| 1. |
- Lazaridis, Iosif, et al.
(författare)
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Ancient human genomes suggest three ancestral populations for present-day Europeans
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 409-
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Tidskriftsartikel (refereegranskat)abstract
- We sequenced the genomes of a similar to 7,000-year-old farmer from Germany and eight similar to 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes(1-4) with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians(3), who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had similar to 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
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| 2. |
- Liebi, Marianne, 1984, et al.
(författare)
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3D nanoscale analysis of bone healing around degrading Mg implants evaluated by X-ray scattering tensor tomography
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 134, s. 804-817
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Tidskriftsartikel (refereegranskat)abstract
- The nanostructural adaptation of bone is crucial for its biocompatibility with orthopedic implants. The bone nanostructure also determines its mechanical properties and performance. However, the bone's temporal and spatial nanoadaptation around degrading implants remains largely unknown. Here, we present insights into this important bone adaptation by applying scanning electron microscopy, elemental analysis, and small-angle X-ray scattering tensor tomography (SASTT). We extend the novel SASTT reconstruction method and provide a 3D scattering reciprocal space map per voxel of the sample's volume. From this reconstruction, parameters such as the thickness of the bone mineral particles are quantified, which provide additional information on nanostructural adaptation of bone during healing. We selected a rat femoral bone and a degrading ZX10 magnesium implant as model system, and investigated it over the course of 18 months, using a sham as control. We observe that the bone's nanostructural adaptation starts with an initially fast interfacial bone growth close to the implant, which spreads by a re-orientation of the nanostructure in the bone volume around the implant, and is consolidated in the later degradation stages. These observations reveal the complex bulk bone-implant interactions and enable future research on the related biomechanical bone responses. Statement of significance: Traumatic bone injuries are among the most frequent causes of surgical treatment, and often require the placement of an implant. The ideal implant supports and induces bone formation, while being mechanically and chemically adapted to the bone structure, ensuring a gradual load transfer. While magnesium implants fulfill these requirements, the nanostructural changes during bone healing and implant degradation remain not completely elucidated. Here, we unveil these processes in rat femoral bones with ZX10 magnesium implants and show different stages of bone healing in such a model system.
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| 3. |
- Shapiro, Amy D., et al.
(författare)
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Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:11, s. 3422-3432
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Tidskriftsartikel (refereegranskat)abstract
- Despite current therapies, there remains an unmet need for treatment for patients with hemophilia. The main parts of two phase 2 trials established clinical proof-of-concept for once-daily, subcutaneous concizumab prophylaxis in patients with hemophilia A/B with inhibitors (HAwI/HBwI; explorer4) and severe hemophilia A without inhibitors (HA; explorer5). Here, we present results from extension parts of these trials, included to evaluate longer term safety and efficacy. Both trials included main ($24 weeks) and extension (52-102 weeks) parts, with patients receiving concizumab 0.15 mg/kg with potential dose escalation to concizumab 0.20 or 0.25 mg/kg if they experienced $3 treated spontaneous bleeding episodes within 12 weeks. Endpoints included annualized bleeding rate (ABR), adverse events (AEs), and occurrence of antidrug antibodies. Thromboembolic events were AEs of special interest. Thirty-six patients with HA, 15 with HAwI, and 10 with HBwI were exposed to concizumab. Estimated ABRs during the main 1 extension parts at last dose level were 4.8 (95% confidence interval [CI], 3.2-7.2) and 6.4 (95% CI, 4.1-9.9) in explorer4 and explorer5, respectively (spontaneous ABRs were 1.8 [95% CI, 1.2-2.6] and 2.1 [95% CI, 1.3-3.3]). Most AEs were mild, with no deaths, events leading to withdrawal, or thromboembolic events. Anti-drug antibodies developed in 25% of patients and were low titer and transient, with no observed clinical effect in most cases. Results of the main 1 extension parts of these trials were consistent with results of the main parts. Ongoing phase 3 trials will further evaluate concizumab as a once-daily, subcutaneous treatment across hemophilia subtypes.
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| 4. |
- Weinhofer, Isabelle, et al.
(författare)
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Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy.
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
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