| 51. |
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| 52. |
- Zhang, Guojie, et al.
(författare)
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Comparative genomics reveals insights into avian genome evolution and adaptation
- 2014
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1311-1320
-
Tidskriftsartikel (refereegranskat)abstract
- Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.
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| 53. |
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| 54. |
- Brown, C.L, et al.
(författare)
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Social Activity and Cognitive Functioning Over Time
- 2012
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Ingår i: Journal of Aging Research. - : Hindawi Limited. - 2090-2204 .- 2090-2212.
-
Tidskriftsartikel (refereegranskat)abstract
- Social activity is typically viewed as part of an engaged lifestyle that may help mitigate the deleterious effects of advanced age on cognitive function. As such, social activity has been examined in relation to cognitive abilities later in life. However, longitudinal evidence for this hypothesis thus far remains inconclusive. The current study sought to clarify the relationship between social activity and cognitive function over time using a coordinated data analysis approach across four longitudinal studies. A series of multilevel growth models with social activity included as a covariate is presented. Four domains of cognitive function were assessed: reasoning, memory, fluency, and semantic knowledge. Results suggest that baseline social activity is related to some, but not all, cognitive functions. Baseline social activity levels failed to predict rate of decline in most cognitive abilities. Changes in social activity were not consistently associated with cognitive functioning. Our findings do not provide consistent evidence that changes in social activity correspond to immediate benefits in cognitive functioning, except perhaps for verbal fluency.
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| 55. |
- de Vries, Claire E. E., et al.
(författare)
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Outcomes of the first global multidisciplinary consensus meeting including persons living with obesity to standardize patient-reported outcome measurement in obesity treatment research
- 2022
-
Ingår i: Obesity Reviews. - : John Wiley & Sons. - 1467-7881 .- 1467-789X. ; 23:8
-
Tidskriftsartikel (refereegranskat)abstract
- Quality of life is a key outcome that is not rigorously measured in obesity treatment research due to the lack of standardization of patient-reported outcomes (PROs) and PRO measures (PROMs). The S.Q.O.T. initiative was founded to Standardize Quality of life measurement in Obesity Treatment. A first face-to-face, international, multidisciplinary consensus meeting was conducted to identify the key PROs and preferred PROMs for obesity treatment research. It comprised of 35 people living with obesity (PLWO) and healthcare providers (HCPs). Formal presentations, nominal group techniques, and modified Delphi exercises were used to develop consensus-based recommendations. The following eight PROs were considered important: self-esteem, physical health/functioning, mental/psychological health, social health, eating, stigma, body image, and excess skin. Self-esteem was considered the most important PRO, particularly for PLWO, while physical health was perceived to be the most important among HCPs. For each PRO, one or more PROMs were selected, except for stigma. This consensus meeting was a first step toward standardizing PROs (what to measure) and PROMs (how to measure) in obesity treatment research. It provides an overview of the key PROs and a first selection of the PROMs that can be used to evaluate these PROs.
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| 56. |
- Dixon-Suen, Suzanne C, et al.
(författare)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 57. |
- Figlioli, G, et al.
(författare)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 58. |
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| 59. |
- Jarvis, Erich D., et al.
(författare)
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Whole-genome analyses resolve early branches in the tree of life of modern birds
- 2014
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
-
Tidskriftsartikel (refereegranskat)abstract
- To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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| 60. |
- Kennedy, L J, et al.
(författare)
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Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele.
- 2006
-
Ingår i: Tissue Antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 68:1, s. 82-6
-
Tidskriftsartikel (refereegranskat)abstract
- Dogs exhibit a range of immune-mediated conditions including a lymphocytic thyroiditis which has many similarities to Hashimoto's thyroiditis in man. We have recently reported an association in Doberman Pinschers between canine hypothyroidism and a rare DLA class II haplotype that contains the DLA-DQA1*00101 allele. We now report a further series of 173 hypothyroid dogs in a range of breeds where a significant association with DLA-DQA1*00101 is shown.
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| 61. |
- Lindwall, Magnus, 1975, et al.
(författare)
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Dynamic associations of change in physical activity and change in cognitive function: Coordinated analyses of four longitudinal studies
- 2012
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Ingår i: Journal of Aging Research. - : Hindawi Limited. - 2090-2204 .- 2090-2212. ; 2012
-
Tidskriftsartikel (refereegranskat)abstract
- The present study used a coordinated analyses approach to examine the association of physical activity and cognitive change in four longitudinal studies. A series of multilevel growth models with physical activity included both as a fixed (between-person) and time-varying (within-person) predictor of four domains of cognitive function (reasoning, memory, fluency, and semantic knowledge) was used. Baseline physical activity predicted fluency, reasoning and memory in two studies. However, there was a consistent pattern of positive relationships between time-specific changes in physical activity and time-specific changes in cognition, controlling for expected linear trajectories over time, across all four studies. This pattern was most evident for the domains of reasoning and fluency.
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| 62. |
- Mitchell, M.B, et al.
(författare)
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Cognitively stimulating activities: Effects on cognition across four studies with up to 21 years of longitudinal data
- 2012
-
Ingår i: Journal of Aging Research. - : Hindawi Limited. - 2090-2204 .- 2090-2212. ; 2012
-
Tidskriftsartikel (refereegranskat)abstract
- Engagement in cognitively stimulating activities has been considered to maintain or strengthen cognitive skills, thereby minimizing age-related cognitive decline. While the idea that there may be a modifiable behavior that could lower risk for cognitive decline is appealing and potentially empowering for older adults, research findings have not consistently supported the beneficial effects of engaging in cognitively stimulating tasks. Using observational studies of naturalistic cognitive activities, we report a series of mixed effects models that include baseline and change in cognitive activity predicting cognitive outcomes over up to 21 years in four longitudinal studies of aging. Consistent evidence was found for cross-sectional relationships between level of cognitive activity and cognitive test performance. Baseline activity at an earlier age did not, however, predict rate of decline later in life, thus not supporting the concept that engaging in cognitive activity at an earlier point in time increases one's ability to mitigate future age-related cognitive decline. In contrast, change in activity was associated with relative change in cognitive performance. Results therefore suggest that change in cognitive activity from one's previous level has at least a transitory association with cognitive performance measured at the same point in time.
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| 63. |
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| 64. |
- Abu-Hayyeh, S., et al.
(författare)
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Prognostic and Mechanistic Potential of Progesterone Sulfates in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum
- 2016
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 63:4, s. 1287-1298
-
Tidskriftsartikel (refereegranskat)abstract
- A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9-15 weeks of gestation and prior to symptom onset (group 1 cases/samples: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first-trimester samples all progesterone sulfates were significantly elevated in serum from low-risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5-dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high-risk population. Delineation of a progesterone sulfate-TGR5 pruritus axis identifies a therapeutic target for itch management in ICP.
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| 65. |
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| 66. |
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| 67. |
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| 68. |
- Beaty, D.W, et al.
(författare)
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The potential science and engineering value of samples delivered to Earth by Mars sample return : International MSR Objectives and Samples Team (iMOST)
- 2019
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Ingår i: Meteoritics and Planetary Science. - : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 54:S1, s. 3-152
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Tidskriftsartikel (refereegranskat)abstract
- Executive Summary: Return of samples from the surface of Mars has been a goal of the international Mars science community for many years. Affirmation by NASA and ESA of the importance of Mars exploration led the agencies to establish the international MSR Objectives and Samples Team (iMOST). The purpose of the team is to re-evaluate and update the sample-related science and engineering objectives of a Mars Sample Return (MSR) campaign. The iMOST team has also undertaken to define the measurements and the types of samples that can best address the objectives. Seven objectives have been defined for MSR, traceable through two decades of previously published international priorities. The first two objectives are further divided into sub-objectives. Within the main part of the report, the importance to science and/or engineering of each objective is described, critical measurements that would address the objectives are specified, and the kinds of samples that would be most likely to carry key information are identified. These seven objectives provide a framework for demonstrating how the first set of returned Martian samples would impact future Martian science and exploration. They also have implications for how analogous investigations might be conducted for samples returned by future missions from other solar system bodies, especially those that may harbor biologically relevant or sensitive material, such as Ocean Worlds (Europa, Enceladus, Titan) and others. Summary of Objectives and Sub-Objectives for MSR Identified by iMOST: Objective 1 Interpret the primary geologic processes and history that formed the Martian geologic record, with an emphasis on the role of water. Intent To investigate the geologic environment(s) represented at the Mars 2020 landing site, provide definitive geologic context for collected samples, and detail any characteristics that might relate to past biologic processesThis objective is divided into five sub-objectives that would apply at different landing sites. 1.1 Characterize the essential stratigraphic, sedimentologic, and facies variations of a sequence of Martian sedimentary rocks. Intent To understand the preserved Martian sedimentary record. Samples A suite of sedimentary rocks that span the range of variation. Importance Basic inputs into the history of water, climate change, and the possibility of life 1.2 Understand an ancient Martian hydrothermal system through study of its mineralization products and morphological expression. Intent To evaluate at least one potentially life-bearing “habitable” environment Samples A suite of rocks formed and/or altered by hydrothermal fluids. Importance Identification of a potentially habitable geochemical environment with high preservation potential. 1.3 Understand the rocks and minerals representative of a deep subsurface groundwater environment. Intent To evaluate definitively the role of water in the subsurface. Samples Suites of rocks/veins representing water/rock interaction in the subsurface. Importance May constitute the longest-lived habitable environments and a key to the hydrologic cycle. 1.4 Understand water/rock/atmosphere interactions at the Martian surface and how they have changed with time. Intent To constrain time-variable factors necessary to preserve records of microbial life. Samples Regolith, paleosols, and evaporites. Importance Subaerial near-surface processes could support and preserve microbial life. 1.5 Determine the petrogenesis of Martian igneous rocks in time and space. Intent To provide definitive characterization of igneous rocks on Mars. Samples Diverse suites of ancient igneous rocks. Importance Thermochemical record of the planet and nature of the interior. Objective 2 Assess and interpret the potential biological history of Mars, including assaying returned samples for the evidence of life. Intent To investigate the nature and extent of Martian habitability, the conditions and processes that supported or challenged life, how different environments might have influenced the preservation of biosignatures and created nonbiological “mimics,” and to look for biosignatures of past or present life.This objective has three sub-objectives: 2.1 Assess and characterize carbon, including possible organic and pre-biotic chemistry. Samples All samples collected as part of Objective 1. Importance Any biologic molecular scaffolding on Mars would likely be carbon-based. 2.2 Assay for the presence of biosignatures of past life at sites that hosted habitable environments and could have preserved any biosignatures. Samples All samples collected as part of Objective 1. Importance Provides the means of discovering ancient life. 2.3 Assess the possibility that any life forms detected are alive, or were recently alive. Samples All samples collected as part of Objective 1. Importance Planetary protection, and arguably the most important scientific discovery possible. Objective 3 Quantitatively determine the evolutionary timeline of Mars. Intent To provide a radioisotope-based time scale for major events, including magmatic, tectonic, fluvial, and impact events, and the formation of major sedimentary deposits and geomorphological features. Samples Ancient igneous rocks that bound critical stratigraphic intervals or correlate with crater-dated surfaces. Importance Quantification of Martian geologic history. Objective 4 Constrain the inventory of Martian volatiles as a function of geologic time and determine the ways in which these volatiles have interacted with Mars as a geologic system. Intent To recognize and quantify the major roles that volatiles (in the atmosphere and in the hydrosphere) play in Martian geologic and possibly biologic evolution. Samples Current atmospheric gas, ancient atmospheric gas trapped in older rocks, and minerals that equilibrated with the ancient atmosphere. Importance Key to understanding climate and environmental evolution. Objective 5 Reconstruct the processes that have affected the origin and modification of the interior, including the crust, mantle, core and the evolution of the Martian dynamo. Intent To quantify processes that have shaped the planet's crust and underlying structure, including planetary differentiation, core segregation and state of the magnetic dynamo, and cratering. Samples Igneous, potentially magnetized rocks (both igneous and sedimentary) and impact-generated samples. Importance Elucidate fundamental processes for comparative planetology. Objective 6 Understand and quantify the potential Martian environmental hazards to future human exploration and the terrestrial biosphere. Intent To define and mitigate an array of health risks related to the Martian environment associated with the potential future human exploration of Mars. Samples Fine-grained dust and regolith samples. Importance Key input to planetary protection planning and astronaut health. Objective 7 Evaluate the type and distribution of in-situ resources to support potential future Mars exploration. Intent To quantify the potential for obtaining Martian resources, including use of Martian materials as a source of water for human consumption, fuel production, building fabrication, and agriculture. Samples Regolith. Importance Production of simulants that will facilitate long-term human presence on Mars. Summary of iMOST Findings: Several specific findings were identified during the iMOST study. While they are not explicit recommendations, we suggest that they should serve as guidelines for future decision making regarding planning of potential future MSR missions. The samples to be collected by the Mars 2020 (M-2020) rover will be of sufficient size and quality to address and solve a wide variety of scientific questions. Samples, by definition, are a statistical representation of a larger entity. Our ability to interpret the source geologic units and processes by studying sample sub sets is highly dependent on the quality of the sample context. In the case of the M-2020 samples, the context is expected to be excellent, and at multiple scales. (A) Regional and planetary context will be established by the on-going work of the multi-agency fleet of Mars orbiters. (B) Local context will be established at field area- to outcrop- to hand sample- to hand lens scale using the instruments carried by M-2020. A significant fraction of the value of the MSR sample collection would come from its organization into sample suites, which are small groupings of samples designed to represent key aspects of geologic or geochemical variation. If the Mars 2020 rover acquires a scientifically well-chosen set of samples, with sufficient geological diversity, and if those samples were returned to Earth, then major progress can be expected on all seven of the objectives proposed in this study, regardless of the final choice of landing site. The specifics of which parts of Objective 1 could be achieved would be different at each of the final three candidate landing sites, but some combination of critically important progress could be made at any of them. An aspect of the search for evidence of life is that we do not know in advance how evidence for Martian life would be preserved in the geologic record. In order for the returned samples to be most useful for both understanding geologic processes (Objective 1) and the search for life (Objective 2), the sample collection should contain BOTH typical and unusual samples from the rock units explored. This consideration should be incorporated into sample selection and the design of the suites. The retrieval missions of a MSR campaign should (1) minimize stray magnetic fields to which the samples would be exposed and carry a magnetic witness plate to record exposure, (2) collect and return atmospheric gas sample(s), and (3) collect additional dust and/or regolith sample mass if possible.
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| 69. |
- Blanckenhorn, Wolf U, et al.
(författare)
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Proximate causes of Rensch's rule : Does sexual size dimorphism in arthropods result from sex differences in development time?
- 2007
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Ingår i: American Naturalist. ; 169:2, s. 245-257
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Tidskriftsartikel (refereegranskat)abstract
- A prominent interspecific pattern of sexual size dimorphism (SSD) is Rensch's rule, according to which male body size is more variable or evolutionarily divergent than female body size. Assuming equal growth rates of males and females, SSD would be entirely mediated, and Rensch's rule proximately caused, by sexual differences in development times, or sexual bimaturism (SBM), with the larger sex developing for a proportionately longer time. Only a subset of the seven arthropod groups investigated in this study exhibits Rensch's rule. Furthermore, we found only a weak positive relationship between SSD and SBM overall, suggesting that growth rate differences between the sexes are more important than development time differences in proximately mediating SSD in a wide but by no means comprehensive range of arthropod taxa. Except when protandry is of selective advantage ( as in many butterflies, Hymenoptera, and spiders), male development time was equal to ( in water striders and beetles) or even longer than ( in drosophilid and sepsid flies) that of females. Because all taxa show female-biased SSD, this implies faster growth of females in general, a pattern markedly different from that of primates and birds (analyzed here for comparison). We discuss three potential explanations for this pattern based on life-history trade-offs and sexual selection.
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| 70. |
- Brown, Christopher A., et al.
(författare)
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Multiscale analyses and characterizations of surface topographies
- 2018
-
Ingår i: CIRP Annals - Manufacturing Technology. - : Elsevier BV. - 1726-0604 .- 0007-8506. ; 67:2, s. 839-862
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Tidskriftsartikel (refereegranskat)abstract
- This work studies multiscale analyses and characterizations of surface topographies from the engineering and scientific literature with an emphasis on production engineering research and design. It highlights methods that provide strong correlations between topographies and performance or topographies and processes, and methods that can confidently discriminate topographies that were processed or that perform differently. These methods have commonalities in geometric characterizations at certain scales, which are observable with statistics and measurements. It also develops a semantic and theoretical framework and proposes a new system for organizing and designating multiscale analyses. Finally, future possibilities for multiscale analyses are discussed.
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| 71. |
- Challis, B G, et al.
(författare)
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Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36).
- 2004
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 101:13, s. 4695-700
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Tidskriftsartikel (refereegranskat)abstract
- Inactivating mutations of the pro-opiomelanocortin (POMC) gene in both mice and humans leads to hyperphagia and obesity. To further examine the mechanisms whereby POMC-deficiency leads to disordered energy homeostasis, we have generated mice lacking all POMC-derived peptides. Consistent with a previously reported model, Pomc(-/-) mice were obese and hyperphagic. They also showed reduced resting oxygen consumption associated with lowered serum levels of thyroxine. Hypothalami from Pomc(-/-) mice showed markedly increased expression of melanin-concentrating hormone mRNA in the lateral hypothalamus, but expression of neuropeptide Y mRNA in the arcuate nucleus was not altered. Provision of a 45% fat diet increased energy intake and body weight in both Pomc(-/-) and Pomc(+/-) mice. The effects of leptin on food intake and body weight were blunted in obese Pomc(-/-) mice whereas nonobese Pomc(-/-) mice were sensitive to leptin. Surprisingly, we found that Pomc(-/-) mice maintained their acute anorectic response to peptide-YY(3-36) (PYY(3-36)). However, 7 days of PYY(3-36) administration had no effect on cumulative food intake or body weight in wild-type or Pomc(-/-) mice. Thus, POMC peptides seem to be necessary for the normal response of energy balance to high-fat feeding, but not for the acute anorectic effect of PYY(3-36) or full effects of leptin on feeding. The finding that the loss of only one copy of the Pomc gene is sufficient to render mice susceptible to the effects of high fat feeding emphasizes the potential importance of this locus as a site for gene-environment interactions predisposing to obesity.
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| 72. |
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| 73. |
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| 74. |
- DeWitt, Douglas S., et al.
(författare)
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Pre-clinical testing of therapies for traumatic brain injury
- 2018
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:23, s. 2737-2754
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Tidskriftsartikel (refereegranskat)abstract
- Despite the large number of promising neuroprotective agents identified in experimental traumatic brain injury (TBI) studies, none has yet shown meaningful improvements in long-term outcome in clinical trials. To develop recommendations and guidelines for pre-clinical testing of pharmacological or biological therapies for TBI, the Moody Project for Translational Traumatic Brain Injury Research hosted a symposium attended by investigators with extensive experience in pre-clinical TBI testing. The symposium participants discussed issues related to pre-clinical TBI testing including experimental models, therapy and outcome selection, study design, data analysis, and dissemination. Consensus recommendations included the creation of a manual of standard operating procedures with sufficiently detailed descriptions of modeling and outcome measurement procedures to permit replication. The importance of the selection of clinically relevant outcome variables, especially related to behavior testing, was noted. Considering the heterogeneous nature of human TBI, evidence of therapeutic efficacy in multiple, diverse (e.g., diffuse vs. focused) rodent models and a species with a gyrencephalic brain prior to clinical testing was encouraged. Basing drug doses, times, and routes of administration on pharmacokinetic and pharmacodynamic data in the test species was recommended. Symposium participants agreed that the publication of negative results would reduce costly and unnecessary duplication of unsuccessful experiments. Although some of the recommendations are more relevant to multi-center, multi-investigator collaborations, most are applicable to pre-clinical therapy testing in general. The goal of these consensus guidelines is to increase the likelihood that therapies that improve outcomes in pre-clinical studies will also improve outcomes in TBI patients.
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| 75. |
- Dixon, P. H., et al.
(författare)
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GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements
- 2022
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility. Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.
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| 76. |
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| 77. |
- Hering, Bernhard J., et al.
(författare)
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Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia
- 2016
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:7, s. 1230-1240
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA(1c) <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant. RESULTS The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA(1c) level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.
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| 78. |
- Kanzler, Kathryn E, et al.
(författare)
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Mitigating the Effect of Pain Severity on Activity and Disability in Patients with Chronic Pain : The Crucial Context of Acceptance.
- 2018
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Ingår i: Pain medicine (Malden, Mass.). - : Oxford University Press (OUP). - 1526-2375 .- 1526-4637.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this study was to examine the effect of pain severity on activity levels and physical disability in the context of high pain acceptance. We hypothesized that pain acceptance moderates the effect of pain severity on general activity and physical disability, such that at higher levels of acceptance, the deleterious effect of pain is mitigated.Methods: Two hundred seven patients with chronic pain were recruited from three clinics in a large southwestern military treatment facility. Participants completed an anonymous self-report battery of standardized measures, including the Chronic Pain Acceptance Questionnaire, modified Oswestry Disability Index, and Pain Severity and General Activity subscales of the West Haven-Yale Multidimensional Pain Inventory.Results: Chronic pain acceptance was found to significantly moderate relations between pain severity and general activity (b = 0.0061, t(198) = 2.75, P = 0.007, 95% confidence interval [CI] = 0.002 to 0.011) and pain severity and disability (b = 0.036, t(193) = -2.564, P = 0.011, 95% CI = -0.063 to -0.008). In the context of higher acceptance, the negative effect of pain on activity and disability appeared reduced. Conversely, in the context of low acceptance, the effect of pain on disability appeared accentuated at all levels of pain severity.Conclusions: Higher acceptance mitigated both activity level and disability in a military-affiliated clinical sample of patients with chronic pain. Results further establish the role of acceptance in relation to functioning in a unique sample of people with chronic pain. These findings have implications for understanding and enhancing functioning in chronic pain populations.
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| 79. |
- Léget, P. -F., et al.
(författare)
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Correcting for peculiar velocities of Type la supernovae in clusters of galaxies
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 615
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Tidskriftsartikel (refereegranskat)abstract
- Context. Type Ia supernovae (SNe Ia) are widely used to measure the expansion of the Universe. To perform such measurements the luminosity and cosmological redshift (z) of the SNe Ia have to be determined. The uncertainty on z includes an unknown peculiar velocity, which can be very large for SNe Ia in the virialized cores of massive clusters. Aims. We determine which SNe Ia exploded in galaxy clusters using 145 SNe Ia from the Nearby Supernova Factory. We then study how the correction for peculiar velocities of host galaxies inside the clusters improves the Hubble residuals. Methods. We found 11 candidates for membership in clusters. We applied the biweight technique to estimate the redshift of a cluster. Then, we used the galaxy cluster redshift instead of the host galaxy redshift to construct the Hubble diagram. Results. For SNe Ia inside galaxy clusters, the dispersion around the Hubble diagram when peculiar velocities are taken into account is smaller compared with a case without peculiar velocity correction, which has a wRMS = 0.130 +/- 0.038 mag instead of wRMS = 0.137 +/- 0.036 mag. The significance of this improvement is 3.58 sigma. If we remove the very nearby Virgo cluster member SN2006X (z < 0.01) from the analysis, the significance decreases to 1.34 sigma. The peculiar velocity correction is found to be highest for the SNe Ia hosted by blue spiral galaxies. Those SNe Ia have high local specific star formation rates and smaller stellar masses, which is seemingly counter to what might be expected given the heavy concentration of old, massive elliptical galaxies in clusters. Conclusions. As expected, the Hubble residuals of SNe Ia associated with massive galaxy clusters improve when the cluster redshift is taken as the cosmological redshift of the supernova. This fact has to be taken into account in future cosmological analyses in order to achieve higher accuracy for cosmological redshift measurements. We provide an approach to do so.
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| 80. |
- Léget, P-F, et al.
(författare)
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SUGAR : An improved empirical model of Type Ia supernovae based on spectral features
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
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Tidskriftsartikel (refereegranskat)abstract
- Context. Type Ia supernovae (SNe Ia) are widely used to measure the expansion of the Universe. Improving distance measurements of SNe Ia is one technique to better constrain the acceleration of expansion and determine its physical nature.Aims. This document develops a new SNe Ia spectral energy distribution (SED) model, called the SUpernova Generator And Reconstructor (SUGAR), which improves the spectral description of SNe Ia, and consequently could improve the distance measurements.Methods. This model was constructed from SNe Ia spectral properties and spectrophotometric data from the Nearby Supernova Factory collaboration. In a first step, a principal component analysis-like method was used on spectral features measured at maximum light, which allowed us to extract the intrinsic properties of SNe Ia. Next, the intrinsic properties were used to extract the average extinction curve. Third, an interpolation using Gaussian processes facilitated using data taken at different epochs during the lifetime of an SN Ia and then projecting the data on a fixed time grid. Finally, the three steps were combined to build the SED model as a function of time and wavelength. This is the SUGAR model.Results. The main advancement in SUGAR is the addition of two additional parameters to characterize SNe Ia variability. The first is tied to the properties of SNe Ia ejecta velocity and the second correlates with their calcium lines. The addition of these parameters, as well as the high quality of the Nearby Supernova Factory data, makes SUGAR an accurate and efficient model for describing the spectra of normal SNe Ia as they brighten and fade.Conclusions. The performance of this model makes it an excellent SED model for experiments like the Zwicky Transient Facility, the Large Synoptic Survey Telescope, or the Wide Field Infrared Survey Telescope.
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| 81. |
- Lombardo, S., et al.
(författare)
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SCALA : In situ calibration for integral field spectrographs
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 607
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The scientific yield of current and future optical surveys is increasingly limited by systematic uncertainties in the flux calibration. This is the case for type Ia supernova (SN Ia) cosmology programs, where an improved calibration directly translates into improved cosmological constraints. Current methodology rests on models of stars. Here we aim to obtain flux calibration that is traceable to state-of-the-art detector-based calibration. Methods. We present the SNIFS Calibration Apparatus (SCALA), a color (relative) flux calibration system developed for the SuperNova integral field spectrograph (SNIFS), operating at the University of Hawaii 2.2 m (UH 88) telescope. Results. By comparing the color trend of the illumination generated by SCALA during two commissioning runs, and to previous laboratory measurements, we show that we can determine the light emitted by SCALA with a long-term repeatability better than 1%. We describe the calibration procedure necessary to control for system aging. We present measurements of the SNIFS throughput as estimated by SCALA observations. Conclusions. The SCALA calibration unit is now fully deployed at the UH 88 telescope, and with it color-calibration between 4000 angstrom and 9000 angstrom is stable at the percent level over a one-year baseline.
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| 82. |
- Markmann, James F., et al.
(författare)
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Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes
- 2021
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Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 21:4, s. 1477-1492
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic islet transplant offers a minimally invasive option for beta cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplant (CIT06), a National Institutes of Health-sponsored phase 3, prospective, open-label, single-arm pivotal trial of PHPI, was conducted in 24 patients with impaired awareness of hypoglycemia while receiving intensive insulin therapy. PHPI were manufactured using standardized processes. PHPI transplantation was effective with 62.5% of patients achieving the primary endpoint of freedom from severe hypoglycemic events and HbA(1c) <= 6.5% or reduced by >= 1 percentage point at 1 year posttransplant. Median HbA(1c)declined from 8.1% before to 6.0% at 1 year and 6.3% at 2 and 3 years following transplant (P < .001 for all vs baseline), with related improvements in hypoglycemia awareness and glucose variability. The improved metabolic control was associated with better health-related and diabetes-related quality of life. The procedure was safe and kidney allograft function remained stable after 3 years. These results add to evidence establishing allogeneic islet transplant as a safe and effective treatment for patients with T1D and unstable glucose control despite intensive insulin treatment, supporting the indication for PHPI in the post-renal transplant setting.
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| 83. |
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| 84. |
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| 85. |
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| 86. |
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| 87. |
- Neumann, W. P., et al.
(författare)
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Ergonomics action research I : shifting from hypothesis testing to experiential learning
- 2012
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 55:10, s. 1127-1139
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the case for the need for 'Action Research' (AR) approaches to gain understanding of how ergonomics considerations can best be integrated into the design of new work systems. The AR researchers work collaboratively with other stakeholders to solve a real-world problem: gaining insight into the problem and factors influencing solution building from an embedded position in the development process. This experience is interpreted in terms of available theory and can support further theory development. This non-experimental approach can help provide practical new approaches for integrating ergonomics considerations into real work system design processes. The AR approach suffers from a lack of acceptance by conventionally trained scientists. This paper aims to help overcome this weakness by developing the underlying theory and rationale for using AR approaches in ergonomics research. We propose further development of hybrid approaches which incorporate other evaluation techniques to extend the knowledge gains from AR projects.
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| 88. |
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| 89. |
- Nordin, J., et al.
(författare)
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Understanding type Ia supernovae through their U-band spectra
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 614
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Tidskriftsartikel (refereegranskat)abstract
- Context. Observations of type Ia supernovae (SNe Ia) can be used to derive accurate cosmological distances through empirical standardization techniques. Despite this success neither the progenitors of SNe Ia nor the explosion process are fully understood. The U-band region has been less well observed for nearby SNe, due to technical challenges, but is the most readily accessible band for high-redshift SNe. Aims. Using spectrophotometry from the Nearby Supernova Factory, we study the origin and extent of U-band spectroscopic variations in SNe Ia and explore consequences for their standardization and the potential for providing new insights into the explosion process. Methods. We divide the U-band spectrum into four wavelength regions lambda(uNi), lambda(uTi), lambda(uSi) and lambda(uCa). Two of these span the Ca H&K lambda lambda 3934, 3969 complex. We employ spectral synthesis using SYNAPPS to associate the two bluer regions with Ni/Co and Ti. Results. The flux of the uTi feature is an extremely sensitive temperature/ luminosity indicator, standardizing the SN peak luminosity to 0.116 +/- 0.011 mag root mean square (RMS). A traditional SALT2. 4 fit on the same sample yields a 0.135 mag RMS. Standardization using uTi also reduces the difference in corrected magnitude between SNe originating from different host galaxy environments. Early U-band spectra can be used to probe the Ni + Co distribution in the ejecta, thus offering a rare window into the source of light curve power. The uCa flux further improves standardization, yielding a 0.086 +/- 0.010 mag RMS without the need to include an additional intrinsic dispersion to reach chi(2) /dof similar to 1. This reduction in RMS is partially driven by an improved standardization of Shallow Silicon and 91T-like SNe.
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| 90. |
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| 91. |
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| 92. |
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| 93. |
- Ricordi, Camillo, et al.
(författare)
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National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial : Manufacture of a Complex Cellular Product at Eight Processing Facilities
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:11, s. 3418-3428
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Tidskriftsartikel (refereegranskat)abstract
- Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed.
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| 94. |
- Rigault, M., et al.
(författare)
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Strong dependence of Type Ia supernova standardization on the local specific star formation rate
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644
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Tidskriftsartikel (refereegranskat)abstract
- As part of an on-going effort to identify, understand and correct for astrophysics biases in the standardization of Type Ia supernovae (SN Ia) for cosmology, we have statistically classified a large sample of nearby SNe Ia into those that are located in predominantly younger or older environments. This classification is based on the specific star formation rate measured within a projected distance of 1 kpc from each SN location (LsSFR). This is an important refinement compared to using the local star formation rate directly, as it provides a normalization for relative numbers of available SN progenitors and is more robust against extinction by dust. We find that the SNe Ia in predominantly younger environments are ΔY = 0.163 ± 0.029 mag (5.7σ) fainter than those in predominantly older environments after conventional light-curve standardization. This is the strongest standardized SN Ia brightness systematic connected to the host-galaxy environment measured to date. The well-established step in standardized brightnesses between SNe Ia in hosts with lower or higher total stellar masses is smaller, at ΔM = 0.119 ± 0.032 mag (4.5σ), for the same set of SNe Ia. When fit simultaneously, the environment-age offset remains very significant, with ΔY = 0.129 ± 0.032 mag (4.0σ), while the global stellar mass step is reduced to ΔM = 0.064 ± 0.029 mag (2.2σ). Thus, approximately 70% of the variance from the stellar mass step is due to an underlying dependence on environment-based progenitor age. Also, we verify that using the local star formation rate alone is not as powerful as LsSFR at sorting SNe Ia into brighter and fainter subsets. Standardization that only uses the SNe Ia in younger environments reduces the total dispersion from 0.142 ± 0.008 mag to 0.120 ± 0.010 mag. We show that as environment-ages evolve with redshift, a strong bias, especially on the measurement of the derivative of the dark energy equation of state, can develop. Fortunately, data that measure and correct for this effect using our local specific star formation rate indicator, are likely to be available for many next-generation SN Ia cosmology experiments.
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| 95. |
- Saunders, C., et al.
(författare)
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SNEMO : Improved Empirical Models for Type Ia Supernovae
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 869:2
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Tidskriftsartikel (refereegranskat)abstract
- SN Ia cosmology depends on the ability to fit and standardize observations of supernova magnitudes with an empirical model. We present here a series of new models of SN Ia spectral time series that capture a greater amount of supernova diversity than is possible with the models that are currently customary. These are entitled SuperNova Empirical MOdels (SNEMO; https://snfactory.lbl.gov/snemo). The models are constructed using spectrophotometric time series from 172 individual supernovae from the Nearby Supernova Factory, comprising more than 2000 spectra. Using the available observations, Gaussian processes are used to predict a full spectral time series for each supernova. A matrix is constructed from the spectral time series of all the supernovae, and Expectation Maximization Factor Analysis is used to calculate the principal components of the data. K-fold cross-validation then determines the selection of model parameters and accounts for color variation in the data. Based on this process, the final models are trained on supernovae that have been dereddened using the Fitzpatrick and Massa extinction relation. Three final models are presented here: SNEMO2, a two-component model for comparison with current Type Ia models; SNEMO7, a seven-component model chosen for standardizing supernova magnitudes, which results in a total dispersion of 0.100mag for a validation set of supernovae, of which 0.087 mag is unexplained (a total dispersion of 0.113 mag with an unexplained dispersion of 0.097 mag is found for the total set of training and validation supernovae); and SNEMO15, a comprehensive 15-component model that maximizes the amount of spectral time-series behavior captured.
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| 96. |
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| 97. |
- Taubenberger, S., et al.
(författare)
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SN2012dn from early to late times : 09dc-like supernovae reassessed
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 488:4, s. 5473-5488
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Tidskriftsartikel (refereegranskat)abstract
- As a candidate super-Chandrasekhar' or 09dc-like TypeIa supernova (SNIa), SN 2012dn shares many characteristics with other members of this remarkable class of objects but lacks their extraordinary luminosity. Here, we present and discuss the most comprehensive optical data set of this SN to date, comprised of a densely sampled series of early-time spectra obtained within the Nearby Supernova Factory project, plus photometry and spectroscopy obtained at the Very Large Telescope about 1yr after the explosion. The light curves, colour curves, spectral time series, and ejecta velocities of SN 2012dn are compared with those of other 09dc-like and normal SNeIa, the overall variety within the class of 09dc-like SNeIa is discussed, and new criteria for 09dc-likeness are proposed. Particular attention is directed to additional insight that the late-phase data provide. The nebular spectra show forbidden lines of oxygen and calcium, elements that are usually not seen in late-time spectra of SNeIa, while the ionization state of the emitting iron plasma is low, pointing to low ejecta temperatures and high densities. The optical light curves are characterized by an enhanced fading starting similar to 60d after maximum and very low luminosities in the nebular phase, which is most readily explained by unusually early formation of clumpy dust in the ejecta. Taken together, these effects suggest a strongly perturbed ejecta density profile, which might lend support to the idea that 09dc-like characteristics arise from a brief episode of interaction with a hydrogen-deficient envelope during the first hours or days after the explosion.
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| 98. |
- Turro, Ernest, et al.
(författare)
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Whole-genome sequencing of patients with rare diseases in a national health system.
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 583:7814, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065extensively phenotypedparticipants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data ofUK Biobankparticipants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
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| 99. |
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| 100. |
- Wahlin, Åke, et al.
(författare)
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How health and biological age influence chronological age and sex differences in cognitive aging: Moderating, mediating, or both?
- 2006
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Ingår i: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 21:2, s. 318-332
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Tidskriftsartikel (refereegranskat)abstract
- Much research on cognitive competence in normal older adults has documented age and sex differences. We used cross-sectional data from the Victoria Longitudinal Study (n=386; age 61-95 years) to examine how health and biological age influence age and sex differences in cognitive aging. We found evidence for both moderating and mediating influences. Age differences were moderated by health status, such that the negative effects of age were most pronounced among participants of relatively better health. Sex differences were moderated by health and were pronounced among participants reporting comparatively poorer health. Although health mediated a notable amount of age-related cognitive variation, BioAge mediated considerably more variance, even after statistical control for differences in health. A complex pattern emerged for the mediation of sex differences: whereas BioAge accounted for sex-related variation in cognitive performance, health operated to suppress these differences. Overall, both health and BioAge predicted cognitive variation independently of chronological age.
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