Secondary findings in inherited heart conditions: a genotype-first feasibility study to assess phenotype, behavioural and psychosocial outcomes.

Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: Rhodes Scholarships; doi: https://doi.org/10.13039/501100000697Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Funder: British Heart Foundation (BHF); doi: https://doi.org/10.13039/501100000274Disclosing secondary findings (SF) from genome sequencing (GS) can alert carriers to disease risk. However, evidence around variant-disease association and consequences of disclosure for individuals and healthcare services is limited. We report on the feasibility of an approach to identification of SF in inherited cardiac conditions (ICC) genes in participants in a rare disease GS study, followed by targeted clinical evaluation. Qualitative methods were used to explore behavioural and psychosocial consequences of disclosure. ICC genes were analysed in genome sequence data from 7203 research participants; a two-stage approach was used to recruit genotype-blind variant carriers and matched controls. Cardiac-focused medical and family history collection and genetic counselling were followed by standard clinical tests, blinded to genotype. Pathogenic ICC variants were identified in 0.61% of individuals; 20 were eligible for the present study. Four variant carriers and seven non-carrier controls participated. One variant carrier had a family history of ICC and was clinically affected; a second was clinically unaffected and had no relevant family history. One variant, in two unrelated participants, was subsequently reclassified as being of uncertain significance. Analysis of qualitative data highlights participant satisfaction with approach, willingness to follow clinical recommendations, but variable outcomes of relatives' engagement with healthcare services. In conclusion, when offered access to SF, many people choose not to pursue them. For others, disclosure of ICC SF in a specialist setting is valued and of likely clinical utility, and can be expected to identify individuals with, and without a phenotype

PRISM (Polarized Radiation Imaging and Spectroscopy Mission): A White Paper on the Ultimate Polarimetric Spectro-Imaging of the Microwave and Far-Infrared Sky

PRISM (Polarized Radiation Imaging and Spectroscopy Mission) was proposed to ESA in response to the Call for White Papers for the definition of the L2 and L3 Missions in the ESA Science Programme. PRISM would have two instruments: (1) an imager with a 3.5m mirror (cooled to 4K for high performance in the far-infrared---that is, in the Wien part of the CMB blackbody spectrum), and (2) an Fourier Transform Spectrometer (FTS) somewhat like the COBE FIRAS instrument but over three orders of magnitude more sensitive. Highlights of the new science (beyond the obvious target of B-modes from gravity waves generated during inflation) made possible by these two instruments working in tandem include: (1) the ultimate galaxy cluster survey gathering 10e6 clusters extending to large redshift and measuring their peculiar velocities and temperatures (through the kSZ effect and relativistic corrections to the classic y-distortion spectrum, respectively) (2) a detailed investigation into the nature of the cosmic infrared background (CIB) consisting of at present unresolved dusty high-z galaxies, where most of the star formation in the universe took place, (3) searching for distortions from the perfect CMB blackbody spectrum, which will probe a large number of otherwise inaccessible effects (e.g., energy release through decaying dark matter, the primordial power spectrum on very small scales where measurements today are impossible due to erasure from Silk damping and contamination from non-linear cascading of power from larger length scales). These are but a few of the highlights of the new science that will be made possible with PRISM.Comment: 20 pages Late

Cooldown Strategies and Transient Thermal Simulations for the Simons Observatory

The Simons Observatory (SO) will provide precision polarimetry of the cosmic microwave background (CMB) using a series of telescopes which will cover angular scales from arc-minutes to tens of degrees, contain over 60,000 detectors, and observe in frequency bands between 27 GHz and 270 GHz. SO will consist of a six-meter-aperture telescope initially coupled to ~35,000 detectors along with an array of 0.5m aperture refractive cameras, coupled to an additional 30,000+ detectors. The large aperture telescope receiver (LATR) is coupled to a six-meter crossed Dragone telescope and will be 2.4m in diameter, weigh over 3 tons, and have five cryogenic stages (80 K, 40 K, 4 K, 1 K and 100 mK). The LATR is coupled to the telescope via 13 independent optics tubes containing cryogenic optical elements and detectors. The cryostat will be cooled by by two Cryomech PT90 (80 K) and three Cryomech PT420 (40 K and 4 K) pulse tube cryocoolers, with cooling of the 1 K and 100 mK stages by a commercial dilution refrigerator system. The second component, the small aperture telescope (SAT), is a single optics tube refractive cameras of 42cm diameter. Cooling of the SAT stages will be provided by two Cryomech PT420, one of which is dedicated to the dilution refrigeration system which will cool the focal plane to 100 mK. SO will deploy a total of three SATs. In order to estimate the cool down time of the camera systems given their size and complexity, a finite difference code based on an implicit solver has been written to simulate the transient thermal behavior of both cryostats. The result from the simulations presented here predict a 35 day cool down for the LATR. The simulations suggest additional heat switches between stages would be effective in distribution cool down power and reducing the time it takes for the LATR to cool. The SAT is predicted to cool down in one week, which meets the SO design goals

Simons Observatory large aperture receiver simulation overview

The Simons Observatory (SO) will make precision temperature and polarization measurements of the cosmic microwave background (CMB) using a series of telescopes which will cover angular scales between one arcminute and tens of degrees, contain over 60,000 detectors, and sample frequencies between 27 and 270 GHz. SO will consist of a six-meter-aperture telescope coupled to over 30,000 detectors along with an array of half-meter aperture refractive cameras, which together couple to an additional 30,000+ detectors. SO will measure fundamental cosmological parameters of our universe, find high redshift clusters via the Sunyaev-Zeldovich effect, constrain properties of neutrinos, and seek signatures of dark matter through gravitational lensing. In this paper we will present results of the simulations of the SO large aperture telescope receiver (LATR). We will show details of simulations performed to ensure the structural integrity and thermal performance of our receiver, as well as will present the results of finite element analyses (FEA) of designs for the structural support system. Additionally, a full thermal model for the LATR will be described. The model will be used to ensure we meet our design requirements. Finally, we will present the results of FEA used to identify the primary vibrational modes, and planned methods for suppressing these modes. Design solutions to each of these problems that have been informed by simulation will be presented.Comment: 14 pages, 10 figures, Proceedings of SPI

PRISM (Polarized Radiation Imaging and Spectroscopy Mission): an extended white paper

Contains fulltext : 126057.pdf (preprint version ) (Open Access