| 1. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
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| 3. |
- Alström, Per, Professor, et al.
(författare)
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Morphology, vocalizations, and mitochondrial DNA suggest that the Graceful Prinia is two species
- 2021
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Ingår i: Ornithology. - : Oxford University Press (OUP). - 0004-8038 .- 2732-4613 .- 1938-4254. ; 138:2
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Tidskriftsartikel (refereegranskat)abstract
- Prinias (Cisticolidae:Prinia) are resident warblers of open areas across Africa and Asia and include many polytypic species whose species limits have not been seriously reevaluated recently. Based on an integrative taxonomic analysis of morphology, song, and mitochondrial DNA (mtDNA), we suggest that 2 species should be recognized in the Graceful Prinia (Prinia gracilis) complex. In addition, our morphological analyses show the existence of a well-marked undescribed form in southeastern Somalia, which we name herein as a new subspecies. Prinia gracilisis a small, drab, long-tailed species with streaking above and plain pale underparts that has been suggested to fall into 2 groups: the southwestern nominate group (from Egypt to Oman) and the northeastern lepida group (from Turkey through India). However, the characters presented to justify this grouping are variable and show a mosaic pattern, and whether genetic and vocal differences exist is unknown. We found consistent between-group song differences, with the nominate group giving consistently longer inter-phrase intervals, whereas the members of the lepida group sing an essentially continuous reel. An mtDNA tree suggests a deep split between the nominate and lepida groups, with a coalescence time between these clades of similar to 2.2 million years ago. Vocal and mtDNA analyses provided evidence that the northeastern Arabian Peninsula taxon carpenteri belongs to the lepida group. We found that, of all the morphological characters proposed, only proportions and tail barring and spotting relatively consistently distinguish the 2 groups. However, these characters strongly suggest that the eastern Arabian Peninsula is populated by taxa of both the gracilis and lepida groups, in different areas, but we lack genetic and bioacoustic data to corroborate this. Although further study is needed in potential contact zones, we suggest that 2 species should be recognized in the P. gracilis complex, and we propose the retention of the English name Graceful Prinia for P. gracilis sensu stricto, while we suggest that P. lepida be known as Delicate Prinia.
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| 5. |
- Augustin, Tim, et al.
(författare)
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Thomson-Coil Actuator System for Enhanced Active Resonant DC Circuit Breakers
- 2022
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Ingår i: IEEE Journal of Emerging and Selected Topics in Power Electronics. - : Institute of Electrical and Electronics Engineers (IEEE). - 2168-6777 .- 2168-6785. ; 10:1, s. 800-810
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Tidskriftsartikel (refereegranskat)abstract
- Enhanced active resonant (EAR) dc circuit breakers (DCCBs) are a promising set of recently proposed DCCB concepts. As other DCCBs, EAR DCCBs still require a fast mechanical switch. The requirements on the actuator of the mechanical switch depend on the DCCB concept and the dc grid and are derived here for an EAR DCCB. Thomson-coil actuators (TCAs) can open and close mechanical switches sufficiently fast to satisfy the requirements. This work studies experimentally a TCA system with active damping for an off-the-shelf industrial vacuum interrupter used as mechanical switch in an EAR DCCB. The prototype is explained in detail, and extensive measurement results are presented, showing that active damping must be perfectly timed to be effective. A novel Thomson-coil (TC) driver is proposed and studied experimentally, which operates the TCA more efficiently by recycling energy during the actuation. Moreover, the novel TC driver reduces the capacitive storage by 50% and allows for faster recharging with lower charging current. Finally, the autoreclosing and proactive commutation operation of the TCA system and the interruption capability of the prototype EAR DCCB are demonstrated experimentally.
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| 6. |
- Crespo, M. M., et al.
(författare)
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ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part III: Pharmacology, medical and surgical management of post-transplant extrapulmonary conditions statements
- 2021
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 40:11, s. 1279-1300
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Tidskriftsartikel (refereegranskat)abstract
- Patients with connective tissues disease (CTD) are often on immunomodulatory agents before lung transplantation (LTx). Till now, there's no consensus on the safety of using these agents perioperative and post-transplant. The International Society for Heart and Lung Transplantation-supported consensus document on LTx in patients with CTD addresses the risk and contraindications of perioperative and post-transplant management of the biologic disease-modifying antirheumatic drugs (bDMARD), kinase inhibitor DMARD, and biologic agents used for LTx candidates with underlying CTD, and the recommendations and management of non-gastrointestinal extrapulmonary manifestations, and esophageal disorders by medical and surgical approaches for CTD transplant recipients. (C) 2021 International Society for Heart and Lung Transplantation. All rights reserved.
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| 7. |
- Dellgren, Goeran, et al.
(författare)
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Effect of once-per-daytacrolimus versus twice-per-day ciclosporin on 3-year incidence of chronic lung allograft dysfunction after lung transplantation in Scandinavia (ScanCLAD): a multicentre randomised controlled trial
- 2024
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Ingår i: LANCET RESPIRATORY MEDICINE. - 2213-2600. ; 12:1, s. 34-44
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Tidskriftsartikel (refereegranskat)abstract
- Background Evidence is low regarding the choice of calcineurin inhibitor for immunosuppression after lung transplantation. We aimed to compare the use of tacrolimus once per day with ciclosporin twice per day according to the current definition of chronic lung allograft dysfunction (CLAD) after lung transplantation. Methods ScanCLAD is an investigator-initiated, open-label, multicentre, randomised, controlled trial in Scandinavia evaluating whether an immunosuppressive protocol based on anti-thymocyte globulin induction followed by tacrolimus (once per day), mycophenolate mofetil, and corticosteroids reduces the incidence of CLAD after de novo lung transplantation compared with a protocol using ciclosporin (twice per day), mycophenolate mofetil, and corticosteroids. Patients aged 18-70 years who were scheduled to undergo double lung transplantation were randomly allocated (1:1) to receive either oral ciclosporin (2-3 mg/kg before transplantation and 3 mg/kg [twice per day] from postoperative day 1) or oral tacrolimus (005-01 mg/kg before transplantation and 01-02 mg/kg from postoperative day 1). The primary endpoint was CLAD at 36 months post transplantation, determined by repeated lung function tests and adjudicated by an independent committee, and was assessed with a competing-risks analysis with death and re-transplantation as competing events. The primary outcome was assessed in the modified intention-to-treat (mITT) population, defined as those who underwent transplantation and received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02936505) and EudraCT (2015-004137-27). Findings Between Oct 21, 2016, and July 10, 2019, 383 patients were screened for eligibility. 249 patients underwent double lung transplantation and received at least one dose of study drug, and were thus included in the mITT population: 125 (50%) in the ciclosporin group and 124 (50%) in the tacrolimus group. The mITT population consisted of 138 (55%) men and 111 (45%) women, with a mean age of 552 years (SD 102), and no patients were lost to follow-up. In the mITT population, CLAD occurred in 48 patients (cumulative incidence 39% [95% CI 31-48]) in the ciclosporin group and 16 patients (13% [8-21]) in the tacrolimus group at 36 months post transplantation (hazard ratio [HR] 028 [95% CI 015-052], log-rank p<00001). Overall survival did not differ between groups at 3 years in the mITT population (74% [65-81] for ciclosporin vs 79% [70-85] for tacrolimus; HR 072 [95% CI 041-127], log-rank p=025). However, in the per protocol CLAD population (those in the mITT population who also had at least one post-baseline lung function test allowing assessment of CLAD), allograft survival was significantly better in the tacrolimus group (HR 049 [95% CI 026-091], log-rank p=0021). Adverse events totalled 1516 in the ciclosporin group and 1459 in the tacrolimus group. The most frequent adverse events were infection (453 events), acute rejection (165 events), and anaemia (129 events) in the ciclosporin group, and infection (568 events), anaemia (108 events), and acute rejection (98 events) in the tacrolimus group. 112 (90%) patients in the ciclosporin group and 108 (87%) in the tacrolimus group had at least one serious adverse event. Interpretation Immunosuppression based on use of tacrolimus once per day significantly reduced the incidence of CLAD compared with use of ciclosporin twice per day. These findings support the use of tacrolimus as the first choice of calcineurin inhibitor after lung transplantation.
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| 8. |
- Edvardsson Rasmussen, Jesper, 1984-
(författare)
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Inner ear proteomics and barriers : Clinical and experimental findings
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hearing is important in many aspects of life, including communication, assessing one’s surroundings, entertainment and social interaction. Hearing loss is common and according to the Global Burden of Disease Study, 5% of the global population require hearing rehabilitation (1). Pharmacological treatment options are limited, so understanding cellular mechanisms in the damaged inner ear is crucial for developing novel therapies.In this thesis, the human inner ear proteome in patients with sporadic vestibular schwannoma (VS) and its association with hearing loss were investigated. Ototoxic effects induced by furosemide were also examined, focusing on inner ear barrier function, furosemide sensitive Na-K-Cl co-transporter 1 (NKCC1), Fetuin-A, linked to tumour-associated hearing loss, and Pigment epithelium-derived factor (PEDF), potentially important for blood-endolymph barrier integrity.Translabyrinthine surgery on 35 patients, 32 with VS and three with meningioma, provided samples from perilymph, endolymph, endolymphatic sac tissue, VS biopsies and cerebrospinal fluid (CSF) for proteome analysis. Effects of furosemide on the inner ear barriers were studied in mice using 9.4Tesla MRI, and in guinea pigs using immunohistochemistry and mRNA in situ hybridisation focusing on NKCC1, Fetuin-A, and PEDF.Proteomic analysis revealed consistent sets of proteins in perilymph (91/315) and endolymph (545/1211). The proteomes of perilymph and CSF exhibited specific differences, with proteins unique to each fluid, thereby emphasizing the distinct origin of perilymph separate from CSF. Fetuin-A was inversely related to tumour-associated hearing loss, while patients with severe to profound hearing loss exhibited upregulation of complement factor H-related protein 2 (CFHR2).Furosemide compromised the blood-endolymph barrier, allowing gadolinium contrast into scala media. It affected NKCC1 of type II fibrocytes coinciding with the onset of hearing loss following high-dose furosemide, suggesting early disruption in potassium ion recirculation. Fetuin-A and PEDF were identified in the cochlea at protein and mRNA level. Their staining intensity increased in various cochlear subsites 120 minutes after furosemide administration, indicating their involvement in the cochlear response to the effects of furosemide.In summary, this thesis uncovered significant inter-individual variability in both the perilymph and endolymph proteome, alongside a consistent subset of proteins. Further, associations between hearing loss and proteome changes suggest inflammation as a potential mechanism for hearing degradation caused by vestibular schwannomas. Experimentally, impact of furosemide on blood-inner ear barriers were visualised in vivo and type II fibrocytes were identified as potential initial targets for NKCC1 blockade. Fetuin-A and PEDF were confirmed in several cell types in the cochlea and may increase in response to very high furosemide doses.
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| 9. |
- Felldin, Marie, et al.
(författare)
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Initial Report From a Swedish High-volume Transplant Center After the First Wave of the COVID-19 Pandemic.
- 2021
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Ingår i: Transplantation. - 1534-6080. ; 105:1, s. 108-114
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Tidskriftsartikel (refereegranskat)abstract
- Solid organ transplant (SOT) recipients may be more vulnerable to coronavirus disease 2019 (COVID-19). Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the optimal management strategy for these patients is yet unclear.We present 53 SOT recipients (31 kidney transplant recipients, 8 liver transplant recipients, 5 heart transplant recipients, 5 lung transplant recipients, 3 liver-kidney transplant recipients, and 1 kidney-after-heart transplant recipient), transplanted at a Swedish high-volume transplant center and each diagnosed with COVID-19 between February 21, 2020 and June 22, 2020. Demographic, clinical, and treatment data were extracted from the electronic patient files.Patients reported fever (61%), cough (43%), diarrhea (31%), and upper respiratory symptoms (29%). The median age was 56 years, and 57% were male. According to severity, 55% had mild, 13% had moderate, 19% had severe, and 13% had critical disease. Thirty-seven patients (70%) were hospitalized, with 8 requiring intensive care. Thirteen of the 37 patients were initially managed as outpatients but later hospitalized. One patient received hydroxychloroquine, and no patients received antivirals. Antimetabolites and calcineurin inhibitors were held or reduced in two-thirds. Twenty-seven of 37 hospitalized patients (73%) received low-molecular-weight heparin. Five (13.5%) hospitalized patients died. Overall survival for the entire cohort was 90.5%. No rejection episodes were noted.Hospitalization, lowering of immunosuppression, and prophylactic anticoagulation were the most common therapeutic interventions for SOT recipients with COVID-19. A significant proportion of patients could be managed on an outpatient basis, while keeping a low threshold for admission. Mild and moderate disease forms seem to have a good outcome.
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