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Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1Î² secretion in response to anti-MPO antibodies. - Scientific reports
ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1Î², IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1Î² in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis, and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.
Non-linear, cata-Condensed, Polycyclic Aromatic Hydrocarbon Materials: A Generic Approach and Physical Properties. - Chemistry (Weinheim an der Bergstrasse, Germany)
A generic approach to the regiospecific synthesis of halogenated polycyclic aromatics is made possible by the one- or two-directional benzannulation reactions of readily available (ortho-allylaryl)trichloroacetates (the "BHQ" reaction). Palladium-catalysed cross-coupling reactions of the so-formed haloaromatics enable the synthesis of functionalised polycyclic aromatic hydrocarbons (PAHs) with surgical precision. Overall, this new methodology enables the facile mining of chemical space in search of new electronic functional materials.Â© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Low-dose ionising radiation and cardiovascular diseases - Strategies for molecular epidemiological studies in Europe. - Mutation research. Reviews in mutation research
It is well established that high-dose ionising radiation causes cardiovascular diseases. In contrast, the evidence for a causal relationship between long-term risk of cardiovascular diseases after moderate doses (0.5-5Gy) is suggestive and weak after low doses (<0.5Gy). However, evidence is emerging that doses under 0.5Gy may also increase long-term risk of cardiovascular disease. This would have major implications for radiation protection with respect to medical use of radiation for diagnostic purposes and occupational or environmental radiation exposure. Therefore, it is of great importance to gain information about the presence and possible magnitude of radiation-related cardiovascular disease risk at doses of less than 0.5Gy. The biological mechanisms implicated in any such effects are unclear and results from epidemiological studies are inconsistent. Molecular epidemiological studies can improve the understanding of the pathogenesis and the risk estimation of radiation-induced circulatory disease at low doses. Within the European DoReMi (Low Dose Research towards Multidisciplinary Integration) project, strategies to conduct molecular epidemiological studies in this field have been developed and evaluated. Key potentially useful European cohorts are the Mayak workers, other nuclear workers, uranium miners, Chernobyl liquidators, the Techa river residents and several diagnostic or low-dose radiotherapy patient cohorts. Criteria for informative studies are given and biomarkers to be investigated suggested. A close collaboration between epidemiology, biology and dosimetry is recommended, not only among experts in the radiation field, but also those in cardiovascular diseases.Copyright Â© 2015 Elsevier B.V. All rights reserved.
Ambient temperature and risk of first primary basal cell carcinoma: A nationwide United States cohort study. - Journal of photochemistry and photobiology. B, Biology
The Earth's surface is warming and animal studies have shown higher temperatures promote ultraviolet radiation (UVR) skin carcinogenesis. There are, however, no population studies of long-term temperature exposure and basal cell carcinoma (BCC) risk. We linked average lifetime summer ambient temperatures (based on weather station data) and satellite-based UVR estimates to self-reported lifetime residences in the U.S. Radiologic Technologists' cohort. We assessed the relationship between time-dependent average lifetime summer ambient temperature (20-year lag) in quintiles and BCC in whites, using Cox proportional hazards regression. Risks were adjusted for time-dependent lagged average lifetime UVR and time outdoors, body mass index, eye color, and sex (baseline hazard stratified on birth cohort). During a median 19.4years follow-up, we identified 3556 BCC cases. There was no significant trend in risk between temperature and BCC. However, BCC risk was highest in the fourth quintile of temperature (Q4 vs. Q1; hazards ratio (HR)=1.18; 95% confidence interval (CI)=1.06-1.31, p-trend=0.09). BCC risk was strongly related to average lifetime ambient UVR exposure (Q5 vs. Q1; HR=1.54 (95% CI=1.35-1.75, p-trend=<0.001)). Future studies of temperature and BCC risk should include a broad range of UVR and temperature values, along with improved indicators of exposure to temperatures and UVR.Published by Elsevier B.V.
Breast cancer incidence in a cohort of U.S. flight attendants. - American journal of industrial medicine
Flight attendants may have elevated breast cancer incidence (BCI). We evaluated BCI's association with cosmic radiation dose and circadian rhythm disruption among 6,093 female former U.S. flight attendants.We collected questionnaire data on BCI and risk factors for breast cancer from 2002-2005. We conducted analyses to evaluate (i) BCI in the cohort compared to the U.S. population; and (ii) exposure-response relations. We applied an indirect adjustment to estimate whether parity and age at first birth (AFB) differences between the cohort and U.S. population could explain BCI that differed from expectation.BCI was elevated but may be explained by lower parity and older AFB in the cohort than among U.S. women. BCI was not associated with exposure metrics in the cohort overall. Significant positive associations with both were observed only among women with parity of three or more.Future cohort analyses may be informative on the role of these occupational exposures and non-occupational risk factors.Â© 2015 Wiley Periodicals, Inc.
Getting the balance right: adverse events of therapy in anti-neutrophil cytoplasm antibody vasculitis. - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Antineutrophil cytoplasm antibody associated systemic vasculitides (AASV) have traditionally been managed with a combination of cyclophosphamide and glucocorticoids during the induction phase, followed by azathioprine in the maintenance phase. Whilst these therapies have markedly improved the prognosis in AASV, treatment related adverse events remain a major challenge and include complications such as infection, glucocorticoid related side effects, malignancy, cardiovascular disease, infertility and death. Newer biologic therapies have been shown to demonstrate equivalent efficacy as cyclophosphamide for remission but the hoped for reduction in adverse events has yet to be realised. More recent efforts have been focused on refining existing therapeutic regimens and strategies, tailoring individual treatment to disease severity, patient age and kidney function to derive maximum treatment efficacy while minimising treatment toxicity. In particular, current interventional trials are targeting a reduction in corticosteroid exposure in an effort to make induction and maintenance regimens safer.Â© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Task-based measures of image quality and their relation to radiation dose and patient risk. - Physics in medicine and biology
The theory of task-based assessment of image quality is reviewed in the context of imaging with ionizing radiation, and objective figuresÂ of merit (FOMs) for image quality are summarized. The variation of the FOMs with the task, the observer and especially with the mean number of photons recorded in the image is discussed. Then various standard methods for specifying radiation dose are reviewed and related to the mean number of photons in the image and hence to image quality. Current knowledge of the relation between local radiation dose and the risk of various adverse effects is summarized, and some graphical depictions of the tradeoffs between image quality and risk are introduced. Then various dose-reduction strategies are discussed in terms of their effect on task-based measures of image quality.
Postoperative doppler evaluation of liver transplants. - The Indian journal of radiology & imaging
Doppler ultrasound plays an important role in the postoperative management of hepatic transplantation, by enabling early detection and treatment of various vascular complications. This article describes the normal Doppler findings following liver transplantation and reviews the imaging appearances of various vascular complications associated with it. The article also discusses transient waveform abnormalities, often seen on a post-transplant Doppler examination, and the importance of differentiating them from findings suggestive of ominous vascular complications.
Radiation organ doses received in a nationwide cohort of U.S. radiologic technologists: methods and findings. - Radiation research
In this article, we describe recent methodological enhancements and findings from the dose reconstruction component of a study of health risks among U.S. radiologic technologists. An earlier version of the dosimetry published in 2006 used physical and statistical models, literature-reported exposure measurements for the years before 1960, and archival personnel monitoring badge data from cohort members through 1984. The data and models previously described were used to estimate annual occupational radiation doses for 90,000 radiological technologists, incorporating information about each individual's employment practices based on a baseline survey conducted in the mid-1980s. The dosimetry methods presented here, while using many of the same methods as before, now estimate 2.23 million annual badge doses (personal dose equivalent) for the years 1916-1997 for 110,374 technologists, but with numerous methodological improvements. Every technologist's annual dose is estimated as a probability density function to reflect uncertainty about the true dose. Multiple realizations of the entire cohort distribution were derived to account for shared uncertainties and possible biases in the input data and assumptions used. Major improvements in the dosimetry methods from the earlier version include: A substantial increase in the number of cohort member annual badge dose measurements; Additional information on individual apron usage obtained from surveys conducted in the mid-1990s and mid-2000s; Refined modeling to develop lognormal annual badge dose probability density functions using censored data regression models; Refinements of cohort-based annual badge probability density functions to reflect individual work patterns and practices reported on questionnaires and to more accurately assess minimum detection limits; and Extensive refinements in organ dose conversion coefficients to account for uncertainties in radiographic machine settings for the radiographic techniques employed. For organ dose estimation, we rely on well-researched assumptions about critical exposure-related variables and their changes over the decades, including the peak kilovoltage and filtration typically used in conducting radiographic examinations, and the usual body location for wearing radiation monitoring badges, the latter based on both literature and national recommendations. We have derived organ dose conversion coefficients based on air-kerma weighting of photon fluences from published X-ray spectra and derived energy-dependent transmission factors for protective lead aprons of different thicknesses. Findings are presented on estimated organ doses for 12 organs and tissues: red bone marrow, female breast, thyroid, brain, lung, heart, colon, ovary, testes, skin of trunk, skin of head and neck and arms, and lens of the eye.
Analysis of thyroid malignant pathologic findings identified during 3 rounds of screening (1997-2008) of a cohort of children and adolescents from belarus exposed to radioiodines after the Chernobyl accident. - Cancer
Recent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear.A cohort of 11,664 individuals in Belarus who were aged â‰¤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression.In total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1; <1%). Higher I-131 doses were associated with higher frequency of solid and diffuse sclerosing variants of thyroid cancer (Pâ€‰<â€‰.01) and histologic features of cancer aggressiveness, such as lymphatic vessel invasion, intrathyroidal infiltration, and multifocality (all Pâ€‰<â€‰.03). Latency was not correlated with radiation dose. Fifty-two patients with self-reported thyroid cancers which were diagnosed before 1997 were younger at the time of the accident and had a higher percentage of solid variant cancers compared with patients who had screening-detected thyroid cancers (all Pâ€‰<â€‰.0001).I-131 thyroid radiation doses were associated with a significantly greater frequency of solid and diffuse sclerosing variants of thyroid cancer and various features of tumor aggressiveness.Â© 2014 American Cancer Society.
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