Air pollution from traffic and cancer incidence: a Danish cohort study

<p>Abstract</p> <p>Background</p> <p>Vehicle engine exhaust includes ultrafine particles with a large surface area and containing absorbed polycyclic aromatic hydrocarbons, transition metals and other substances. Ultrafine particles and soluble chemicals can be transported from the airways to other organs, such as the liver, kidneys, and brain. Our aim was to investigate whether air pollution from traffic is associated with risk for other cancers than lung cancer.</p> <p>Methods</p> <p>We followed up 54,304 participants in the Danish Diet Cancer and Health cohort for 20 selected cancers in the Danish Cancer Registry, from enrolment in 1993-1997 until 2006, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used modeled concentration of nitrogen oxides (NO_x) and amount of traffic at the residence as indicators of traffic-related air pollution and used Cox models to estimate incidence rate ratios (IRRs) after adjustment for potential confounders.</p> <p>Results</p> <p>NO_xat the residence was significantly associated with risks for cervical cancer (IRR, 2.45; 95% confidence interval [CI], 1.01;5.93, per 100 μg/m³NO_x) and brain cancer (IRR, 2.28; 95% CI, 1.25;4.19, per 100 μg/m³NO_x).</p> <p>Conclusions</p> <p>This hypothesis-generating study indicates that traffic-related air pollution might increase the risks for cervical and brain cancer, which should be tested in future studies.</p

Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction

<p>Abstract</p> <p>Background</p> <p>Reliable predictions of Cytotoxic T lymphocyte (CTL) epitopes are essential for rational vaccine design. Most importantly, they can minimize the experimental effort needed to identify epitopes. NetCTL is a web-based tool designed for predicting human CTL epitopes in any given protein. It does so by integrating predictions of proteasomal cleavage, TAP transport efficiency, and MHC class I affinity. At least four other methods have been developed recently that likewise attempt to predict CTL epitopes: EpiJen, MAPPP, MHC-pathway, and WAPP. In order to compare the performance of prediction methods, objective benchmarks and standardized performance measures are needed. Here, we develop such large-scale benchmark and corresponding performance measures and report the performance of an updated version 1.2 of NetCTL in comparison with the four other methods.</p> <p>Results</p> <p>We define a number of performance measures that can handle the different types of output data from the five methods. We use two evaluation datasets consisting of known HIV CTL epitopes and their source proteins. The source proteins are split into all possible 9 mers and except for annotated epitopes; all other 9 mers are considered non-epitopes. In the RANK measure, we compare two methods at a time and count how often each of the methods rank the epitope highest. In another measure, we find the specificity of the methods at three predefined sensitivity values. Lastly, for each method, we calculate the percentage of known epitopes that rank within the 5% peptides with the highest predicted score.</p> <p>Conclusion</p> <p>NetCTL-1.2 is demonstrated to have a higher predictive performance than EpiJen, MAPPP, MHC-pathway, and WAPP on all performance measures. The higher performance of NetCTL-1.2 as compared to EpiJen and MHC-pathway is, however, not statistically significant on all measures. In the large-scale benchmark calculation consisting of 216 known HIV epitopes covering all 12 recognized HLA supertypes, the NetCTL-1.2 method was shown to have a sensitivity among the 5% top-scoring peptides above 0.72. On this dataset, the best of the other methods achieved a sensitivity of 0.64. The NetCTL-1.2 method is available at <url>http://www.cbs.dtu.dk/services/NetCTL</url>.</p> <p>All used datasets are available at <url>http://www.cbs.dtu.dk/suppl/immunology/CTL-1.2.php</url>.</p

Road Traffic Noise and Incident Myocardial Infarction: A Prospective Cohort Study

BACKGROUND Both road traffic noise and ambient air pollution have been associated with risk for ischemic heart disease, but only few inconsistent studies include both exposures. METHODS In a population-based cohort of 57 053 people aged 50 to 64 years at enrolment in 1993-1997, we identified 1600 cases of first-ever MI between enrolment and 2006. The mean follow-up time was 9.8 years. Exposure to road traffic noise and air pollution from 1988 to 2006 was estimated for all cohort members from residential address history. Associations between exposure to road traffic noise and incident MI were analysed in a Cox regression model with adjustment for air pollution (NO(x)) and other potential confounders: age, sex, education, lifestyle confounders, railway and airport noise. RESULTS We found that residential exposure to road traffic noise (L(den)) was significantly associated with MI, with an incidence rate ratio IRR of 1.12 per 10 dB for both of the two exposure windows: yearly exposure at the time of diagnosis (95% confidence interval (CI): 1.02-1.22) and 5-years time-weighted mean (95% CI: 1.02-1.23) preceding the diagnosis. Visualizing of the results using restricted cubic splines showed a linear dose-response relationship. CONCLUSIONS Exposure to long-term residential road traffic noise was associated with a higher risk for MI, in a dose-dependent manner

NetCTLpan: pan-specific MHC class I pathway epitope predictions

Reliable predictions of immunogenic peptides are essential in rational vaccine design and can minimize the experimental effort needed to identify epitopes. In this work, we describe a pan-specific major histocompatibility complex (MHC) class I epitope predictor, NetCTLpan. The method integrates predictions of proteasomal cleavage, transporter associated with antigen processing (TAP) transport efficiency, and MHC class I binding affinity into a MHC class I pathway likelihood score and is an improved and extended version of NetCTL. The NetCTLpan method performs predictions for all MHC class I molecules with known protein sequence and allows predictions for 8-, 9-, 10-, and 11-mer peptides. In order to meet the need for a low false positive rate, the method is optimized to achieve high specificity. The method was trained and validated on large datasets of experimentally identified MHC class I ligands and cytotoxic T lymphocyte (CTL) epitopes. It has been reported that MHC molecules are differentially dependent on TAP transport and proteasomal cleavage. Here, we did not find any consistent signs of such MHC dependencies, and the NetCTLpan method is implemented with fixed weights for proteasomal cleavage and TAP transport for all MHC molecules. The predictive performance of the NetCTLpan method was shown to outperform other state-of-the-art CTL epitope prediction methods. Our results further confirm the importance of using full-type human leukocyte antigen restriction information when identifying MHC class I epitopes. Using the NetCTLpan method, the experimental effort to identify 90% of new epitopes can be reduced by 15% and 40%, respectively, when compared to the NetMHCpan and NetCTL methods. The method and benchmark datasets are available at http://www.cbs.dtu.dk/services/NetCTLpan/

Identification of CD8+ T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL

West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies.In a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell epitopes, which we propose are restricted by 11 different HLA class I alleles. Aiming for optimal coverage of human populations, we suggest that 11 of these new WNV epitopes would be sufficient to cover from 48% to 93% of ethnic populations in various areas of the World.The 26 identified CD8(+) T cell epitopes contribute to our knowledge of the immune response against WNV infection and greatly extend the list of known WNV CD8(+) T cell epitopes. A polytope incorporating these and other epitopes could possibly serve as the basis for a WNV vaccine

A mixed methods inquiry into the validity of data

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Altered sense of Agency in children with spastic cerebral palsy

<p>Abstract</p> <p>Background</p> <p>Children diagnosed with spastic Cerebral Palsy (CP) often show perceptual and cognitive problems, which may contribute to their functional deficit. Here we investigated if altered ability to determine whether an observed movement is performed by themselves (sense of agency) contributes to the motor deficit in children with CP.</p> <p>Methods</p> <p>Three groups; ₁₎CP children, ₂₎healthy peers, and ₃₎healthy adults produced straight drawing movements on a pen-tablet which was not visible for the subjects. The produced movement was presented as a virtual moving object on a computer screen. Subjects had to evaluate after each trial whether the movement of the object on the computer screen was generated by themselves or by a computer program which randomly manipulated the visual feedback by angling the trajectories 0, 5, 10, 15, 20 degrees away from target.</p> <p>Results</p> <p>Healthy adults executed the movements in 310 seconds, whereas healthy children and especially CP children were significantly slower (p < 0.002) (on average 456 seconds and 543 seconds respectively). There was also a statistical difference between the healthy and age matched CP children (p = 0.037). When the trajectory of the object generated by the computer corresponded to the subject's own movements all three groups reported that they were responsible for the movement of the object. When the trajectory of the object deviated by more than 10 degrees from target, healthy adults and children more frequently than CP children reported that the computer was responsible for the movement of the object. CP children consequently also attempted to compensate more frequently from the perturbation generated by the computer.</p> <p>Conclusions</p> <p>We conclude that CP children have a reduced ability to determine whether movement of a virtual moving object is caused by themselves or an external source. We suggest that this may be related to a poor integration of their intention of movement with visual and proprioceptive information about the performed movement and that altered sense of agency may be an important functional problem in children with CP.</p

Exposure to road traffic and railway noise and associations with blood pressure and self-reported hypertension: a cohort study

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies suggest that long-term exposure to transport noise increases the risk for cardiovascular disorders. The effect of transport noise on blood pressure and hypertension is uncertain.</p> <p>Methods</p> <p>In 1993-1997, 57,053 participants aged 50-64 year were enrolled in a population-based cohort study. At enrolment, systolic and diastolic blood pressure was measured. Incident hypertension during a mean follow-up of 5.3 years was assessed by questionnaire. Residential long-term road traffic noise (L_den) was estimated for 1- and 5-year periods preceding enrolment and preceding diagnosis of hypertension. Residential exposure to railway noise was estimated at enrolment. We conducted a cross-sectional analysis of associations between road traffic and railway noise and blood pressure at enrolment with linear regression, adjusting for long-term air pollution, meteorology and potential lifestyle confounders (N = 44,083). Incident self-reported hypertension was analyzed with Cox regression, adjusting for long-term air pollution and potential lifestyle confounders.</p> <p>Results</p> <p>We found a 0.26 mm Hg higher systolic blood pressure (95% confidence intervals (CI): -0.11; 0.63) per 10 dB(A) increase in 1-year mean road traffic noise levels, with stronger associations in men (0.59 mm Hg (CI: 0.13; 1.05) per 10 dB(A)) and older participants (0.65 mm Hg (0.08; 1.22) per 10 dB(A)). Road traffic noise was not associated with diastolic blood pressure or hypertension. Exposure to railway noise above 60 dB was associated with 8% higher risk for hypertension (95% CI: -2%; 19%, P = 0.11).</p> <p>Conclusions</p> <p>While exposure to road traffic noise was associated with systolic blood pressure in subgroups, we were not able to identify associations with hypertension.</p