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Shafi S.,Kings College London | Vantourout P.,Kings College London | Vantourout P.,Cancer Research UK Research Institute | Wallace G.,University of Birmingham | And 7 more authors.
Science Translational Medicine | Year: 2011

DNA damage or other physicochemical stresses may increase the expression of major histocompatibility complex class I-related stress antigens, which then activate lymphocytes. This lymphoid stress surveillance (LSS) not only can limit tumor formation but may also promote immunopathology. MICA is a highly polymorphic human stress antigen implicated in tumor surveillance, inflammation, and transplant rejection. However, LSS has not been conclusively demonstrated in humans, and the functional role for MICA polymorphisms remains to be established. We show that MICA coding sequence polymorphisms substantially affected RNA and protein expression. All donors tested showed LSS responses of γδ T and natural killer cells, but unexpectedly, each was individually "tuned."Hence, some responded optimally to highly expressed alleles, whereas others responded better to lower MICA expression, challenging the orthodoxy that higher stress antigen levels promote greater responsiveness. These individual variations in LSS tuning may help explain patient-specific differences in tumor immune surveillance, transplant rejection, and inflammation, as well as provide insight into immune evasion and immunosuppression. Source


Grant P.,St thomasHospital
Quality Management in Health Care | Year: 2011

Background: Health care is a highly regulated environment. This has driven what could be characterized as a paper-safe approach, whereby organizations are required to demonstrate to a multiplicity of regulators, inspectorates, and accrediting bodies that they are paper safe. However, for many organizations, this has not produced a system that is actually patient safe; rather, it has in practice operated as a parallel system that does not reflect the true state of safety. This project looks at a quality improvement and patient safety program and critically asks the question of whether it is flawed because of failure to address issues surrounding doctors and cultural change. Methods: Johnson & Schole's cultural web framework was used to explore the attitudes of junior doctors toward a patient safety and quality improvement program. Data collection was through the use of focus groups backed up with quantitative data from a web based questionnaire survey. Results: It has been demonstrated that doctors represent a dominant subculture within the National Health Service and their beliefs, attitudes, and value are often at odds or unrecognized by senior health care managers. Conclusions: Unless the cultural differences are adequately addressed, transformational change projects such as "Best & Safest Care" are unlikely to succeed. A better understanding of the organizational context allows for more appropriate change interventions to be developed. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Santos A.F.,St thomasHospital | Santos A.F.,and Asthma Center in Allergic Mechanisms of Asthma | Santos A.F.,University of Coimbra | Du Toit G.,St thomasHospital | And 11 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background The management of peanut allergy relies on allergen avoidance and epinephrine autoinjector for rescue treatment in patients at risk of anaphylaxis. Biomarkers of severity and threshold of allergic reactions to peanut could significantly improve the care for patients with peanut allergy.Objective We sought to assess the utility of the basophil activation test (BAT) to predict the severity and threshold of reactivity to peanut during oral food challenges (OFCs).Methods The severity of the allergic reaction and the threshold dose during OFCs to peanut were determined. Skin prick tests, measurements of specific IgE to peanut and its components, and BATs to peanut were performed on the day of the challenge.Results Of the 124 children submitted to OFCs to peanut, 52 (median age, 5 years) reacted with clinical symptoms that ranged from mild oral symptoms to anaphylaxis. Severe reactions occurred in 41% of cases, and 57% reacted to 0.1 g or less of peanut protein. The ratio of the percentage of CD63+ basophils after stimulation with peanut and after stimulation with anti-IgE (CD63 peanut/anti-IgE) was independently associated with severity (P =.001), whereas the basophil allergen threshold sensitivity CD-sens (1/EC50 × 100, where EC50 is half maximal effective concentration) value was independently associated with the threshold (P =.020) of allergic reactions to peanut during OFCs. Patients with CD63 peanut/anti-IgE levels of 1.3 or greater had an increased risk of severe reactions (relative risk, 3.4; 95% CI, 1.8-6.2). Patients with a CD-sens value of 84 or greater had an increased risk of reacting to 0.1 g or less of peanut protein (relative risk, 1.9; 95% CI, 1.3-2.8).Conclusions Basophil reactivity is associated with severity and basophil sensitivity is associated with the threshold of allergic reactions to peanut. CD63 peanut/anti-IgE and CD-sens values can be used to estimate the severity and threshold of allergic reactions during OFCs. © 2014 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma and Immunology. Source

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