| 1. |
- Tran, K. B., et al.
(author)
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The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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In: Lancet. - 0140-6736. ; 400:10352, s. 563-591
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Journal article (peer-reviewed)abstract
- Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. 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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| 4. |
- Novak, R., et al.
(author)
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Robotic fluidic coupling and interrogation of multiple vascularized organ chips
- 2020
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In: Nature Biomedical Engineering. - : Nature Research. - 2157-846X.
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Journal article (peer-reviewed)abstract
- Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an ‘interrogator’ that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood–brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.
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| 5. |
- Herland, Anna, et al.
(author)
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Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips
- 2020
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In: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 4:4, s. 421-436
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Journal article (peer-reviewed)abstract
- Analyses of drug pharmacokinetics (PKs) and pharmacodynamics (PDs) performed in animals are often not predictive of drug PKs and PDs in humans, and in vitro PK and PD modelling does not provide quantitative PK parameters. Here, we show that physiological PK modelling of first-pass drug absorption, metabolism and excretion in humans—using computationally scaled data from multiple fluidically linked two-channel organ chips—predicts PK parameters for orally administered nicotine (using gut, liver and kidney chips) and for intravenously injected cisplatin (using coupled bone marrow, liver and kidney chips). The chips are linked through sequential robotic liquid transfers of a common blood substitute by their endothelium-lined channels (as reported by Novak et al. in an associated Article) and share an arteriovenous fluid-mixing reservoir. We also show that predictions of cisplatin PDs match previously reported patient data. The quantitative in-vitro-to-in-vivo translation of PK and PD parameters and the prediction of drug absorption, distribution, metabolism, excretion and toxicity through fluidically coupled organ chips may improve the design of drug-administration regimens for phase-I clinical trials.
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| 6. |
- Parameswaran, Poornima, et al.
(author)
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Six RNA Viruses and Forty-One Hosts : Viral Small RNAs and Modulation of Small RNA Repertoires in Vertebrate and Invertebrate Systems
- 2010
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 6:2, s. e1000764-
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Journal article (peer-reviewed)abstract
- We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection in animal cells. Small RNA-based mechanisms such as RNA interference (RNAi) have been shown in plant and invertebrate systems to play a key role in host responses to viral infection. Although homologs of the key RNAi effector pathways are present in mammalian cells, and can launch an RNAi-mediated degradation of experimentally targeted mRNAs, any role for such responses in mammalian host-virus interactions remains to be characterized. Six different viruses were examined in 41 experimentally susceptible and resistant host systems. We identified virus-derived small RNAs (vsRNAs) from all six viruses, with total abundance varying from "vanishingly rare'' (less than 0.1% of cellular small RNA) to highly abundant (comparable to abundant micro-RNAs "miRNAs''). In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host miRNA profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We also found evidence for populations of vsRNAs that exist as duplexed siRNAs with zero to three nucleotide 39 overhangs. Using populations of cells carrying a Hepatitis C replicon, we observed strand-selective loading of siRNAs onto Argonaute complexes. These experiments define vsRNAs as one possible component of the interplay between animal viruses and their hosts.
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| 7. |
- Houshmand, F., et al.
(author)
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Exciton effect in new generation of carbon nanotubes : graphdiyne nanotubes
- 2020
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In: Journal of Molecular Modeling. - : Springer. - 1610-2940 .- 0948-5023. ; 26:7, s. 1-10
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Journal article (peer-reviewed)abstract
- Graphdiyne-based nanotubes (GDNTs) are a novel type of carbon nanotubes. While conventional carbon nanotubes (CNTs) aregenerated by rolling graphene sheets, GDNTs are generated by rolling sheets that are similar to graphene but where the edges areelongated by the introduction of additional acetylene bonds between vertices (C6 aromatic rings). Such nanotubes are predicted tohave many useful practical applications, but a thorough understanding of the relationship between their structure and theirphysical properties is still missing. We present a theoretical study of the electronic and optical properties of GDNTs. Thestructural, electronic, and optical properties of GDNTs with different diameters (i.e., 2–10 additional acetylene bonds) havebeen studied systematically by using density function theory (DFT) and self-consistent charge density functional tight-binding(SCC-DFTB) and by solving the Bethe–Salpeter equation (BSE), with and without considering the electron-hole interactions.The results indicate that the GDNTs are semiconductors with the direct band gap in close range, which is beneficial forphotoelectronic devices and applications. Moreover, the absorption spectra of the GDNTs with different edge structures, (armchair,and zigzag) revealed little differences between the optical spectra of armchair and zigzag GDNTs, which could mean thatfine separation between those structures (a process that is likely difficult and expensive in practice) will not be necessary.Importantly, the nanotubes were highly stable based on their cohesive energies, and their exciton binding energies were as largeas about ~ 1 eV. From a methodological point of view, SCC-DFTB was found to be in agreement with more elaborate DFTcalculations for most systems.
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| 8. |
- Jalili, Armin, et al.
(author)
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A nonlinearity error calibration technique for pipelined ADCs
- 2011
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In: Integration. - Amsterdam, The Netherlands : Elsevier. - 0167-9260 .- 1872-7522. ; 44:3, s. 229-241
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Journal article (peer-reviewed)abstract
- This paper presents a digital background calibration technique that measures and cancels offset, linear and nonlinear errors in each stage of a pipelined analog to digital converter (ADC) using a single algorithm. A simple two-step subranging ADC architecture is used as an extra ADC in order to extract the data points of the stage-under-calibration and perform correction process without imposing any changes on the main ADC architecture which is the main trend of the current work. Contrary to the conventional calibration methods that use high resolution reference ADCs, averaging and chopping concepts are used in this work to allow the resolution of the extra ADC to be lower than that of the main ADC.
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| 9. |
- Jalili, Armin, et al.
(author)
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Calibration of high-resolution flash ADCS based on histogram test methods
- 2010
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In: Electronics, Circuits, and Systems (ICECS), 2010 17th IEEE International Conference on. - : IEEE. - 9781424481552 ; , s. 114-117
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Conference paper (other academic/artistic)abstract
- In this paper a calibration technique for high-resolution, flash analog- to-digital converters (ADCs) based on histogram test methods is proposed. A probability density function, PDF, generator circuit is utilized to generate a triangular signal with a constant PDF, i.e., uniform distribution, as a test signal. In the proposed technique both offset estimation and trimming are performed without imposing any changes on the comparator structure in the ADC. The proposed algorithm estimates the offset values and stores them in a RAM. The trimming circuit uses the stored values and performs the trimming by adjusting the reference voltages to the comparators. An 8-bit flash ADC with a 1-V reference voltage, a comparator offset distribution with σos ≈ 30 mV, and a 10-bit test signal with about 3% nonlinearity are used in the simulations. The results show that the calibration improves the DNL and INL from about 3.6/3.9 LSB to about 0.9/0.75 LSB, respectively.
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| 10. |
- Jalili, Armin, et al.
(author)
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Calibration of sigma-delta analog-to-digital converters based on histogram test methods
- 2010
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In: NORCHIP, 2010. - : IEEE. - 9781424489725 ; , s. 1-4
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Conference paper (peer-reviewed)abstract
- In this paper we present a calibration technique for sigma-delta analog-to-digital converters (ΣΔADC) in which highspeed, low-resolution flash subADCs are used. The calibration technique as such is mainly targeting calibration of the flash subADC, but we also study how the correction depends on where in the ΣΔ modulator the calibration signals are applied. It is shown that the calibration technique can cope with errors that occur in the feedback digital-to-analog converter (DAC) and the input accumulator. Behavioral-level simulation results show an improvement of in effective number of bits (ENOB) from 6.6 to 11.3. Fairly large offset and gain errors have been introduced which illustrates a robust calibration technique.
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