370 research outputs found
The Heritability of Kidney Function Using an Older Australian Twin Population
Introduction: Twin studies are unique population models which estimate observed rather than inferred genetic components of complex traits. Nonmonogenic chronic kidney disease (CKD) is a complex disease process with strong genetic and environmental influences, amenable to twin studies. We aimed to assess the heritability of CKD using twin analysis and modeling within Older Australian Twin Study (OATS) data. Methods: OATS had 109 dizygotic (DZ) and 126 monozygotic (MZ) twin pairs with paired serum creatinine levels. Heritability of kidney function as estimated glomerular filtration rate (eGFR CKD Epidemiology Collaboration [CKD-EPI]) was modeled using the ACE model to estimate additive heritability (A), common (C), and unique (E) environmental factors. Intratwin pair analysis using mixed effects logistic regression allowed analysis of variation in eGFR from established CKD risk factors. Results: The median age was 69.71 (interquartile range 78.4–83.0) years, with 65% female, and a mean CKD-EPI of 82.8 ml/min (SD 6.7). The unadjusted ACE model determined kidney function to be 33% genetically determined (A), 18% shared genetic-environmental (C), and 49% because of unique environment (E). This remained unchanged when adjusted for age, hypertension, and sex. Hypertension was associated with eGFR; however, intertwin variance in hypertension did not explain variance in eGFR. Two or more hypertension medications were associated with decreased eGFR (P = 0.009). Conclusion: This study estimates observed heritability at 33%, notably higher than inferred heritability in genome-wide association study (GWAS) (7.1%–18%). Epigenetics and other genomic phenomena may explain this heritability gap. Difference in antihypertension medications explains part of unique environmental exposures, though discordance in hypertension and diabetes does not
Test evaluation trials present different challenges for trial managers compared to Intervention trials
Introduction
Test evaluation trials present different challenges for trial managers compared to intervention trials. There has been very little research on the management of test evaluation trials and how this impacts on trial success, in comparison with intervention trials. Evaluations of medical tests present specific challenges, because they are a pivot point bridging the complexities of pathways prompting testing with treatment decision-making. We systematically explored key differences in the trial design and management of test evaluation trials compared to intervention trials at the different stages of study design and delivery. We identified challenges in test evaluation trials that were more pronounced than in intervention trials, based on experience from 10 test evaluation trials.
Methods
We formed a focus group of 7 trial managers and a statistician who had been involved in the day-to-day management of both test evaluation trials and intervention trials. We used discussion and content analysis to group challenges from 10 trials into a structured thematic format. The trials covered a range of medical conditions, diagnostic tests, clinical pathways and conditions including chronic kidney disease, chronic pelvic pain, colitis, detrusor over-activity, group B streptococcal colonisation, tuberculosis and colorectal, lung, ovarian and thyroid cancers.
Results
We identified 10 common themes underlying challenges that are more pronounced in test evaluation compared to intervention trials. We illustrate these themes with examples from 10 trials, including with 31 specific challenges we experienced. The themes were ethics/governance; accessing patient populations; recruitment; patient preference; test processes, clinical pathways and samples storage; uncertainty of diagnostic results; verifying diagnosis (reference standard); follow-up; adverse effects; and diagnostic impact.
Conclusion
We present 10 common themes, including 31 challenges, in test evaluation trials that will be helpful to others designing and managing future test evaluation trials. Proactive identification of potential challenges at the design and planning stages of test evaluation trials will enable strategies to improve trial design and management that may be different from standard strategies used for intervention trials. Future work could extend this topic to include challenges for other trial stakeholders including participants, clinicians, statisticians and funders
Relevance of magnetism to cuprate superconductivity: Lanthanides versus charge-compensated cuprates
We address what seemed to be a contradiction between the lanthanide series
REBaCuO (RE123) and the charge-compensated series
(CaLa)(BaLa)CuO (CLBLCO)
regarding the superexchange () dependence of the maximum superconductivity
(SC) critical temperature ; RE and are implicit variables.
This is done by measuring the N\'{e}el temperature and the temperature
dependence of the magnetic order parameter for RE=Nd, Sm, Eu, Gd, Dy, Yb, Y,
and for Y(BaSr)CuO, at various very light dopings. The doping is
determined by thermopower, and the magnetic properties by muon spin rotation.
We find that the normalized-temperature dependence of the order parameter is
identical for all RE123 in the undoped limit (with the exception of Gd123)
implying identical out-of-plane magnetic coupling. The extrapolation of
to zero doping suggests that, despite the variations in ionic radii, varies
too weakly in this system to test the relation between SC and magnetism. This
stands in contrast to CLBLCO where both and vary
considerably in the undoped limit, and a positive correlation between the two
quantities was observed.Comment: 6 pages, 5 figure
Being a Self-Employed Older Woman: From Discrimination to Activism
This article presents an autobiographical account of an older woman’s lived experience of self-employment. Little is known about women who experience ongoing self-employment into their 50s and beyond. Shoshanna’s personal narrative describes her experiences and the challenges she has faced as she reflects upon her attempts to grow and sustain her business and the implications of ageism and gender inequality in laying a claim to entrepreneurship. The narrative proceeds to reflect on her activist work, as it is constructed through the creation of a social enterprise to support older people. Shoshanna’s narrative provides valuable insights into the intersection of age and gender in self-employment moving from discrimination to active support
Frame dragging with optical vortices
General Relativistic calculations in the linear regime have been made for
electromagnetic beams of radiation known as optical vortices. These exotic
beams of light carry a physical quantity known as optical orbital angular
momentum (OAM). It is found that when a massive spinning neutral particle is
placed along the optical axis, a phenomenon known as inertial frame dragging
occurs. Our results are compared with those found previously for a ring laser
and an order of magnitude estimate of the laser intensity needed for a
precession frequency of 1 Hz is given for these "steady" beams of light.Comment: 13 pages, 2 figure
Infrared ellipsometry study of the confined electrons in a high-mobility <i>γ</i>-Al₂O₃/SrTiO₃ heterostructure
With infrared ellipsometry we studied the response of the confined electrons in γ-Al₂O₃/SrTiO₃ (GAO/STO) heterostructures in which they originate predominantly from oxygen vacancies. From the analysis of a so-called Berreman mode, that develops near the highest longitudinal optical phonon mode of SrTiO₃, we derive the sheet carrier density, N s , the mobility, μ, and the depth profile of the carrier concentration. Notably, we find that N s and the shape of the depth profile are similar as in LaAlO₃/SrTiO₃ (LAO/STO) heterostructures for which the itinerant carriers are believed to arise from a polar discontinuity. Despite an order of magnitude higher mobility in GAO/STO, as obtained from transport measurements, the derived mobility in the infrared range exhibits only a twofold increase. We interpret this finding in terms of the polaronic nature of the confined charge carriers in GAO/STO and LAO/STO which leads to a strong, frequency-dependent interaction with the STO phonons
Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease
BACKGROUND: There is growing support for a biopsy avoidant approach to diagnose coeliac disease in both children and adults, using a serological diagnosis instead. AIMS: To assess the diagnostic accuracy of serological tests for coeliac disease in adults and children. METHODS: Seven electronic databases were searched between January 1990 and August 2020. Eligible diagnostic studies evaluated the accuracy of serological tests for coeliac disease against duodenal biopsy. Risk of bias assessment was performed using QUADAS-2. Bivariate random-effects meta-analyses were used to estimate serology sensitivity and specificity at the most commonly reported thresholds. RESULTS: 113 studies (n = 28,338) were included, all in secondary care populations. A subset of studies were included in meta-analyses due to variations in diagnostic thresholds. Summary sensitivity and specificity of immunoglobulin A (IgA) anti-tissue transglutaminase were 90.7% (95% confidence interval: 87.3%, 93.2%) and 87.4% (84.4%, 90.0%) in adults (5 studies) and 97.7% (91.0%, 99.4%) and 70.2% (39.3%, 89.6%) in children (6 studies); and of IgA endomysial antibodies were 88.0% (75.2%, 94.7%) and 99.6% (92.3%, 100%) in adults (5 studies) and 94.5% (88.9%, 97.3%) and 93.8% (85.2%, 97.5%) in children (5 studies). CONCLUSIONS: Anti-tissue transglutaminase sensitivity appears to be sufficient to rule out coeliac disease in children. The high specificity of endomysial antibody in adults supports its use to rule in coeliac disease. This evidence underpins the current development of clinical guidelines for a serological diagnosis of coeliac disease. Studies in primary care are needed to evaluate serological testing strategies in this setting
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