| 1. |
- Björnfot, Cecilia, et al.
(författare)
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Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
- 2024
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
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Tidskriftsartikel (refereegranskat)abstract
- White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
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| 2. |
- Adrian-Kalchhauser, I., et al.
(författare)
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The round goby genome provides insights into mechanisms that may facilitate biological invasions
- 2020
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Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The invasive benthic round goby (Neogobius melanostomus) is the most successful temperate invasive fish and has spread in aquatic ecosystems on both sides of the Atlantic. Invasive species constitute powerful in situ experimental systems to study fast adaptation and directional selection on short ecological timescales and present promising case studies to understand factors involved the impressive ability of some species to colonize novel environments. We seize the unique opportunity presented by the round goby invasion to study genomic substrates potentially involved in colonization success. Results We report a highly contiguous long-read-based genome and analyze gene families that we hypothesize to relate to the ability of these fish to deal with novel environments. The analyses provide novel insights from the large evolutionary scale to the small species-specific scale. We describe expansions in specific cytochrome P450 enzymes, a remarkably diverse innate immune system, an ancient duplication in red light vision accompanied by red skin fluorescence, evolutionary patterns of epigenetic regulators, and the presence of osmoregulatory genes that may have contributed to the round goby's capacity to invade cold and salty waters. A recurring theme across all analyzed gene families is gene expansions. Conclusions The expanded innate immune system of round goby may potentially contribute to its ability to colonize novel areas. Since other gene families also feature copy number expansions in the round goby, and since other Gobiidae also feature fascinating environmental adaptations and are excellent colonizers, further long-read genome approaches across the goby family may reveal whether gene copy number expansions are more generally related to the ability to conquer new habitats in Gobiidae or in fish.
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| 3. |
- Bickham, S., et al.
(författare)
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Low cutoff G.657-compatible fiber for data center interconnects operating in the 1064 and 1310 nm windows
- 2020
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 11286
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Konferensbidrag (refereegranskat)abstract
- Optical interconnects in data centers have traditionally used 850 nm GaAs-based vertical-cavity surface-emitting lasers (VCSELs) in combination with multimode fiber, having a reach up to 100 m in length. Longer links typically use standard single-mode fiber in conjunction with either InP-based edge-emitting lasers or silicon photonic transmitters operating in the 1310 nm or 1550 nm window. Single-mode GaAs-based VCSELs operating at 1064 nm offer another path for achieving longer system reach. Potential advantages of these VCSELs include better power efficiency, modulation speeds reaching 50 Gbps and large-scale fabrication volumes. The longer wavelength is also beneficial due to the lower attenuation and chromatic dispersion of optical fibers at that wavelength. However, one practical issue for single-mode transmission is that the G.657 standard for single-mode fiber requires that the 22-meter cable cutoff wavelength be less than 1260 nm, and these fibers are typically few-moded at 1064 nm. The large differences between the group velocities of the LP01 and LP11 modes can lead to degradation of the system performance due to multi-path interference if the higher order modes are present. To resolve this quandary, we have designed and validated the performance of a new optical fiber which is single-moded at wavelengths less than 1064 nm, but also has G.657-compliant mode field diameter and dispersion characteristics that enable it to be used in the 1310 nm window.
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| 4. |
- Buffolo, M., et al.
(författare)
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Modeling of the Optical and Electrical Degradation of 845 nm VCSILs
- 2023
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Ingår i: 2023 Conference on Lasers and Electro-Optics, CLEO 2023.
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Konferensbidrag (refereegranskat)abstract
- Optical and electrical degradation of novel micro-transfer-printed VCSILs is investigated. Modeling of experimental data suggests that the main degradation mechanism is represented by the relocation of impurities, originating from the p-side, toward the active region.
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| 5. |
- Caut, Alexander, 1994, et al.
(författare)
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Angled Flip-Chip Integration of VCSELs on Silicon Photonic Integrated Circuits
- 2022
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Ingår i: Journal of Lightwave Technology. - 0733-8724 .- 1558-2213. ; 40:15, s. 5190-5200
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Tidskriftsartikel (refereegranskat)abstract
- An investigation of angled flip-chip integration of a singlemode 850 nm vertical-cavity surface-emitting laser (VCSEL) on a silicon nitride photonic integrated circuit (PIC) is presented. Using numerical FDTD simulations, we consider the conditions under which the VCSEL can be integrated at an angle over a grating coupler with high coupling efficiency and low optical feedback. With both coupling efficiency and feedback decreasing with increasing angle, there is a trade-off. With co-directional coupling, first-order diffraction loss sets in at a critical angle, which further reduces the coupling efficiency. No such critical angle exists for contra-directional coupling. We also experimentally demonstrate angled flip-chip integration of GaAs-based 850 nm single transverse and polarization mode VCSELs over grating couplers on a silicon-nitride PIC. At the output grating coupler, light is either collected by an optical fiber or converted to a photocurrent using a flip-chip integrated GaAs-based photodetector. The latter forms an on-PIC optical link. We measured an insertion loss of 21.9, 17.6 and 20.1 dB with a singlemode fiber, multimode fiber and photodetector over the output grating coupler, respectively.
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| 6. |
- Caut, Alexander, 1994, et al.
(författare)
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Channel Scalability of Silicon Nitride (De-)multiplexers for Optical Interconnects at 1 μm
- 2024
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Ingår i: Journal of Lightwave Technology. - 0733-8724 .- 1558-2213. ; 42:1, s. 276-286
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an investigation of the channel scalability of silicon nitride (Si3N4)-based (de-)multiplexers in the 1-μm band (1015-1055 nm). We discuss 4-, 8- and 16-channel demultiplexers based on arrayed waveguide gratings (AWGs) and cascaded Mach-Zehnder interferometers (MZIs), with corresponding channel spacings of 8, 4 and 2 nm. Gaussian and flat-top response devices are considered for both technologies and we analyze the insertion loss, temperature sensitivity, response flatness, footprint and crosstalk (XT). We study the impact of the number of channels on the insertion loss and XT level. In the experimental part, we demonstrate a 4-channel Gaussian AWG. We also demonstrate 4-channel Gaussian and flat-top cascaded MZIs, based on multimode interferometers (MMIs) and directional couplers (DCs). The AWG is attractive due to its small footprint but its high manufacturing complexity makes the device more prone to fabrication defects, which can lead to higher loss and higher XT. For the Gaussian AWG and MZI, the XT level is approximately the same and increases with the number of channels from -28 to -23 dB at 4 and 16 channels respectively. The flat-top MZI has no extra-loss with respect to the flat-top AWG and has a better tolerance to high temperature operations. However, due to wavelength sensitive DCs, the XT of the flat-top MZI is higher than that of the flat-top AWG except for a 16-channel system.
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| 7. |
- Eliasson, Gabriella, et al.
(författare)
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Comorbid conditions as predictors of mortality in severe COPD - an eight-year follow-up cohort study
- 2023
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Ingår i: European Clinical Respiratory Journal. - : Taylor & Francis. - 2001-8525. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Co-morbidities are common in chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. The aim of the present study was to explore the prevalence of several comorbid conditions in severe COPD, and to investigate and compare their associations with long-term mortality.Methods: In May 2011 to March 2012, 241 patients with COPD stage 3 or 4 were included in the study. Information was collected on sex, age, smoking history, weight and height, current pharmacological treatment, number of exacerbations the recent year and comorbid conditions. At December 31st, 2019, mortality data (all-cause and cause specific) were collected from the National Cause of Death Register. Data were analyzed using Cox-regression analysis with gender, age, previously established predictors of mortality and comorbid conditions as independent variables, and all-cause mortality and cardiac and respiratory mortality, respectively, as dependent variables.Results: Out of 241 patients, 155 (64%) were deceased at the end of the study period; 103 patients (66%) died of respiratory disease and 25 (16%) of cardiovascular disease. Impaired kidney function was the only comorbid condition independently associated with increased all-cause mortality (HR (95% CI) 3.41 (1.47-7.93) p=0.004) and respiratory mortality (HR (95%CI) 4.63 (1.61 to 13.4), p = 0.005). In addition, age >= 70, BMI <22 and lower FEV1 expressed as %predicted were significantly associated with increased all-cause and respiratory mortality.Conclusion: In addition to the risk factors high age, low BMI and poor lung function; impaired kidney function appears to be an important risk factor for mortality in the long term, which should be taken into account in the medical care of patients with severe COPD.
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| 8. |
- GBD 2021 Risk Factors Collaborators,, et al.
(författare)
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Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.
- 2024
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Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 403:10440, s. 2162-2203
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021.The GBD 2021 risk factor analysis used data from 54561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk-outcome pairs. Pairs were included on the basis of data-driven determination of a risk-outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk-outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk-outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws.Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7-9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4-9·2]), smoking (5·7% [4·7-6·8]), low birthweight and short gestation (5·6% [4·8-6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8-6·0]). For younger demographics (ie, those aged 0-4 years and 5-14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9-27·7]) and environmental and occupational risks (decrease of 22·0% [15·5-28·8]), coupled with a 49·4% (42·3-56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9-21·7] for high BMI and 7·9% [3·3-12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6-1·9) for high BMI and 1·3% (1·1-1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4-78·8) for child growth failure and 66·3% (60·2-72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP).Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions.Bill & Melinda Gates Foundation.
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| 9. |
- Girardi, Marcello, 1991, et al.
(författare)
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3D Integration of Microcombs
- 2023
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Ingår i: 2023 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference, CLEO/Europe-EQEC 2023.
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Konferensbidrag (refereegranskat)abstract
- Microcombs based on silicon nitride are a promising technology in applications such as sensing, metrology and telecommunication [1]. These applications often require to combine a nonlinear waveguide with a linear integrated processor on the same chip to perform functionalities such as splitting, demultiplexing, and optical buffering. However, there is a fundamental performance tradeoff between linear and nonlinear waveguides. For microcomb generation, thick waveguide cores are necessary to achieve the desired anomalous dispersion, while for linear operation a thin core improves the loss of a single mode (SM) waveguide [2]. The dissimilar requirements in waveguide thickness brings challenges for planar integrated technologies. Here, we propose and demonstrate wafer-level three-dimensional integration of microcombs using two different Si3N4 core thicknesses: a thick core featuring dispersion-engineered microcombs and a thinner core for linear processing (see Fig. 1a). This technology breaks off the fundamental tradeoff between loss and confinement in thick waveguides and opens the door to combine high-performance microcombs with ultra-low-loss silicon nitride waveguide technology [3]. We demonstrate this approach by efficiently coupling a microcomb between two layers of Si3N4 and demultiplexing a few lines with an arrayed waveguide grating (AWG) (Fig 1b).
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| 10. |
- Girardi, Marcello, 1991, et al.
(författare)
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Multilayer integration in silicon nitride: decoupling linear and nonlinear functionalities for ultralow loss photonic integrated systems
- 2023
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Ingår i: Optics Express. - 1094-4087 .- 1094-4087. ; 31:19, s. 31435-31446
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Tidskriftsartikel (refereegranskat)abstract
- Silicon nitride is an excellent material platform for its extremely low loss in a large wavelength range, which makes it ideal for the linear processing of optical signals on a chip. Moreover, the Kerr nonlinearity and the lack of two-photon absorption in the near infrared enable efficient nonlinear optics, e.g., frequency comb generation. However, linear and nonlinear operations require distinct engineering of the waveguide core geometry, resulting in a tradeoff between optical loss and single-mode behavior, which hinders the development of high-performance, ultralow-loss linear processing blocks on a single layer. Here, we demonstrate a dual-layer photonic integration approach with two silicon-nitride platforms exhibiting ultralow optical losses, i.e., a few dB/m, and individually optimized to perform either nonlinear or linear processing tasks. We demonstrate the functionality of this approach by integrating a power-efficient microcomb with an arrayed waveguide grating demultiplexer to filter a few frequency comb lines in the same monolithically integrated chip. This approach can significantly improve the integration of linear and nonlinear optical elements on a chip and opens the way to the development of fully integrated processing of Kerr nonlinear sources.
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