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1.	Abbafati, Cristiana, et al. (författare) 2020 Tidskriftsartikel (refereegranskat)
2.	Abele, H., et al. (författare) Particle physics at the European Spallation Source 2023 Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84 Forskningsöversikt (refereegranskat)abstract Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
3.	Micah, Angela E., et al. (författare) Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050 2021 Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343 Forskningsöversikt (refereegranskat)abstract Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
4.	Patel, Y, et al. (författare) Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders 2021 Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 78:1, s. 47-63 Tidskriftsartikel (refereegranskat)
5.	van Dongen, J, et al. (författare) DNA methylation signatures of a broad spectrum of aggressive behavior: a meta-analysis of epigenome-wide studies across the lifespan 2020 Ingår i: BEHAVIOR GENETICS. - 0001-8244. ; 50:6, s. 485-487 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
6.	Amare, Azmeraw T, et al. (författare) Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. 2023 Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261 Tidskriftsartikel (refereegranskat)abstract Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
7.	Boedhoe, PSW, et al. (författare) Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups 2020 Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 177:9, s. 834-843 Tidskriftsartikel (refereegranskat)
8.	Kollhoff, A., et al. (författare) The first widespread solar energetic particle event observed by Solar Orbiter on 2020 November 29 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656 Tidskriftsartikel (refereegranskat)abstract Context. On 2020 November 29, the first widespread solar energetic particle (SEP) event of solar cycle 25 was observed at four widely separated locations in the inner (≲1 AU) heliosphere. Relativistic electrons as well as protons with energies > 50 MeV were observed by Solar Orbiter (SolO), Parker Solar Probe, the Solar Terrestrial Relations Observatory (STEREO)-A and multiple near-Earth spacecraft. The SEP event was associated with an M4.4 class X-ray flare and accompanied by a coronal mass ejection and an extreme ultraviolet (EUV) wave as well as a type II radio burst and multiple type III radio bursts.Aims. We present multi-spacecraft particle observations and place them in context with source observations from remote sensing instruments and discuss how such observations may further our understanding of particle acceleration and transport in this widespread event.Methods. Velocity dispersion analysis (VDA) and time shift analysis (TSA) were used to infer the particle release times at the Sun. Solar wind plasma and magnetic field measurements were examined to identify structures that influence the properties of the energetic particles such as their intensity. Pitch angle distributions and first-order anisotropies were analyzed in order to characterize the particle propagation in the interplanetary medium.Results. We find that during the 2020 November 29 SEP event, particles spread over more than 230° in longitude close to 1 AU. The particle onset delays observed at the different spacecraft are larger as the flare–footpoint angle increases and are consistent with those from previous STEREO observations. Comparing the timing when the EUV wave intersects the estimated magnetic footpoints of each spacecraft with particle release times from TSA and VDA, we conclude that a simple scenario where the particle release is only determined by the EUV wave propagation is unlikely for this event. Observations of anisotropic particle distributions at SolO, Wind, and STEREO-A do not rule out that particles are injected over a wide longitudinal range close to the Sun. However, the low values of the first-order anisotropy observed by near-Earth spacecraft suggest that diffusive propagation processes are likely involved.
9.	Telloni, D., et al. (författare) Study of two interacting interplanetary coronal mass ejections encountered by Solar Orbiter during its first perihelion passage Observations and modeling 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656 Tidskriftsartikel (refereegranskat)abstract Context. Solar Orbiter, the new-generation mission dedicated to solar and heliospheric exploration, was successfully launched on February 10, 2020, 04:03 UTC from Cape Canaveral. During its first perihelion passage in June 2020, two successive interplanetary coronal mass ejections (ICMEs), propagating along the heliospheric current sheet (HCS), impacted the spacecraft.Aims. This paper addresses the investigation of the ICMEs encountered by Solar Orbiter on June 7-8, 2020, from both an observational and a modeling perspective. The aim is to provide a full description of those events, their mutual interaction, and their coupling with the ambient solar wind and the HCS.Methods. Data acquired by the MAG magnetometer, the Energetic Particle Detector suite, and the Radio and Plasma Waves instrument are used to provide information on the ICMEs' magnetic topology configuration, their magnetic connectivity to the Sun, and insights into the heliospheric plasma environment where they travel, respectively. On the modeling side, the Heliospheric Upwind eXtrapolation model, the 3D COronal Rope Ejection technique, and the EUropean Heliospheric FORecasting Information Asset (EUHFORIA) tool are used to complement Solar Orbiter observations of the ambient solar wind and ICMEs, and to simulate the evolution and interaction of the ejecta in the inner heliosphere, respectively.Results. Both data analysis and numerical simulations indicate that the passage of two distinct, dynamically and magnetically interacting (via magnetic reconnection processes) ICMEs at Solar Orbiter is a possible scenario, supported by the numerous similarities between EUHFORIA time series at Solar Orbiter and Solar Orbiter data.Conclusions. The combination of in situ measurements and numerical simulations (together with remote sensing observations of the corona and inner heliosphere) will significantly lead to a deeper understanding of the physical processes occurring during the CME-CME interaction.
10.	van Dongen, J, et al. (författare) DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan 2021 Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:6, s. 2148-2162 Tidskriftsartikel (refereegranskat)abstract DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.
11.	Maksimovic, M., et al. (författare) First observations and performance of the RPW instrument on board the Solar Orbiter mission 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656 Tidskriftsartikel (refereegranskat)abstract The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is designed to measure in situ magnetic and electric fields and waves from the continuum up to several hundred kHz. The RPW also observes solar and heliospheric radio emissions up to 16 MHz. It was switched on and its antennae were successfully deployed two days after the launch of Solar Orbiter on February 10, 2020. Since then, the instrument has acquired enough data to make it possible to assess its performance and the electromagnetic disturbances it experiences. In this article, we assess its scientific performance and present the first RPW observations. In particular, we focus on a statistical analysis of the first observations of interplanetary dust by the instrument's Thermal Noise Receiver. We also review the electro-magnetic disturbances that RPW suffers, especially those which potential users of the instrument data should be aware of before starting their research work.
12.	Verploegen, MFA, et al. (författare) Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study 2022 Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - 1460-2385. Tidskriftsartikel (refereegranskat)
13.	Abend, Sven, et al. (författare) Terrestrial very-long-baseline atom interferometry : Workshop summary 2024 Ingår i: AVS Quantum Science. - : American Institute of Physics (AIP). - 2639-0213. ; 6:2 Forskningsöversikt (refereegranskat)abstract This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more kilometer--scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions.
14.	Menkveld, Albert J., et al. (författare) Nonstandard Errors 2024 Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390 Tidskriftsartikel (refereegranskat)abstract In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
15.	Aran, A., et al. (författare) Evidence for local particle acceleration in the first recurrent galactic cosmic ray depression observed by Solar Orbiter : The ion event on 19 June 2020 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656 Tidskriftsartikel (refereegranskat)abstract Context. In mid-June 2020, the Solar Orbiter (SolO) mission reached its first perihelion at 0.51 au and started its cruise phase, with most of the in situ instruments operating continuously.Aims. We present the in situ particle measurements of the first proton event observed after the first perihelion obtained by the Energetic Particle Detector (EPD) suite on board SolO. The potential solar and interplanetary (IP) sources of these particles are investigated.Methods. Ion observations from similar to 20 keV to similar to 1 MeV are combined with available solar wind data from the Radio and Plasma Waves (RPW) instrument and magnetic field data from the magnetometer on board SolO to evaluate the energetic particle transport conditions and infer the possible acceleration mechanisms through which particles gain energy. We compare > 17-20 MeV ion count rate measurements for two solar rotations, along with the solar wind plasma data available from the Solar Wind Analyser (SWA) and RPW instruments, in order to infer the origin of the observed galactic cosmic ray (GCR) depressions.Results. The lack of an observed electron event and of velocity dispersion at various low-energy ion channels and the observed IP structure indicate a local IP source for the low-energy particles. From the analysis of the anisotropy of particle intensities, we conclude that the low-energy ions were most likely accelerated via a local second-order Fermi process. The observed GCR decrease on 19 June, together with the 51.8-1034.0 keV nuc(-1) ion enhancement, was due to a solar wind stream interaction region (SIR). The observation of a similar GCR decrease in the next solar rotation favours this interpretation and constitutes the first observation of a recurrent GCR decrease by SolO. The analysis of the recurrence times of this SIR suggests that it is the same SIR responsible for the He-4 events previously measured in April and May. Finally, we point out that an IP structure more complex than a common SIR cannot be discarded, mainly due to the lack of solar wind temperature measurements and the lack of a higher cadence of solar wind velocity observations.
16.	Lucas-Herald, AK, et al. (författare) Gonadectomy in conditions affecting sex development: a registry-based cohort study 2021 Ingår i: European journal of endocrinology. - 1479-683X. ; 184:6, s. 791-801 Tidskriftsartikel (refereegranskat)
17.	Lucas-Herald, AK, et al. (författare) Gonadectomy in conditions affecting sex development: a registry-based cohort study 2021 Ingår i: European journal of endocrinology. - 1479-683X. ; 184:6, s. 791-801 Tidskriftsartikel (refereegranskat)
18.	Pironi, Loris, et al. (författare) Characteristics of adult patients with chronic intestinal failure due to short bowel syndrome: An international multicenter survey 2021 Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 45, s. 433-441 Tidskriftsartikel (refereegranskat)abstract Background and aims: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. Methods: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as <1, 1–2, 2–3 and >3 L/day. Results: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn’ disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. Conclusions: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.
19.	Kim, Hyun-Tae, et al. (författare) Validation of D-T fusion power prediction capability against 2021 JET D-T experiments 2023 Ingår i: Nuclear Fusion. - 0029-5515 .- 1741-4326. ; 63:11 Tidskriftsartikel (refereegranskat)abstract JET experiments using the fuel mixture envisaged for fusion power plants, deuterium and tritium (D-T), provide a unique opportunity to validate existing D-T fusion power prediction capabilities in support of future device design and operation preparation. The 2021 JET D-T experimental campaign has achieved D-T fusion powers sustained over 5 s in ITER-relevant conditions i.e. operation with the baseline or hybrid scenario in the full metallic wall. In preparation of the 2021 JET D-T experimental campaign, extensive D-T predictive modelling was carried out with several assumptions based on D discharges. To improve the validity of ITER D-T predictive modelling in the future, it is important to use the input data measured from 2021 JET D-T discharges in the present core predictive modelling, and to specify the accuracy of the D-T fusion power prediction in comparison with the experiments. This paper reports on the validation of the core integrated modelling with TRANSP, JINTRAC, and ETS coupled with a quasilinear turbulent transport model (Trapped Gyro Landau Fluid or QualLiKiz) against the measured data in 2021 JET D-T discharges. Detailed simulation settings and the heating and transport models used are described. The D-T fusion power calculated with the interpretive TRANSP runs for 38 D-T discharges (12 baseline and 26 hybrid discharges) reproduced the measured values within 20 % . This indicates the additional uncertainties, that could result from the measurement error bars in kinetic profiles, impurity contents and neutron rates, and also from the beam-thermal fusion reaction modelling, are less than 20 % in total. The good statistical agreement confirms that we have the capability to accurately calculate the D-T fusion power if correct kinetic profiles are predicted, and indicates that any larger deviation of the D-T fusion power prediction from the measured fusion power could be attributed to the deviation of the predicted kinetic profiles from the measured kinetic profiles in these plasma scenarios. Without any posterior adjustment of the simulation settings, the ratio of predicted D-T fusion power to the measured fusion power was found as 65%-96% for the D-T baseline and 81%-97% for D-T hybrid discharge. Possible reasons for the lower D-T prediction are discussed and future works to improve the fusion power prediction capability are suggested. The D-T predictive modelling results have also been compared to the predictive modelling of the counterpart D discharges, where the key engineering parameters are similar. Features in the predicted kinetic profiles of D-T discharges such as underprediction of ne are also found in the prediction results of the counterpart D discharges, and it leads to similar levels of the normalized neutron rate prediction between the modelling results of D-T and the counterpart D discharges. This implies that the credibility of D-T fusion power prediction could be a priori estimated by the prediction quality of the preparatory D discharges, which will be attempted before actual D-T experiments.
20.	Kretzschmar, M., et al. (författare) Whistler waves observed by Solar Orbiter/RPW between 0.5 AU and 1 AU 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656 Tidskriftsartikel (refereegranskat)abstract Context. Solar wind evolution differs from a simple radial expansion, while wave-particle interactions are assumed to be the major cause for the observed dynamics of the electron distribution function. In particular, whistler waves are thought to inhibit the electron heat flux and ensure the diffusion of the field-aligned energetic electrons (Strahl electrons) to replenish the halo population.Aims. The goal of our study is to detect and characterize the electromagnetic waves that have the capacity to modify the electron distribution functions, with a special focus on whistler waves.Methods. We carried out a detailed analysis of the electric and magnetic field fluctuations observed by the Solar Orbiter spacecraft during its first orbit around the Sun, between 0.5 and 1 AU. Using data from the Search Coil Magnetometer and electric antenna, both part of the Radio and Plasma Waves (RPW) instrumental suite, we detected the electromagnetic waves with frequencies above 3 Hz and determined the statistical distribution of their amplitudes, frequencies, polarization, and k-vector as a function of distance. Here, we also discuss the relevant instrumental issues regarding the phase between the electric and magnetic measurements as well as the effective length of the electric antenna.Results. An overwhelming majority of the observed waves are right-handed circularly polarized in the solar wind frame and identified as outwardly propagating quasi-parallel whistler waves. Their occurrence rate increases by a least a factor of 2 from 1 AU to 0.5 AU. These results are consistent with the regulation of the heat flux by the whistler heat flux instability. Near 0.5 AU, whistler waves are found to be more field-aligned and to have a smaller normalized frequency (f/f(ce)), larger amplitude, and greater bandwidth than at 1 AU.
21.	Matteini, L., et al. (författare) Solar Orbiter's encounter with the tail of comet C/2019 Y4 (ATLAS) : Magnetic field draping and cometary pick-up ion waves 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656 Tidskriftsartikel (refereegranskat)abstract Context. Solar Orbiter is expected to have flown close to the tail of comet C/2019 Y4 (ATLAS) during the spacecraft’s first perihelion in June 2020. Models predict a possible crossing of the comet tails by the spacecraft at a distance from the Sun of approximately 0.5 AU.Aims. This study is aimed at identifying possible signatures of the interaction of the solar wind plasma with material released by comet ATLAS, including the detection of draped magnetic field as well as the presence of cometary pick-up ions and of ion-scale waves excited by associated instabilities. This encounter provides us with the first opportunity of addressing such dynamics in the inner Heliosphere and improving our understanding of the plasma interaction between comets and the solar wind.Methods. We analysed data from all in situ instruments on board Solar Orbiter and compared their independent measurements in order to identify and characterize the nature of structures and waves observed in the plasma when the encounter was predicted.Results. We identified a magnetic field structure observed at the start of 4 June, associated with a full magnetic reversal, a local deceleration of the flow and large plasma density, and enhanced dust and energetic ions events. The cross-comparison of all these observations support a possible cometary origin for this structure and suggests the presence of magnetic field draping around some low-field and high-density object. Inside and around this large scale structure, several ion-scale wave-forms are detected that are consistent with small-scale waves and structures generated by cometary pick-up ion instabilities.Conclusions. Solar Orbiter measurements are consistent with the crossing through a magnetic and plasma structure of cometary origin embedded in the ambient solar wind. We suggest that this corresponds to the magnetotail of one of the fragments of comet ATLAS or to a portion of the tail that was previously disconnected and advected past the spacecraft by the solar wind.
22.	Carbone, F., et al. (författare) Statistical study of electron density turbulence and ion-cyclotron waves in the inner heliosphere : Solar Orbiter observations 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656 Tidskriftsartikel (refereegranskat)abstract Context. The recently released spacecraft potential measured by the RPW instrument on board Solar Orbiter has been used to estimate the solar wind electron density in the inner heliosphere. Aims. The measurement of the solar wind's electron density, taken in June 2020, has been analysed to obtain a thorough characterization of the turbulence and intermittency properties of the fluctuations. Magnetic field data have been used to describe the presence of ion-scale waves. Methods. To study and quantify the properties of turbulence, we extracted selected intervals. We used empirical mode decomposition to obtain the generalized marginal Hilbert spectrum, equivalent to the structure functions analysis, which additionally reduced issues typical of non-stationary, short time series. The presence of waves was quantitatively determined by introducing a parameter describing the time-dependent, frequency-filtered wave power. Results. A well-defined inertial range with power-law scalng was found almost everywhere in the sample studied. However, the Kolmogorov scaling and the typical intermittency effects are only present in fraction of the samples. Other intervals have shallower spectra and more irregular intermittency, which are not described by models of turbulence. These are observed predominantly during intervals of enhanced ion frequency wave activity. Comparisons with compressible magnetic field intermittency (from the MAG instrument) and with an estimate of the solar wind velocity (using electric and magnetic field) are also provided to give general context and help determine the cause of these anomalous fluctuations.
23.	Cooper, Alan, et al. (författare) A global environmental crisis 42,000 years ago 2021 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 371:6531, s. 811-818 Tidskriftsartikel (refereegranskat)abstract Geological archives record multiple reversals of Earth’s magnetic poles, but the global impacts of these events, if any, remain unclear. Uncertain radiocarbon calibration has limited investigation of the potential effects of the last major magnetic inversion, known as the Laschamps Excursion [41 to 42 thousand years ago (ka)]. We use ancient New Zealand kauri trees (Agathis australis) to develop a detailed record of atmospheric radiocarbon levels across the Laschamps Excursion. We precisely characterize the geomagnetic reversal and perform global chemistry-climate modeling and detailed radiocarbon dating of paleoenvironmental records to investigate impacts. We find that geomagnetic field minima ~42 ka, in combination with Grand Solar Minima, caused substantial changes in atmospheric ozone concentration and circulation, driving synchronous global climate shifts that caused major environmental changes, extinction events, and transformations in the archaeological record.
24.	Cooper, Alan, et al. (författare) Response to comment on “A global environmental crisis 42,000 years ago” 2021 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6570 Tidskriftsartikel (refereegranskat)abstract Our paper about the impacts of the Laschamps Geomagnetic Excursion 42,000 years ago has provoked considerable scientific and public interest, particularly in the so-called Adams Event associated with the initial transition of the magnetic poles. Although we welcome the opportunity to discuss our new ideas, Hawks’ assertions of misrepresentation are especially disappointing given his limited examination of the material.
25.	Dimmock, A. P., et al. (författare) Analysis of multiscale structures at the quasi-perpendicular Venus bow shock Results from Solar Orbiter's first Venus flyby 2022 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 660 Tidskriftsartikel (refereegranskat)abstract Context. Solar Orbiter is a European Space Agency mission with a suite of in situ and remote sensing instruments to investigate the physical processes across the inner heliosphere. During the mission, the spacecraft is expected to perform multiple Venus gravity assist maneuvers while providing measurements of the Venusian plasma environment. The first of these occurred on 27 December 2020, in which the spacecraft measured the regions such as the distant and near Venus magnetotail, magnetosheath, and bow shock. Aims. This study aims to investigate the outbound Venus bow shock crossing measured by Solar Orbiter during the first flyby. We study the complex features of the bow shock traversal in which multiple large amplitude magnetic field and density structures were observed as well as higher frequency waves. Our aim is to understand the physical mechanisms responsible for these high amplitude structures, characterize the higher frequency waves, determine the source of the waves, and put these results into context with terrestrial bow shock observations. Methods. High cadence magnetic field, electric field, and electron density measurements were employed to characterize the properties of the large amplitude structures and identify the relevant physical process. Minimum variance analysis, theoretical shock descriptions, coherency analysis, and singular value decomposition were used to study the properties of the higher frequency waves to compare and identify the wave mode. Results. The non-planar features of the bow shock are consistent with shock rippling and/or large amplitude whistler waves. Higher frequency waves are identified as whistler-mode waves, but their properties across the shock imply they may be generated by electron beams and temperature anisotropies. Conclusions. The Venus bow shock at a moderately high Mach number (similar to 5) in the quasi-perpendicular regime exhibits complex features similar to the Earth's bow shock at comparable Mach numbers. The study highlights the need to be able to distinguish between large amplitude waves and spatial structures such as shock rippling. The simultaneous high frequency observations also demonstrate the complex nature of energy dissipation at the shock and the important question of understanding cross-scale coupling in these complex regions. These observations will be important to interpreting future planetary missions and additional gravity assist maneuvers.
26.	Jones, Geraint H., et al. (författare) The Comet Interceptor Mission 2024 Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1 Tidskriftsartikel (refereegranskat)abstract Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
27.	Khotyaintsev, Yu, V, et al. (författare) Density fluctuations associated with turbulence and waves First observations by Solar Orbiter 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656 Tidskriftsartikel (refereegranskat)abstract Aims. The aim of this work is to demonstrate that the probe-to-spacecraft potential measured by RPW on Solar Orbiter can be used to derive the plasma (electron) density measurement, which exhibits both a high temporal resolution and a high level of accuracy. To investigate the physical nature of the solar wind turbulence and waves, we analyze the density and magnetic field fluctuations around the proton cyclotron frequency observed by Solar Orbiter during the first perihelion encounter (similar to 0.5AU away from the Sun). Methods. We used the plasma density based on measurements of the probe-to-spacecraft potential in combination with magnetic field measurements by MAG to study the fields and density fluctuations in the solar wind. In particular, we used the polarization of the wave magnetic field, the phase between the compressible magnetic field and density fluctuations, and the compressibility ratio (the ratio of the normalized density fluctuations to the normalized compressible fluctuations of B) to characterize the observed waves and turbulence. Results. We find that the density fluctuations are 180 degrees out of phase (anticorrelated) with the compressible component of magnetic fluctuations for intervals of turbulence, whereas they are in phase for the circular-polarized waves. We analyze, in detail, two specific events with a simultaneous presence of left- and right-handed waves at di fferent frequencies. We compare the observed wave properties to a prediction of the three-fluid (electrons, protons, and alphas) model. We find a limit on the observed wavenumbers, 10(-6) < k < 7 > 10(-6) m(-1), which corresponds to a wavelength of 7 x 10(6) > lambda > 10(6) m. We conclude that it is most likely that both the leftand right-handed waves correspond to the low-wavenumber part (close to the cut-o ff at Omega(cHe++)) of the proton-band electromagnetic ion cyclotron (left-handed wave in the plasma frame confined to the frequency range Omega(cHe++) < omega < Omega(cp)) waves propagating in the outwards and inwards directions, respectively. The fact that both wave polarizations are observed at the same time and the identified wave mode has a low group velocity suggests that the double-banded events occur in the source regions of the waves.
28.	Mueller, SC, et al. (författare) The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group 2021 Ingår i: The journal of sexual medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 18:6, s. 1122-1129 Tidskriftsartikel (refereegranskat)
29.	Petzold, Axel, et al. (författare) Diagnosis and classification of optic neuritis 2022 Ingår i: Lancet Neurology. - : ELSEVIER SCIENCE INC. - 1474-4422 .- 1474-4465. ; 21:12, s. 1120-1134 Forskningsöversikt (refereegranskat)abstract There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.
30.	Reimer, Paula J., et al. (författare) The IntCal20 Northern Hemisphere Radiocarbon Age Calibration Curve (0-55 cal kBP) 2020 Ingår i: Radiocarbon. - 0033-8222. ; 62:4, s. 725-757 Tidskriftsartikel (refereegranskat)abstract Radiocarbon (C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
31.	Stancampiano, MR, et al. (författare) Testosterone Therapy and Its Monitoring in Adolescent Boys with Hypogonadism: Results of an International Survey from the I-DSD Registry 2021 Ingår i: Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation. - : S. Karger AG. - 1661-5433. ; 15:4, s. 236-243 Tidskriftsartikel (refereegranskat)abstract It is unclear whether testosterone replacement therapy (TRT) in adolescent boys, affected by a range of endocrine diseases that may be associated with hypogonadism, is particularly common. The aim of this study was to assess the contemporary practice of TRT in boys included in the I-DSD Registry. All participating centres in the I-DSD Registry that had boys between 10 and 18 years of age and with a condition that could be associated with hypogonadism were invited to provide further information in 2019. Information on 162 boys was collected from 15 centres that had a median (range) number of 6 boys per centre (1.35). Of these, 30 (19%) from 9 centres were receiving TRT and the median (range) age at the start was 12.6 years (10.8–16.2), with 6 boys (20%) starting at <12 years. Median (range) age of boys not on TRT was 11.7 years (10.7–17.7), and 69 out of 132 (52%) were <12 years. TRT had been initiated in 20 of 71 (28%) boys with a disorder of gonadal development, 3 of 14 (21%) with a disorder of androgen synthesis, and all 7 (100%) boys with hypogonadotropic hypogonadism. The remainder who did not have TRT included 15 boys with partial androgen insensitivity, 52 with non-specific XY DSD, and 3 with persistent Müllerian duct syndrome. Before starting TRT, liver function and blood count were checked in 19 (68%) and 18 boys (64%), respectively, a bone age assessment was performed in 23 (82%) and bone mineral density assessment in 12 boys (43%). This snapshot of contemporary practice reveals that TRT in boys included in the I-DSD Registry is not very common, whilst the variation in starting and monitoring therapy is quite marked. Standardisation of practice may lead to more effective assessment of treatment outcomes.
32.	Steinvall, Konrad, et al. (författare) Solar wind current sheets and deHoffmann-Teller analysis First results from Solar Orbiter's DC electric field measurements 2021 Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656 Tidskriftsartikel (refereegranskat)abstract Context. Solar Orbiter was launched on 10 February 2020 with the purpose of investigating solar and heliospheric physics using a payload of instruments designed for both remote and in situ studies. Similar to the recently launched Parker Solar Probe, and unlike earlier missions, Solar Orbiter carries instruments designed to measure low-frequency DC electric fields. Aims. In this paper, we assess the quality of the low-frequency DC electric field measured by the Radio and Plasma Waves instrument (RPW) on Solar Orbiter. In particular, we investigate the possibility of using Solar Orbiter's DC electric and magnetic field data to estimate the solar wind speed. Methods. We used a deHoffmann-Teller (HT) analysis, based on measurements of the electric and magnetic fields, to find the velocity of solar wind current sheets, which minimises a single component of the electric field. By comparing the HT velocity to the proton velocity measured by the Proton and Alpha particle Sensor (PAS), we have developed a simple model for the effective antenna length, L-eff of the E-field probes. We then used the HT method to estimate the speed of the solar wind. Results. Using the HT method, we find that the observed variations in E-y are often in excellent agreement with the variations in the magnetic field. The magnitude of E-y, however, is uncertain due to the fact that the L-eff depends on the plasma environment. Here, we derive an empirical model relating L-eff to the Debye length, which we can use to improve the estimate of E-y and, consequently, the estimated solar wind speed. Conclusions. The low-frequency electric field provided by RPW is of high quality. Using the deHoffmann-Teller analysis, Solar Orbiter's magnetic and electric field measurements can be used to estimate the solar wind speed when plasma data are unavailable.
33.	Norgren, C., et al. (författare) Millisecond observations of nonlinear wave-electron interaction in electron phase space holes 2022 Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 29:1 Tidskriftsartikel (refereegranskat)abstract Electron phase space holes (EHs) associated with electron trapping are commonly observed as bipolar electric field signatures in both space and laboratory plasma. Until recently, it has not been possible to resolve EHs in electron measurements. We report observations of EHs in the plasma sheet boundary layer, here identified as the separatrix region of magnetic reconnection in the magnetotail. The intense EHs are observed together with an electron beam moving toward the X line, showing signs of thermalization. Using the electron drift instrument onboard the satellites of the Magnetospheric Multiscale mission, we make direct millisecond measurements of the electron particle flux associated with individual electron phase space holes. The electron flux is measured at a millisecond cadence in a narrow parallel speed range within that of the trapped electrons. The flux modulations are of order unity and are direct evidence of the strong nonlinear wave-electron interaction that may effectively thermalize beams and contribute to transforming directed drift energy to thermal energy.
34.	Oehri, Jacqueline, et al. (författare) Vegetation type is an important predictor of the arctic summer land surface energy budget 2022 Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13 Tidskriftsartikel (refereegranskat)abstract Despite the importance of high-latitude surface energy budgets (SEBs) for land-climate interactions in the rapidly changing Arctic, uncertainties in their prediction persist. Here, we harmonize SEB observations across a network of vegetated and glaciated sites at circumpolar scale (1994–2021). Our variance-partitioning analysis identifies vegetation type as an important predictor for SEB-components during Arctic summer (June-August), compared to other SEB-drivers including climate, latitude and permafrost characteristics. Differences among vegetation types can be of similar magnitude as between vegetation and glacier surfaces and are especially high for summer sensible and latent heat fluxes. The timing of SEB-flux summer-regimes (when daily mean values exceed 0 Wm−2) relative to snow-free and -onset dates varies substantially depending on vegetation type, implying vegetation controls on snow-cover and SEB-flux seasonality. Our results indicate complex shifts in surface energy fluxes with land-cover transitions and a lengthening summer season, and highlight the potential for improving future Earth system models via a refined representation of Arctic vegetation types.
35.	Palmerio, Erika, et al. (författare) CMEs and SEPs During November-December 2020 : A Challenge for Real-Time Space Weather Forecasting 2022 Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 20:5 Tidskriftsartikel (refereegranskat)abstract Predictions of coronal mass ejections (CMEs) and solar energetic particles (SEPs) are a central issue in space weather forecasting. In recent years, interest in space weather predictions has expanded to include impacts at other planets beyond Earth as well as spacecraft scattered throughout the heliosphere. In this sense, the scope of space weather science now encompasses the whole heliospheric system, and multipoint measurements of solar transients can provide useful insights and validations for prediction models. In this work, we aim to analyze the whole inner heliospheric context between two eruptive flares that took place in late 2020, that is, the M4.4 flare of 29 November and the C7.4 flare of 7 December. This period is especially interesting because the STEREO-A spacecraft was located similar to 60 degrees east of the Sun-Earth line, giving us the opportunity to test the capabilities of "predictions at 360 degrees" using remote-sensing observations from the Lagrange L1 and L5 points as input. We simulate the CMEs that were ejected during our period of interest and the SEPs accelerated by their shocks using the WSA-Enlil-SEPMOD modeling chain and four sets of input parameters, forming a "mini-ensemble." We validate our results using in situ observations at six locations, including Earth and Mars. We find that, despite some limitations arising from the models' architecture and assumptions, CMEs and shock-accelerated SEPs can be reasonably studied and forecast in real time at least out to several tens of degrees away from the eruption site using the prediction tools employed here.
36.	Rimkute, Inga, et al. (författare) Histo-blood group antigens of glycosphingolipids predict susceptibility of human intestinal enteroids to norovirus infection 2020 Ingår i: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 295:47, s. 15974-15987 Tidskriftsartikel (refereegranskat)abstract The molecular mechanisms behind infection and propagation of human restricted pathogens such as human norovirus (HuNoV) have defied interrogation because they were previously unculturable. However, human intestinal enteroids (HIEs) have emerged to offer unique ex vivo models for targeted studies of intestinal biology, including inflammatory and infectious diseases. Carbohydrate-dependent histo-blood group antigens (HBGAs) are known to be critical for clinical infection. To explore whether HBGAs of glycosphingolipids contribute to HuNoV infection, we obtained HIE cultures established from stem cells isolated from jejunal biopsies of six individuals with different ABO, Lewis, and secretor genotypes. We analyzed their glycerolipid and sphingolipid compositions and quantified interaction kinetics and the affinity of HuNoV virus-like particles (VLPs) to lipid vesicles produced from the individual HIE-lipid extracts. All HIEs had a similar lipid and glycerolipid composition. Sphingolipids included HBGA-related type 1 chain glycosphingolipids (GSLs), with HBGA epitopes corresponding to the geno- and phenotypes of the different HIEs. As revealed by single-particle interaction studies of Sydney GII.4 VLPs with glycosphingolipid-containing HIE membranes, both binding kinetics and affinities explain the patterns of susceptibility toward GII.4 infection for individual HIEs. This is the first time norovirus VLPs have been shown to interact specifically with secretor gene-dependent GSLs embedded in lipid membranes of HIEs that propagate GII.4 HuNoV ex vivo, highlighting the potential of HIEs for advanced future studies of intestinal glycobiology and host-pathogen interactions.
37.	Rosenhahn, Erik, et al. (författare) Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications 2022 Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 109:8, s. 1421-1435 Tidskriftsartikel (refereegranskat)abstract PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy, and progressive microcephaly. Further common clinical findings included muscular hyper- and hypotonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, ventriculomegaly, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM domain region that is essential for protein-protein interaction. For further insight into the effects of PPFIBP1 loss of function, we performed automated behavioral phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model, which revealed defects in spontaneous and light-induced behavior and confirmed resistance to the acetylcholinesterase inhibitor aldicarb, suggesting a defect in the neuronal presynaptic zone. In conclusion, we establish bi-allelic loss-of-function variants in PPFIBP1 as a cause of an autosomal recessive severe neurodevelopmental disorder with early-onset epilepsy, microcephaly, and periventricular calcifications.
38.	Yang, Zhijian, et al. (författare) Genetic Landscape of the ACE2 Coronavirus Receptor 2022 Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36 Tidskriftsartikel (refereegranskat)abstract Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
39.	Bell, Jane C., et al. (författare) Survival of infants born with esophageal atresia among 24 international birth defects surveillance programs 2021 Ingår i: Birth Defects Research. - : Wiley. - 2472-1727. ; 113:12, s. 945-957 Tidskriftsartikel (refereegranskat)abstract Background: Esophageal atresia (EA) affects around 2.3–2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions. Methods: We included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s–2010s. Results: We included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1–90.5) at 1-month, 84.5% (95% CI 83.0–85.9) at 1-year and 82.7% (95% CI 81.2–84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies. Conclusions: Almost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies.
40.	Breitfeld, H. T., et al. (författare) The onshore West Baram Delta deposits: Provenance and drainage in the Middle Miocene to Pliocene in NW Borneo and comparison to the Champion Delta 2023 Ingår i: Marine and Petroleum Geology. - 0264-8172. ; 158 Tidskriftsartikel (refereegranskat)abstract The Baram Delta province in NW Borneo forms a major hydrocarbon reservoir offshore northern Sarawak and Brunei. The delta sequence is thereby subdivided into the West Baram delta to the south and the Champion delta to the north. Onshore are the remains of the Neogene delta deposits exposed and provide the possibility to study the equivalent offshore successions in outcrop. This study focuses on the Neogene West Baram delta successions which were studied for sedimentological facies and provenance characteristics. The successions consist of the Lambir, Miri, Tukau, and the enigmatic southern Lambir/Belait-Sarawak formations. Deposition took place in various mixed-energy delta environments between the Langhian and early Pliocene. The sediments are all quartzrich and heavy minerals are dominated by ultra-stable zircon, rutile and tourmaline. Dominant detrital zircon age clusters are in the Early Cretaceous and Permian-Triassic. Based on light mineral petrography, heavy mineral assemblages, and detrital zircon U-Pb geochronology, all formations are interpreted as derived from multirecycled sources, likely the underlying Paleogene Rajang Group turbidites and the Oligocene to Lower Miocene Nyalau-Tatau delta deposits. Additionally, literature data of the Champion Delta and one sample from Labuan analysed for provenance in this study are used to demonstrate that the Champion Delta can be distinguished from the West Baram Delta by having higher chrome spinel and garnet contents and slightly different detrital zircon age populations. The Champion Delta deposits are interpreted as sourced by recycling of the Crocker Formation and older turbidites (e.g., Sapulut Formation) with potentially input from ultra-mafic basement rocks of Sabah.
41.	Carsten, Hobohm, et al. (författare) Land Use Change and the Future of Biodiversity 2021 Ingår i: Perspectives for Biodiversity and Ecosystems. - Cham : Springer. - 2214-2827 .- 2214-2835. - 9783030577094 ; , s. 451-483 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract This synthesis report is a meta-analysis of perspectives for biodiversity and ecosystems, with a strong focus on human impacts on the environment, and a work order to enable and manage the protection, survival and evolution of all species on Earth. The goal is to protect nature without any further species loss (Zero Extinction). With this report, we assess alarming signals from the environment; determine the needs of threatened biota and the required actions to manage and protect landscapes and ecosystems; and identify some inescapable tendencies, challenges but also possibilities. The story of humans on Earth is at a critical juncture. Human behaviour is inherently dependent on physical and societal relations, including orientation and positioning within the physical environment. There is no single cultural benefit that is independent of provisioning through ecosystem services. Humans are part of the environment, acquire all needs from it and, as such, depend on its integrity and management for life and well-being. Moreover, if human impacts to the environment continue to increase the risk of rebound effects impacting human life and health will increase as well. Whenever a biome, ecosystem, habitat or species is heavily impacted or threatened with irreversible transformation or extinction, prevailing environmental conditions are relevant and should be observed, analysed and remedied as necessary and where possible. Ecology examines the evolutionary, historical and more recent interplay between biological life and the abiotic environment, while the role of social science and the humanities is to question the physical and social landscape, and how and why it should be protected or influenced, e.g. by nature conservation measures under political and economic, ethical and legal considerations. Thus, for all inter-relationships between natural and sociocultural processes, a joint venture in the form of social-ecological thinking is necessary to combine natural sciences and the humanities. With this contribution, we combine ecological knowledge with social science knowledge (s.l.) through the participation of scientists of many different disciplines. We analyse history and current processes to assess risks, threats and possibilities, and call for an array of regulations and measures that can contribute to halting of biodiversity loss and that assist in achieving a sustainable future. Regulations comprise creativity, cultural incentives, social norms, environmental education and economic investments—such as payments for sustainable agriculture, forestry, and fishery; investments in water, soil and air purity; and much clearer and stronger legal restrictions and consequences around waste streams and environmental degradation. Moreover, a gradual change from profit-oriented economies in the short-run to environmentally-sensitive policies that include systematic environmental programmes in the long term might help to decrease pressure on ecosystems and biota. Such economics might also include the real costs of consumerism, including the impacts of particular products on the environment and on human health. The greatest hurdle for the continued existence of many critically endangered species is the impact of widespread anthropogenic-driven change in the usage of water, air and land, and industry intensification in agriculture, aquaculture, forestry, urbanisation, transportation and mining sectors. However, there is not one simple solution to solve these issues. We conclude that many of the current developments have to be adjusted or gradually altered in a step-wise manner, especially with respect to existing sociocultural behaviours. Therefore, various concepts, decisions and measures should be discussed and implemented at all scales from local to supranational and among researchers, practitioners and politicians.
42.	Chen, YQ, et al. (författare) Angiopoietin-like protein 8 differentially regulates ANGPTL3 and ANGPTL4 during postprandial partitioning of fatty acids 2020 Ingår i: Journal of lipid research. - 1539-7262. ; 61:8, s. 1203-1220 Tidskriftsartikel (refereegranskat)
43.	Dettwiler, Ines, et al. (författare) TIDE Analysis of Cryptosporidium Infections by gp60 Typing Reveals Obscured Mixed Infections 2022 Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:4, s. 686-695 Tidskriftsartikel (refereegranskat)abstract Background. Cryptosporidiosis is a parasitic disease associated with potentially fatal diarrhea. The most used method in Cryptosporidium subtyping is based on the glycoprotein gene gp60. Each infection can represent a parasite population, and it is important to investigate the influence on transmission and virulence, as well as any impact on public health investigations. However, an easy-to-use method for detection is lacking. Methods. Here we report on the use of the bioinformatic program TIDE for deconvolution of gp60 chromatograms. A combination of single oocyst analysis and cloning successfully confirmed the within-sample parasite population diversity. Retrospective sample analysis was conducted on archived chromatograms. Results. For Cryptosporidium parvum, 8.6% multistrain infections (13 of 152) obscured by currently used consensus base calling were detected. Importantly, we show that single oocysts can harbor a mixed population of sporozoites. We also identified a striking dominance of unappreciated polymerase stutter artefacts in all 218 chromatograms analyzed, challenging the uncritical use of gp60 typing. Conclusions. We demonstrate the value of a new, easy-to-use analytical procedure for critical characterization of C. parvum and Cryptosporidium hominis in epidemiological investigations, also applicable retrospectively. Our findings illuminate the hidden parasite diversity with important implications for tracing zoonotic and person-to-person transmissions.
44.	Gonzalez, Maria Camila, et al. (författare) Cognitive and motor decline in dementia with lewy bodies and Parkinson's disease dementia 2023 Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:6, s. 980-986 Tidskriftsartikel (refereegranskat)abstract Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD).Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts.Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157).Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]).Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.
45.	Halama, R., et al. (författare) Boron isotope record of peak metamorphic ultrahigh-pressure and retrograde fluid-rock interaction in white mica (Lago di Cignana, Western Alps) 2020 Ingår i: Contributions to Mineralogy and Petrology. - : Springer Science and Business Media LLC. - 0010-7999 .- 1432-0967. ; 175:3 Tidskriftsartikel (refereegranskat)abstract This study presents boron (B) concentration and isotope data for white mica from (ultra)high-pressure (UHP), subduction-related metamorphic rocks from Lago di Cignana (Western Alps, Italy). These rocks are of specific geological interest, because they comprise the most deeply subducted rocks of oceanic origin worldwide. Boron geochemistry can track fluid-rock interaction during their metamorphic evolution and provide important insights into mass transfer processes in subduction zones. The highest B contents (up to 345 mu g/g B) occur in peak metamorphic phengite from a garnet-phengite quartzite. The B isotopic composition is variable (delta B-11 = - 10.3 to - 3.6%) and correlates positively with B concentrations. Based on similar textures and major element mica composition, neither textural differences, prograde growth zoning, diffusion nor a retrograde overprint can explain this correlation. Modelling shows that B devolatilization during metamorphism can explain the general trend, but fails to account for the wide compositional and isotopic variability in a single, well-equilibrated sample. We, therefore, argue that this trend represents fluid-rock interaction during peak metamorphic conditions. This interpretation is supported by fluid-rock interaction modelling of boron leaching and boron addition that can successfully reproduce the observed spread in delta B-11 and [B]. Taking into account the local availability of serpentinites as potential source rocks of the fluids, the temperatures reached during peak metamorphism that allow for serpentine dehydration, and the high positive delta B-11 values (delta B-11 = 20 +/- 5) modelled for the fluids, an influx of serpentinite-derived fluid appears likely. Paragonite in lawsonite pseudomorphs in an eclogite and phengite from a retrogressed metabasite have B contents between 12 and 68 mu g/g and delta B-11 values that cluster around 0% (delta B-11 = - 5.0 to + 3.5). White mica in both samples is related to distinct stages of retrograde metamorphism during exhumation of the rocks. The variable B geochemistry can be successfully modelled as fluid-rock interaction with low-to-moderate (< 3) fluid/rock ratios, where mica equilibrates with a fluid into which B preferentially partitions, causing leaching of B from the rock. The metamorphic rocks from Lago di Cignana show variable retention of B in white mica during subduction-related metamorphism and exhumation. The variability in the B geochemical signature in white mica is significant and enhances our understanding of metamorphic processes and their role in element transfer in subduction zones.
46.	Karczewski, Konrad J., et al. (författare) The mutational constraint spectrum quantified from variation in 141,456 humans 2020 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 581, s. 434-443 Tidskriftsartikel (refereegranskat)abstract Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes1. Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve the power of gene discovery for both common and rare diseases.
47.	Leigard, E, et al. (författare) Increasing perioperative age and comorbidity: a 16-year cohort study at two University hospital sites in Sweden 2024 Ingår i: International journal of surgery (London, England). - 1743-9159. ; 110:7, s. 4124-4131 Tidskriftsartikel (refereegranskat)
48.	Maurer, Marcus, et al. (författare) Definition, aims, and implementation of GA2 LEN/HAEi Angioedema Centers of Reference and Excellence 2020 Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 75:8, s. 2115-2123 Tidskriftsartikel (refereegranskat)
49.	Megyesfalvi, Zsolt, et al. (författare) Clinical insights into small cell lung cancer : Tumor heterogeneity, diagnosis, therapy, and future directions 2023 Ingår i: CA: a cancer journal for clinicians. - 0007-9235. ; 73:6, s. 620-652 Forskningsöversikt (refereegranskat)abstract Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or without immunotherapy. In patients with disease confined to the chest, standard therapy includes thoracic radiotherapy and concurrent platinum-etoposide chemotherapy. Patients with metastatic (extensive-stage) disease are treated with a combination of platinum-etoposide chemotherapy plus immunotherapy with an anti-programmed death-ligand 1 monoclonal antibody. Although SCLC is initially very responsive to platinum-based chemotherapy, these responses are transient because of the development of drug resistance. In recent years, the authors have witnessed an accelerating pace of biologic insights into the disease, leading to the redefinition of the SCLC classification scheme. This emerging knowledge of SCLC molecular subtypes has the potential to define unique therapeutic vulnerabilities. Synthesizing these new discoveries with the current knowledge of SCLC biology and clinical management may lead to unprecedented advances in SCLC patient care. Here, the authors present an overview of multimodal clinical approaches in SCLC, with a special focus on illuminating how recent advancements in SCLC research could accelerate clinical development.
50.	Mutgan, Ayse Ceren, et al. (författare) A comprehensive map of proteoglycan expression and deposition in the pulmonary arterial wall in health and pulmonary hypertension 2024 Ingår i: American Journal of Physiology - Lung Cellular and Molecular Physiology. - 1040-0605. ; 327:2, s. 173-188 Tidskriftsartikel (refereegranskat)abstract Changes in the extracellular matrix of pulmonary arteries (PAs) are a key aspect of vascular remodeling in pulmonary hypertension (PH). Yet, our understanding of the alterations affecting the proteoglycan (PG) family remains limited. We sought to investigate the expression and spatial distribution of major vascular PGs in PAs from healthy individuals and various PH groups (chronic obstructive pulmonary disease: PH-COPD, pulmonary fibrosis: PH-PF, idiopathic: IPAH). PG regulation, deposition, and synthesis were notably heightened in IPAH, followed by PH-PF, with minor alterations in PH-COPD. Single-cell analysis unveiled cell-type and disease-specific PG regulation. Agrin expression, a basement membrane PG, was increased in IPAH, with PA endothelial cells (PAECs) identified as a major source. PA smooth muscle cells (PASMCs) mainly produced large-PGs, aggrecan and versican, and small-leucine-like proteoglycan (SLRP) biglycan, whereas the major PGs produced by adventitial fibroblasts were SLRP decorin and lumican. In IPAH and PF-PH, the neointima-forming PASMC population increased the expression of all investigated large-PGs and SLRPs, except fibroblast-predominant decorin (DCN). Expression of lumican, versican, and biglycan also positively correlated with collagen 1a1/1a2 expression in PASMCs in patients with IPAH and PH-PF. We demonstrated that transforming growth factor-beta (TGF-b) regulates versican and biglycan expression, indicating their contribution to vessel fibrosis in IPAH and PF-PH. We furthermore show that certain circulating PG levels display a disease-dependent pattern, with increased decorin and lumican across all patient groups, while versican was elevated in PH-COPD and IPAH and biglycan reduced in IPAH. These findings suggest unique compartment-specific PG regulation in different forms of PH, indicating distinct pathological processes. NEW & NOTEWORTHY Idiopathic pulmonary arterial hypertension (IPAH) pulmonary arteries (PAs) displayed the greatest proteoglycan (PG) changes, with PH associated with pulmonary fibrosis (PH-PF) and PH associated with chronic obstructive pulmonary disease (PH-COPD) following. Agrin, an endothelial cell-specific PG, was solely upregulated in IPAH. Among all cells, neo-intimaforming smooth muscle cells (SMCs) displayed the most significant PG increase. Increased levels of circulating decorin, lumican, and versican, mainly derived from SMCs, and adventitial fibroblasts, may serve as systemic indicators of pulmonary remodeling, reflecting perivascular fibrosis and neointima formation.

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