6 research outputs found

    Vertical T cell immunodominance and epitope entropy determine HIV-1 escape.

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    HIV-1 accumulates mutations in and around reactive epitopes to escape recognition and killing by CD8+ T cells. Measurements of HIV-1 time to escape should therefore provide information on which parameters are most important for T cell–mediated in vivo control of HIV-1. Primary HIV-1–specific T cell responses were fully mapped in 17 individuals, and the time to virus escape, which ranged from days to years, was measured for each epitope. While higher magnitude of an individual T cell response was associated with more rapid escape, the most significant T cell measure was its relative immunodominance measured in acute infection. This identified subject-level or “vertical” immunodominance as the primary determinant of in vivo CD8+ T cell pressure in HIV-1 infection. Conversely, escape was slowed significantly by lower population variability, or entropy, of the epitope targeted. Immunodominance and epitope entropy combined to explain half of all the variability in time to escape. These data explain how CD8+ T cells can exert significant and sustained HIV-1 pressure even when escape is very slow and that within an individual, the impacts of other T cell factors on HIV-1 escape should be considered in the context of immunodominance

    Home mechanical ventilation: A Canadian Thoracic Society clinical practice guideline

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    Preventive airway management and home mechanical ventilation (HMV) is a complex, interdisciplinary component of respiratory care and clinical practice. However, the rising costs of hospital care and the advent of commercially available equipment, coupled with the desire of individuals to maintain an in-home quality of life has fuelled the demand for HMV. The Canadian Thoracic Society HMV Guidelines Committee developed this up-to-date, evidence-based, clinical practice guideline as a resource for physicians, health care providers, policy makers and patients at risk for or currently using ventilatory support in the home

    Home Mechanical Ventilation: A Canadian Thoracic Society Clinical Practice Guideline

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    Increasing numbers of patients are surviving episodes of prolonged mechanical ventilation or benefitting from the recent availability of user-friendly noninvasive ventilators. Although many publications pertaining to specific aspects of home mechanical ventilation (HMV) exist, very few comprehensive guidelines that bring together all of the current literature on patients at risk for or using mechanical ventilatory support are available. The Canadian Thoracic Society HMV Guideline Committee has reviewed the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. The guideline provides a disease-specific review of illnesses including amyotrophic lateral sclerosis, spinal cord injury, muscular dystrophies, myotonic dystrophy, kyphoscoliosis, post-polio syndrome, central hypoventilation syndrome, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease as well as important common themes such as airway clearance and the process of transition to home. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information.Peer Reviewe
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