Berufsgenossenschaft Rohstoffe und chemische Industrie

This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m(-3) for inhalable and 1.29 mg m(-3) for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m(-3)). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements <LOD from the regression equation with manganese to estimate determinants of the exposure to welding fume. Concentrations were mainly predicted by the welding process and were significantly higher when local exhaust ventilation (LEV) was inefficient or when welding was performed in confined spaces. Substitution of high-emission techniques like FCAW, efficient LEV, and using PAPRs where applicable can reduce exposure to welding fume. However, harmonizing the different exposure metrics for UFP (as particle counts) and for the respirable or inhalable fraction of the welding fume (expressed as their mass) remains challenging.

The renin-angiotensin system plays an important role in the progression of chronic renal disease. Although the expression of renin and angiotensin-converting enzyme in experimental and human renal disease has been well characterized, no information is available regarding human angiotensin type 1 (AT1) receptor expression. The net effect of renin depends on AT1 receptor expression, among other factors. Receptor expression was determined in renal biopsy samples (including all tissue components) and isolated glomeruli from patients with glomerulonephritis (GN) or diabetic nephropathy (non-insulin-dependent diabetes mellitus). Biopsy samples and isolated glomeruli from tumor-free tissue from tumor nephrectomies served as controls. Human AT1 receptor gene expression was determined by quantitative reverse transcription-PCR, using an AT1 receptor deletion mutant as the internal standard. In whole biopsy samples from 37 patients with various types of GN, AT1 receptor mRNA levels were lower, compared with nine control biopsy samples (P < 0.001). AT1 receptor mRNA levels were also significantly lower (P < 0.001) in eight samples from patients with diabetic nephropathy. In microdissected glomeruli, AT1 receptor gene expression was significantly lower in samples from patients (n = 22) with various types of GN, compared with 12 microdissected tumor nephrectomy control samples (P < 0.0023). It is concluded that AT1 receptor mRNA expression is low in glomeruli of patients with chronic renal disease. This may reflect a regulatory response to (inappropriately) high intrarenal angiotensin II concentrations.

BACKGROUND: SYNERGY is a large pooled analysis of case-control studies on the joint effects of occupational carcinogens and smoking in the development of lung cancer. A quantitative job-exposure matrix (JEM) will be developed to assign exposures to five major lung carcinogens [asbestos, chromium, nickel, polycyclic aromatic hydrocarbons (PAH), and respirable crystalline silica (RCS)]. We assembled an exposure database, called ExpoSYN, to enable such a quantitative exposure assessment. METHODS: Existing exposure databases were identified and European and Canadian research institutes were approached to identify pertinent exposure measurement data. Results of individual air measurements were entered anonymized according to a standardized protocol. RESULTS: The ExpoSYN database currently includes 356 551 measurements from 19 countries. In total, 140 666 personal and 215 885 stationary data points were available. Measurements were distributed over the five agents as follows: RCS (42%), asbestos (20%), chromium (16%), nickel (15%), and PAH (7%). The measurement data cover the time period from 1951 to present. However, only a small portion of measurements (1.4%) were performed prior to 1975. The major contributing countries for personal measurements were Germany (32%), UK (22%), France (14%), and Norway and Canada (both 11%). CONCLUSIONS: ExpoSYN is a unique occupational exposure database with measurements from 18 European countries and Canada covering a time period of >50 years. This database will be used to develop a country-, job-, and time period-specific quantitative JEM. This JEM will enable data-driven quantitative exposure assessment in a multinational pooled analysis of community-based lung cancer case-control studies.

UNLABELLED: What's known on the subject? and What does the study add? The prognosis of bladder cancer significantly depends on tumour stage and time of diagnosis so early diagnosis is desirable to decrease mortality and treatment costs. The NMP22 test is approved for clinical application by the Food and Drug Administration (FDA) of the US. Previous studies have reported values of 47-100% for sensitivity and 58-91% for specificity with this test, but there is no new data on the predictive value of NMP22 for screening bladder cancer (BC). The most important risk factor for BC is the tobacco consumption but occupational exposure to carcinogenic substances, especially aromatic amines, is regarded as another risk factor. The UroScreen study is a prospective longitudinal study for the early detection of BC. To our knowledge, it is the largest prospective validation study conducted over the longest period of time. The study results led us to conclude that, based on the currently available data, NMP22 should not be regarded as an alternative to endoscopy, and we could not make a general recommendation for screening or follow-up. The UroScreen results indicate that urine-based molecular markers could be a suitable addition to urine cytology and the detection of microhaematuria. OBJECTIVE: To evaluate the value of nuclear matrix protein-22 (NMP22) in bladder cancer (BC) screening, and its effect on variables in a prospective study in a high-risk population. PATIENTS AND METHODS: A total of 1772 chemical workers (mean age 62 years) exposed to carcinogenic aromatic amines were enrolled in the study. In all, 7091 screening check-ups in 1609 subjects were performed. Urine samples were collected for a quantitative NMP22 immunoassay, urine analysis and creatinine concentration assessment. Cystoscopy and subsequent transurethral resection were performed where there were suspicious findings. RESULTS: Histopathological analysis found three papillary urothelial neoplasms of low malignant potential, five recurrent BCs and 13 primary BCs. Three tumours were at a muscle-invasive stage (pT2, pT3a or pT3b). We found higher NMP22 concentrations (>10 U/mL) in 224 patients, which correctly predicted BC in six cases (sensitivity 97.29%, specificity 28.57%; negative predictive value 99.04%, positive predictive value 12.24%). Gross haematuria affected NMP22 results (odd ratio [OR] 3.49, 95% confidence interval [CI] 1.81-6.73). Infection also affected NMP22 results (OR 4.13, 95% CI 2.31-7.35). NMP22 was more frequently positive in urine with creatinine concentration >2.5 g/L (OR 1.61, 95% CI 0.91-2.86). CONCLUSIONS: NMP22 outcomes are affected by haematuria, infection and concentrated urine. NMP22 alone cannot be recommended for primary screening in a high-risk population nor as an alternative to cystoscopy during follow-up. A NMP22 test might be a useful adjunct to urine cytology.

We present the first tests of a new method, the correlated component analysis (CCA) based on second-order statistics, to estimate the mixing matrix, a key ingredient to separate astrophysical foregrounds superimposed to the Cosmic Microwave Background (CMB). In the present application, the mixing matrix is parametrized in terms of the spectral indices of Galactic synchrotron and thermal dust emissions, while the free-free spectral index is prescribed by basic physics, and is thus assumed to be known. We consider simulated observations of the microwave sky with angular resolution and white stationary noise at the nominal levels for the Planck satellite, and realistic foreground emissions, with a position-dependent synchrotron spectral index. We work with two sets of Planck frequency channels: the low-frequency set, from 30 to 143 GHz, complemented with the Haslam 408 MHz map, and the high-frequency set, from 217 to 545 GHz. The concentration of intense free-free emission on the Galactic plane introduces a steep dependence of the spectral index of the global Galactic emission with Galactic latitude, close to the Galactic equator. This feature makes difficult for the CCA to recover the synchrotron spectral index in this region, given the limited angular resolution of Planck, especially at low frequencies. A cut of a narrow strip around the Galactic equator (|b| < 3 ), however, allows us to overcome this problem. We show that, once this strip is removed, the CCA allows an effective foreground subtraction, with residual uncertainties inducing a minor contribution to errors on the recovered CMB power spectrum.

BACKGROUND: A work force based case-control study of lung cancer was performed in non-silicotic subjects exposed to crystalline silica to investigate the association between silica dust and lung cancer excluding the influence of silicosis. METHODS: Two hundred and forty seven patients with lung cancer and 795 control subjects were enrolled, all of whom had been employed in the German stone, quarrying, or ceramics industries. Smoking was used as a matching criterion. Exposure to silica was quantified by measurements, if available, or otherwise by industrial hygienists. Several indices (peak, average and cumulative exposure) were used to analyse the relationship between the level of exposure and risk of lung cancer as odds ratios (OR). RESULTS: The risk of lung cancer is associated with the year of and age at first exposure to silica, duration of exposure, and latency. All odds ratios were adjusted for these factors. Considering the peak exposure, the OR for workers exposed to high levels (>/=0.15 mg/m3 respirable silica dust which is the current occupational threshold value for Germany) compared with those exposed to low levels (<0.15 mg/m3) was 0.85 (95% CI 0.58 to 1. 25). For the time weighted average exposure the OR was 0.91 (95% CI 0.57 to 1.46). The OR for the cumulative exposure was 1.02 (95% CI 0. 67 to 1.55). No increase in risk was evident with increasing exposure. CONCLUSIONS: This study shows no association between exposure to crystalline silica and lung cancer. The exclusion of subjects with silicosis may have led to dilution with respect to the level of exposure and therefore reduced the power to detect a small risk. Alternatively, the risk of getting lung cancer may be restricted to subjects with silicosis and is not directly linked to silica dust.

In Germany over 2.5 million employees have an increased risk of skin cancer due to their occupational exposure to natural UV-irradiation. The medical consultation board "Occupational diseases" of the Ministry of Labor and Social affairs has investigated the association between occupational UV-irradiation and skin cancer risk and recommends to add the following new occupational disease into the appendix1 of the German ordinance on occupational diseases: "Squamous cell carcinoma and multiple actinic keratosis due to natural UV-irradiation". In this article we report in the view of the German Society of Occupational and Environmental Dermatology (ABD) and the German Statutory accident insurance (DGUV), whose criteria have to be fulfilled for the notification and recognition of an occupational skin cancer due to natural UV-irradiation.

UNLABELLED: Study Type - Diagnostic (validating cohort). LEVEL OF EVIDENCE: 1b. What's known on the subject? and What does the study add? Microscopic haematuria (µH) is frequently detected in elderly adults. The American Urological Association recommends the follow-up of subjects with µH on bladder cancer. Whereas gross haematuria is considered an important sign of the presence of bladder cancer, the disease-predictive value of µH is less clear. No association of µH with the development of bladder tumours in a prospective screening cohort of chemical workers was observed. The positive predictive value of µH for bladder cancer was as low as 1.2%. Haematuria interfered with NMP22 but not with cytology and UroVysion(TM) test results. OBJECTIVE: • To assess the positive predictive value (PPV) of microhaematuria (µH) and gross haematuria (GH) in bladder cancer screening and the influence of haematuria on tumour tests in a prospective study. PATIENTS AND METHODS: • From September 2003 to January 2010, 1323 men took part in an annual voluntary bladder cancer screening programme for chemical workers with former exposure to aromatic amines. • In 5315 urine samples haematuria was determined with a dipstick, followed by a microscopic blood cell count in the sediment. Haematuria was categorized into traces, µH and GH. • Urinary leukocytes and other factors were investigated as potential predictors of haematuria using a generalized estimating equation model for repeated urinalysis. The risk of haematuria for positive tumour tests was analysed correspondingly. • The bladder cancer risk was estimated for the highest degree of haematuria occurring during the study with Poisson regression. RESULTS: • As of July 2010, 15 bladder tumours were detected in 14 participants. • GH was found in four out of nine high-grade tumours and associated with a rate ratio of 3.82, 95% confidence interval (CI) 0.50-29.15 for the development of bladder lesions. • The PPV of GH was 11.4%, but only 1.2% for µH. µH occurred in 18.8% of urine samples and was not associated with bladder cancer [rate ratio (RR) 0.72, 95% CI 0.11-4.78]. • Abundant urinary leukocytes were associated with µH [odds ratio (OR) 8.34, 95% CI 2.26-30.69] and even stronger with GH (OR 22.25, 95% CI 6.42-77.06). • Haematuria and leukocytes influenced NMP22 positivity (µH: OR 1.63, 95% CI 1.06-2.51, abundant leukocytes: OR 8.90, 95% CI 1.58-50.16), but not test results for urine cytology and UroVysion(TM) . CONCLUSION: • While the PPV of µH for bladder cancer was low, there was a strong influence of haematuria and leukocytes on the protein-based tumour test NMP22®. • Erythrocytes and leukocytes should be determined at least semi-quantitatively for the interpretation of positive NMP22 test results. • In addition, a panel of tumour tests that includes methods not affected by the presence of erythrocytes or leukocytes such as cytology and UroVysion(TM) would improve bladder cancer screening.

BACKGROUND: Previous cohort studies have found an elevated risk of lung cancer among rock and slag wool (RSW) production workers. The aim of the present study was to investigate the risk of lung cancer associated with exposure to RSW while controlling for other occupational exposures and tobacco smoking. METHODS: Since 1971, a total of 196 lung cancer cases occurred among men who worked in seven plants in Denmark, Norway, Sweden, and Germany, with start of production between 1937 and 1950. We obtained information on occupational history and extra-occupational factors from either the subject or the next of kin for 133 cases and 513 matched controls. We assessed occupational exposure on the basis of interview data combined with information from expert panels set up in each factory. RESULTS: For cumulative exposure to RSW assessed with a 15-year lag, the smoking-adjusted odds ratios in the second, third, and fourth quartiles of exposure were 1.3 (95% confidence interval [CI] = 0.7-2.3), 1.0 (CI = 0.5-1.9), and 0.7 (CI = 0.3-1.3). Similar results were obtained when we included only those workers employed for more than 1 year, when we included other indicators of RSW exposure, and after control for co-exposures. CONCLUSIONS: This study provides no evidence of a carcinogenic effect on the lung of rock and slag wool under exposure circumstances in the production industry during the last four to five decades.

Complicated mandibular fractures were recognised in one foal, one pony and four horses. The foal was two months old while the adult animals ranged in age from 12 to 24 years. Three horses had a unilateral horizontal ramus fracture. Two fractures were open and one was closed. Comminution was present in one of these patients while the other two horses had marked displacement of the fragments. Two suffered from comminuted fractures of the horizontal and vertical ramus of the mandible. One of these patients had open and infected fractures. One foal had a bilateral horizontal ramus fracture with marked periosteal 'new bone' formation and malalignement which required corrective osteotomy. Each horse underwent locking compression plate (LCP) osteosynthesis consisting of open fracture reduction and application of one to three 4.5/5.0 mm LCP at the ventral, lateral or caudal aspect of the mandible under fluoroscopic control. Two 3.5 mm LCP were used in the foal. Plate fixation was supported by application of a cerclage wire construct between the incisor and premolar teeth in most patients. Complete fracture healing, with an excellent functional and cosmetic outcome, was achieved in all of the patients. Complications encountered included seroma formation, screw and wire breakage, as well as implant and apical tooth root infections. The LCP was removed after fracture healing had occurred in four patients.

We conducted a cross-shift study with 66 bitumen-exposed mastic asphalt workers and 49 construction workers without exposure to bitumen. Exposure was assessed using personal monitoring of airborne bitumen exposure, urinary 1-hydroxypyrene (1-OHP), and the sum of 1-, 2 + 9-,3-,4-hydroxyphenanthrene (OHPH). Genotoxic effects in WBC were determined with nonspecific DNA adduct levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and the formation of DNA strand breaks and alkali-labile sites. Concentration of fumes and aerosols of bitumen correlated significantly with the concentrations of 1-OHP and OHPH after shift (r(s) = 0.27; P = 0.03 and r(s) = 0.55; P < 0.0001, respectively). Bitumen-exposed workers had more DNA strand breaks than the reference group (P < 0.0001) at both time points and a significant correlation with 1-OHP and OHPH in the postshift urines (r(s) = 0.32; P = 0.001 and r(s) = 0.27; P = 0.004, respectively). Paradoxically, we measured higher levels of DNA strand breaks, although not significant, in both study groups before shift. 8-OxodGuo adduct levels did not correlate with DNA strand breaks. Further, 8-oxodGuo levels were associated neither with personal exposure to bitumen nor with urinary metabolite concentrations. Significantly more DNA adducts were observed after shift not only in bitumen-exposed workers but also in the reference group. Only low-exposed workers had significantly elevated 8-oxodGuo adduct levels before as well as after shift (P = 0.0002 and P = 0.02, respectively). Our results show that exposure to fumes and aerosols of bitumen may contribute to an increased DNA damage assessed with strand breaks.

BACKGROUND: Irritant contact dermatitis of the hands is very common in dental laboratory technicians due to frequent contact with various irritants. Barrier creams (HS) are often avoided because a tight grip of tools and small objects is necessary; furthermore dental objects must not be contaminated by HS. In this study the efficacy of HS applied during working hours was compared to skin care products (HP) applied only after work. METHOD: 2 popular commercial HS (HS-1, HS-2) and 2 moisturizers containing urea and beeswax respectively (HP-1, HP-2) were evaluated in 5 laboratories by a total of 192 technicians. Every technician used one HS (several applications during working hours) and one HP applied at home at least once daily for 4 weeks each with a wash-out period of 2 weeks in between. The sequence HS-HP, HP-HS was randomized for every laboratory in two single blind cross over designs for both combinations (HS-1 with HP-1, HS-2 with HP-2). The technicians scored the products on a scale of efficacy (worse, none, good, very good). The skin condition was evaluated by a dermatologist at the beginning of the study, after 4, 6 and 10 weeks on a scale for erythema, infiltration, vesicles, fissures and scaling to produce a sum score. Furthermore, transepidermal water loss (TEWL) was measured on the back of the hand and on the ventral aspect of the forearm at the beginnung and the end of the 4 weeks application period. The quotient of these two parameters was used for statistical evaluation (covariance analysis). RESULTS: The assessment of either "good" or "very good" was as follows: HS-1 58%; HS-2 67%; HP-1 77%; HP-2 98%. Both HP, particularly HP-2, were judged superior to either HS. This was confirmed by the improvement of the skin condition (HS-1 35%; HS-2 44%; HP-1 55%; HP-2 56%). Statistical significance of the differences in TEWL data was clearly demonstrated: HP-1 better than HS-1 (p = 0.007); HP-2 better than HS-2 (p = 0.03). The acceptance of the products was high. The majority was willing to continue its usage after the study (68 %-89 %). CONCLUSIONS: The results demonstrate that the use of after work moisturizers is highly beneficial and under the chosen study conditions even superior to barrier creams applied at work. This approach is more practical for many professions and may effectively reduce the frequency of irritant contact dermatitis.

The correlations between semi-automated sputum cytometry (ASC), conventional cytology and the final diagnosis was investigated in industrially-exposed workers. Slides of sputum samples from 201 former uranium miners with silicosis, 100 patients with asbestosis, 103 workers resected for lung cancer, and 200 controls (50% smokers), were stained using the Papanicolaou (Pap) method and the Feulgen reaction with thionin. Cytometry was performed using the Cyto-Savant automated system. Atypical nuclei were found in 72 of 404 patient samples, 327 samples were normal and five were inadequate for ASC analysis. Thirteen tumours (Pap IV, Pap V) and 11 cases of severe dysplasia were identified by cytology. Lung cancer was confirmed in 20 patients. Compared to the final diagnosis of lung cancer, the sensitivity of ASC was 75% (15 out of 20) and specificity 89.8% (520 out of 579). The results represent a diagnostic efficiency of 89.3%. The combination of ASC with cytology increased sensitivity to 80% (16 out of 20) without significant loss of specificity (89.7% or 523 out of 581). In this investigation of a limited number of patients with occupational radon or asbestos exposure, semi-automated sputum cytometry appears to be sensitive and reliable for the detection of malignant changes in the tracheobronchial mucosa. Together with conventional cytology, it would be reasonable to test the validity of the combined methods in a large-scale feasibility study of early lung cancer detection.

UNLABELLED: What's known on the subject? and what does the study add?: UroVysion™ is a multicolour fluorescence in situ hybridisation assay that detects DNA gain at chromosomes 3, 7 and 17 and loss at the 9p21 locus in exfoliated urothelial cells. This cell-based test is time-consuming and costly compared with voided urine cytology or other molecular markers for the early detection of bladder cancer. We determined copy number changes at chromosomes 3, 7 and 17 and at the 9p21 locus with UroVysion in a prospective screening study among chemical workers. Strong correlations between DNA gains yield a similar performance in detecting bladder cancer with just one of the probes for chromosomes 3, 7 or 17 instead of all, supporting the development of a simpler and cheaper assay. OBJECTIVE: To explore changes at chromosomes 3, 7, 17 and 9p21 in order to assess associations with bladder cancer for possible improvements of the UroVysion™ assay regarding screening. SUBJECTS AND METHODS: In all, 1609 men took part in the prospective study UroScreen. Annual screening for bladder cancer was offered to male chemical workers with former exposure to aromatic amines as a voluntary surveillance programme between 2003 and 2010. In all, 191 434 cells in 6517 UroVysion tests were analysed for copy number variations (CNV) at chromosome 3, 7, 17 (gains) and 9p21 (deletions) in 1595 men. We assessed CNVs at single or multiple loci using polysomy indices (PIs, called multiple PI and PI 3, PI 7 and PI 17). We calculated Spearman's rank correlation coefficients (rs ) between these PIs and receiver operating characteristic (ROC) curves with areas under the curves (AUCs). We applied Cox regression to estimate hazard ratios (HRs) to assess the risk of developing bladder cancer. RESULTS: Nine out of 21 bladder tumours detected in 20 participants ('cases') had a positive UroVysion test, including seven high-grade carcinomas and seven overlapping results with a positive cytology. Four cases with negative test results did not attend screening annually. No case was found because of a complete loss of 9p21 in at least 12 cells. There were strong correlations between pairwise combinations of gains at chromosome 3, 7 or 17, ranging between rs = 0.98 and rs = 0.99 in cases and between rs = 0.84 and rs = 0.88 in non-cases (P < 0.001). Associations were less pronounced with CNVs at 9p21 among cases and were lacking in non-cases. Estimates of the relative risk of DNA gain for developing a bladder tumour assessed with PIs (threshold 10% of cells) were 47.7 (95% confidence interval [CI] 18.3-124.1) for the multiple PI, 44.5 (95%CI 16.5-119.9) for PI 3, 34.7 (95%CI 13.1-92.1) for PI 7 and 52.4 (95%CI 20.7-132.6) for PI 17, as well as 7.9 (95%CI 3.0-20.6) for a complete loss of 9p21 (threshold 2.5% of cells), respectively. ROC analyses showed similar AUCs for multiple PI compared with PIs of single chromosomes 3, 7 and 17 (all AUCs between 0.79 and 0.80) and a lower AUC for a homozygous loss of 9p21 (AUC 0.72). CONCLUSIONS: The UroVysion assay showed a reasonable performance in detecting bladder cancer in the present study population and shared positive test results with cytology, which is much cheaper. A simpler, faster and cheaper version of the UroVysion assay might rely on the very strong correlations between gains at chromosomes 3, 7 and 17, resulting in a similar performance in detecting bladder cancer with single-probe PIs compared with the full set of these probes. Loss of 9p21 was less predictive for developing bladder cancer in UroScreen.

BACKGROUND: Chromosomal instability in exfoliated urothelial cells has been associated with the development of bladder cancer. Here, we analyzed the accumulation of copy number variations (CNVs) using fluorescence in situ hybridization in cancer cases and explored factors associated with the detection of CNVs in tumor-free men. METHODS: The prospective UroScreen study was designed to investigate the performance of UroVysion™ and other tumor tests for the early detection of bladder cancer in chemical workers from 2003-2010. We analyzed a database compiling CNVs of chromosomes 3, 7, and 17 and at 9p21 that were detected in 191,434 exfoliated urothelial cells from 1,595 men. We assessed the accumulation of CNVs in 1,400 cells isolated from serial samples that were collected from 18 cancer cases up to the time of diagnosis. A generalized estimating equation model was applied to evaluate the influence of age, smoking, and urine status on CNVs in cells from tumor-free men. RESULTS: Tetrasomy of chromosomes 3, 7 and 17, and DNA loss at 9p21 were the most frequently observed forms of CNV. In bladder cancer cases, we observed an accumulation of CNVs that started approximately three years before diagnosis. During the year prior to diagnosis, cells from men with high-grade bladder cancer accumulated more CNVs than those obtained from cases with low-grade cancer (CNV < 2: 7.5% vs. 1.1%, CNV > 2: 16-17% vs. 9-11%). About 1% of cells from tumor-free men showed polysomy of chromosomes 3, 7, or 17 or DNA loss at 9p21. Men aged ≥50 years had 1.3-fold more cells with CNVs than younger men; however, we observed no further age-related accumulation of CNVs in tumor-free men. Significantly more cells with CNVs were detected in samples with low creatinine concentrations. CONCLUSIONS: We found an accumulation of CNVs during the development of bladder cancer starting three years before diagnosis, with more altered cells identified in high-grade tumors. Also, a small fraction of cells with CNVs were exfoliated into urine of tumor-free men, mainly exhibiting tetraploidy or DNA loss at 9p21. Whether these cells are preferentially cleared from the urothelium or are artifacts needs further exploration.

Abstract Since the mid-1990s the German BITUMEN Forum has worked on a comprehensive program on the safety and health at work with bitumen. Determining the concentration of emissions arising from handling hot bituminous substances has been one of the main priorities of the forum's work. Almost all branches of industry in Germany that use bitumen have been examined. More than 2000 samples were gathered between 1991 and 2006. The measuring method determined vapors and aerosols emitted from hot bitumen. With the results of these measurement data it is possible to show how exposures to vapors and aerosols of bitumen vary with production and different uses e.g., rolled asphalt, mastic asphalt, roofing, and joint fillers. With the exception of work with mastic asphalt, all uses of bitumen show exposures to vapors and aerosols of bitumen of less than 10 mg/m 3 . The situation for mastic asphalt is entirely different. At the workplaces at mechanical as well as manual work with mastic asphalt very often exposures above 10 mg/m3 vapors and aerosols of bitumen have been observed. The main reason for this significant effect is the processing temperature. In paving with rolled asphalt—with a maximum laying temperature of approximately 180°C (356°F)—the highest exposures are about 10 mg/m 3 . But for mastic asphalt work (laying temperature of approximately 250°C; 482°F) the exposures are up to more than 50 mg/m 3 . The results of these measurements in almost all branches of industry in Germany that use bitumen will be presented. Keywords: asphaltGerman BITUMEN Forumroofingvapors and aerosols of bitumen

Soft tissue sarcomas (STS) are heterogeneous malignant tumors of mesenchymal origin. Due to low incidence and high number of different histological subtypes, their pathogenesis and thus potential targets for their therapy remain barely investigated. Several studies revealed significant higher EPHB4 expression in malignancies such as prostate and colorectal cancer showing survival advantages for these tumor cells. Therefore we studied the expression of EPHB4 in a total of 46 clinical human specimens of different STS and human fibroblasts. EPHB4 mRNA and protein expression were significantly increased in synovial sarcoma. After targeting EPHB4 in fibrosarcoma, synovial sarcoma, liposarcoma and MFH sarcoma cell lines by siRNA or by inhibition of autophosphorylation using the specific EPHB4 kinase inhibitor NVP-BHG712 a decreased proliferation rate/vitality of synovial- and fibrosarcoma cells was observed. Silencing of EPHB4 significantly reduced the transmigration of synovial sarcoma cells towards fibroblasts and endothelial cells. In addition, we assessed the anti-metastatic effect of EPHB4 inhibition in vivo by intraperitoneal administration of the EPHB4 inhibitor in an appropriate sarcoma lung metastasis xenograft model. As result 43% of NVP-BHG712 treated mice (n = 3/7) developed pulmonary metastases whereas all control mice (n = 5) revealed lung metastases. The residual 57% of mice (n = 4/7) showed only small local tumor cell spots. Size measurements of the Vimentin positive area explained significant decrease in lung metastasis formation (p < 0.05) after EPHB4 kinase inhibition. In summary, these data provide first evidence of the importance of EPHB4 in the tumorigenesis of synovial sarcoma and present EPHB4 as a potential target in the therapy of this malignancy.

Occupational health in a changing world has to face up to psychosocial risks to protect the health of employees now and in the future. Faster production, service and communication processes, a service- and knowledge-based society, an increasing proportion of intellectual work, growing complexity of work-related demands, new technologies and constant availability, mobility demands, and job insecurity contribute to the problem of psychosocial risks in the workplace. Psychosocial risks affect both physical and psychosocial health. There is scientific evidence of the link between psychosocial work-related stress and cardiovascular diseases, affective disorders or musculoskeletal disorders, especially chronic back pain.The Framework Directive on Safety and Health makes it very clear that employers are obliged "to ensure the safety and health of workers in every aspect relating to work". In spite of these far reaching obligations, a kind of taboo sometimes makes it hard to focus on topics that have psychosocial implications. A large number of models, instruments and methods are now available to gauge psychosocial risks in the workplace. Given the clear contrast between knowledge and application, there is not a lack of knowledge in this regard, but rather a lack of application.In Germany, statutory accident insurance institutions are guided by two key principles: putting prevention before rehabilitation and rehabilitation before compensation. To prevent work-related health risks the BG RCI has developed several prevention tools to help employers and employees deal with psychosocial risks in the workplace.

BACKGROUND: Urinary biomarkers have the potential to improve the early detection of bladder cancer. Most of the various known markers, however, have only been evaluated in studies with cross-sectional design. For proper validation a longitudinal design would be preferable. We used the prospective study UroScreen to evaluate survivin, a potential biomarker that has multiple functions in carcinogenesis. METHODS/RESULTS: Survivin was analyzed in 5,716 urine samples from 1,540 chemical workers previously exposed to aromatic amines. The workers participated in a surveillance program with yearly examinations between 2003 and 2010. RNA was extracted from urinary cells and survivin was determined by Real-Time PCR. During the study, 19 bladder tumors were detected. Multivariate generalized estimation equation (GEE) models showed that β-actin, representing RNA yield and quality, had the strongest influence on survivin positivity. Inflammation, hematuria and smoking did not confound the results. Survivin had a sensitivity of 21.1% for all and 36.4% for high-grade tumors. Specificity was 97.5%, the positive predictive value (PPV) 9.5%, and the negative predictive value (NPV) 99.0%. CONCLUSIONS: In this prospective and so far largest study on survivin, the marker showed a good NPV and specificity but a low PPV and sensitivity. This was partly due to the low number of cases, which limits the validity of the results. Compliance, urine quality, problems with the assay, and mRNA stability influenced the performance of survivin. However, most issues could be addressed with a more reliable assay in the future. One important finding is that survivin was not influenced by confounders like inflammation and exhibited a relatively low number of false-positives. Therefore, despite the low sensitivity, survivin may still be considered as a component of a multimarker panel.

Abstract Using VDI 3673 or NFPA guidelines for venting we distinguish between a homogeneous and inhomogeneous dust distribution in principle. Experiments were conducted in a 12 m 3 ‐silo to measure the dust distribution, turbulence and the reduced explosion pressure using three different ways of generating the dust/air mixture: ring nozzles with pressurized dust chambers [1] (homogeneous distribution), [2] pneumatically fed vertically downwards [2] and tangentially [3]. Additionally, the dust feeding rate, the conveying velocity and the ignition position was changed. The reduction of the conveying velocity and therefore the decrease of the RMS turbulence velocity will cause a strong reduction of the explosion pressure and the pressure rate, respectively. The results show that the dust concentration in the pneumatically filled silo is inhomogeneous. However, the RMS turbulence velocity and the reduced explosion pressure for the homogeneous distribution and the vertical filling are of the same order. In comparison, the tangential feeding results in lower values. The calculations for the pneumatical vertical filling according to VDI 3673 guideline (inhomogeneous distribution) underestimate the resulting pressure for small vent areas, but the equations for the homogeneous distribution cover the experimental data.