669 research outputs found
Triplicity and Physical Characteristics of Asteroid (216) Kleopatra
To take full advantage of the September 2008 opposition passage of the M-type
asteroid (216) Kleopatra, we have used near-infrared adaptive optics (AO)
imaging with the W.M. Keck II telescope to capture unprecedented high
resolution images of this unusual asteroid. Our AO observations with the W.M.
Keck II telescope, combined with Spitzer/IRS spectroscopic observations and
past stellar occultations, confirm the value of its IRAS radiometric radius of
67.5 km as well as its dog-bone shape suggested by earlier radar observations.
Our Keck AO observations revealed the presence of two small satellites in orbit
about Kleopatra (see Marchis et al., 2008). Accurate measurements of the
satellite orbits over a full month enabled us to determine the total mass of
the system to be 4.64+/-0.02 10^18 Kg. This translates into a bulk density of
3.6 +/-0.4 g/cm3, which implies a macroscopic porosity for Kleopatra of ~
30-50%, typical of a rubble-pile asteroid. From these physical characteristics
we measured its specific angular momentum, very close to that of a spinning
equilibrium dumbbell.Comment: 35 pages, 3 Tables, 9 Figures. In press to Icaru
The structure of Chariklo's rings from stellar occultations
Two narrow and dense rings (called C1R and C2R) were discovered around the
Centaur object (10199) Chariklo during a stellar occultation observed on 2013
June 3. Following this discovery, we planned observations of several
occultations by Chariklo's system in order to better characterize the physical
properties of the ring and main body. Here, we use 12 successful occulations by
Chariklo observed between 2014 and 2016. They provide ring profiles (physical
width, opacity, edge structure) and constraints on the radii and pole position.
Our new observations are currently consistent with the circular ring solution
and pole position, to within the km formal uncertainty for the ring
radii derived by Braga-Ribas et al. The six resolved C1R profiles reveal
significant width variations from to 7.5 km. The width of the fainter
ring C2R is less constrained, and may vary between 0.1 and 1 km. The inner and
outer edges of C1R are consistent with infinitely sharp boundaries, with
typical upper limits of one kilometer for the transition zone between the ring
and empty space. No constraint on the sharpness of C2R's edges is available. A
1 upper limit of m is derived for the equivalent width of
narrow (physical width <4 km) rings up to distances of 12,000 km, counted in
the ring plane
The theoretical and empirical basis of a BioPsychoSocial (BPS) risk screener for detection of older people's health related needs, planning of community programs, and targeted care interventions
Background This study introduces the conceptual basis and operational measure, ofBioPyschoSocial (BPS) healthand related risk to better understand how well older people are managing and to screen for risk status. The BPS Risk Screener is constructed to detectvulnerabilityat older ages, and seeks to measure dynamic processes that place equal emphasis on Psycho-emotional and Socio-interpersonal risks, as Bio-functional ones. We validate the proposed measure and describe its application to programming. Methods We undertook a quantitative cross-sectional, psychometric study withn = 1325 older Singaporeans, aged 60 and over. We adapted the EASYCare 2010 and Lubben Social Network Scale questionnaires to help determine the BPS domains using factor analysis from which we derive the BPS Risk Screener items. We then confirm its structure, and test the scoring system. The score is initially validated against self-reported general health then modelled against: number of falls; cognitive impairment; longstanding diseases; and further tested against service utilization (linked administrative data). Results Three B, P and S clusters are defined and identified and a BPSmanaging score(‘doing’ well, or ‘some’, ‘many’, and ‘overwhelming problems’) calculated such that the risk of problematic additive BPS effects, what we term health‘loads’, are accounted for. Thirty-five items (factor loadings over 0.5) clustered into three distinct B, P, S domains and were found to be independently associated with self-reported health: B: 1.99 (1.64 to 2.41), P: 1.59 (1.28 to 1.98), S: 1.33 (1.10 to 1.60). The fit improved when combined into the managing score 2.33 (1.92 to 2.83, < 0.01). The score was associated with mounting risk for all outcomes. Conclusions BPS domain structures, and the novel scoring system capturing dynamic BPS additive effects, which can combine to engender vulnerability, are validated through this analysis. The resulting tool helps render clients’ risk status and related intervention needs transparent. Given its explicit and empirically supported attention to P and S risks, which have the potential to be more malleable than B ones, especially in the older old, this tool is designed to be change sensitive
Mucositis after Allogeneic Hematopoietic Stem Cell Transplantation: A Cohort Study of Methotrexate- and Non-Methotrexate-Containing Graft-versus-Host Disease Prophylaxis Regimens
AbstractOral mucositis occurs in up to 75% of recipients of high-dose chemoradiotherapy conditioning regimens used for allogeneic hematopoietic stem cell transplantation (HSCT). As a result of mucositis, narcotic analgesia and total parenteral nutrition (TPN) are commonly required after HSCT. Methotrexate, an antiproliferative graft-versus-host disease (GVHD) prophylaxis agent, impairs mucosal regeneration and worsens and prolongs mucositis. We assessed the effect of substituting sirolimus for methotrexate as GVHD prophylaxis on outcomes associated with mucositis. Two patient cohorts undergoing allogeneic HLA-matched related donor peripheral blood stem cell transplantation with cyclophosphamide/total body irradiation conditioning were prospectively analyzed for mucositis severity and retrospectively reviewed for correlative outcomes. GVHD prophylaxis consisted of sirolimus/tacrolimus (ST) in the study group and tacrolimus/methotrexate (TM) in the control group. Thirty patients received ST and 24 patients received TM as GVHD prophylaxis between October 2000 and May 2003. Mild, moderate, and severe mucositis was noted in 37%, 57%, and 7% of the ST group and 8%, 42%, and 50% of the TM group (P = .0002). Less TPN was used in the ST group than the TM group (17% versus 43% of posttransplantation hospital days; P = .02). The total number of narcotic days was lower in the ST group in comparison with the TM group (median, 13.5 versus 17 days; P = .08). The time to first hospital discharge was shorter in the ST group compared with the TM group (median, 18 versus 22 days; P = .07). The substitution of sirolimus for methotrexate as GVHD prophylaxis is associated with a reduction in mucositis severity. As a result, TPN and narcotic use are reduced, and hospitalization duration is shortened. Less toxic GVHD prophylaxis regimens without methotrexate may have a significant effect on patient quality of life, patient outcomes, and economic outcomes associated with allogeneic stem cell transplantation
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Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.
Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies
Working With the Tangible: Radiation, A Twenty-First Century Interpretation
The intangible means of expression was a topic of investigation across various disciplines when Michael Chekhov was developing his pedagogic practice. In the world of science, Harold Saxton Burr and Albert Szent-Gyorgi, were examining the body as a conductor of energy. Their research was relevant to Chekhov's approach regarding how the actor communicates with internal and external stimulus. This article begins with an analysis of Chekhov's theories on Radiation, it moves on to offer insights into science and energy work with reference to cell Biologist James Oschman and his concept of ‘the living matrix’ and Mae Wan Ho's critique of quantum cohesion. Examples of praxis demonstrate that contemporary science and body work can provide a greater understanding of how Radiation and the organisation of energy can enhance performance
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Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.
Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist
Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.
Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article
PTPN22.6, a Dominant Negative Isoform of PTPN22 and Potential Biomarker of Rheumatoid Arthritis
PTPN22 is a tyrosine phosphatase and functions as a damper of TCR signals. A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease. The effect of the R-to-W conversion on the phosphatase activity of PTPN22 protein and the impact of the minor T allele of the C1858T SNP on the activation of T cells has remained controversial. In addition, how the overall activity of PTPN22 is regulated and how the R-to-W conversion contributes to rheumatoid arthritis is still poorly understood. Here we report the identification of an alternative splice form of human PTPN22, namely PTPN22.6. It lacks the nearly entire phosphatase domain and can function as a dominant negative isoform of the full length PTPN22. Although conversion of R620 to W620 in the context of PTPN22.1 attenuated T cell activation, expression of the tryptophan variant of PTPN22.6 reciprocally led to hyperactivation of human T cells. More importantly, the level of PTPN22.6 in peripheral blood correlates with disease activity of rheumatoid arthritis. Our data depict a model that can reconcile the conflicting observations on the functional impact of the C1858T SNP and also suggest that PTPN22.6 is a novel biomarker of rheumatoid arthritis
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