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Sökning: WFRF:(von Seth E)

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1.
  • Singh, B. P., et al. (författare)
  • Experimental access to Transition Distribution Amplitudes with the PANDA experiment at FAIR
  • 2015
  • Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion (pi N) TDAs from (p) over barp -> e(+)e(-)pi(0) reaction with the future PANDA detector at the FAIR facility. At high center-of-mass energy and high invariant mass squared of the lepton pair q(2), the amplitude of the signal channel (p) over barp -> e(+)e(-)pi(0) admits a QCD factorized description in terms of pi N TDAs and nucleon Distribution Amplitudes (DAs) in the forward aid backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring (p) over barp -> e(+)e(-)pi(0) with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. (p) over barp -> pi(+)pi(-)pi(0) were performed for the center-of-mass energy squared s = 5 GeV2 and s = 10 GeV2, in the kinematic regions 3.0 < q(2) < 4.3 GeV2 and 5 < q(2) < 9 GeV2, respectively, with a neutral pion scattered in the forward or backward cone vertical bar cos theta(pi 0)vertical bar > 0.5 in the proton-antiproton center-of-mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of 5 . 10(7) (1 . 10(7)) at low (high) q(2) for s = 5 GeV2, and of 1 . 10(8) (6 . 10(6)) at low (high) q(2) for s = 10 GeV2, while keeping the signal reconstruction efficiency at around 40%. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 of integrated luminosity. The cross sections obtained from the simulations are used to show that a test of QCD collinear factorization can be done at the lowest order by measuring scaling laws and angular distributions. The future measurement of the signal channel cross section with PANDA will provide a new test of the perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing pi N TDAs.
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  • Erni, W., et al. (författare)
  • Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
  • 2013
  • Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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  • Dussex, Nicolas, et al. (författare)
  • Population genomics of the critically endangered kākāpō
  • 2021
  • Ingår i: Cell Genomics. - : Elsevier BV. - 2666-979X. ; 1:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary The kākāpō is a flightless parrot endemic to New Zealand. Once common in the archipelago, only 201 individuals remain today, most of them descending from an isolated island population. We report the first genome-wide analyses of the species, including a high-quality genome assembly for kākāpō, one of the first chromosome-level reference genomes sequenced by the Vertebrate Genomes Project (VGP). We also sequenced and analyzed 35 modern genomes from the sole surviving island population and 14 genomes from the extinct mainland population. While theory suggests that such a small population is likely to have accumulated deleterious mutations through genetic drift, our analyses on the impact of the long-term small population size in kākāpō indicate that present-day island kākāpō have a reduced number of harmful mutations compared to mainland individuals. We hypothesize that this reduced mutational load is due to the island population having been subjected to a combination of genetic drift and purging of deleterious mutations, through increased inbreeding and purifying selection, since its isolation from the mainland ∼10,000 years ago. Our results provide evidence that small populations can survive even when isolated for hundreds of generations. This work provides key insights into kākāpō breeding and recovery and more generally into the application of genetic tools in conservation efforts for endangered species.
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  • Mansoor, Rashid, et al. (författare)
  • Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
  • 2022
  • Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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  • Bergquist, A, et al. (författare)
  • Epidemiology of cholangiocarcinoma
  • 2015
  • Ingår i: Best practice & research. Clinical gastroenterology. - : Elsevier BV. - 1532-1916 .- 1521-6918. ; 29:2, s. 221-232
  • Tidskriftsartikel (refereegranskat)
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  • Bergquist, Annika, et al. (författare)
  • Impact on follow-up strategies in patients with primary sclerosing cholangitis
  • 2023
  • Ingår i: Liver international (Print). - Chichester, United Kingdom : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 43:1, s. 127-138
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.METHODS: We collected retrospective data from 2,975 PSC patients from 27 centers. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from January 1, 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.RESULTS: A broad variety of different follow-up strategies were reported. All except one center used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centers used scheduled ERCP in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, were 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.CONCLUSIONS: Follow-up strategies vary considerably across centers. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumor detection and increased endoscopic treatment of asymptomatic benign biliary strictures.
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  • Cockerill, Christopher Alan, 1994-, et al. (författare)
  • Genomic Consequences of Fragmentation in the Endangered Fennoscandian Arctic Fox (Vulpes lagopus)
  • 2022
  • Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 13:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Accelerating climate change is causing severe habitat fragmentation in the Arctic, threatening the persistence of many cold-adapted species. The Scandinavian arctic fox (Vulpes lagopus) is highly fragmented, with a once continuous, circumpolar distribution, it struggled to recover from a demographic bottleneck in the late 19th century. The future persistence of the entire Scandinavian population is highly dependent on the northernmost Fennoscandian subpopulations (Scandinavia and the Kola Peninsula), to provide a link to the viable Siberian population. By analyzing 43 arctic fox genomes, we quantified genomic variation and inbreeding in these populations. Signatures of genome erosion increased from Siberia to northern Sweden indicating a stepping-stone model of connectivity. In northern Fennoscandia, runs of homozygosity (ROH) were on average ~1.47-fold longer than ROH found in Siberia, stretching almost entire scaffolds. Moreover, consistent with recent inbreeding, northern Fennoscandia harbored more homozygous deleterious mutations, whereas Siberia had more in heterozygous state. This study underlines the value of documenting genome erosion following population fragmentation to identify areas requiring conservation priority. With the increasing fragmentation and isolation of Arctic habitats due to global warming, understanding the genomic and demographic consequences is vital for maintaining evolutionary potential and preventing local extinctions.
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  • Kutschera, Verena E., et al. (författare)
  • GenErode : a bioinformatics pipeline to investigate genome erosion in endangered and extinct species
  • 2022
  • Ingår i: BMC Bioinformatics. - : Springer Nature. - 1471-2105. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Many wild species have suffered drastic population size declines over the past centuries, which have led to 'genomic erosion' processes characterized by reduced genetic diversity, increased inbreeding, and accumulation of harmful mutations. Yet, genomic erosion estimates of modern-day populations often lack concordance with dwindling population sizes and conservation status of threatened species. One way to directly quantify the genomic consequences of population declines is to compare genome-wide data from pre-decline museum samples and modern samples. However, doing so requires computational data processing and analysis tools specifically adapted to comparative analyses of degraded, ancient or historical, DNA data with modern DNA data as well as personnel trained to perform such analyses. Results: Here, we present a highly flexible, scalable, and modular pipeline to compare patterns of genomic erosion using samples from disparate time periods. The GenErode pipeline uses state-of-the-art bioinformatics tools to simultaneously process whole-genome re-sequencing data from ancient/historical and modern samples, and to produce comparable estimates of several genomic erosion indices. No programming knowledge is required to run the pipeline and all bioinformatic steps are well-documented, making the pipeline accessible to users with different backgrounds. GenErode is written in Snakemake and Python3 and uses Conda and Singularity containers to achieve reproducibility on high-performance compute clusters. The source code is freely available on GitHub (https://github.com/NBISweden/GenErode). Conclusions: GenErode is a user-friendly and reproducible pipeline that enables the standardization of genomic erosion indices from temporally sampled whole genome re-sequencing data.
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18.
  • Larsson, Petter, et al. (författare)
  • Consequences of past climate change and recent human persecution on mitogenomic diversity in the arctic fox
  • 2019
  • Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 374:1788
  • Tidskriftsartikel (refereegranskat)abstract
    • Ancient DNA provides a powerful means to investigate the timing, rate and extent of population declines caused by extrinsic factors, such as past climate change and human activities. One species probably affected by both these factors is the arctic fox, which had a large distribution during the last glaciation that subsequently contracted at the start of the Holocene. More recently, the arctic fox population in Scandinavia went through a demographic bottleneck owing to human persecution. To investigate the consequences of these processes, we generated mitogenome sequences from a temporal dataset comprising Pleistocene, historical and modern arctic fox samples. We found no evidence that Pleistocene populations in mid-latitude Europe or Russia contributed to the present-day gene pool of the Scandinavian population, suggesting that postglacial climate warming led to local population extinctions. Furthermore, during the twentieth-century bottleneck in Scandinavia, at least half of the mitogenome haplotypes were lost, consistent with a 20-fold reduction in female effective population size. In conclusion, these results suggest that the arctic fox in mainland Western Europe has lost genetic diversity as a result of both past climate change and human persecution. Consequently, it might be particularly vulnerable to the future challenges posed by climate change. This article is part of a discussion meeting issue 'The past is a foreign country: how much can the fossil record actually inform conservation?'
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  • Nordenvall, C., et al. (författare)
  • Colectomy prior to diagnosis of primary sclerosing cholangitis is associated with improved prognosis in a nationwide cohort study of 2594 PSC-IBD patients
  • 2018
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : WILEY. - 0269-2813 .- 1365-2036. ; 47:2, s. 238-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Despite the close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), the association between colectomy and the prognosis of PSC remains controversial. Aim: To explore whether colectomy prior to PSC-diagnosis is associated with transplant-free survival. Methods; A nationwide cohort study in Sweden including all patients aged 18 to 69 years in whom both PSC and IBD was diagnosed between 1987 and 2014 was undertaken. Each patient was followed from date of both PSC and IBD diagnoses until liver transplantation or death, or 31 December 2014. Patients with colon in situ, and colectomy prior to PSC-diagnosis were compared. Survival analyses were performed using the Kaplan-Meier method and multivariable Cox regression models. Results: Of the 2594 PSC-IBD patients, 205 patients were treated with colectomy before PSC-diagnosis. During follow-up, liver transplantations were performed in 327 patients and 509 died. The risk of liver transplantation or death was lower in patients treated with colectomy prior to PSC-diagnosis (HR 0.71, 95% CI 0.53-0.95) than in patients with colon in situ. Male gender, longer time between IBD and PSC-diagnosis and older age were all associated with an increased risk of liver transplantation or death. Colectomy after PSC-diagnosis was however not associated with an increased risk of liver transplantation or death during long-term follow-up. Conclusions: In PSC-IBD patients, colectomy prior to PSC-diagnosis is associated with a decreased risk of liver transplantation or death.
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  • von Seth, J, et al. (författare)
  • Genomic insights into the conservation status of the world's last remaining Sumatran rhinoceros populations
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Small populations are often exposed to high inbreeding and mutational load that can increase the risk of extinction. The Sumatran rhinoceros was widespread in Southeast Asia, but is now restricted to small and isolated populations on Sumatra and Borneo, and most likely extinct on the Malay Peninsula. Here, we analyse 5 historical and 16 modern genomes from these populations to investigate the genomic consequences of the recent decline, such as increased inbreeding and mutational load. We find that the Malay Peninsula population experienced increased inbreeding shortly before extirpation, which possibly was accompanied by purging. The populations on Sumatra and Borneo instead show low inbreeding, but high mutational load. The currently small population sizes may thus in the near future lead to inbreeding depression. Moreover, we find little evidence for differences in local adaptation among populations, suggesting that future inbreeding depression could potentially be mitigated by assisted gene flow among populations.
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  • Zimmer, Christine L., et al. (författare)
  • A biliary immune landscape map of primary sclerosing cholangitis reveals a dominant network of neutrophils and tissue-resident T cells
  • 2021
  • Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:599
  • Tidskriftsartikel (refereegranskat)abstract
    • The human biliary system, a mucosal barrier tissue connecting the liver and intestine, is an organ often affected by serious inflammatory and malignant diseases. Although these diseases are linked to immunological processes, the biliary system represents an unexplored immunological niche. By combining endoscopy-guided sampling of the biliary tree with a high-dimensional analysis approach, comprehensive mapping of the human biliary immunological landscape in patients with primary sclerosing cholangitis (PSC), a severe biliary inflammatory disease, was conducted. Major differences in immune cell composition in bile ducts compared to blood were revealed. Furthermore, biliary inflammation in patients with PSC was characterized by high presence of neutrophils and T cells as compared to control individuals without PSC. The biliary T cells displayed a CD103(+)CD69(+) effector memory phenotype, a combined gut and liver homing profile, and produced interleukin-17 (IL-17) and IL-22. Biliary neutrophil infiltration in PSC associated with CXCL8, possibly produced by resident T cells, and CXCL16 was linked to the enrichment of T cells. This study uncovers the immunological niche of human bile ducts, defines a local immune network between neutrophils and biliary-resident T cells in PSC, and provides a resource for future studies of the immune responses in biliary disorders.
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