Best practice guidelines for the molecular genetic diagnosis of Type 1 (HFE-related) hereditary haemochromatosis

BACKGROUND: Hereditary haemochromatosis (HH) is a recessively-inherited disorder of iron over-absorption prevalent in Caucasian populations. Affected individuals for Type 1 HH are usually either homozygous for a cysteine to tyrosine amino acid substitution at position 282 (C282Y) of the HFE gene, or compound heterozygotes for C282Y and for a histidine to aspartic acid change at position 63 (H63D). Molecular genetic testing for these two mutations has become widespread in recent years. With diverse testing methods and reporting practices in use, there was a clear need for agreed guidelines for haemochromatosis genetic testing. The UK Clinical Molecular Genetics Society has elaborated a consensus process for the development of disease-specific best practice guidelines for genetic testing. METHODS: A survey of current practice in the molecular diagnosis of haemochromatosis was conducted. Based on the results of this survey, draft guidelines were prepared using the template developed by UK Clinical Molecular Genetics Society. A workshop was held to develop the draft into a consensus document. The consensus document was then posted on the Clinical Molecular Genetics Society website for broader consultation and amendment. RESULTS: Consensus or near-consensus was achieved on all points in the draft guidelines. The consensus and consultation processes worked well, and outstanding issues were documented in an appendix to the guidelines. CONCLUSION: An agreed set of best practice guidelines were developed for diagnostic, predictive and carrier testing for hereditary haemochromatosis and for reporting the results of such testing

Modeling reverse auction-based subsidies and stormwater fee policies for Low Impact Development (LID) adoption: a system dynamics analysis

Abstract Many urban areas around the world are facing increasing pressure on stormwater management systems due to urbanization and extreme weather events caused by climate change. Low impact development (LID), including blue-green infrastructure such as rain gardens, has become an attractive addition to traditional gray infrastructure for managing stormwater. Municipalities have a limited suite of policy instruments for incentivizing installation of LID on private property. We built a system dynamics model of integrated socio-economic and hydrologic systems in Oslo, Norway to illustrate implementation of two economic incentive mechanisms: subsidies based on reverse auctions and stormwater fees. We find that policy effectiveness depends on 1) communicating realistic expectations of LID performance to landowners and 2) municipal subsidies to reach landowners without intrinsic interests in LID. Under certain conditions, lower municipal economic incentives can outperform higher economic incentives and lead to sustained long-term adoption of LID on private property.publishedVersio

The infrared imaging spectrograph (IRIS) for TMT: sensitivities and simulations

We present sensitivity estimates for point and resolved astronomical sources for the current design of the InfraRed Imaging Spectrograph (IRIS) on the future Thirty Meter Telescope (TMT). IRIS, with TMT's adaptive optics system, will achieve unprecedented point source sensitivities in the near-infrared (0.84 - 2.45 {\mu}m) when compared to systems on current 8-10m ground based telescopes. The IRIS imager, in 5 hours of total integration, will be able to perform a few percent photometry on 26 - 29 magnitude (AB) point sources in the near-infrared broadband filters (Z, Y, J, H, K). The integral field spectrograph, with a range of scales and filters, will achieve good signal-to-noise on 22 - 26 magnitude (AB) point sources with a spectral resolution of R=4,000 in 5 hours of total integration time. We also present simulated 3D IRIS data of resolved high-redshift star forming galaxies (1 < z < 5), illustrating the extraordinary potential of this instrument to probe the dynamics, assembly, and chemical abundances of galaxies in the early universe. With its finest spatial scales, IRIS will be able to study luminous, massive, high-redshift star forming galaxies (star formation rates ~ 10 - 100 M yr-1) at ~100 pc resolution. Utilizing the coarsest spatial scales, IRIS will be able to observe fainter, less massive high-redshift galaxies, with integrated star formation rates less than 1 M yr-1, yielding a factor of 3 to 10 gain in sensitivity compared to current integral field spectrographs. The combination of both fine and coarse spatial scales with the diffraction-limit of the TMT will significantly advance our understanding of early galaxy formation processes and their subsequent evolution into presentday galaxies.Comment: SPIE Astronomical Instrumentation 201

The infrared imaging spectrograph (IRIS) for TMT: spectrograph design

The Infra-Red Imaging Spectrograph (IRIS) is one of the three first light instruments for the Thirty Meter Telescope (TMT) and is the only one to directly sample the diffraction limit. The instrument consists of a parallel imager and off-axis Integral Field Spectrograph (IFS) for optimum use of the near infrared (0.84um-2.4um) Adaptive Optics corrected focal surface. We present an overview of the IRIS spectrograph that is designed to probe a range of scientific targets from the dynamics and morphology of high-z galaxies to studying the atmospheres and surfaces of solar system objects, the latter requiring a narrow field and high Strehl performance. The IRIS spectrograph is a hybrid system consisting of two state of the art IFS technologies providing four plate scales (4mas, 9mas, 25mas, 50mas spaxel sizes). We present the design of the unique hybrid system that combines the power of a lenslet spectrograph and image slicer spectrograph in a configuration where major hardware is shared. The result is a powerful yet economical solution to what would otherwise require two separate 30m-class instruments.Comment: 15 pages, 11 figure

Subtype diversity and reassortment potential for co‐circulating avian influenza viruses at a diversity hot spot

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106946/1/jane12167.pd

Factors that sustain indigenous youth mentoring programs : a qualitative systematic review

Background Indigenous youth worldwide continue to experience disproportional rates of poorer mental health and well-being compared to non-Indigenous youth. Mentoring has been known to establish favorable outcomes in many areas of health but is still in its early phases of research within Indigenous contexts. This paper explores the barriers and facilitators of Indigenous youth mentoring programs to improve mental health outcomes and provides evidence for governments’ response to the United Nations Declaration on the Rights of Indigenous Peoples. Methods A systematic search for published studies was conducted on PubMed, Embase, Scopus, CINAHL, and grey literature through Trove, OpenGrey, Indigenous HealthInfoNet, and Informit Indigenous Collection. All papers included in the search were peer-reviewed and published from 2007 to 2021. The Joanna Briggs Institute approaches to critical appraisal, data extraction, data synthesis, and confidence of findings were used. Results A total of eight papers describing six mentoring programs were included in this review; six papers were from Canada, and two originated from Australia. Studies included mentor perspectives (n=4) (incorporating views of parents, carers, Aboriginal assistant teachers, Indigenous program facilitators, young adult health leaders, and community Elders), mentee perspectives (n=1), and both mentor and mentee perspectives (n=3). Programs were conducted nationally (n=3) or within specific local Indigenous communities (n=3) with varying mentor styles and program focus. Five synthesized findings were identified from the data extraction process, each consisting of four categories. These synthesized findings were: establishing cultural relevancy, facilitating environments, building relationships, facilitating community engagement, and leadership responsibilities, which were discussed in the context of extant mentoring theoretical frameworks. Conclusion Mentoring is an appropriate strategy for improving general well-being. However, more research is needed to explore program sustainability and maintaining outcomes in the long term

Cloning and functional characterization of the fatty acid elongase 1 (FAE1) gene from high erucic Crambe abyssinica cv. Prophet.

A genomic fatty acid elongation 1 (FAE1) clone was isolated from Crambe abyssinica. The genomic clone corresponds to a 1521-bp open reading frame, which encodes a protein of 507 amino acids. In yeast cells expression of CrFAE led to production of new very long chain monounsaturated fatty acids such as eicosenoic (20:1(delta11)) and erucic (22:1(delta13)) acids. Seed-specific expression in Arabidopsis thaliana resulted in up to a 12-fold increase in the proportion of erucic acid. On the other hand, in transgenic high-erucic Brassica carinata plants, the proportion of erucic acid was as high as 51.9% in the best transgenic line, a net increase of 40% compared to wild type. These results indicate that the CrFAE gene encodes a condensing enzyme involved in the biosynthesis of very long-chain fatty acids utilizing monounsaturated and saturated acyl substrates, with a strong capability for improving the erucic acid content

The infrared imaging spectrograph (IRIS) for TMT: the science case

The InfraRed Imaging Spectrograph (IRIS) is a first-light instrument being designed for the Thirty Meter Telescope (TMT). IRIS is a combination of an imager that will cover a 16.4" field of view at the diffraction limit of TMT (4 mas sampling), and an integral field unit spectrograph that will sample objects at 4-50 mas scales. IRIS will open up new areas of observational parameter space, allowing major progress in diverse fields of astronomy. We present the science case and resulting requirements for the performance of IRIS. Ultimately, the spectrograph will enable very well-resolved and sensitive studies of the kinematics and internal chemical abundances of high-redshift galaxies, shedding light on many scenarios for the evolution of galaxies at early times. With unprecedented imaging and spectroscopy of exoplanets, IRIS will allow detailed exploration of a range of planetary systems that are inaccessible with current technology. By revealing details about resolved stellar populations in nearby galaxies, it will directly probe the formation of systems like our own Milky Way. Because it will be possible to directly characterize the stellar initial mass function in many environments and in galaxies outside of the the Milky Way, IRIS will enable a greater understanding of whether stars form differently in diverse conditions. IRIS will reveal detailed kinematics in the centers of low-mass galaxies, allowing a test of black hole formation scenarios. Finally, it will revolutionize the characterization of reionization and the first galaxies to form in the universe.Comment: to appear in Proc. SPIE 773