract
- The isotopic distribution of nuclei produced in the 50Ti + 249Cf reaction has been studied at the gas-filled recoil separator TASCA at GSI Darmstadt, which separates ions according to differences in magnetic rigidity. The bombardment was performed at an energy around the Bass barrier and with the TASCA magnetic fields set for collecting fusion-evaporation reaction products. Fifty-three isotopes located “north-east” of 208Pb were identified as recoiling products formed in non-fusion channels of the reaction. These recoils were implanted with energies in two distinct ranges; besides one with higher energy, a significant low-energy contribution was identified. The latter observation was not expected to occur according to kinematics of the known types of reactions, namely quasi-elastic, multi-nucleon transfer, deep-inelastic collisions or quasifission. The present observations are discussed within the framework of two-body kinematics passing through the formation of a composite system.
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| 7. |
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| 8. |
- Forsberg, U., et al.
(author)
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Recoil-α-fission and recoil-α-α-fission events observed in the reaction 48Ca + 243Am
- 2016
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In: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 953, s. 117-138
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Journal article (peer-reviewed)abstract
- Products of the fusion-evaporation reaction 48Ca + 243Am were studied with the TASISpec set-up at the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany. Amongst the detected thirty correlated α-decay chains associated with the production of element Z=115, two recoil-α-fission and five recoil-α-α-fission events were observed. The latter five chains are similar to four such events reported from experiments performed at the Dubna gas-filled separator, and three such events reported from an experiment at the Berkeley gas-filled separator. The four chains observed at the Dubna gas-filled separator were assigned to start from the 2n-evaporation channel 289115 due to the fact that these recoil-α-α-fission events were observed only at low excitation energies. Contrary to this interpretation, we suggest that some of these recoil-α-α-fission decay chains, as well as some of the recoil-α-α-fission and recoil-α-fission decay chains reported from Berkeley and in this article, start from the 3n-evaporation channel 288115.
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| 9. |
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| 10. |
- Rudolph, Dirk, et al.
(author)
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Selected Spectroscopic Results on Element 115 Decay Chains
- 2015
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In: Journal of Radioanalytical and Nuclear Chemistry. - : Springer Science and Business Media LLC. - 0236-5731 .- 1588-2780. ; 303:2, s. 1185-1190
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Journal article (peer-reviewed)abstract
- Thirty correlated alpha-decay chains were observed in an experiment studying the fusion-evaporation reaction 48Ca + 243Am at the GSI Helmholtzzentrum f¨ur Schwerionenforschung. The decay characteristics of the majority of these 30 chains are consistent with previous observations and interpretations of such chains to originate from isotopes of element Z = 115. High-resolution alpha-photon coincidence spectroscopy in conjunction with comprehensive Monte-Carlo simulations allow to propose excitation schemes of atomic nuclei of the heaviest elements, thereby probing nuclear structure models near the ‘Island of Stability’ with unprecedented experimental precision.
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| 11. |
- Såmark-Roth, A., et al.
(author)
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Low-lying states in 219Ra and 215Rn : Sampling microsecond α-decaying nuclei
- 2018
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In: Physical Review C. - 2469-9985. ; 98:4
-
Journal article (peer-reviewed)abstract
- Short-lived α-decaying nuclei "northeast" of 208Pb in the chart of nuclides were studied using the reaction 48Ca+243Am with the decay station TASISpec at TASCA, GSI Darmstadt. Decay energies and times from pile-up events were extracted with a tailor-made pulse-shape analysis routine and specific α-decay chains were identified in a correlation analysis. Decay chains starting with the even-even 220Ra and its odd-A neighbors, 219Fr, and 219,221Ra, with a focus on the 219Ra→215Rn decay, were studied by means of α-γ spectroscopy. A revised α-decay scheme of 219Ra is proposed, including a new decay branch from a previously not considered isomeric state at 17 keV excitation energy. Conclusions on nuclear structure are drawn from the experimental data, aided by Geant4 simulations and a discussion on theoretical calculations.
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| 12. |
- Gates, J. M., et al.
(author)
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Decay Spectroscopy of Element 115 Daughters: 280Rg -> 276Mt and 276Mt -> 272Bh
- 2015
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:2
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Journal article (peer-reviewed)abstract
- Forty-six decay chains, assigned to the decay of 288-115, were produced using the 243Am(48Ca,3n)288-115 reaction at the Lawrence Berkeley National Laboratory 88-in. cyclotron. The resulting series of α decays were studied using α-photon and α-x-ray spectroscopies. Multiple α-photon coincidences were observed in the element 115 decay chain members, particularly in the third- and fourth-generation decays (presumed to be 280Rg and 276Mt, respectively). Upon combining these data with those from 22 288-115 decay chains observed in a similar experiment, updated level schemes in 276Mt and 272Bh (populated by the α decay of 280Rg and 276Mt, respectively) are proposed. Photons were observed in the energy range expected for K x rays coincident with the α decay of both 280Rg and 276Mt. However, Compton scattering of higher-energy γ rays and discrete transitions are present in the K x-ray region preventing a definitive Z identification to be made based on observation of characteristic K x-ray energies.
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| 13. |
- Giacoppo, F., et al.
(author)
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Recent upgrades of the SHIPTRAP setup : On the finish line towards direct mass spectroscopy of superheavy elements
- 2017
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In: Acta Physica Polonica B. - 0587-4254. ; 48:3, s. 423-429
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Journal article (peer-reviewed)abstract
- With the Penning-trap mass spectrometer SHIPTRAP at GSI, Darmstadt, it is possible to investigate exotic nuclei in the region of the heaviest elements. Few years ago, challenging experiments led to the direct measurements of the masses of neutron-deficient isotopes with Z = 102; 103 around N = 152. Thanks to recent advances in cooling and ion-manipulation techniques, a major technical upgrade of the setup has been recently accomplished to boost its efficiency. At present, the gap to reach more rare and shorter-lived species at the limits of the nuclear landscape has been narrowed.
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| 14. |
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| 15. |
- Block, Benjamin D., et al.
(author)
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The unique methodological challenges of winter limnology
- 2019
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In: Limnology and Oceanography. - : Wiley-Blackwell. - 1541-5856. ; 17:1, s. 42-57
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Research review (peer-reviewed)abstract
- Winter is an important season for many limnological processes, which can range from biogeochemical transformations to ecological interactions. Interest in the structure and function of lake ecosystems under ice is on the rise. Although limnologists working at polar latitudes have a long history of winter work, the required knowledge to successfully sample under winter conditions is not widely available and relatively few limnologists receive formal training. In particular, the deployment and operation of equipment in below 0 degrees C temperatures pose considerable logistical and methodological challenges, as do the safety risks of sampling during the ice-covered period. Here, we consolidate information on winter lake sampling and describe effective methods to measure physical, chemical, and biological variables in and under ice. We describe variation in snow and ice conditions and discuss implications for sampling logistics and safety. We outline commonly encountered methodological challenges and make recommendations for best practices to maximize safety and efficiency when sampling through ice or deploying instruments in ice-covered lakes. Application of such practices over a broad range of ice-covered lakes will contribute to a better understanding of the factors that regulate lakes during winter and how winter conditions affect the subsequent ice-free period.
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| 16. |
- Evans, M., et al.
(author)
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Use of fast-acting insulin aspart in insulin pump therapy in clinical practice
- 2019
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 21:9, s. 2039-2047
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Journal article (peer-reviewed)abstract
- Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) containing the additional excipients niacinamide and L-arginine. The improved pharmacological profile and greater early glucose-lowering action of faster aspart compared with IAsp suggests that faster aspart may be advantageous for people with diabetes using continuous subcutaneous insulin infusion (CSII). The recent onset 5 trial was the first to evaluate the efficacy and safety of an ultra-fast-acting insulin in CSII therapy in a large number of participants with type 1 diabetes (T1D). Non-inferiority of faster aspart to IAsp in terms of change from baseline in HbA1c was confirmed, with an estimated treatment difference (ETD) of 0.09% (95% CI, 0.01; 0.17; P < 0.001 for non-inferiority [0.4% margin]). Faster aspart was superior to IAsp in terms of change from baseline in 1-hour post-prandial glucose (PPG) increment after a meal test (ETD [95% CI], −0.91 mmol/L [−1.43; −0.39]; P = 0.001), with statistically significant improvements also at 30 minutes and 2 hours. The overall rate of severe or blood glucose-confirmed hypoglycaemia was not statistically significantly different between treatments, with an estimated rate ratio of 1.00 (95% CI, 0.85; 1.16). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and the 4-week run-in periods (4 vs 0). Experience from clinical practice indicates that all pump settings should be reviewed when initiating faster aspart with CSII, and that the use of continuous glucose monitoring or flash glucose monitoring, along with a good understanding of meal content and bolus type, may also facilitate optimal use. This review summarizes the available clinical evidence for faster aspart administered via CSII and highlights practical considerations based on clinical experience that may help healthcare providers and individuals with T1D successfully initiate and adjust faster aspart with CSII. © 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
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| 17. |
- Khuyagbaatar, J., et al.
(author)
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New Short-Lived Isotope 221U and the Mass Surface Near N=126
- 2015
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In: Physical Review Letters. - 1079-7114. ; 115:24
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Journal article (peer-reviewed)abstract
- Two short-lived isotopes 221U and 222U were produced as evaporation residues in the fusion reaction 50Ti+176Yb at the gas-filled recoil separator TASCA. An α decay with an energy of Eα=9.31(5) MeV and half-life T1/2=4.7(7) μs was attributed to 222U. The new isotope 221U was identified in α-decay chains starting with Eα=9.71(5) MeV and T1/2=0.66(14) μs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width.
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| 18. |
- Lubart, Quentin, 1989, et al.
(author)
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High throughput size-determination and multiplexed fluorescence analysis of single biological particles in a nanofluidic device
- 2019
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In: 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019. ; , s. 1420-1421
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Conference paper (peer-reviewed)abstract
- Biological nanoparticles, such as exosomes and viruses, are responsible for a multitude of important functions, but methods to characterize them on the single particle level are rare. We here present a nanofluidic platform for multi-parametric characterization of biological nanoparticles with high throughput. The device consists of feeding microchannels and an array of ~100 nanochannels where the nanoparticles can be characterized. We determine the size by analyzing the Brownian motion of the particles and quantify their content based on fluorescence imaging of up to three different colors. We successfully benchmark our method against existing techniques, such as Nanoparticle Tracking Analysis (NTA).
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| 19. |
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| 20. |
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