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2.
  • Cruz, Raquel, et al. (författare)
  • Novel genes and sex differences in COVID-19 severity
  • 2022
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Gõmez-Elvira, Javier, et al. (författare)
  • Curiosity's rover environmental monitoring station : Overview of the first 100 sols
  • 2014
  • Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:7, s. 1680-1688
  • Tidskriftsartikel (refereegranskat)abstract
    • In the first 100 Martian solar days (sols) of the Mars Science Laboratory mission, the Rover Environmental Monitoring Station (REMS) measured the seasonally evolving diurnal cycles of ultraviolet radiation, atmospheric pressure, air temperature, ground temperature, relative humidity, and wind within Gale Crater on Mars. As an introduction to several REMS-based articles in this issue, we provide an overview of the design and performance of the REMS sensors and discuss our approach to mitigating some of the difficulties we encountered following landing, including the loss of one of the two wind sensors. We discuss the REMS data set in the context of other Mars Science Laboratory instruments and observations and describe how an enhanced observing strategy greatly increased the amount of REMS data returned in the first 100 sols, providing complete coverage of the diurnal cycle every 4 to 6 sols. Finally, we provide a brief overview of key science results from the first 100 sols. We found Gale to be very dry, never reaching saturation relative humidities, subject to larger diurnal surface pressure variations than seen by any previous lander on Mars, air temperatures consistent with model predictions and abundant short timescale variability, and surface temperatures responsive to changes in surface properties and suggestive of subsurface layering. Key Points Introduction to the REMS results on MSL mission Overiview of the sensor information Overview of operational constraints
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  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Monzon, Alexander Miguel, et al. (författare)
  • A STRP-ed definition of Structured Tandem Repeats in Proteins
  • 2023
  • Ingår i: Journal of Structural Biology. - 1047-8477 .- 1095-8657. ; 215:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Tandem Repeat Proteins (TRPs) are a class of proteins with repetitive amino acid sequences that have been studied extensively for over two decades. Different features at the level of sequence, structure, function and evolution have been attributed to them by various authors. And yet many of its salient features appear only when looking at specific subclasses of protein tandem repeats. Here, we attempt to rationalize the existing knowledge on Tandem Repeat Proteins (TRPs) by pointing out several dichotomies. The emerging picture is more nuanced than generally assumed and allows us to draw some boundaries of what is not a proper TRP. We conclude with an operational definition of a specific subset, which we have denominated STRPs (Structural Tandem Repeat Proteins), which separates a subclass of tandem repeats with distinctive features from several other less well-defined types of repeats. We believe that this definition will help researchers in the field to better characterize the biological meaning of this large yet largely understudied group of proteins.
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10.
  • Ozolins, Oskars, et al. (författare)
  • 100 GHz Externally Modulated Laser for Optical Interconnects
  • 2017
  • Ingår i: Journal of Lightwave Technology. - : Institute of Electrical and Electronics Engineers (IEEE). - 0733-8724 .- 1558-2213. ; 35:6, s. 1174-1179
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on a 116 Gb/s on-off keying (OOK), four pulse amplitude modulation (PAM) and 105-Gb/s 8-PAM optical transmitter using an InP-based integrated and packaged externally modulated laser for high-speed optical interconnects with up to 30 dB static extinction ratio and over 100-GHz 3-dB bandwidth with 2 dB ripple. In addition, we study the tradeoff between power penalty and equalizer length to foresee transmission distances with standard single mode fiber.
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  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. III. Imaging of the Galactic Center Supermassive Black Hole
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first event-horizon-scale images and spatiotemporal analysis of Sgr A* taken with the Event Horizon Telescope in 2017 April at a wavelength of 1.3 mm. Imaging of Sgr A* has been conducted through surveys over a wide range of imaging assumptions using the classical CLEAN algorithm, regularized maximum likelihood methods, and a Bayesian posterior sampling method. Different prescriptions have been used to account for scattering effects by the interstellar medium toward the Galactic center. Mitigation of the rapid intraday variability that characterizes Sgr A* has been carried out through the addition of a "variability noise budget" in the observed visibilities, facilitating the reconstruction of static full-track images. Our static reconstructions of Sgr A* can be clustered into four representative morphologies that correspond to ring images with three different azimuthal brightness distributions and a small cluster that contains diverse nonring morphologies. Based on our extensive analysis of the effects of sparse (u, v)-coverage, source variability, and interstellar scattering, as well as studies of simulated visibility data, we conclude that the Event Horizon Telescope Sgr A* data show compelling evidence for an image that is dominated by a bright ring of emission with a ring diameter of similar to 50 mu as, consistent with the expected "shadow" of a 4 x 10(6) M (circle dot) black hole in the Galactic center located at a distance of 8 kpc.
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  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. IV. Variability, Morphology, and Black Hole Mass
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we quantify the temporal variability and image morphology of the horizon-scale emission from Sgr A*, as observed by the EHT in 2017 April at a wavelength of 1.3 mm. We find that the Sgr A* data exhibit variability that exceeds what can be explained by the uncertainties in the data or by the effects of interstellar scattering. The magnitude of this variability can be a substantial fraction of the correlated flux density, reaching similar to 100% on some baselines. Through an exploration of simple geometric source models, we demonstrate that ring-like morphologies provide better fits to the Sgr A* data than do other morphologies with comparable complexity. We develop two strategies for fitting static geometric ring models to the time-variable Sgr A* data; one strategy fits models to short segments of data over which the source is static and averages these independent fits, while the other fits models to the full data set using a parametric model for the structural variability power spectrum around the average source structure. Both geometric modeling and image-domain feature extraction techniques determine the ring diameter to be 51.8 +/- 2.3 mu as (68% credible intervals), with the ring thickness constrained to have an FWHM between similar to 30% and 50% of the ring diameter. To bring the diameter measurements to a common physical scale, we calibrate them using synthetic data generated from GRMHD simulations. This calibration constrains the angular size of the gravitational radius to be 4.8(-0.7)(+1.4) mu as, which we combine with an independent distance measurement from maser parallaxes to determine the mass of Sgr A* to be 4.0(-0.6)(+1.1) x 10(6) M-circle dot.
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  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. V. Testing Astrophysical Models of the Galactic Center Black Hole
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we provide a first physical interpretation for the Event Horizon Telescope's (EHT) 2017 observations of Sgr A*. Our main approach is to compare resolved EHT data at 230 GHz and unresolved non-EHT observations from radio to X-ray wavelengths to predictions from a library of models based on time-dependent general relativistic magnetohydrodynamics simulations, including aligned, tilted, and stellar-wind-fed simulations; radiative transfer is performed assuming both thermal and nonthermal electron distribution functions. We test the models against 11 constraints drawn from EHT 230 GHz data and observations at 86 GHz, 2.2 mu m, and in the X-ray. All models fail at least one constraint. Light-curve variability provides a particularly severe constraint, failing nearly all strongly magnetized (magnetically arrested disk (MAD)) models and a large fraction of weakly magnetized models. A number of models fail only the variability constraints. We identify a promising cluster of these models, which are MAD and have inclination i <= 30 degrees. They have accretion rate (5.2-9.5) x 10(-9) M (circle dot) yr(-1), bolometric luminosity (6.8-9.2) x 10(35) erg s(-1), and outflow power (1.3-4.8) x 10(38) erg s(-1). We also find that all models with i >= 70 degrees fail at least two constraints, as do all models with equal ion and electron temperature; exploratory, nonthermal model sets tend to have higher 2.2 mu m flux density; and the population of cold electrons is limited by X-ray constraints due to the risk of bremsstrahlung overproduction. Finally, we discuss physical and numerical limitations of the models, highlighting the possible importance of kinetic effects and duration of the simulations.
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  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. VI. Testing the Black Hole Metric
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Astrophysical black holes are expected to be described by the Kerr metric. This is the only stationary, vacuum, axisymmetric metric, without electromagnetic charge, that satisfies Einstein's equations and does not have pathologies outside of the event horizon. We present new constraints on potential deviations from the Kerr prediction based on 2017 EHT observations of Sagittarius A* (Sgr A*). We calibrate the relationship between the geometrically defined black hole shadow and the observed size of the ring-like images using a library that includes both Kerr and non-Kerr simulations. We use the exquisite prior constraints on the mass-to-distance ratio for Sgr A* to show that the observed image size is within similar to 10% of the Kerr predictions. We use these bounds to constrain metrics that are parametrically different from Kerr, as well as the charges of several known spacetimes. To consider alternatives to the presence of an event horizon, we explore the possibility that Sgr A* is a compact object with a surface that either absorbs and thermally reemits incident radiation or partially reflects it. Using the observed image size and the broadband spectrum of Sgr A*, we conclude that a thermal surface can be ruled out and a fully reflective one is unlikely. We compare our results to the broader landscape of gravitational tests. Together with the bounds found for stellar-mass black holes and the M87 black hole, our observations provide further support that the external spacetimes of all black holes are described by the Kerr metric, independent of their mass.
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  • Beilin, Ruth, et al. (författare)
  • Analysing how drivers of agricultural land abandonment affect biodiversity and cultural landscapes using case studies from Scandinavia, Iberia and Oceania
  • 2014
  • Ingår i: Land use policy. - : Elsevier BV. - 0264-8377 .- 1873-5754. ; 36, s. 60-72
  • Tidskriftsartikel (refereegranskat)abstract
    • Agricultural land abandonment (ALA) is widespread in many countries of the global north. It impacts rural communities, traditional landscapes, biodiversity and ecosystem services. It is an opportunity for ecosystem restoration or new landscape functions. We explored ALA in study areas in Australia, Portugal and Sweden. In each, we assessed plant species diversity, historical trajectories of land cover change; and the socioeconomic past, present and future in interviews with farmers. The ALA data was integrated and analysed by identifying the drivers of change. The relative importance of each driver and its scale of action was estimated, both in the past (1950-2010) and in the future (2010-2030). ALA has transformed rural landscapes in the study areas of Portugal and Sweden. It is at a much earlier stage with potential to increase in the Australian case. We identified a set of driving forces, classified into pressures, frictions and attractors that clarify why ALA, noting its temporal and spatial scale, occurs differently in each study area. The effect of the drivers is related to social and historical contexts. Pressures and attractors encouraging agricultural abandonment are strongest in Portugal and Sweden. Generally more (institutionalized) frictions are in place in these European sites, intended to prevent further change, based on the benefits assumed for biodiversity and aesthetics. In Australia, the stimulation of driving forces to promote a well-managed abandonment of some cleared areas could be highly beneficial for biodiversity, minimally disruptive for current dairy farming operations and would bring opportunities for alternative types of rural development.
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18.
  • Bertran, Esther, et al. (författare)
  • Role of CXCR4/SDF-1 alpha in the migratory phenotype of hepatoma cells that have undergone epithelial-mesenchymal transition in response to the transforming growth factor-beta.
  • 2009
  • Ingår i: Cellular Signalling. - : Elsevier BV. - 0898-6568 .- 1873-3913. ; 21:11, s. 1595-1606
  • Tidskriftsartikel (refereegranskat)abstract
    • Treatment of FaO rat hepatoma cells with TGF-beta selects cells that survive to its apoptotic effect and undergo epithelial-mesenchymal transitions (EMT). We have established a cell line (T beta T-FaO, from TGF-beta-treated FaO) that shows a mesenchymal, de-differentiated, phenotype in the presence of TGF-beta and is refractory to its suppressor effects. In the absence of this cytokine, cells revert to an epithelial phenotype in 3-4 weeks and recover the response to TGF-beta. T beta T-FaO show higher capacity to migrate than that observed in the parental FaO cells. We found that FaO cells express low levels of CXCR4 and do not respond to SDF-1 alpha. However, TGF-beta up-regulates CXCR4, through a NF kappaB-dependent mechanism, and T beta T-FaO cells show elevated levels of CXCR4, which is located in the presumptive migration front. A specific CXCR4 antagonist (AMD3100) attenuates the migratory capacity of T beta T-FaO cells on collagen gels. Extracellular SDF-1 alpha activates the ERKs pathway in T beta T-FaO, but not in FaO cells, increasing cell scattering and protecting cells from apoptosis induced by serum deprivation. Targeted knock-down of CXCR4 with specific siRNA blocks the T beta T-FaO response to SDF-1 alpha. Thus, the SDF-1/CXCR4 axis might play an important role in mediating cell migration and survival after a TGF-beta-induced EMT in hepatoma cells.
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  • Broderick, Avery E., et al. (författare)
  • Characterizing and Mitigating Intraday Variability: Reconstructing Source Structure in Accreting Black Holes with mm-VLBI
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The extraordinary physical resolution afforded by the Event Horizon Telescope has opened a window onto the astrophysical phenomena unfolding on horizon scales in two known black holes, M87* and Sgr A*. However, with this leap in resolution has come a new set of practical complications. Sgr A* exhibits intraday variability that violates the assumptions underlying Earth aperture synthesis, limiting traditional image reconstruction methods to short timescales and data sets with very sparse (u, v) coverage. We present a new set of tools to detect and mitigate this variability. We develop a data-driven, model-agnostic procedure to detect and characterize the spatial structure of intraday variability. This method is calibrated against a large set of mock data sets, producing an empirical estimator of the spatial power spectrum of the brightness fluctuations. We present a novel Bayesian noise modeling algorithm that simultaneously reconstructs an average image and statistical measure of the fluctuations about it using a parameterized form for the excess variance in the complex visibilities not otherwise explained by the statistical errors. These methods are validated using a variety of simulated data, including general relativistic magnetohydrodynamic simulations appropriate for Sgr A* and M87*. We find that the reconstructed source structure and variability are robust to changes in the underlying image model. We apply these methods to the 2017 EHT observations of M87*, finding evidence for variability across the EHT observing campaign. The variability mitigation strategies presented are widely applicable to very long baseline interferometry observations of variable sources generally, for which they provide a data-informed averaging procedure and natural characterization of inter-epoch image consistency.
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  • Broeske, Ann-Marie, et al. (författare)
  • DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction
  • 2009
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:11, s. 69-1207
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA methylation is a dynamic epigenetic mark that undergoes extensive changes during differentiation of self-renewing stem cells. However, whether these changes are the cause or consequence of stem cell fate remains unknown. Here, we show that alternative functional programs of hematopoietic stem cells (HSCs) are governed by gradual differences in methylation levels. Constitutive methylation is essential for HSC self-renewal but dispensable for homing, cell cycle control and suppression of apoptosis. Notably, HSCs from mice with reduced DNA methyltransferase 1 activity cannot suppress key myeloerythroid regulators and thus can differentiate into myeloerythroid, but not lymphoid, progeny. A similar methylation dosage effect controls stem cell function in leukemia. These data identify DNA methylation as an essential epigenetic mechanism to protect stem cells from premature activation of predominant differentiation programs and suggest that methylation dynamics determine stem cell functions in tissue homeostasis and cancer.
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23.
  • Bull, Philip, et al. (författare)
  • Beyond ΛCDM : Problems, solutions, and the road ahead
  • 2016
  • Ingår i: Physics of the Dark Universe. - : Elsevier BV. - 2212-6864. ; 12, s. 56-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite its continued observational successes, there is a persistent (and growing) interest in extending cosmology beyond the standard model, Lambda CDM. This is motivated by a range of apparently serious theoretical issues, involving such questions as the cosmological constant problem, the particle nature of dark matter, the validity of general relativity on large scales, the existence of anomalies in the CMB and on small scales, and the predictivity and testability of the inflationary paradigm. In this paper, we summarize the current status of Lambda CDM as a physical theory, and review investigations into possible alternatives along a number of different lines, with a particular focus on highlighting the most promising directions. While the fundamental problems are proving reluctant to yield, the study of alternative cosmologies has led to considerable progress, with much more to come if hopes about forthcoming high-precision observations and new theoretical ideas are fulfilled.
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  • Byrne, Karl Smith, et al. (författare)
  • Vasectomy and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2017
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 35:12, s. 1297-1303
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Vasectomy is a commonly used form of male sterilization, and some studies have suggested that it may be associated with an increased risk of prostate cancer, including more aggressive forms of the disease. We investigated the prospective association of vasectomy with prostate cancer in a large European cohort, with a focus on high-grade and advanced-stage tumors, and death due to prostate cancer. Patients and Methods A total of 84, 753 men from the European Prospective Investigation into Cancer and Nutrition (EPIC), aged 35 to 79 years, provided information on vasectomy status (15% with vasectomy) at recruitment and were followed for incidence of prostate cancer and death. We estimated the association of vasectomy with prostate cancer risk overall, by tumor subtype, and for death due to prostate cancer, using multivariable-adjusted Cox proportional hazards models. Results During an average follow-up of 15.4 years, 4, 377 men were diagnosed with prostate cancer, including 641 who had undergone a vasectomy. Vasectomy was not associated with prostate cancer risk (hazard ratio [HR], 1.05; 95% CI, 0.96 to 1.15), and no evidence for heterogeneity in the association was observed by stage of disease or years since vasectomy. There was some evidence of heterogeneity by tumor grade (P = .02), with an increased risk for low-intermediate grade (HR, 1.14; 95% CI, 1.01 to 1.29) but not high-grade prostate cancer (HR, 0.83; 95% CI, 0.64 to 1.07). Vasectomy was not associated with death due to prostate cancer (HR, 0.88; 95% CI, 0.68 to 1.12). Conclusion These findings from a large European prospective study show no elevated risk for overall, high-grade or advanced-stage prostate cancer, or death due to prostate cancer in men who have undergone a vasectomy compared with men who have not.
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25.
  • Carraminana, Albert, et al. (författare)
  • Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
  • 2019
  • Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
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29.
  • Engert, Andreas, et al. (författare)
  • The European Hematology Association Roadmap for European Hematology Research : a consensus document
  • 2016
  • Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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30.
  • Gatica-Ortega, María Elena, et al. (författare)
  • Contact dermatitis from glucose sensors in Spain : A multicentric approach
  • 2021
  • Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 85:5, s. 554-562
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Allergic contact dermatitis from glucose sensors may interfere with their ongoing application. Objective: To evaluate a series of Spanish patients with contact dermatitis to glucose sensors regarding former sources of contact allergens, patch test results, and outcomes from the ongoing use of the device. Methods: A series of patients with contact dermatitis from glucose sensors was investigated in eight dermatology departments across Spain (epidemiological features, brands, latency time to develop dermatitis, the ability to continue using the devices as well as the patch test results). Results: Thirty patients were evaluated (mean age 20.9 years). A total of 66.7% were children and 66.7% female. Ninety per cent used Freestyle Libre (FSL). Eight of 26 (30.8%) reacted to isobornyl acrylate (IBOA) and two of 20 (10.0%) to N,N dimethylacrylamide (DMAA). The mean latency time to develop dermatitis was 9 months. Sixteen of 29 (55.2%) patients continued using the same sensor causing the reaction. Thirteen of 29 (44.8%) patients were unable to continue using the sensor because of severe reactions. Of these, five were positive to IBOA, one to IBOA and DMAA, one to DMAA, one to colophony, and one to isopropyl alcohol wipes. In one patient, the outcome was unknown. Conclusion: The frequency of sensitisation to IBOA and DMAA, was lower than in other European series, but similar to a previously published Spanish article. Legislation requiring manufacturers to provide information regarding the composition of medical devices and cooperate with the investigations into contact dermatitis is urgently needed.
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31.
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32.
  • González-Castaño, Miriam, et al. (författare)
  • 3D-printed structured catalysts for CO 2 methanation reaction: Advancing of gyroid-based geometries
  • 2022
  • Ingår i: Energy Conversion and Management. - : Elsevier BV. - 0196-8904. ; 258
  • Forskningsöversikt (refereegranskat)abstract
    • This work investigates the CO2 methanation rate of structured catalysts by tuning the geometry of 3D-printed metal Fluid Guiding Elements (FGEs) structures based on periodically variable pseudo-gyroid geometries. The enhanced performance showed by the structured catalytic systems is mostly associated with the capability of the FGEs substrate geometries for efficient heat usages. Thus, variations on the channels diameter resulted in ca. 25% greater CO2 conversions values at intermediate temperature ranges. The highest void fraction evidenced in the best performing catalyst (3D-1) favored the radial heat transfer and resulted in significantly enhanced catalytic activity, achieving close to equilibrium (75%) conversions at 400 °C and 120 mL/min. For the 3D-1 catalyst, a mathematical model based on an experimental design was developed thus enabling the estimation of its behavior as a function of temperature, spatial velocity, hydrogen to carbon dioxide (H2/CO2) ratio, and inlet CO2 concentration. Its optimal operating conditions were established under 3 different scenarios: 1) no restrictions, 2) minimum H2:CO2 ratios, and 3) minimum temperatures and H2/CO2 ratio. For instance, for the lattest scenario, the best CO2 methanation conditions require operating at 431 °C, 200 mL/min, H2/CO2 = 3 M ratio, and inlet CO2 concentration = 10 %.
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33.
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34.
  • Halbritter, Aud H., et al. (författare)
  • Plant trait and vegetation data along a 1314 m elevation gradient with fire history in Puna grasslands, Perú
  • 2024
  • Ingår i: SCIENTIFIC DATA. - 2052-4463. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Alpine grassland vegetation supports globally important biodiversity and ecosystems that are increasingly threatened by climate warming and other environmental changes. Trait-based approaches can support understanding of vegetation responses to global change drivers and consequences for ecosystem functioning. In six sites along a 1314 m elevational gradient in Puna grasslands in the Peruvian Andes, we collected datasets on vascular plant composition, plant functional traits, biomass, ecosystem fluxes, and climate data over three years. The data were collected in the wet and dry season and from plots with different fire histories. We selected traits associated with plant resource use, growth, and life history strategies (leaf area, leaf dry/wet mass, leaf thickness, specific leaf area, leaf dry matter content, leaf C, N, P content, C and N isotopes). The trait dataset contains 3,665 plant records from 145 taxa, 54,036 trait measurements (increasing the trait data coverage of the regional flora by 420%) covering 14 traits and 121 plant taxa (ca. 40% of which have no previous publicly available trait data) across 33 families.
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35.
  • Jorstad, S.G., et al. (författare)
  • The Event Horizon Telescope Image of the Quasar NRAO 530
  • 2023
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 943:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the observations of the quasar NRAO 530 with the Event Horizon Telescope (EHT) on 2017 April 5-7, when NRAO 530 was used as a calibrator for the EHT observations of Sagittarius A*. At z = 0.902, this is the most distant object imaged by the EHT so far. We reconstruct the first images of the source at 230 GHz, at an unprecedented angular resolution of similar to 20 mu as, both in total intensity and in linear polarization (LP). We do not detect source variability, allowing us to represent the whole data set with static images. The images reveal a bright feature located on the southern end of the jet, which we associate with the core. The feature is linearly polarized, with a fractional polarization of similar to 5%-8%, and it has a substructure consisting of two components. Their observed brightness temperature suggests that the energy density of the jet is dominated by the magnetic field. The jet extends over 60 mu as along a position angle similar to -28 degrees. It includes two features with orthogonal directions of polarization (electric vector position angle), parallel and perpendicular to the jet axis, consistent with a helical structure of the magnetic field in the jet. The outermost feature has a particularly high degree of LP, suggestive of a nearly uniform magnetic field. Future EHT observations will probe the variability of the jet structure on microarcsecond scales, while simultaneous multiwavelength monitoring will provide insight into the high-energy emission origin.
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36.
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37.
  • Kakkar, Aditya, et al. (författare)
  • Design of coherent optical systems impaired by EEPN
  • 2016
  • Ingår i: 2016 Optical Fiber Communications Conference and Exhibition, OFC 2016. - Washington, D.C. : Institute of Electrical and Electronics Engineers (IEEE). - 9781943580071
  • Konferensbidrag (refereegranskat)abstract
    • We present experimental validation of novel analytical expressions essential for the design of coherent optical systems impaired by EEPN. These expressions enable a simple and accurate EEPN analysis for any system specification. 
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38.
  • Kakkar, Aditya, et al. (författare)
  • Design of coherent optical systems impaired by EEPN
  • 2016
  • Ingår i: 2016 Optical Fiber Communications Conference and Exhibition (OFC 2016). - 9781943580071
  • Konferensbidrag (refereegranskat)abstract
    • We present experimental validation of novel analytical expressions essential for the design of coherent optical systems impaired by EEPN. These expressions enable a simple and accurate EEPN analysis for any system specification.
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39.
  • Kakkar, Aditya, et al. (författare)
  • Overcoming EEPN in Coherent Transmission Systems
  • 2016
  • Ingår i: 2016 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO). - Washington, D.C. : IEEE conference proceedings. - 9781943580118
  • Konferensbidrag (refereegranskat)abstract
    • We for the first time experimentally demonstrate a simple technique to overcome EEPN. Performance recovery from above FEC to <1 dB penalty for 28 Gbd 16-QAM over 520 km with high LO linewidth is achieved.
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40.
  • Mur, Pilar, et al. (författare)
  • Germline variation in the oxidative DNA repair genes NUDT1 and OGG1 is not associated with hereditary colorectal cancer or polyposis
  • 2018
  • Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 39:9, s. 1214-1225
  • Tidskriftsartikel (refereegranskat)abstract
    • The causal association of NUDT1 (=MTH1) and OGG1 with hereditary colorectal cancer (CRC) remains unclear. Here, we sought to provide additional evidence for or against the causal contribution of NUDT1 and OGG1 mutations to hereditary CRC and/or polyposis. Mutational screening was performed using pooled DNA amplification and targeted next-generation sequencing in 529 families (441 uncharacterized MMR-proficient familial nonpolyposis CRC and 88 polyposis cases). Cosegregation, in silico analyses, in vitro functional assays, and case-control associations were carried out to characterize the identified variants. Five heterozygous carriers of novel (n=1) or rare (n=4) NUDT1 variants were identified. In vitro deleterious effects were demonstrated for c.143G>A p.G48E (catalytic activity and protein stability) and c.403G>T p.G135W (protein stability), although cosegregation data in the carrier families were inconclusive or nonsupportive. The frequency of missense, loss-of-function, and splice-site NUDT1 variants in our familial CRC cohort was similar to the one observed in cancer-free individuals, suggesting lack of association with CRC predisposition. No OGG1 pathogenic mutations were identified. Our results suggest that the contribution of NUDT1 and OGG1 germline mutations to hereditary CRC and to polyposis is inexistent or, at most, negligible. The inclusion of these genes in routine genetic testing is not recommended.
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41.
  • Navarro-Dominguez, Beatriz, et al. (författare)
  • Tandem Repeat DNA Provides Many Cytological Markers for Hybrid Zone Analysis in Two Subspecies of the Grasshopper Chorthippus parallelus
  • 2023
  • Ingår i: Genes. - : MDPI. - 2073-4425. ; 14:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent advances in next generation sequencing (NGS) have greatly increased our understanding of non-coding tandem repeat (TR) DNA. Here we show how TR DNA can be useful for the study of hybrid zones (HZ), as it serves as a marker to identify introgression in areas where two biological entities come in contact. We used Illumina libraries to analyse two subspecies of the grasshopper Chorthippus parallelus, which currently form a HZ in the Pyrenees. We retrieved a total of 152 TR sequences, and used fluorescent in situ hybridization (FISH) to map 77 families in purebred individuals from both subspecies. Our analysis revealed 50 TR families that could serve as markers for analysis of this HZ, using FISH. Differential TR bands were unevenly distributed between chromosomes and subspecies. Some of these TR families yielded FISH bands in only one of the subspecies, suggesting the amplification of these TR families after the geographic separation of the subspecies in the Pleistocene. Our cytological analysis of two TR markers along a transect of the Pyrenean hybrid zone showed asymmetrical introgression of one subspecies into the other, consistent with previous findings using other markers. These results demonstrate the reliability of TR-band markers for hybrid zone studies.
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42.
  • Navarro, Jaime Rodrigo, et al. (författare)
  • Carrier Phase Recovery Algorithms for Coherent Optical Circular mQAM Systems
  • 2016
  • Ingår i: Journal of Lightwave Technology. - 0733-8724 .- 1558-2213. ; 34:11, s. 2717-2723
  • Tidskriftsartikel (refereegranskat)abstract
    • The phase noise tolerance of circular multilevel quadrature amplitude modulation (C-mQAM) constellations employing different carrier phase recovery (CPR) algorithms is studied. A differential decoding scheme and a bit mapping for this type of constellations are proposed. A novel CPR scheme for C-mQAM constellations is also presented. The particular distribution of the constellation points in a C-mQAM signal is exploited to reduce the required Nth power for the removal of the modulation component by a factor of two. Hence, the computational complexity of the proposed algorithm is drastically reduced. The combined linewidth symbol duration product (Delta nu T-s) tolerance of different CPR algorithms for C-mQAM constellations is studied and compared with the proposed CPR scheme. The results are analyzed at 3.8e-3 and 1e-2 bit error rate forward error correction limits. The proposed CPR scheme achieves similar Delta nu Ts tolerance compared to single stage BPS algorithm while its computational complexity is reduced by group factors of 27.2 vertical bar 32.3, and 30.5 vertical bar 32.6 (in the form of multipliers vertical bar adders) for C-16QAM and C-64QAM, respectively.
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43.
  • Navarro, Jaime Rodrigo, et al. (författare)
  • Phase noise tolerant carrier recovery scheme for 28 Gbaud circular 16QAM
  • 2015
  • Ingår i: European Conference on Optical Communication, ECOC. - : Institute of Electrical and Electronics Engineers (IEEE). - 9788460817413
  • Konferensbidrag (refereegranskat)abstract
    • We propose a novel carrier phase recovery scheme for circular 16QAM coherent transmission systems. Experimental results show low penalties (<1.4 dB) even for linewidths where square 16QAM exhibits irretrievable (above the FEC limit) error floor.
  •  
44.
  • Navarro, Jaime Rodrigo, et al. (författare)
  • Two-Stage n-PSK Partitioning Carrier Phase Recovery Scheme for Circular mQAM Coherent Optical Systems
  • 2016
  • Ingår i: Photonics. - : MDPI AG. - 2304-6732. ; 3:2
  • Tidskriftsartikel (refereegranskat)abstract
    • A novel two-stage n-PSK partitioning carrier phase recovery (CPR) scheme for circular multilevel quadrature amplitude modulation (C-mQAM) constellations is presented. The first stage of the algorithm provides an initial rough estimation of the received constellation, which is utilized in the second stage for CPR. The performance of the proposed algorithm is studied through extensive simulations at the forward error correction bit error rate targets of 3.8 x 10(-3) and 1 x 10(-2) and is compared with different CPR algorithms. A significant improvement in the combined linewidth symbol duration product (Delta vT(s)) tolerance is achieved compared to the single-stage n-PSK partitioning scheme. Superior performance in the Delta vT(s) tolerance compared to the blind phase search algorithm is also reported. The relative improvements with respect to other CPR schemes are also validated experimentally for a 28-Gbaud C-16QAM back-to-back transmission system. The computational complexity of the proposed CPR scheme is studied, and reduction factors of 24.5 broken vertical bar 30.1 and 59.1 broken vertical bar 63.3 are achieved for C-16QAM and C-64QAM, respectively, compared to single-stage BPS in the form of multipliers broken vertical bar adders.
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45.
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46.
  • Olalde, I., et al. (författare)
  • The Beaker phenomenon and the genomic transformation of northwest Europe
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
  • Tidskriftsartikel (refereegranskat)abstract
    • From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
  •  
47.
  • Ozolins, Oskars, et al. (författare)
  • High-speed optical and wireless transmission-challenges and achievements
  • 2016
  • Ingår i: Advances in Wireless and Optical Communications (RTUWO), 2016. - : IEEE. - 9781509015368 - 9781509015351
  • Konferensbidrag (refereegranskat)abstract
    • The cloud services together with the huge size datasets are driving demand for bandwidth in datacenters. The 400 Gbps client-side links are demanding a solution. The intensity modulation and direct-detection systems together with integrated semiconductor lasers and modulators appear as promising solution in four optical lanes at 100 Gbps net rate in order to reduce complexity, size, power consumption and cost.
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48.
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49.
  • Popov, Sergei, et al. (författare)
  • Ultra-Broadband High-Linear Integrated Transmitter for Low Complexity Optical Interconnect Applications
  • 2016
  • Ingår i: Optics InfoBase Conference Papers. - : Optics Info Base, Optical Society of America. - 9780960038008
  • Konferensbidrag (refereegranskat)abstract
    • We report on a high-speed optical transmitter using InP-based integrated externally modulated laser for optical interconnect applications with up to 30 dB static extinction ratio and over 100 GHz 3 dB bandwidth with 2 dB ripple. It is evaluated with up to 116 Gbit/s on-offkeying, 4-pulse amplitude modulation (PAM) and up to 105 Gbit/s 8-PAM optical signals with different digital equalization implementations. Low number of taps is required for a high and stable performance. Results reveal that digital equalization significantly boosts the passive optical interconnect scalability.
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50.
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