| 1. |
- Hansmann, G., et al.
(författare)
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Selexipag for the treatment of children with pulmonary arterial hypertension: First multicenter experience in drug safety and efficacy
- 2020
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 39:7, s. 695-706
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) investigated the safety and efficacy of add-on selexipag, an oral prostacyclin receptor agonist approved for pulmonary arterial hypertension (PAH) in adults, in the largest, exploratory pediatric cohort to date. METHODS: This is a prospective observational study of 15 consecutive children with PAH, treated with oral add-on selexipag at 3 centers. Most patients underwent cardiac catheterizations at baseline and median of 8 months follow-up. All patients had clinical, echocardiographic, and N-terminal pro b-type natriuretic peptide studies, including the EPPVDN pediatric pulmonary hypertension (PH) risk score. RESULTS: There was no death during the use of selexipag. Two of 15 patients ultimately underwent lung transplantation. One patient with heritable PAH died on intravenous treprostinil (off selexipag). The mean right atrial pressure, the ratio of pulmonary arterial pressure (PAP) to systemic arterial pressure (SAP) (mean PAP/mean SAP, diastolic PAP/diastolic SAP: -17%), and transpulmonary pressure gradients (TPG) (mean TPG: -17%; p < 0.01; diastolic TPG: -6 mm Hg; p < 0.05) were improved after the therapy (n = 10). Selexipag therapy was associated with a better right ventricular systolic function (tricuspid annular plane systolic excursion: +14.5%; p < 0.01) and functional class. Improvement was seen in non-invasive and combined invasive/non-invasive PH risk scores (lower risk: +18%-22%, higher risk: -35%-37%; p < 0.05). Overall, the efficacy of selexipag was variable, often with a better response in less sick patients. CONCLUSIONS: Oral selexipag use in children with PAH is well tolerated and safe when closely monitored. Add-on selexipag therapy improved several outcome-relevant variables in about 50% of patients and prevented disease progression in additional 27% of patients. The novel EPPVDN pediatric PH risk score indicated these drug effects properly, can be useful in clinical follow-up, and should be validated in larger prospective studies. (C) 2020 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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| 2. |
- Hanson, Britt, et al.
(författare)
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Non-uniform dystrophin re-expression after CRISPR-mediated exon excision in the dystrophin/utrophin double-knockout mouse model of DMD
- 2022
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Ingår i: Molecular Therapy Nucleic Acids. - : Elsevier. - 2162-2531. ; 30, s. 379-397
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Tidskriftsartikel (refereegranskat)abstract
- Duchenne muscular dystrophy (DMD) is the most prevalent inherited myopathy affecting children, caused by genetic loss of the gene encoding the dystrophin protein. Here we have investigated the use of the Staphylococcus aureus CRISPR-Cas9 system and a double-cut strategy, delivered using a pair of adeno-associated virus serotype 9 (AAV9) vectors, for dystrophin restoration in the severely affected dystrophin/utrophin double-knockout (dKO) mouse. Single guide RNAs were designed to excise Dmd exon 23, with flanking intronic regions repaired by non-homologous end joining. Exon 23 deletion was confirmed at the DNA level by PCR and Sanger sequencing, and at the RNA level by RT-qPCR. Restoration of dystrophin protein expression was demonstrated by western blot and immunofluorescence staining in mice treated via either intraperitoneal or intravenous routes of delivery. Dystrophin restoration was most effective in the diaphragm, where a maximum of 5.7% of wild-type dystrophin expression was observed. CRISPR treatment was insufficient to extend lifespan in the dKO mouse, and dystrophin was expressed in a within-fiber patchy manner in skeletal muscle tissues. Further analysis revealed a plethora of non-productive DNA repair events, including AAV genome integration at the CRISPR cut sites. This study highlights potential challenges for the successful development of CRISPR therapies in the context of DMD.
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| 3. |
- Hansson, Lena, et al.
(författare)
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Att utgå från frågor och situationer i förskolans vardag: Vilket naturvetenskapligt innehåll kan det leda till? : Starting from questions and everyday situations in preschool: What kind of science content could that lead to?
- 2014
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Ingår i: NorDiNa : Nordic Studies in Science Education. - 1504-4556. ; 10:1, s. 77-89
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Tidskriftsartikel (refereegranskat)abstract
- Identifying and building on children's questions and everyday situations is often discussed as a basis for science learning in preschool. With a starting point in such questions and situations, children should be given the opportunity to investigate and search for answers. What questions and situations do preschool teachers identify as possible bases for science learning? What science content is present? To what extent are the questions possible to investigate for children and preschool teachers through experiments and observations or theoretical studies? The paper presents children's questions and everyday situations that might form the basis for science learning, as identified by preschool teachers taking part in a science in-service training course. Based on a content analysis, we discuss possibilities and difficulties that preschool teachers may face in their practice when they try to use these questions and situations as a basis for science learning.
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| 4. |
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| 5. |
- Davies, Jonathan R., et al.
(författare)
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High-resolution crystal structures of the botulinum neurotoxin binding domains from subtypes A5 and A6
- 2020
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Ingår i: FEBS Open Bio. - : Wiley. - 2211-5463. ; 10:8, s. 1474-1481
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Tidskriftsartikel (refereegranskat)abstract
- Clostridium botulinumneurotoxins (BoNTs) cause flaccid paralysis through inhibition of acetylcholine release from motor neurons; however, at tiny doses, this property is exploited for use as a therapeutic. Each member of the BoNT family of proteins consists of three distinct domains: a binding domain that targets neuronal cell membranes (H-C), a translocation domain (H-N) and a catalytic domain (LC). Here, we present high-resolution crystal structures of the binding domains of BoNT subtypes/A5 (H-C/A5) and/A6 (H-C/A6). These structures show that the core fold identified in other subtypes is maintained, but with subtle differences at the expected receptor-binding sites.
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| 6. |
- Engström, Susanne, 1962-, et al.
(författare)
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Kursändring – svenska som andraspråk inte längre ett hinder inom KPU:n
- 2020
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Konferensbidrag (refereegranskat)abstract
- Efter ett antal omgångar av kompletterande pedagogisk utbildning (KPU) ser vi hur studenter med svenska som andraspråk generellt har större svårigheter att lyckas genomföra lärarutbildningen inom avsedd tidsram, jämfört med studenter med svenska som förstaspråk. Problemen handlar inte om ämneskunskaper utan om förmågor inom akademiskt skrivande och tillgodogörande av ordrik akademisk litteratur. Av tradition förväntas goda kunskaper i svenska inom lärarutbildningar liksom inom många andra akademiska utbildningar. Lärarutbildningen innefattar dessutom strukturer i form av seminarier, reflekterande skrivuppgifter, hemtentamina etc., metoder som hos vissa studenter kan upplevas främmande och ovana.Projektets syfte är att utveckla insikter hos ett arbetslag inom högre utbildning, genom fortbildning i seminarieform, för att åstadkomma förändringar inom kurser så att bland andra studenter med svenska som andraspråk i högre grad får förutsättningar att nå godkänd nivå. Arbetslaget arbetar till största delen inom ramen för lärarutbildningar varför projektet till sitt innehåll bland annat tar utgångspunkt i Bigestans (2015; 2018) studier av ULV-utbildning men även i Bayatis (2014) forskning om synen på studenters språkhantering och rasistiska föreställningar som framträder inom lärarutbildningar.Projektets upplägg med seminarier baseras på forskning om kollektivt lärande och lärande i social interaktion inom arbetsorganisationer samt med inspiration från Simons & Ruijters (2001) och deras tredelade modell för arbetsrelaterat lärande. Vi låter deltagarna ta utgångspunkt i erfarenheter från praktiken (den egna lärarutbildningen), från relevant forskning (föreläsningar och litteratur) och bidra till den gemensamma organisationen genom att vidareutveckla pågående kurser. Intentionen är att seminariedeltagarna tillsammans kan skapa ny kunskap, att ett kollektivt lärande utvecklas genom att individuella perspektiv överskrids.Fortbildningsprojektet består av en inledande föreläsning (Bigestans) och tre uppföljande seminarier med följande teman: kursinnehåll, examinationsmoment och konkreta undervisningssituationer. Inför seminarierna läser deltagarna litteratur, under seminarierna diskuteras frågeställningar formulerade med syfte att utmana och stimulera reflekterande. Dessutom behandlas konkreta frågeställningar kopplade till de kurser som deltagarna valt att utveckla. Vid respektive träff samlas exit-tickets in med syfte att få inblick i deltagares reflektioner och slutsatser.107Efter det sista seminariet fyller deltagarna i en enkät med syfte att utvärdera projektet. De kurser som utvecklats under seminarieserien analyseras, med syftet att se hur innehåll, examinationsformer och litteratur förändrats. Resultatet visar hur deltagarna utvecklar nya lärdomar om och begrepp kopplade till situationen för studenter med svenska som andraspråk och hur de erhåller nya insikter om hur kurser kan genomföras. Ett av resultaten visar sig vara behovet av ytterligare fortbildning inom rollen som handledare inom självständiga arbeten.
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| 7. |
- Hansman, Reuben
(författare)
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Constraining the Uplift History of the Al Hajar Mountains, Oman
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mountain building is the result of large compressional forces in the Earth’s crust where two tectonic plates collide. This is why mountains only form at plate boundaries, of which the Al Hajar Mountains in Oman and the United Arab Emirates is thought to be an example of. These mountains have formed near the Arabian–Eurasian convergent plate boundary where continental collision began by 30 Ma at the earliest. However, the time at which the Al Hajar Mountains developed is less well constrained. Therefore, the timing of both the growth of the mountains, and the Arabian–Eurasian collision, needs to be understood first to be able to identify a correlation. Following this a causal link can be determined. Here we show, using apatite fission track and apatite and zircon (U-Th)/He dating, as well as stratigraphic constraints, that the Al Hajar Mountains were uplifted from 45 Ma to 15 Ma. We found that the mountains developed 33 Myr to 10 Myr earlier than the Arabian–Eurasian plate collision. Furthermore, the plate collision is ongoing, but the Al Hajar Mountains are tectonically quiescent. Our results indicate that the uplift of the Al Hajar Mountains cannot be correlated in time to the Arabian–Eurasian collision. Therefore the Al Hajar Mountains are not the result of this converging plate boundary.
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| 8. |
- Hansman, Reuben J., et al.
(författare)
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Absolute ages of multiple generations of brittle structures by U-Pb dating of calcite
- 2018
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Ingår i: Geology. - 0091-7613 .- 1943-2682. ; 46:3, s. 207-210
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Tidskriftsartikel (refereegranskat)abstract
- Direct dating of brittle structures is challenging, especially absolute dating of diagenesis followed by a series of superimposed brittle deformation events. We report 22 calcite U-Pb ages from tectonites and carbonate host rocks that date 3 diagenetic and 6 brittle deformation events. Results show that U-Pb dating of calcite fibers from these structures is compatible with overprinting relationships. Ages indicate that diagenesis occurred between 147 +/- 6 Ma and 103 +/- 34 Ma, and was followed by top-to-the-south, layer-parallel shearing due to ophiolite obduction at 84 +/- 5 Ma (2 sigma errors). Sheared top-to-the- northeast, layer-parallel veins were dated as 64 +/- 4 Ma and are interpreted to have developed during postobduction exhumation. After this event, a series of strike-slip structures, which crosscut and reactivated older faults due to northwest-southeast horizontal shortening, were dated as 55 +/- 22 Ma and 43 +/- 6 Ma. Eight ages from strike-slip faults and thrusts resulting from northeast-southwest shortening range from 40.6 +/- 0.5 Ma to 16.1 +/- 0.2 Ma. The youngest ages are from minor overprinting fibers ranging in age between 7.5 +/- 0.9 Ma and 1.6 +/- 0.6 Ma. Our results show that U-Pb dating of calcite fibers can be successfully used to constrain a complicated succession of brittle deformation structures that encompasses two orogenies and an intervening extension period.
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| 9. |
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