| 1. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 2. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Darling, Kate F., et al.
(författare)
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The genetic diversity, phylogeography and morphology of Elphidiidae (Foraminifera) in the Northeast Atlantic
- 2016
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Ingår i: Marine Micropaleontology. - : Elsevier BV. - 0377-8398. ; 129, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- Genetic characterisation (SSU rRNA genotyping) and Scanning Electron Microscope (SEM) imaging of individual tests were used in tandem to determine the modern species richness of the foraminiferal family Elphidiidae (Elphidium, Haynesina and related genera) across the Northeast Atlantic shelf biomes. Specimens were collected at 25 locations from the High Arctic to Iberia, and a total of 1013 individual specimens were successfully SEM imaged and genotyped. Phylogenetic analyses were carried out in combination with 28 other elphidiid sequences from GenBank and seventeen distinct elphidiid genetic types were identified within the sample set, seven being sequenced for the first time. Genetic types cluster into seven main clades which largely represent their general morphological character. Differences between genetic types at the genetic, morphological and biogeographic levels are indicative of species level distinction. Their biogeographic distributions, in combination with elphidiid SSU sequences from GenBank and high resolution images from the literature show that each of them exhibits species-specific rather than clade-specific biogeographies. Due to taxonomic uncertainty and divergent taxonomic concepts between schools, we believe that morphospecies names should not be placed onto molecular phylogenies unless both the morphology and genetic type have been linked to the formally named holotype, or equivalent. Based on strict morphological criteria, we advocate using only a three-stage approach to taxonomy for practical application in micropalaeontological studies. It comprises genotyping, the production of a formal morphological description of the SEM images associated with the genetic type and then the allocation of the most appropriate taxonomic name by comparison with the formal type description. Using this approach, we were able to apply taxonomic names to fifteen genetic types. One of the remaining two may be potentially cryptic, and one is undescribed in the literature. In general, the phylogeographic distribution is in agreement with our knowledge of the ecology and biogeographical distribution of the corresponding morphospecies, highlighting the generally robust taxonomic framework of the Elphidiidae in time and space.
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| 4. |
- Morris, John A, et al.
(författare)
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An atlas of genetic influences on osteoporosis in humans and mice.
- 2019
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 51, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR)=58, P=1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P<0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.
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| 5. |
- Bird, Clare, et al.
(författare)
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The genetic diversity, morphology, biogeography, and taxonomic designations of Ammonia (Foraminifera) in the Northeast Atlantic
- 2020
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Ingår i: Marine Micropaleontology. - : Elsevier BV. - 0377-8398.
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Tidskriftsartikel (refereegranskat)abstract
- The genetic diversity, morphology and biogeography of Ammonia specimens was investigated across the Northeast (NE) Atlantic margins, to enhance the regional (palaeo)ecological studies based on this genus. Living specimens were collected from 22 sampling locations ranging from Shetland to Portugal to determine the distribution of Ammonia genetic types across the NE Atlantic shelf biomes. We successfully imaged (via scanning electron microscopy, SEM) and genotyped 378 Ammonia specimens, based on the small subunit (SSU) rRNA gene, linking morphology to genetic type. Phylogenetic analyses enabled identification of seven genetic types and subtypes inhabiting the NE Atlantic margins. Where possible, we linked SSU genetic types to the established large subunit (LSU) T-type nomenclature of Hayward et al. (2004). SSU genetic types with no matching T-type LSU gene sequences in GenBank were allocated new T-numbers to bring them in line with the widely adopted T-type nomenclature. The genetic types identified in the NE Atlantic margins are T1, T2, T3, T6, and T15, with both T2 and T3 being split further into the subtypes T2A and T2B, and T3S and T3V respectively. The seven genetic types and subtypes exhibit different biogeographical distributions and/or ecological preferences, but co-occurrence of two or more genetic types is common. A shore-line transect at Dartmouth (South England) demonstrates that sampling position on shore (high, middle or low shore) influences the genetic type collected, the numbers of genetic types that co-occur, and the numbers of individuals collected. We performed morphometric analysis on the SEM images of 158 genotyped Ammonia specimens. T15 and the subtypes T3S and T3V can be morphologically distinguished. We can unequivocally assign the taxonomic names A. batava and A. falsobeccarii to T3S and T15, respectively. However, the end members of T1, T2A, T2B and T6 cannot be unambiguously distinguished, and therefore these genetic types are partially cryptic. However, we confirm that T2A can be assigned to A. aberdoveyensis, but caution must be taken in warm provinces where the presence of T2B will complicate the morphological identification of T2A. We suggest that T6 should not currently be allocated to the Pliocene species A. aomoriensis due to morphological discrepancies with the taxonomic description and to the lack of genetic information. Of significance is that these partially cryptic genetic types frequently co-occur, which has considerable implications for precise species identification and accurate data interpretation.
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