| 1. |
- Casey, Jillian P, et al.
(author)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Journal article (peer-reviewed)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 2. |
- Lindblad-Toh, Kerstin, et al.
(author)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Journal article (peer-reviewed)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 3. |
- Andreoni, Igor, et al.
(author)
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Target-of-opportunity Observations of Gravitational-wave Events with Vera C. Rubin Observatory
- 2022
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 260:1
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Journal article (peer-reviewed)abstract
- The discovery of the electromagnetic counterpart to the binary neutron star (NS) merger GW170817 has opened the era of gravitational-wave multimessenger astronomy. Rapid identification of the optical/infrared kilonova enabled a precise localization of the source, which paved the way to deep multiwavelength follow-up and its myriad of related science results. Fully exploiting this new territory of exploration requires the acquisition of electromagnetic data from samples of NS mergers and other gravitational-wave sources. After GW170817, the frontier is now to map the diversity of kilonova properties and provide more stringent constraints on the Hubble constant, and enable new tests of fundamental physics. The Vera C. Rubin Observatory's Legacy Survey of Space and Time can play a key role in this field in the 2020s, when an improved network of gravitational-wave detectors is expected to reach a sensitivity that will enable the discovery of a high rate of merger events involving NSs (∼tens per year) out to distances of several hundred megaparsecs. We design comprehensive target-of-opportunity observing strategies for follow-up of gravitational-wave triggers that will make the Rubin Observatory the premier instrument for discovery and early characterization of NS and other compact-object mergers, and yet unknown classes of gravitational-wave events.
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| 4. |
- Barna, Barnabas, et al.
(author)
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SN 2019muj-a well-observed Type Iax supernova that bridges the luminosity gap of the class
- 2021
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 501:1, s. 1078-1099
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Journal article (peer-reviewed)abstract
- We present early-time (t < +50 d) observations of SN 2019muj (=ASASSN-19tr), one of the best-observed members of the peculiar SN Iax class. Ultraviolet and optical photometric and optical and near-infrared spectroscopic follow-up started from similar to 5 d before maximum light [t(max)(B) on 58707.8 MJD] and covers the photospheric phase. The early observations allow us to estimate the physical properties of the ejecta and characterize the possible divergence from a uniform chemical abundance structure. The estimated bolometric light-curve peaks at 1.05 x 10(42) erg s(-1) and indicates that only 0.031 M-circle dot of Ni-56 was produced, making SN 2019muj a moderate luminosity object in the Iax class with peak absolute magnitude of M-V = -16.4 mag. The estimated date of explosion is t(0) = 58698.2 MJD and implies a short rise time of t(rise) = 9.6 d in B band. We fit of the spectroscopic data by synthetic spectra, calculated via the radiative transfer code TARDIS. Adopting the partially stratified abundance template based on brighter SNe Iax provides a good match with SN 2019muj. However, without earlier spectra, the need for stratification cannot be stated in most of the elements, except carbon, which is allowed to appear in the outer layers only. SN 2019muj provides a unique opportunity to link extremely low-luminosity SNe Iax to well-studied, brighter SNe Iax.
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| 5. |
- Case, Laura K., et al.
(author)
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Innocuous pressure sensation requires A-type afferents but not functional Rho Iota Epsilon Zeta Omicron 2 channels in humans
- 2021
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In: Nature Communications. - : Nature Research. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking A beta fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for A beta afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection. The mechanisms underlying deep pressure sensing are not fully understood. Here the authors demonstrate that while two individuals lacking A beta fibers demonstrate impaired deep pressure sensing, seven individuals with PIEZO2 loss of function mutations display normal deep pressure responses.
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| 6. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 7. |
- Foley, Jonathan A., et al.
(author)
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Solutions for a cultivated planet
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7369, s. 337-342
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Journal article (peer-reviewed)abstract
- Increasing population and consumption are placing unprecedented demands on agriculture and natural resources. Today, approximately a billion people are chronically malnourished while our agricultural systems are concurrently degrading land, water, biodiversity and climate on a global scale. To meet the world's future food security and sustainability needs, food production must grow substantially while, at the same time, agriculture's environmental footprint must shrink dramatically. Here we analyse solutions to this dilemma, showing that tremendous progress could be made by halting agricultural expansion, closing 'yield gaps' on underperforming lands, increasing cropping efficiency, shifting diets and reducing waste. Together, these strategies could double food production while greatly reducing the environmental impacts of agriculture.
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| 8. |
- Hosseinzadeh, Griffin, et al.
(author)
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Weak Mass Loss from the Red Supergiant Progenitor of the Type II SN 2021yja
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 935:1
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Journal article (peer-reviewed)abstract
- We present high-cadence optical, ultraviolet (UV), and near-infrared data of the nearby (D approximate to 23 Mpc) Type II supernova (SN) 2021yja. Many Type II SNe show signs of interaction with circumstellar material (CSM) during the first few days after explosion, implying that their red supergiant (RSG) progenitors experience episodic or eruptive mass loss. However, because it is difficult to discover SNe early, the diversity of CSM configurations in RSGs has not been fully mapped. SN 2021yja, first detected within approximate to 5.4 hours of explosion, shows some signatures of CSM interaction (high UV luminosity and radio and x-ray emission) but without the narrow emission lines or early light-curve peak that can accompany CSM. Here we analyze the densely sampled early light curve and spectral series of this nearby SN to infer the properties of its progenitor and CSM. We find that the most likely progenitor was an RSG with an extended envelope, encompassed by low-density CSM. We also present archival Hubble Space Telescope imaging of the host galaxy of SN 2021yja, which allows us to place a stringent upper limit of less than or similar to 9 M-circle dot; on the progenitor mass. However, this is in tension with some aspects of the SN evolution, which point to a more massive progenitor. Our analysis highlights the need to consider progenitor structure when making inferences about CSM properties, and that a comprehensive view of CSM tracers should be made to give a fuller view of the last years of RSG evolution.
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| 9. |
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| 10. |
- Menkveld, Albert J., et al.
(author)
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Nonstandard Errors
- 2024
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In: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Journal article (peer-reviewed)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 11. |
- Moles, Angela T, et al.
(author)
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Correlations between physical and chemical defences in plants : tradeoffs, syndromes, or just many different ways to skin a herbivorous cat?
- 2013
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In: New Phytologist. - : Wiley-Blackwell. - 0028-646X .- 1469-8137. ; 198:1, s. 252-263
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Journal article (peer-reviewed)abstract
- Most plant species have a range of traits that deter herbivores. However, understanding of how different defences are related to one another is surprisingly weak. Many authors argue that defence traits trade off against one another, while others argue that they form coordinated defence syndromes. We collected a dataset of unprecedented taxonomic and geographic scope (261 species spanning 80 families, from 75 sites across the globe) to investigate relationships among four chemical and six physical defences. Five of the 45 pairwise correlations between defence traits were significant and three of these were tradeoffs. The relationship between species' overall chemical and physical defence levels was marginally nonsignificant (P=0.08), and remained nonsignificant after accounting for phylogeny, growth form and abundance. Neither categorical principal component analysis (PCA) nor hierarchical cluster analysis supported the idea that species displayed defence syndromes. Our results do not support arguments for tradeoffs or for coordinated defence syndromes. Rather, plants display a range of combinations of defence traits. We suggest this lack of consistent defence syndromes may be adaptive, resulting from selective pressure to deploy a different combination of defences to coexisting species.
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| 12. |
- Rainford, Louise, et al.
(author)
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Education and training in radiation protection in Europe : an analysis from the EURAMED rocc-n-roll project
- 2022
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In: Insights into Imaging. - : Springer. - 1869-4101. ; 13:1
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Journal article (peer-reviewed)abstract
- Background: A Strengths, weaknesses, opportunities and threats analysis was performed to understand the status quo of education and training in radiation protection (RP) and to develop a coordinated European approach to RP training needs based on stakeholder consensus and existing activities in the field. Fourteen team members represented six European professional societies, one European voluntary organisation, two international healthcare organisations and five professions, namely: Medical Physicists; Nuclear Medicine Physicians; Radiologists; Radiation Oncologists and Radiographers. Four subgroups analysed the "Strengths", "Weaknesses", "Opportunities" and "Threats" related to E&T in RP developed under previous European Union (EU) programmes and on the Guidelines on Radiation Protection Education and Training of Medical Professionals in the EU.Results: Consensus agreement identified four themes for strengths and opportunities, namely: (1) existing structures and training recommendations; (2) RP training needs assessment and education & training (E&T) model(s) development; (3) E&T dissemination, harmonisation, and accreditation; (4) financial supports. Weaknesses and Threats analysis identified two themes: (1) awareness and prioritisation at a national/global level and (2) awareness and prioritisation by healthcare professional groups and researchers.Conclusions: A lack of effective implementation of RP principles in daily practice was identified. EuRnR strategic planning needs to consider processes at European, national and local levels. Success is dependent upon efficient governance structures and expert leadership. Financial support is required to allow the stakeholder professional agencies to have sufficient resources to achieve a pan European radiation protection training network which is sustainable and accredited across multiple national domains.
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| 13. |
- Rockström, Johan, et al.
(author)
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A safe operating space for humanity
- 2009
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7263, s. 472-475
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Journal article (peer-reviewed)
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| 14. |
- Rockström, Johan, et al.
(author)
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Planetary Boundaries : Exploring the Safe Operating Space for Humanity
- 2009
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In: Ecology and Society. - 1708-3087. ; 14:2, s. 32-
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Journal article (peer-reviewed)abstract
- Anthropogenic pressures on the Earth System have reached a scale where abrupt global environmental change can no longer be excluded. We propose a new approach to global sustainability in which we define planetary boundaries within which we expect that humanity can operate safely. Transgressing one or more planetary boundaries may be deleterious or even catastrophic due to the risk of crossing thresholds that will trigger non-linear, abrupt environmental change within continental- to planetary-scale systems. We have identified nine planetary boundaries and, drawing upon current scientific understanding, we propose quantifications for seven of them. These seven are climate change (CO2 concentration in the atmosphere <350 ppm and/or a maximum change of +1 W m(-2) in radiative forcing); ocean acidification (mean surface seawater saturation state with respect to aragonite >= 80% of pre-industrial levels); stratospheric ozone (<5% reduction in O-3 concentration from pre-industrial level of 290 Dobson Units); biogeochemical nitrogen (N) cycle (limit industrial and agricultural fixation of N-2 to 35 Tg N yr(-1)) and phosphorus (P) cycle (annual P inflow to oceans not to exceed 10 times the natural background weathering of P); global freshwater use (<4000 km(3) yr(-1) of consumptive use of runoff resources); land system change (<15% of the ice-free land surface under cropland); and the rate at which biological diversity is lost (annual rate of <10 extinctions per million species). The two additional planetary boundaries for which we have not yet been able to determine a boundary level are chemical pollution and atmospheric aerosol loading. We estimate that humanity has already transgressed three planetary boundaries: for climate change, rate of biodiversity loss, and changes to the global nitrogen cycle. Planetary boundaries are interdependent, because transgressing one may both shift the position of other boundaries or cause them to be transgressed. The social impacts of transgressing boundaries will be a function of the social-ecological resilience of the affected societies. Our proposed boundaries are rough, first estimates only, surrounded by large uncertainties and knowledge gaps. Filling these gaps will require major advancements in Earth System and resilience science. The proposed concept of "planetary boundaries" lays the groundwork for shifting our approach to governance and management, away from the essentially sectoral analyses of limits to growth aimed at minimizing negative externalities, toward the estimation of the safe space for human development. Planetary boundaries define, as it were, the boundaries of the "planetary playing field" for humanity if we want to be sure of avoiding major human-induced environmental change on a global scale.
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| 15. |
- Santos, Joana, et al.
(author)
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Education and training in radiation protection in Europe : results from the EURAMED Rocc-n-Roll project survey
- 2023
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In: Insights into Imaging. - : Springer. - 1869-4101. ; 14:1
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Journal article (peer-reviewed)abstract
- Purpose: To analyse the existing radiation protection (RP) education and training (E&T) capabilities in the European Union and identify associated needs, problems and challenges.Method: An online survey was disseminated via the EURAMED Rocc-n-Roll consortium network and prominent medical societies in the field of radiological research. The survey sections analyse the RP E&T during undergraduate, residency/internship and continuous professional development; RP E&T problems and legal implementation. Differences were analysed by European geographic regions, profession, years of professional experience and main area of practice/research.Results: The majority of the 550 respondents indicated that RP topics are part of undergraduate curricula in all courses for their profession and country (55%); however, hands-on practical training is not included according to 30% of the respondents. The lack of E&T, practical aspects in current E&T, and mandatory continuing E&T were considered the major problems. The legal requirement that obtained higher implementation score was the inclusion of the practical aspects of medical radiological procedures on education (86%), and lower score was obtained for the inclusion of RP E&T on medical and dental school curriculums (61%).Conclusions: A heterogeneity in RP E&T during undergraduate, residency/internship and continuous professional development is evident across Europe. Differences were noted per area of practice/research, profession, and European geographic region. A large variation in RP E&T problem rating was also obtained.
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| 16. |
- Slaven, Sean E., et al.
(author)
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Revision Arthroscopic Bankart Repair Results in High Failure Rates and a Low Return to Duty Rate Without Recurrent Instability
- 2023
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In: ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY. - : Elsevier BV. - 0749-8063 .- 1526-3231. ; 39:4, s. 913-918
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Journal article (peer-reviewed)abstract
- Purpose: The purpose of this study was to determine, in a military population without critical bone loss, the rate of recurrent instability after revision arthroscopic stabilization for failed primary arthroscopic Bankart repair. Methods: Fortyone revision arthroscopic stabilizations were performed at a single military institution between 2005 to 2016 for recurrent anterior shoulder instability after primary arthroscopic Bankart repair. Minimum follow-up was 2 years, and shoulders with glenoid bone loss >20% were excluded. The primary outcome of interest was the incidence of failure, defined by recurrent instability. Results: Age at revision surgery averaged 22.9 +/- 4.3 years, and 88% were either service academy cadets or active duty combat arms soldiers. Mean follow-up was 7.8 years. Twenty-three patients (56%) returned to duty without recurrent instability after revision arthroscopic stabilization. Eighteen patients (44%) experienced recurrent instability after return to duty. Glenoid bone loss averaged 6.2% (95% confidence interval [CI], 3.2%-9.2%) in the successful group and 5.7% (95% CI, 3.1%-8.3%) in the failure group (P = .808). Conclusions: Revision arthroscopic stabilization of failed primary arthroscopic Bankart repair has a failure rate of 44% in a young military population. The similar amounts of bone loss between groups indicates that bone loss is not the primary determinant of failure in revision arthroscopic stabilization.
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| 17. |
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- 2019
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Journal article (peer-reviewed)
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