| 1. |
- Furberg, Helena, et al.
(författare)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Tidskriftsartikel (refereegranskat)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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| 2. |
- Abbot, Stewart, et al.
(författare)
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Report of the international conference on manufacturing and testing of pluripotent stem cells
- 2018
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Ingår i: Biologicals. - : Elsevier BV. - 1045-1056. ; 56, s. 67-83
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Sessions included an overview of past cell therapy (CT) conferences sponsored by the International Alliance for Biological Standardization (IABS). The sessions highlighted challenges in the field of human pluripotent stem cells (hPSCs) and also addressed specific points on manufacturing, bioanalytics and comparability, tumorigenicity testing, storage, and shipping. Panel discussions complemented the presentations. The conference concluded that a range of new standardization groups is emerging that could help the field, but ways must be found to ensure that these efforts are coordinated. In addition, there are opportunities for regulatory convergence starting with a gap analysis of existing guidelines to determine what might be missing and what issues might be creating divergence. More specific global regulatory guidance, preferably from WHO, would be welcome. IABS and the California Institute for Regenerative Medicine (CIRM) will explore with stakeholders the development of a practical and innovative road map to support early CT product (CTP) developers.
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| 3. |
- Figtree, Gemma A., et al.
(författare)
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Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors JACC State-of-the-Art Review
- 2023
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 82:13, s. 1343-1359
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Forskningsöversikt (refereegranskat)abstract
- Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed. (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. 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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| 4. |
- Adrian, Juliane, et al.
(författare)
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A Glossary for Research on Human Crowd Dynamics
- 2019
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Ingår i: Collective Dynamics. - 2366-8539. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- This article presents a glossary of terms that are frequently used in research onhuman crowds. This topic is inherently multidisciplinary as it includes work in and across computer science, engineering, mathematics, physics, psychology and social science, for example. We do not view the glossary presented here as a collection of finalised and formal definitions. Instead, we suggest it is a snapshot of current views and the starting point of an ongoing process that we hope will be useful in providing some guidance on the use of terminology to develop a mutual understanding across disciplines. The glossary was developed collaboratively during a multidisciplinary meeting. We deliberately allowseveral definitions of terms, to reflect the confluence of disciplines in the field. This also reflects the fact not all contributors necessarily agree with all definitions in this glossary.
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| 5. |
- Belcher, Stephen E., et al.
(författare)
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A global perspective on Langmuir turbulence in the ocean surface boundary layer
- 2012
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 39, s. L18605-
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Tidskriftsartikel (refereegranskat)abstract
- The turbulent mixing in thin ocean surface boundary layers (OSBL), which occupy the upper 100 m or so of the ocean, control the exchange of heat and trace gases between the atmosphere and ocean. Here we show that current parameterizations of this turbulent mixing lead to systematic and substantial errors in the depth of the OSBL in global climate models, which then leads to biases in sea surface temperature. One reason, we argue, is that current parameterizations are missing key surface-wave processes that force Langmuir turbulence that deepens the OSBL more rapidly than steady wind forcing. Scaling arguments are presented to identify two dimensionless parameters that measure the importance of wave forcing against wind forcing, and against buoyancy forcing. A global perspective on the occurrence of wave-forced turbulence is developed using re-analysis data to compute these parameters globally. The diagnostic study developed here suggests that turbulent energy available for mixing the OSBL is under-estimated without forcing by surface waves. Wave-forcing and hence Langmuir turbulence could be important over wide areas of the ocean and in all seasons in the Southern Ocean. We conclude that surface-wave-forced Langmuir turbulence is an important process in the OSBL that requires parameterization. Citation: Belcher, S. E., et al. (2012), A global perspective on Langmuir turbulence in the ocean surface boundary layer, Geophys. Res. Lett., 39, L18605, doi: 10.1029/2012GL052932.
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| 6. |
- Clark, Peter, et al.
(författare)
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LSQ13ddu : a rapidly evolving stripped-envelope supernova with early circumstellar interaction signatures
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 492:2, s. 2208-2228
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the rapidly evolving and unusual supernova LSQ13ddu, discovered by the La Silla-QUEST survey. LSQ13ddu displayed a rapid rise of just 4.8 +/- 0.9 d to reach a peak brightness of -19.70 +/- 0.02 mag in the LSQgr band. Early spectra of LSQ13ddu showed the presence of weak and narrow He I features arising from interaction with circumstellar material (CSM). These interaction signatures weakened quickly, with broad features consistent with those seen in stripped-envelope SNe becoming dominant around two weeks after maximum. The narrow He I velocities are consistent with the wind velocities of luminous blue variables but its spectra lack the typically seen hydrogen features. The fast and bright early light curve is inconsistent with radioactive Ni-56 powering but can be explained through a combination of CSM interaction and an underlying Ni-56 decay component that dominates the later time behaviour of LSQ13ddu. Based on the strength of the underlying broad features, LSQ13ddu appears deficient in He compared to standard SNe Ib.
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| 7. |
- Clark, Peter, et al.
(författare)
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Probing the progenitors of Type Ia supernovae using circumstellar material interaction signatures
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 507:3, s. 4367-4388
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Tidskriftsartikel (refereegranskat)abstract
- This work aims to study different probes of Type Ia supernova (SN Ia) progenitors that have been suggested to be linked to the presence of circumstellar material (CSM). In particular, we have investigated, for the first time, the link between narrow blueshifted Na I D absorption profiles and the presence and strength of the broad high-velocity Ca II near-infrared triplet absorption features seen in SNe la around maximum light. With the probes exploring different distances from the SN; Na I D > 10(17) cm, high-velocity Ca TT features < 10(15) cm. For this, we have used a new intermediate-resolution X-shooter spectral sample of 15 SNe Ia. We do not identify a link between these two probes, implying either that, one (or both) is not physically related to the presence of CSM or that the occurrence of CSM at the distance explored by one probe is not linked to its presence at the distance probed by the other. However, the previously identified statistical excess in the presence of blueshifted (over redshifted) Na I D absorption is confirmed in this sample at high significance and is found to be stronger in SNe Ia hosted by late-type galaxies. This excess is difficult to explain as being from an interstellar-medium origin as has been suggested by some recent modelling, as such an origin is not expected to show a bias for blueshifted absorption. However, a circumstellar origin for these features also appears unsatisfactory based on our new results, given the lack of link between the two probes of CSM investigated.
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| 8. |
- Cooper, Declan L.M., et al.
(författare)
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Consistent patterns of common species across tropical tree communities
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 728-734
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Tidskriftsartikel (refereegranskat)abstract
- Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations 1–6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories 7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.
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| 9. |
- Dittrich, Christian, et al.
(författare)
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ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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| 10. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 11. |
- Friedman, James S., et al.
(författare)
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Mutations in a BTB-Kelch Protein, KLHL7, Cause Autosomal-Dominant Retinitis Pigmentosa
- 2009
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 84:6, s. 792-800
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Tidskriftsartikel (refereegranskat)abstract
- Retinitis pigmentosa (RP) refers to a genetically heterogeneous group of progressive neurodegenerative diseases that result in dysfunction and/or death of rod and cone photoreceptors in the retina. So far, 18 genes have been identified for autosomal-dominant (ad) RP. Here, we describe an adRP locus (RP42) at chromosome 7p15 through linkage analysis in a six-generation Scandinavian family and identify a disease-causing mutation, c.449G -> A (p.S150N), in exon 6 of the KLHL7 gene. Mutation screening of KLHL7 in 502 retinopathy probands has revealed three different missense mutations in six independent families. KLHL7 is widely expressed, including expression in rod photoreceptors, and encodes a 75 kDa protein of the BTB-Kelch Subfamily within the BTB superfamily. BTB-Kelch proteins have been implicated in ubiquitination through Cullin E3 ligases. Notably, all three putative disease-causing KLHL7 mutations are within a conserved BACK domain; homology modeling suggests that mutant amino acid side chains can potentially fill the cleft between two helices, thereby affecting the ubiquitination complexes. Mutations in an identical region of another BTB-Kelch protein, gigaxonin, have previously been associated with giant axonal neuropathy. Our studies suggest an additional role of the ubiquitin-proteasome protein-degradation pathway in maintaining neuronal health and in disease.
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| 12. |
- Helbig, Manuel, et al.
(författare)
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Integrating continuous atmospheric boundary layer and tower-based flux measurements to advance understanding of land-atmosphere interactions
- 2021
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Ingår i: Agricultural and Forest Meteorology. - : Elsevier BV. - 0168-1923. ; 307
-
Forskningsöversikt (refereegranskat)abstract
- The atmospheric boundary layer mediates the exchange of energy, matter, and momentum between the land surface and the free troposphere, integrating a range of physical, chemical, and biological processes and is defined as the lowest layer of the atmosphere (ranging from a few meters to 3 km). In this review, we investigate how continuous, automated observations of the atmospheric boundary layer can enhance the scientific value of co-located eddy covariance measurements of land-atmosphere fluxes of carbon, water, and energy, as are being made at FLUXNET sites worldwide. We highlight four key opportunities to integrate tower-based flux measurements with continuous, long-term atmospheric boundary layer measurements: (1) to interpret surface flux and atmospheric boundary layer exchange dynamics and feedbacks at flux tower sites, (2) to support flux footprint modelling, the interpretation of surface fluxes in heterogeneous and mountainous terrain, and quality control of eddy covariance flux measurements, (3) to support regional-scale modeling and upscaling of surface fluxes to continental scales, and (4) to quantify land-atmosphere coupling and validate its representation in Earth system models. Adding a suite of atmospheric boundary layer measurements to eddy covariance flux tower sites, and supporting the sharing of these data to tower networks, would allow the Earth science community to address new emerging research questions, better interpret ongoing flux tower measurements, and would present novel opportunities for collaborations between FLUXNET scientists and atmospheric and remote sensing scientists.
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| 13. |
- Hosseinzadeh, Griffin, et al.
(författare)
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Type Ibn Supernovae Show Photometric Homogeneity and Spectral Diversity at Maximum Light
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 836:2
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Tidskriftsartikel (refereegranskat)abstract
- Type Ibn supernovae (SNe) are a small yet intriguing class of explosions whose spectra are characterized by low-velocity helium emission lines with little to no evidence for hydrogen. The prevailing theory has been that these are the core-collapse explosions of very massive stars embedded in helium-rich circumstellar material (CSM). We report optical observations of six new SNe Ibn: PTF11rfh, PTF12ldy, iPTF14aki, iPTF15ul, SN 2015G, and iPTF15akq. This brings the sample size of such objects in the literature to 22. We also report new data, including a near-infrared spectrum, on the Type Ibn SN 2015U. In order to characterize the class as a whole, we analyze the photometric and spectroscopic properties of the full Type Ibn sample. We find that, despite the expectation that CSM interaction would generate a heterogeneous set of light curves, as seen in SNe IIn, most Type Ibn light curves are quite similar in shape, declining at rates around 0.1 mag day(-1) during the first month after maximum light, with a few significant exceptions. Early spectra of SNe Ibn come in at least two varieties, one that shows narrow P Cygni lines and another dominated by broader emission lines, both around maximum light, which may be an indication of differences in the state of the progenitor system at the time of explosion. Alternatively, the spectral diversity could arise from viewing-angle effects or merely from a lack of early spectroscopic coverage. Together, the relative light curve homogeneity and narrow spectral features suggest that the CSM consists of a spatially confined shell of helium surrounded by a less dense extended wind.
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| 14. |
- Köhn, Linda, et al.
(författare)
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Breakpoint characterization of a novel approximately 59 kb genomic deletion on 19q13.42 in autosomal-dominant retinitis pigmentosa with incomplete penetrance.
- 2009
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 17:5, s. 651-655
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify and characterize the underlying molecular mechanisms in autosomal-dominant retinitis pigmentosa (adRP) with incomplete penetrance in two Swedish families. An extended genealogical study and haplotype analysis indicated a common origin. Mutation identification was carried out by multiplex ligation-dependent probe amplification (MLPA) and sequencing. Clinical examinations of adRP families including electroretinography revealed obligate gene carriers without abnormalities, which indicated incomplete penetrance. Linkage analysis resulted in mapping of the disease locus to 19q13.42 (RP11). Sequence analyses did not reveal any mutations segregating with the disease in eight genes including PRPF31. Subsequent MLPA detected a large genomic deletion of 11 exons in the PRPF31 gene and, additionally, three genes upstream of the PRPF31. Breakpoints occurred in intron 11 of PRPF31 and in LOC441864, 'similar to osteoclast-associated receptor isoform 5.' An almost 59 kb deletion segregated with the disease in all affected individuals and was present in several asymptomatic family members but not in 20 simplex RP cases or 94 healthy controls tested by allele-specific PCR. A large genomic deletion resulting in almost entire loss of PRPF31 and three additional genes identified as the cause of adRP in two Swedish families provide an additional evidence that mechanism of the disease evolvement is haploinsufficiency. Identification of the deletion breakpoints allowed development of a simple tool for molecular testing of this genetic subtype of adRP.
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| 15. |
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| 16. |
- Köhn, Linda, et al.
(författare)
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PITPNM3 is an uncommon cause of cone and cone-rod dystrophies.
- 2010
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Ingår i: Ophthalmic Genetics. - : Informa Healthcare. - 1381-6810 .- 1744-5094. ; 31:3, s. 139-140
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Tidskriftsartikel (refereegranskat)abstract
- The first mutation in PITPNM3, a human homologue of the Drosophila retinal degeneration (rdgB not not) gene was reported in two large Swedish families with autosomal dominant cone dystrophy. To establish the global impact that PITPNM3 has on retinal degenerations we screened 163 patients from Denmark, Germany, the UK, and USA. Four sequence variants, two missence mutations and two intronic changes were identified in the screen. Thus, mutations in PITPNM3 do not appear to be a major cause of cone or cone-rod dystrophy.
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| 17. |
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| 18. |
- Müller-Bravo, Tomás E., et al.
(författare)
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The low-luminosity Type II SN2016aqf : a well-monitored spectral evolution of the Ni/Fe abundance ratio
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 497:1, s. 361-377
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Tidskriftsartikel (refereegranskat)abstract
- Low-luminosity Type II supernovae (LL SNe II) make up the low explosion energy end of core-collapse SNe, but their study and physical understanding remain limited. We present SN 2016aqf, an LL SN II with extensive spectral and photometric coverage. We measure a V-band peak magnitude of −14.58 mag, a plateau duration of ∼100 d, and an inferred 56Ni mass of 0.008 ± 0.002 M⊙. The peak bolometric luminosity, Lbol ≈ 1041.4 erg s−1, and its spectral evolution are typical of other SNe in the class. Using our late-time spectra, we measure the [O i] λλ6300, 6364 lines, which we compare against SN II spectral synthesis models to constrain the progenitor zero-age main-sequence mass. We find this to be 12 ± 3 M⊙. Our extensive late-time spectral coverage of the [Fe ii] λ7155 and [Ni ii] λ7378 lines permits a measurement of the Ni/Fe abundance ratio, a parameter sensitive to the inner progenitor structure and explosion mechanism dynamics. We measure a constant abundance ratio evolution of 0.081+0.009−0.010 and argue that the best epochs to measure the ratio are at ∼200–300 d after explosion. We place this measurement in the context of a large sample of SNe II and compare against various physical, light-curve, and spectral parameters, in search of trends that might allow indirect ways of constraining this ratio. We do not find correlations predicted by theoretical models; however, this may be the result of the exact choice of parameters and explosion mechanism in the models, the simplicity of them, and/or primordial contamination in the measured abundance ratio.
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| 19. |
- Murawski, Christopher D., et al.
(författare)
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Terminology for osteochondral lesions of the ankle: proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
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Ingår i: JOURNAL OF ISAKOS JOINT DISORDERS & ORTHOPAEDIC SPORTS MEDICINE. - : Elsevier BV. - 2059-7754 .- 2059-7762. ; 7:2, s. 62-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "terminology for osteochondral lesions of the ankle" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each state-ment was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%-74%; strong consensus, 75%-99%; unanimous, 100%. Results: A total of 11 statements on terminology and classification reached consensus during the 2019 Interna-tional Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. Conclusions: This international consensus derived from leaders in the field will assist clinicians with the appro-priate terminology for osteochondral lesions of the ankle.
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| 20. |
- Opendak, Maya, et al.
(författare)
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Neurobiology of maternal regulation of infant fear : the role of mesolimbic dopamine and its disruption by maltreatment
- 2019
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Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 44:7, s. 1247-1257
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Tidskriftsartikel (refereegranskat)abstract
- Child development research highlights caregiver regulation of infant physiology and behavior as a key feature of early life attachment, although mechanisms for maternal control of infant neural circuits remain elusive. Here we explored the neurobiology of maternal regulation of infant fear using neural network and molecular levels of analysis in a rodent model. Previous research has shown maternal suppression of amygdala-dependent fear learning during a sensitive period. Here we characterize changes in neural networks engaged during maternal regulation and the transition to infant self-regulation. Metabolic mapping of 2deoxyglucose uptake during odor-shock conditioning in postnatal day (PN) 14 rat pups showed that maternal presence blocked fear learning, disengaged mesolimbic circuitry, basolateral amygdala (BLA), and plasticity-related AMPA receptor subunit trafficking. At PN18, when maternal presence only socially buffers threat learning (similar to social modulation in adults), maternal presence failed to disengage the mesolimbic dopaminergic system, and failed to disengage both the BLA and plasticity-related AMPA receptor subunit trafficking. Further, maternal presence failed to block threat learning at PN14 pups following abuse, and mesolimbic dopamine engagement and AMPA were not significantly altered by maternal presence-analogous to compromised maternal regulation of children in abusive relationships. Our results highlight three key features of maternal regulation: (1) maternal presence blocks fear learning and amygdala plasticity through age-dependent suppression of amygdala AMPA receptor subunit trafficking, (2) maternal presence suppresses engagement of brain regions within the mesolimbic dopamine circuit, and (3) early-life abuse compromises network and molecular biomarkers of maternal regulation, suggesting reduced social scaffolding of the brain.
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| 21. |
- Robinson-Drummer, Patrese A., et al.
(författare)
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Infant Trauma Alters Social Buffering of Threat Learning : Emerging Role of Prefrontal Cortex in Preadolescence
- 2019
-
Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media SA. - 1662-5153. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Within the infant-caregiver attachment system, the primary caregiver holds potent reward value to the infant, exhibited by infants' strong preference for approach responses and proximity-seeking towards the mother. A less well-understood feature of the attachment figure is the caregiver's ability to reduce fear via social buffering, commonly associated with the notion of a safe haven in the developmental literature. Evidence suggests this infant system overlaps with the neural network supporting social buffering (attenuation) of fear in the adults of many species, a network known to involve the prefrontal cortex (PFC). Here, using odor-shock conditioning in young developing rats, we assessed when the infant system transitions to the adult-like PFC-dependent social buffering of threat system. Rat pups were odor-shock conditioned (0.55 mA-0.6 mA) at either postnatal day (PN18; dependent on mother) or 28 (newly independent, weaned at PN23). Within each age group, the mother was present or absent during conditioning, with PFC assessment following acquisition using(14)C 2-DG autoradiography and cue testing the following day. Since the human literature suggests poor attachment attenuates the mother's ability to socially buffer the infants, half of the pups at each age were reared with an abusive mother from PN8-12. The results showed that for typical control rearing, the mother attenuated fear in both PN18 and PN28 pups, although the PFC [infralimbic (IL) and ventral prelimbic (vPL) cortices] was only engaged at PN28. Abuse rearing completely disrupted social buffering of pups by the mother at PN18. The results from PN28 pups showed that while the mother modulated learning in both control and abuse-reared pups, the behavioral and PFC effects were attenuated after maltreatment. Our data suggest that pups transition to the adult-like PFC social support circuit after independence from the mother (PN28), and this circuit remains functional after early-life trauma, although its effectiveness appears reduced. This is in sharp contrast to the effects of early life trauma during infancy, where social buffering of the infant is more robustly impacted. We suggest that the infant social buffering circuit is disengaged by early-life trauma, while the adolescent PFC-dependent social buffering circuit may use a safety signal with unreliable safety value.
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| 22. |
- Rubin, Adam, et al.
(författare)
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TYPE II SUPERNOVA ENERGETICS AND COMPARISON OF LIGHT CURVES TO SHOCK-COOLING MODELS
- 2016
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 820:1
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Tidskriftsartikel (refereegranskat)abstract
- During the first few days after explosion, Type II supernovae (SNe) are dominated by relatively simple physics. Theoretical predictions regarding early-time SN light curves in the ultraviolet (UV) and optical bands are thus quite robust. We present, for the first time, a sample of 57 R-band SN II light curves that are well-monitored during their rise, with > 5 detections during the first 10 days after discovery, and a well-constrained time of explosion to within 1-3 days. We show that the energy per unit mass (E/M) can be deduced to roughly a factor of five by comparing early-time optical data to the 2011 model of Rabinak & Waxman, while the progenitor radius cannot be determined based on R-band data alone. We find that SN II explosion energies span a range of E/M = (0.2-20) x 10(51) erg/(10 M-circle dot), and have a mean energy per unit mass of < E/M > = 0.85 x 10(51) erg/(10 M-circle dot), corrected for Malmquist bias. Assuming a small spread in progenitor masses, this indicates a large intrinsic diversity in explosion energy. Moreover, E/M is positively correlated with the amount of Ni-56 produced in the explosion, as predicted by some recent models of core-collapse SNe. We further present several empirical correlations. The peak magnitude is correlated with the decline rate (Delta m(15)), the decline rate is weakly correlated with the rise time, and the rise time is not significantly correlated with the peak magnitude. Faster declining SNe are more luminous and have longer rise times. This limits the possible power sources for such events.
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| 23. |
- Schneiders, Anthony G., et al.
(författare)
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The effect of footwear and sports-surface on dynamic neurological screening for sport-related concussion
- 2010
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Ingår i: Journal of Science and Medicine in Sport. - : Elsevier BV. - 1440-2440 .- 1878-1861. ; 13:4, s. 382-386
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Tidskriftsartikel (refereegranskat)abstract
- The Sport Concussion Assessment Tool (SCAT) is a standardised global assessment for the identification of sport-related concussion (SRC). An integral component of the SCAT is the neurological screen, which contains the assessment of motor performance including gait evaluation. However, it is not known how performance of gait is affected by the surface/footwear interactions encountered in various sporting environments. The purpose of this study was to investigate the effect of footwear and sporting surface on the time to perform a standardised Tandem Gait (TG) task. One hundred and eight amateur athletes were recruited, and three common sports-surfaces (grass, hardwood court, artificial turf) were compared. All groups were tested barefoot and with sports-surface specific footwear. Mixed model ANOVA, controlling for covariates and including a post hoc Bonferroni procedure, was used to investigate the influence of footwear and sports-surface on TG time. The study demonstrated that times for a defined TG task in healthy athletes depended on footwear, sports-surface, and the specific athletic population. The study demonstrated a significant interaction (F(2.104) = 3.35, p = 0.039) between groups (grass, hardwood court and artificial turf), and times were faster wearing footwear compared to barefoot (F(2.138) = 26.31, p = 0.001). In contrast to the footwear conditions, there was no statistical difference between the barefoot conditions on any of the sport-surfaces. These findings suggest that clinicians should standardise footwear and the testing surface at baseline in order to accurately assess motor performance tests when SRC is suspected.
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| 24. |
- Stannard, Kimberley A., et al.
(författare)
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Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model
- 2010
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Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 299:2, s. 95-110
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Tidskriftsartikel (refereegranskat)abstract
- High level galectin-1 expression results in cancer cell evasion of the immune response, increased tumour survival and aggressive metastases. Using a galectin-1 polyclonal antibody, high levels of galectin-1 protein were shown to be expressed by breast cancer cells established from FVB/N MMTV-c-neu mice as well as by the B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as antigenic stimulators, addition of recombinant galectin-1 dose-dependently inhibited lymphocyte production. Disaccharides were identified that inhibited galectin-1 function and increased growth and activation of CD8+ CTL's killing cancer cells. X-ray crystallographic structures of human galectin-1 in complex with inhibitory disaccharides revealed their mode of binding. Combining galectin-blocking carbohydrates as adjuvants with vaccine immunotherapy in vivo to promote immune responses significantly decreased tumour progression and improved the outcomes for tumour challenged mice. This is the first report showing that suitably selected galectin-1 blocking disaccharides will act as adjuvants promoting vaccine stimulated immune responses against tumours in vivo.
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