The Consensus Coding Sequence (Ccds) Project: Identifying a Common Protein-Coding Gene Set for the Human and Mouse Genomes

Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but not identical representation of genes, transcripts, and proteins. The collaborative consensus coding sequence (CCDS) project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier (CCDS ID), and ensures that they are consistently represented on the NCBI, Ensembl, and UCSC Genome Browsers. Importantly, the project coordinates on manually reviewing inconsistent protein annotations between sites, as well as annotations for which new evidence suggests a revision is needed, to progressively converge on a complete protein-coding set for the human and mouse reference genomes, while maintaining a high standard of reliability and biological accuracy. To date, the project has identified 20,159 human and 17,707 mouse consensus coding regions from 17,052 human and 16,893 mouse genes. Three evaluation methods indicate that the entries in the CCDS set are highly likely to represent real proteins, more so than annotations from contributing groups not included in CCDS. The CCDS database thus centralizes the function of identifying well-supported, identically-annotated, protein-coding regions.National Human Genome Research Institute (U.S.) (Grant number 1U54HG004555-01)Wellcome Trust (London, England) (Grant number WT062023)Wellcome Trust (London, England) (Grant number WT077198

Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

Objectives: No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods: In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Results: Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL. Conclusions: We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL. HIV Medicin

Ethical considerations and approaches for conducting clinical research studies related to prosthetics, orthotics and wheelchair technology in the low- and middle-income countries

Rapid developments in prosthetics, orthotics and wheelchair technology have increased clinical research and development initiatives worldwide. Testing technology involving human subjects / participants creates ethical concerns that are under-explored and become a critical issue for prosthetists, orthotists,researchers and their clients, especially those in the low- and middle-income countries. While some research initiatives have aligned with existing institutions, companies, and service providers; some research emerging from institutions / organisations with non-clinical and non-assistive technology backgrounds have raised considerable foundation for concerns. It is essential to develop, apply andpromote appropriate and clear guiding principles for institutions / organisations conducting clinical research studies or trials, particularly in the low- and middle-income countries. Thus, practicing professionals can enable people with disabilities (often among the most excluded and vulnerable group in the society) to provide informed consent, make informed choices, and facilitate their active engagement in clinical research studies or trials without physical, psychological, and socioeconomic harm.The outcome of the consultation between ISPO and Exceed Research Network (ERN) has led to the development of the guiding principles, laid out below, specifically directed towards the clinical research studies or technology trials involving people with disability (not on broader research into disability-relatedissues)

A public opinion survey of four future scenarios for Australia in 2050

Scenario planning and the use of alternative futures have been used successfully to assist organisations, communities and countries to move towards desired outcomes (Dator, 2009). In this study we used a unique combination of scenario planning and a national public opinion survey to explore preferred futures for Australia in 2050. The approach used four future scenarios for Australia in 2050 as the basis for an online national public opinion survey entitled Australia: Our Future, Your Voice. Scenario development was based on a review of a broad range of scenarios for Australia and globally. We then developed four synthesis scenarios based on two axes of individual versus community orientation, and national focus on GDP growth versus a focus on well-being more broadly defined. The scenarios were labelled: (1) Free Enterprise (FE); (2) Strong Individualism (SI); (3) Coordinated Action (CA); and (4) Community Well-being (CW). We created a website that described each of these scenarios and invited people to complete a survey after they had reviewed the scenarios. The survey engaged 2575 adults in two groups: (1) a targeted statistically representative national sample (n = 2083) and (2) a self-selected sample (n = 492). Results from both groups and across all demographic categories revealed that a majority of participants preferred the Community Well-being (CW) scenario. 73% (Representative) and 61% (Self Select) ranked this scenario as 1st or 2nd. We also asked which scenario Australia was headed toward. 32% of the Representative sample and 50% of the Self-Selected sample participants ranked the Free Enterprise (FE) scenario as the most likely future. CW was ranked least likely to be ‘where Australia is heading?’ The dissonance between the future Australians want and where they thought the country is headed has clear policy implications, which we discuss. This extension of scenario planning to include public opinion surveys is novel and this approach can be used to improve thinking, discussion, planning and policy about the future of Australia, as well as potentially other countries and regions

On the importance of first principles in ecological theory development

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On theory in ecology

We argue for expanding the role of theory in ecology to accelerate scientific progress, enhance the ability to address environmental challenges, foster the development of synthesis and unification, and improve the design of experiments and large-scale environmental-monitoring programs. To achieve these goals, it is essential to foster the development of what we call efficient theories, which have several key attributes. Efficient theories are grounded in first principles, are usually expressed in the language of mathematics, make few assumptions and generate a large number of predictions per free parameter, are approximate, and entail predictions that provide well-understood standards for comparison with empirical data. We contend that the development and successive refinement of efficient theories provide a solid foundation for advancing environmental science in the era of big data.10 page(s