| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Smol, T., et al.
(författare)
-
MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype
- 2018
-
Ingår i: Neurogenetics. - : SPRINGER. - 1364-6745 .- 1364-6753. ; 19:2, s. 93-103
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Rice, Gillian I, et al.
(författare)
-
Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease.
- 2017
-
Ingår i: Neuropediatrics. - : Georg Thieme Verlag KG. - 1439-1899 .- 0174-304X. ; 48:3, s. 166-184
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi-Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64-25.71) compared with controls (median: 0.93, IQR: 0.57-1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context.
|
|
| 9. |
- Hüpers, Andre, et al.
(författare)
-
Release of mineral-bound water prior to subduction tied to shallow seismogenic slip off Sumatra
- 2017
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 356:6340, s. 841-844
-
Tidskriftsartikel (refereegranskat)abstract
- Plate-boundary fault rupture during the 2004 Sumatra-Andaman subduction earthquake extended closer to the trench than expected, increasing earthquake and tsunami size. International Ocean Discovery Program Expedition 362 sampled incoming sediments offshore northern Sumatra, revealing recent release of fresh water within the deep sediments. Thermal modeling links this freshening to amorphous silica dehydration driven by rapid burial-induced temperature increases in the past 9 million years. Complete dehydration of silicates is expected before plate subduction, contrasting with prevailing models for subduction seismogenesis calling for fluid production during subduction. Shallow slip offshore Sumatra appears driven by diagenetic strengthening of deeply buried fault-forming sediments, contrasting with weakening proposed for the shallow Tohoku-Oki 2011 rupture, but our results are applicable to other thickly sedimented subduction zones including those with limited earthquake records.
|
|
| 10. |
- McNeill, Lisa C., et al.
(författare)
-
Understanding Himalayan erosion and the significance of the Nicobar Fan
- 2017
-
Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 475, s. 134-142
-
Tidskriftsartikel (refereegranskat)abstract
- A holistic view of the Bengal-Nicobar Fan system requires sampling the full sedimentary section of the Nicobar Fan, which was achieved for the first time by International Ocean Discovery Program (IODP) Expedition 362 west of North Sumatra. We identified a distinct rise in sediment accumulation rate (SAR) beginning similar to 9.5 Ma and reaching 250-350 m/Myr in the 9.5-2 Ma interval, which equal or far exceed rates on the Bengal Fan at similar latitudes. This marked rise in SAR and a constant Himalayan-derived provenance necessitates a major restructuring of sediment routing in the Bengal-Nicobar submarine fan. This coincides with the inversion of the Eastern Himalayan Shillong Plateau and encroachment of the west-propagating Indo-Burmese wedge, which reduced continental accommodation space and increased sediment supply directly to the fan. Our results challenge a commonly held view that changes in sediment flux seen in the Bengal-Nicobar submarine fan were caused by discrete tectonic or climatic events acting on the Himalayan-Tibetan Plateau. Instead, an interplay of tectonic and climatic processes caused the fan system to develop by punctuated changes rather than gradual progradation.
|
|
| 11. |
- Schwartz, David A., et al.
(författare)
-
Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury
- 2022
-
Ingår i: Archives of Pathology & Laboratory Medicine. - : COLL AMER PATHOLOGISTS. - 0003-9985 .- 1543-2165. ; 146:6, s. 660-676
-
Tidskriftsartikel (refereegranskat)abstract
- Context.-Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. Objective.-To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design.-Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results.-Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions.-The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
|
|
| 12. |
- Schwartz, David A., et al.
(författare)
-
Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury : A Study of 68 Cases With SARS-CoV-2 Placentitis From 12 Countries
- 2022
-
Ingår i: Archives of Pathology & Laboratory Medicine. - : Archives of Pathology and Laboratory Medicine. - 0003-9985 .- 1543-2165. ; 146:6, s. 660-676
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear.Objective: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Design: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19.Results: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs.Conclusions: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.
|
|
| 13. |
- Colson, Abigail R., et al.
(författare)
-
Antimicrobial Resistance : Is Health Technology Assessment Part of the Solution or Part of the Problem?
- 2021
-
Ingår i: Value in Health. - : Elsevier. - 1098-3015 .- 1524-4733. ; 24:12, s. 1828-1834
-
Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance is a serious challenge to the success and sustainability of our healthcare systems. There has been increasing policy attention given to antimicrobial resistance in the last few years, and increased amounts of funding have been channeled into funding for research and development of antimicrobial agents. Nevertheless, manufacturers doubt whether there will be a market for new antimicrobial technologies sufficient to enable them to recoup their investment. Health technology assessment (HTA) has a critical role in creating confidence that if valuable technologies can be developed they will be reimbursed at a level that captures their true value. We identify 3 deficiencies of current HTA processes for appraising antimicrobial agents: a methods-centric approach rather than problem-centric approach for dealing with new challenges, a lack of tools for thinking about changing patterns of infection, and the absence of an approach to epidemiological risks. We argue that, to play their role more effectively, HTA agencies need to broaden their methodological tool kit, design and communicate their analysis to a wider set of users, and incorporate long-term policy goals, such as containing resistance, as part of their evaluation criteria alongside immediate health gains.
|
|
| 14. |
|
|
| 15. |
- Nypelö, Tiina, 1982, et al.
(författare)
-
Submicron hierarchy of cellulose nanofibril films with etherified hemicelluloses
- 2017
-
Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 177, s. 126-134
-
Tidskriftsartikel (refereegranskat)abstract
- The lack of simple differentiation of all-polysaccharide-film components in nanoscale hinders unveiling their structure-property dependency. Submicron hierarchy of films of cellulose nanofibrils (CNFs) and carbohydrate-based additives was revealed via visualization of the components by their differentiating adhesion to an Atomic Force Microscope (AFM) tip. The differentiation of the film components revealed that distribution of hydroxypropylated hemicellulose in the CNF matrix could be tuned by addition of a plasticizer. The hemicellulose hydroxypropylation degree of substitution (DS) was detected to be another parameter affecting the film structure due to the water-solubility depending on the DS. This was further verified via Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D). The translucent, self-standing films comprising CNFs, sorbitol and hydroxypropylated hemicellulose were tested for mechanical, optical and oxygen diffusion performance. The performance was linked to their structural evenness, which confirmed that the oxygen diffusion through the film is tremendously affected by the film nano hierarchy.
|
|
