Protective immunity generated following malaria infection may be comprised of Ab or T cells against malaria Ag of different stages; however, the short-lived immunity that is observed suggests ...deficiency in immune memory or regulatory activity. In this study, cellular immune responses were investigated in individuals receiving Plasmodium falciparum sporozoite challenge by the natural (mosquito bite) route as part of a malaria vaccine efficacy trial. Parasitemia, monitored by blood film microscopy and PCR, was subsequently cleared with drugs. All individuals demonstrated stable IFN-γ, IL-2 and IL-4 ex vivo ELISPOT effector responses against P. falciparum-infected RBC (iRBC) Ag, 28 and 90 days after challenge. However, infected RBC-specific central memory responses, as measured by IFN-γ cultured ELISPOT, were low and unstable over time, despite CD4⁺ T cells being highly proliferative by CFSE dilution, and showed an inverse relationship to parasite density. In support of the observation of poor memory, co-culture experiments showed reduced responses to common recall Ag, indicating malaria-specific regulatory activity. This activity could not be accounted for by the expression of IL-10, TGF-β, FOXP3 or CTLA-4, but proliferating T cells expressed high levels of CD95, indicating a pro-apoptotic phenotype. Lastly, there was an inverse relationship between FOXP3 expression, when measured 10 days after challenge, and ex vivo IFN-γ measured more than 100 days later. This study shows that malaria infection elicits specific Th1 and Th2 effector cells, but concomitant weak central memory and regulatory activity, which may help to explain the short-lived immunity observed.
ObjectivesThe contribution of occupational exposures to the cancer burden can be estimated using population-attributable fractions, which is of great importance for policy making. This paper reviews ...occupational carcinogens, and presents the most relevant risk relations to cancer in high-income countries using France as an example, to provide a framework for national estimation of cancer burden attributable to occupational exposure.MethodsOccupational exposures that should be included in cancer burden studies were evaluated using multiple criteria: classified as carcinogenic or probably carcinogenic by the International Agency for Research on Cancer (IARC) Monographs volumes 1–114, being a primary occupational exposure, historical and current presence of the exposure in France and the availability of exposure and risk relation data. Relative risk estimates were obtained from published systematic reviews and from the IARC Monographs.ResultsOf the 118 group 1 and 75 group 2A carcinogens, 37 exposures and 73 exposure-cancer site pairs were relevant. Lung cancer was associated with the most occupational carcinogenic exposures (namely, 18), followed by bladder cancer and non-Hodgkin’s lymphoma. Ionising radiation was associated with the highest number of cancer sites (namely, 20), followed by asbestos and working in the rubber manufacturing industry. Asbestos, bis(chloromethyl)ether, nickel and wood dust had the strongest effect on cancer, with relative risks above 5.ConclusionsA large number of occupational exposures continues to impact the burden of cancer in high-income countries such as France. Information on types of exposures, affected jobs, industries and cancer sites affected is key for prioritising policy and prevention initiatives.
Cancers in France in 2015 attributable to occupational exposures Marant Micallef, Claire; Shield, Kevin D.; Vignat, Jérôme ...
International journal of hygiene and environmental health,
January 2019, 2019-01-00, 2019-01-01, Letnik:
222, Številka:
1
Journal Article
Recenzirano
Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking.
To estimate the number of new cancer cases attributable to ...occupational exposures, using a newly developed methodology and the most recent data, for a comprehensive set of occupational carcinogens in France in 2015.
Surveys among employees, the national labor force data, a cohort of agricultural workers, national monitoring of workers exposed to ionizing radiation and job-exposure matrix in France were used. The number and proportion of new cancer cases attributable to established occupational carcinogens (Group 1) was estimated using estimation of lifetime exposure and risk estimates from cohort studies. Cancer data were obtained from the French Cancer Registries Network.
In France in 2015, an estimated 7905 new cancer cases, 7336 among men and 569 among women, were attributable to occupational exposures, representing 2.3% of all new cancer cases (3.9% and 0.4% among men and women respectively). Among men and women, lung cancer was impacted the most, followed by mesothelioma and bladder cancer in men, and by mesothelioma and ovary in women. These cancers contributed to 89% of the total cancers attributable to occupational carcinogens in men, and to 80% in women. The main contributing occupational agent was asbestos among men (45%) and women (60%).
Currently, occupational exposures contribute to a substantial burden of cancer in France. Enhanced monitoring and implementation of protective labor policies could potentially prevent a large proportion of these cancers.
In recent years, researchers and clinicians have been developing prognostic prediction tools (PPTs) as a way of identifying patients at risk of deterioration. The use of PPTs in the clinical ...environment not only impacts the risk of adverse outcomes for patients, but the use of these tools also effect clinical practice. Much attention has been paid to the clinical performance of PPTs. But more insight is needed on how the use of PPTs impacts clinical practice. The objective of this study was to map some of the ways in which PPTs effect clinical practice. The STUMBL (STUdy evaluating the impact of a prognostic model for Management of BLunt chest wall trauma patients) feasibility trial evaluated the use of a new prognostic prediction tool (PPT) to guide the management blunt chest wall trauma patients in the emergency departments (ED). The trial was undertaken between October 2016 and September 2018 and conducted at four sites in England and Wales. Nested within the feasibility trial was a qualitative study aimed at understanding how ED clinicians experienced and used the PPT. The qualitative methods included a focus group and telephone interviews with 9 ED clinicians. This study focused on participant perceptions of the feasibility and use of the STUMBL tool on clinical practice in the ED.
Clinical practice is reshaped as a result of the introduction of the STUMBL PPT into the clinical environment. The PPT enhanced reflexive awareness of prognostic practice; facilitated communication between patients and professionals; helps to guide patient outcomes; and provides a common ground for clinician discussion on prognostication.
The qualitative data collected offered useful insights into the ways in which the tool changes clinical practice. This was a small study of the effect of one kind of PPT on clinical practice. Nevertheless, this study maps areas in which clinical practice is affected by the introduction of a PPT into the clinical environment. More research is needed to better understand these effects, and to understand how these tools become embedded in clinical practice over the longer term.
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