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The paper aims at describing the activities developed within the project ASTONRAIL (Advanced approaches and practices for rail training and education to innovate rail study programmes & improve rail higher education provision), funded by ERASMUS+ Programme. The project target is to provide a portfolio of new rail skills development strategies, approaches and professional practices in order to strengthen and modernize Europe’s current rail higher education system.

The aim of this study was to evaluate the effect of exposure to manganese (Mn) on fine motor functions. A total of 48 welders and 30 unexposed workers as controls completed questionnaires, underwent blood examinations, and a motor test battery. The shift exposure of welders to respirable Mn was measured with personal samplers. For all subjects accumulations of Mn in the brain were assessed with T1-weighted magnetic resonance imaging. Welders showed normal motor functions on the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale part III. Furthermore welders performed excellent on a steadiness test, showing better results than controls. However, welders were slightly slower than controls in motor tests. There was no association between fine motor test results and the relaxation rates R1 in globus pallidus and substantia nigra as MRI-based biomarkers to quantify Mn deposition in the brain.

Asbestos causes mesothelioma and lung cancer. In the European Union, asbestos was banned in 2005, but it is still in use in many other countries. The aim of this study was to estimate the lung cancer and mesothelioma incidence risk of men with benign asbestos-related lung or pleural diseases.Between 2008 and 2018, 2439 male participants of a German surveillance program for asbestos workers were included in the cohort. All participants had a recognized occupational asbestos-related disease of the pleura or lung. We estimated the mesothelioma and lung cancer risks by calculating standardized incidence ratios (SIR) with corresponding 95% confidence intervals (95% CI).We observed 64 incident lung cancer and 40 mesothelioma cases in the cohort. An SIR of 17.60 (95% CI: 12.57-23.96) was estimated for mesothelioma and 1.27 (95% CI: 0.98-1.62) for lung cancer. The presence of pleural plaques was associated with a strongly increased risk (SIR: 13.14; 95% CI: 8.51-19.40) for mesothelioma, but not for lung cancer (SIR: 1.05; 95% CI: 0.76-1.41). The highest lung-cancer risk (SIR: 2.56; 95% CI 1.10-5.04) was revealed for cohort members with less than 40 years since first asbestos exposure. Lung cancer risks by duration of asbestos exposure did not show a consistent time trend, but for time since last exposure a trend for mesothelioma was seen.Compared to the general population, we demonstrated an association between benign asbestos-related lung or pleural disease and mesothelioma risk in workers with a history of occupational asbestos exposure. Because lung-cancer risk is dominated by smoking habits, a possible effect of asbestos exposure may have been masked. Efforts should be made to ban production and use of asbestos worldwide and to establish safe handling rules of legacy asbestos.

Light is the strongest zeitgeber currently known for the synchronization of the human circadian timing system. Especially shift workers are exposed to altered daily light profiles. Our objective is the characterization of differences in blue-light exposures between day and night shift taking into consideration modifying factors such as chronotype. We describe 24-hour blue-light profiles as measured with ambient light data loggers (LightWatcher) during up to three consecutive days with either day or night shifts in 100 female hospital staff including 511 observations. Linear mixed models were applied to analyze light profiles and to select time-windows for the analysis of associations between shift work, individual factors, and log mean light exposures as well as the duration of darkness per day. Blue-light profiles reflected different daily activities and were mainly influenced by work time. Except for evening (7–9 p.m.), all time windows showed large differences in blue-light exposures between day and night shifts. Night work reduced the duration of darkness per day by almost 4 h ( β ^ = −3:48 hh:mm, 95% CI (−4:27; −3.09)). Late chronotypes had higher light exposures in the morning and evening compared to women with intermediate chronotype (e.g. morning β ^ = 0.50 log(mW/m2/nm), 95% CI (0.08; 0.93)). Women with children had slightly higher light exposures in the afternoon than women without children ( β ^ = 0.48, 95% CI (−0.10; 1,06)). Time windows for the description of light should be chosen carefully with regard to timing of shifts. Our results are helpful for future studies to capture relevant light exposure differences and potential collinearities with individual factors. Improvement of well-being of shift workers with altered light profiles may therefore require consideration of both – light at the workplace and outside working hours.

Objectives Workplace measurements in the past have shown that the applicable occupational exposure limits (OELs) are regularly exceeded in practice when high-emission welding processes are applied. The InterWeld pilot study was planned as part of an intervention study to show under which conditions compliance with the OEL is achievable in gas metal arc welding (GMAW) with solid wire. The investigation focussed on local exhaust ventilation, i.e. captor hoods and welding torches with integrated fume extraction. Methods Forty tests with hand-guided GMAW were configured by experts with regard to all technical parameters and carried out by a professional welder. Effects of protective measures and process parameters on the exposure to respirable welding fumes and airborne manganese (Mn), chromium, nickel, and hexavalent chromium were investigated. Personal sampling was carried out in the welder’s breathing zone outside the face shield at high flow rates (10 l min−1) in order to achieve sufficient filter loading. Particle masses and welding fume concentrations were determined by weighing the sampling filters. Metal concentrations were analysed by inductive coupled plasma mass spectrometry. In order to evaluate the effects on exposure, the measurements were performed under similar conditions. The data were analysed descriptively and with mixed linear models. For measurements below the limit of detection, the exposure level was estimated using multiple imputation. Results Two to five times higher exposures to respirable welding fumes and airborne metals were observed during welding of 10 mm sheets than during welding of 2- or 3-mm sheets. Welding fume and Mn exposure were reduced by 70 and 90% when on-torch extraction or a captor hood was applied. Other airborne metals were reduced to a similar extent. Modifications on welding parameters led to a reduction of exposure against respirable particles by 51 up to 54%. Conclusions Although proper extraction at the point of origin and lower-emitting process variants ensure a drastic reduction in exposure, compliance with current OELs is not guaranteed. In order to ensure adequate health protection, especially at workplaces where thick sheets with long relative arc times are processed, there is a need for technical development.

Practical work in veterinary medicine provides exposure to various allergens which could increase the risk of sensitization. With the ongoing prospective "AllergoVet" study, we are investigating patterns of allergic symptoms and sensitization among veterinary students. Here, we report the results of the introductory self-reported survey on the presence of allergies in the first-year students of veterinary medicine, who had begun their studies in the years 2013-2016. The survey included 553 students who answered a questionnaire (63% response rate, 83% female ratio). The median age was 20 years (IQR: 19-22 years). About half of the responders indicated an interest in participating in the prospective study ("candidates"). Those who were uninterested in participating were termed "noncandidates". A doctor's diagnosis of any kind of atopic disease was reported by every fourth student. Hay fever was reported by 71 (13%) and allergic asthma by 38 (6.9%) students. The prevalence of hay fever in "candidates" (n = 294) and "noncandidates" (n = 259) was 13.5% and 12.2%, respectively. Allergic asthma was reported by 9.9% of "candidates" and 3.5% of "noncandidates", the difference being significant (p = 0.003). We conclude that the prevalence of self-reported allergic symptoms in the first-year students of veterinary medicine is similar to that in the general population. Pre-existing allergic asthma may have increased the motivation for the enrolment into the longitudinal "AllergoVet-study".

Nitric oxide (NO) from upper (nasal NO, nNO) or lower airways (fractional exhaled NO, FeNO) is considered a surrogate marker for Th2-type inflammation, which is influenced by atopy. The aim of this study was to analyze nNO and FeNO in regard to qualitative and quantitative aspects of sensitization. We evaluated 244 non-smoking young adults. All of them were first-year students recruited for a longitudinal study. An inhalation allergy screening tool was used for atopy definition (specific immunoglobulin E (sIgE) to sx1 ≥ 0.35 kU/L), and also sIgE response to three inhalant perennial allergens, house dust mite (HDM, d1), cat (e1), and dog (e5), was determined in the non-pollen season. With respect to sx1, 100 subjects could be classified as atopic. Sensitization to one, two, or three perennial allergens could be demonstrated in 46, 10, and 16 students, respectively. The subjects with positive IgE response to sx1, but not sensitized to HDM, cat, and/or dog, had FeNO levels comparable to those of non-atopic subjects (13.5 vs. 13.0 ppb, respectively; p = 0.485). These levels were significantly lower compared to atopic subjects being sensitized to any perennial allergen (19.0 ppb; p = 0.0003). After grouping the atopic subjects for perennial sensitization patterns, significantly higher FeNO could be detected in subjects with poly-sensitization (n = 26; 26.0 ppb) compared to the mono-sensitized ones (n = 46; 18.0 ppb; p = 0.023). Regarding nNO, no differences could be observed. Applying a two-way ANOVA, we could reveal a significant correlation of specific HDM-IgE CAP-class with FeNO (p < 0.0001) and nNO levels (p = 0.007). Finally, a significant relationship was found between nNO and FeNO for the whole cohort (p < 0.0001). In summary, our findings support the argument that atopy and perennial sensitization should be considered for the interpretation of NO.

Practical work in veterinary medicine provides exposure to various allergens which could increase the risk of sensitization. With the ongoing prospective “AllergoVet” study, we are investigating patterns of allergic symptoms and sensitization among veterinary students. Here, we report the results of the introductory self-reported survey on the presence of allergies in the first-year students of veterinary medicine, who had begun their studies in the years 2013–2016. The survey included 553 students who answered a questionnaire (63% response rate, 83% female ratio). The median age was 20 years (IQR: 19–22 years). About half of the responders indicated an interest in participating in the prospective study (“candidates”). Those who were uninterested in participating were termed “noncandidates”. A doctor’s diagnosis of any kind of atopic disease was reported by every fourth student. Hay fever was reported by 71 (13%) and allergic asthma by 38 (6.9%) students. The prevalence of hay fever in “candidates” (n = 294) and “noncandidates” (n = 259) was 13.5% and 12.2%, respectively. Allergic asthma was reported by 9.9% of “candidates” and 3.5% of “noncandidates”, the difference being significant (p = 0.003). We conclude that the prevalence of self-reported allergic symptoms in the first-year students of veterinary medicine is similar to that in the general population. Pre-existing allergic asthma may have increased the motivation for the enrolment into the longitudinal “AllergoVet-study”.

Ridepooling stellt eine viel diskutierte Mobilitätsform dar. Ad-hoc und in der Regel von mobilen Endgeräten übermittelte Fahrtwünsche einzelner Fahrgäste werden bedarfsgesteuert, fahrplanfrei und vollflexibel zu möglichst effizienten, geteilten Fahrten gebündelt, welche im Regelfall mit Vans oder Kleinbussen durchgeführt werden. Sowohl aus Betreibersicht als auch insbesondere aus der Sicht von Genehmigungsbehörden stellt sich dabei die Frage nach der betrieblichen Effizienz von Ridepooling-Systemen, welche nicht zuletzt für die Bewertung der Konformität zu öffentlichen Verkehrsinteressen, speziell einer effizienten Nutzung öffentlicher Verkehrsinfrastruktur, relevant sein können. In diesem Zuge werden teilweise auch bereits Aspekte wie Umwegfaktor, Besetzungsgrad und Leerkilometeranteil diskutiert. Im vorliegenden Beitrag werden diese Aspekte als ein Teilergebnis der Arbeit des FGSV-Arbeitskreises 1.6.1 "Verkehrliche Anforderungen an Ridepooling-Systeme" zu einem Kennzahlensystem zusammengefügt, die vollständigen Ausführungen finden sich dabei in Liebchen et al. (2020).

Objective Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. Material and methods GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites. Volumes of interest (VOIs) were placed into the striatum and thalamus of both hemispheres of 47 active welders, 20 former welders, 36 men with Parkinson’s disease (PD), 12 men with hemochromatosis (HC), and 39 male controls. Linear mixed models were used to estimate the influence of Mn and Fe exposure on neurometabolites while simultaneously adjusting for cerebrospinal fluid (CSF) content, age and other factors. Exposure to Mn and Fe was assessed by study group, blood concentrations, relaxation rates R1 and R2* in the globus pallidus (GP), and airborne exposure (active welders only). Results The median shift exposure to respirable Mn and Fe in active welders was 23 μg/m3 and 110 μg/m3, respectively. Airborne exposure was not associated with any other neurometabolite concentration. Mn in blood and serum ferritin were highest in active and former welders. GABA concentrations were not associated with any measure of exposure to Mn or Fe. In comparison to controls, tCr in these VOIs was lower in welders and patients with PD or HC. Serum concentrations of ferritin and Fe were associated with N-acetylaspartate, but in opposed directions. Higher R1 values in the GP correlated with lower neurometabolite concentrations, in particular tCr (exp(β) = 0.87, p Conclusions Our results do not provide evidence that striatal and thalamic GABA differ between Mn-exposed workers, PD or HC patients, and controls. This may be due to the low exposure levels of the Mn-exposed workers and the challenges to detect small changes in GABA. Whereas Mn in blood was not associated with any neurometabolite content in these VOIs, a higher metal accumulation in the GP assessed with R1 correlated with generally lower neurometabolite concentrations.

Deciding which business processes to improve is a challenge for all organizations. The literature on business process management (BPM) offers several approaches that support process prioritization. As many approaches share the individual process as unit of analysis, they determine the processes’ need for improvement mostly based on performance indicators, but neglect how processes are interconnected. So far, the interconnections of processes are only captured for descriptive purposes in process model repositories or business process architectures (BPAs). Prioritizing processes without catering for their interconnectedness, however, biases prioritization decisions and causes a misallocation of corporate funds. What is missing are process prioritization approaches that consider the processes’ individual need for improvement and their interconnectedness. To address this research problem, the authors propose the ProcessPageRank (PPR) as their main contribution. The PPR prioritizes processes of a given BPA by ranking them according to their network-adjusted need for improvement. The PPR builds on knowledge from process performance management, BPAs, and network analysis – particularly the Google PageRank. As for evaluation, the authors validated the PPR’s design specification against empirically validated and theory-backed design propositions. They also instantiated the PPR’s design specification as a software prototype and applied the prototype to a real-world BPA.

Purpose Despite an obvious connection, business process improvement and business process management (BPM) capability development have been studied intensely, but in isolation. The authors thus aim to make the case for the research located at the intersection of both streams. The authors thereby focus on the integrated planning of business process improvement and BPM capability development as this is where, in the authors’ opinion, both streams have the closest interaction. The authors refer to the research field located at the intersection of business process improvement and BPM capability development as process project portfolio management. The paper aims to discuss these issues. Design/methodology/approach The authors structure the field of process project portfolio management drawing from extant knowledge related to BPM, project portfolio management, and performance management. The authors also propose a research agenda in terms of exemplary research questions and research methods. Findings The proposed structure shows which business objects and interactions should be considered when engaging in process project portfolio management. The research agenda contains exemplary questions structured along the intersections of BPM, project portfolio management, and performance management. Research limitations/implications This paper’s main limitation is that it reflects the authors’ individual viewpoints based on experiences of several industry projects and prior research. Originality/value This paper addresses a neglected research field, opens up new avenues for interdisciplinary BPM research, and contributes a novel perspective to the ongoing discussion about the future of BPM.

The malignant mesothelioma is a rare malignancy and mainly caused by occupational exposure to asbestos. German cancer registries are providing a national database to investigate temporal and regional patterns of mesothelioma incidence. These may be of interest for healthcare planning and for surveillance programs aiming at the formerly exposed workforce. We analyzed population-based incidence data of malignant mesothelioma by site, type, sex, age, as well as district and state of patient’s residence. Age-standardized incidence rates (AIRs40+) were calculated according to the European standard population truncated to the age of 40 years and older. We present rates at national, state, and district level and trends of incidence of northern states of Germany. In total, 7,547 malignant mesotheliomas were reported to German cancer registries diagnosed between 2009 and 2013—90% located to the pleura. On average, 1,198 men and 312 women were affected each year. We estimated AIR40+ of 4.77 in 100,000 German men and 0.98 in 100,000 German women. Regional clusters were predominantly located to the seaports of West Germany. The highest regional AIR40+ was 20 per 100,000 men. Corresponding rates in northeast Germany were between 2 and 4 per 100,000 men. Regional clusters of high incidence indicate districts with former shipyards and steel industry, but predominantly in the western part of Germany. The West-to-East difference corresponds to patterns of mortality. Twenty years after banning asbestos in Germany, Bremen and Hamburg are presenting the highest mesothelioma incidence but show steadily decreasing trends.

Welders have an increased susceptibility to airway infections with non-typeable Haemophilus influenzae (NTHi), which implicates immune defects and might promote pneumonia and chronic obstructive pulmonary disease (COPD). We hypothesized that welding-fume exposure suppresses Th1-lymphocyte activity. Non-effector CD4+ T-cells from blood of 45 welders (n = 23 gas metal arc welders, GMAW; n = 16 tungsten inert gas welders, TIG; n = 6 others) and 25 non-welders were ex vivo activated towards Th1 via polyclonal T-cell receptor stimulation and IL-12 (first activation step) and then stimulated with NTHi extract or lipopolysaccharide (LPS) (second activation step). IFNγ and IL-2 were measured by ELISA. In the first activation step, IFNγ was reduced in welders compared to non-welders and in the GMAW welders with higher concentrations of respirable particles compared to the lower exposed TIG welders. IFNγ was not influenced by tobacco smoking and correlated negatively with welding-fume exposure, respirable manganese, and iron. In the second activation step, NTHi and LPS induced additional IFNγ, which was reduced in current smokers compared to never smokers in welders as well as in non-welders. Analyzing both activation steps together, IFNγ production was lowest in smoking welders and highest in never smoking non-welders. IL-2 was not associated with any of these parameters. Welding-fume exposure might suppress Th1-based immune responses due to effects of particulate matter, which mainly consists of iron and manganese. For responses to NTHi this is strongest in smoking welders because welding fume suppresses T-cell activation towards Th1 and cigarette smoke suppresses the subsequent Th1-response to NTHi via LPS. Both effects are independent from IL-2-regulated T-cell proliferation. This might explain the increased susceptibility to infections and might promote COPD development.

Due to a potential exposure to several definite or probable carcinogens, the IARC classified manufacturing of art glass, glass containers, and pressed ware as probably carcinogenic to humans in 1993 (Group 2A). Purpose of this study was to update the evidence from recently published scientific reports. We searched for peer-reviewed articles published between 1993 and 2018 and combined result in terms of a meta-analysis. Overall, we considered twelve articles for a meta-analytic approach published after 1992. From a meta-analysis we derived a standardized incidence ratio (mSIR) and a standardized mortality ratio (mSMR) for lung cancer in men of 1.25 (95% CI 0.97–1.59) and 1.41 (95% CI 1.11–1.77), respectively. The estimated odds ratio (mOR) from five case–control studies was 1.25 (95% CI 0.90–1.73). Associated with an employment in glass factories, the estimated mSMR for larynx cancer was 2.38 (95% CI 1.23–4.16) based on two cohort studies; the mOR from four case–control studies was 1.35 (95% CI 0.73–2.52). Reports on elevated cancer risks at other sites were not consistent. Only few studies assessed cancer risk solely in glass workers. Gained evidence from more recent reports supports the IARC rating from 1993. Our combined results add limited evidence to a moderately elevated risk for cancer of the airways.

Although both communities share a common object of research, the Business and Information Systems Engineering (BISE) community from the German-speaking countries and the Information Systems (IS) community centered in North America have developed quite differently. The BISE community features promote connections with industry, attractive topics to students and practical relevance of publications. But due to various reasons numerous BISE researchers struggle with publications in top-ranked journals. While this weakness obviously is a strength of the IS community, we observe that the IS community struggles with its industry connections and enrollment numbers. What the global IS/BISE community needs is a more intense discourse that increases mutual understanding, creates awareness for the need for complementation, and ensures that the opportunity for complementation is seized. This paper offers insights on how by complementation both communities could mitigate some of their weaknesses and the global IS/BISE community could increase its success as a whole.

Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools – like minimally-invasive biomarkers – are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.

We studied determinants of Vitamin D in serum of 67 female health care workers (aged 25-60 years), including age, body mass index, physical activity, and shift work. Overall, vitamin D levels were low, ranging from 6 to 51 ng/mL (median: 20 ng/mL). Lower serum levels were found in samples drawn in winter and spring and in obese subjects. Shift work had only small effects on vitamin D levels. The high prevalence of vitamin D undersupply is in line with observations from the German general population. Vitamin D supply particularly in winter and spring should be ensured to avoid health problems.

Objectives Exposure to hexavalent chromium (Cr(VI)) has been primarily studied in chromate production. Here, we measured personal exposure to respirable Cr(VI) together with airborne and urinary Cr and Ni in welders to explore levels and associations between various measures of exposure. Methods Shift concentrations of Cr(VI), Cr, and Ni were measured in respirable welding fumes in 50 men who used either gas metal arc welding (GMAW) (n = 24) or tungsten inert gas welding (TIG) (n = 19) as their major technique. Cr and Ni were determined in pre- and post-shift urine samples. Concentrations below the limit of quantification (LOQ) were multiply imputed. Spearman correlation coefficients (rs) were calculated with 95% confidence intervals (CIs) to explore associations between the exposure variables, and regression models were applied to estimate the effect of the parent metal on the urinary concentration. Results Regarding the respirable Cr(VI), 62% of the measurements were below the LOQ, the 75th percentile was 0.50 µg m-3, and 8 out of 50 (16%) welders exceeded 1 µg m-3. The highest shift concentration that occurred as a result of shielded metal arc welding (SMAW) was 180 µg m-3. The Cr(VI) content in total Cr ranged from 4 to 82% (median 20%), although the concentration correlated with total Cr (rs 0.55, 95% CI 0.46; 0.64). The correlation between Cr(VI) and Ni was weaker (rs 0.42, 95% CI 0.34; 0.51) than that between total Cr and Ni in welding fumes (rs 0.83, 95% CI 0.74; 0.92). Both Cr(VI) and total Cr influenced the urinary Cr concentrations in post-shift samples (P = 0.0008 and P ≤ 0.0001, respectively). The airborne shift exposure was a weaker determinant than the Cr content in pre-shift urine samples, which strongly correlated with post-shift urinary Cr (rs 0.78, 95% CI 0.69; 0.87). Conclusions The Cr(VI) content in total Cr varied considerably in welding fumes. The majority of welders using GMAW or TIG presented with shift concentrations of respirable Cr(VI) below 1 µg m-3. However, very high Cr(VI) concentrations may occur, for example in SMAW. The urinary concentration of total Cr, cannot be used to precisely determine the shift concentration of respirable Cr(VI) in welders.

The chapter deals with different aspects of modern rail operations and traffic management in combination with energy consumption issues. In the first part of this discussion, a systematic approach on different influence levels of rail traffic management will be outlined and different kinds of tasks and conflicts are allocated to these influence levels. The approaches for conflict resolution are not in the focus of this chapter. Instead it is outlined that traffic management has its entirety as a comprehensive task. A traffic management cycle, developed and presented in the chapter is an overview intended at providing a common understanding. The second part of this discussion provides an overview on how changes in train driving and timetabling can affect energy consumption. It first analyses the potential changes to driver behaviour and their potential influence on energy consumption. Next, it focuses on how vehicles and fixed installations design can affect energy consumption and finally applies these principles to Mass Rapid Transit. The third part of this discussion looks at the aspect of influencing the driving behaviour. Driver Advisory Systems (DAS) can support drivers to ensure energy-efficient driving. A systematisation of DAS in three levels regarding the range of influance is given and explained. It is outlined that an efficient energy-saving measure can be integrated in early stages of the systematic approach of rail traffic management.

Malignant mesothelioma (MM) is a fatal disease mostly associated with asbestos exposure and difficult to detect by non-invasive methods. This study aimed to use recombinant fragments of the megakaryocyte potentiating factor (MPF) for the development of cost-effective MPF ELISAs. Three polypeptides spanning the MPF region (MPF1-148, MPF 34-288, MPF/MSLN254-400) were produced in E.coli as maltose-binding protein hybrids. After isolation, Factor Xa digest, and purification, the polypeptides were used for the generation of rabbit antibodies and development of ELISAs. Forty-one MM patients with known histological subtype before tumor-specific treatment and 70 asbestos-exposed individuals free of any cancer were matched according to age, gender, and smoking. Plasma of all subjects was tested with the three newly developed polyclonal antibody-based ELISAs and a commercial mesothelin assay (MESOMARK™). The latter differentiated patients (median concentration 1.95 nM) from controls (median 1.07 nM, p < 0.0001) and showed an area under curve (AUC) of 0.77 in receiver operating characteristics (ROC) analysis. Of the MPF variants, exclusively the ELISA based on antibodies against the MPF34-288 fragment displayed significantly (p = 0.0002) higher values in patients than in controls (median 1.61 nM versus 0.88 nM; AUC = 0.72). The combination of the MPF34-288 and mesothelin displayed an improved ROC performance (AUC = 0.80). The MPF34-288 ELISA could be a cost-effective and minimal-invasive contribution to support a diagnosis of mesothelioma, especially in regions with a limited medical care.

Objective Magnetic resonance imaging is a non-invasive method that allows the indirect quantification of manganese (Mn) and iron (Fe) accumulation in the brain due to their paramagnetic features. The WELDOX II study aimed to explore the influence of airborne and systemic exposure to Mn and Fe on the brain deposition using the relaxation rates R1 and R2* as biomarkers of metal accumulation in regions of interest in 161 men, including active and former welders. Material and methods We obtained data on the relaxation rates R1 and R2* in regions that included structures within the globus pallidus (GP), substantia nigra (SN), and white matter of the frontal lobe (FL) of both hemispheres, as well as Mn in whole blood (MnB), and serum ferritin (SF). The study subjects, all male, included 48 active and 20 former welders, 41 patients with Parkinson's disease (PD), 13 patients with hemochromatosis (HC), and 39 controls. Respirable Mn and Fe were measured during a working shift for welders. Mixed regression models were applied to estimate the effects of MnB and SF on R1 and R2*. Furthermore, we estimated the influence of airborne Mn and Fe on the relaxation rates in active welders. Results MnB and SF were significant predictors of R1 but not of R2* in the GP, and were marginally associated with R1 in the SN (SF) and FL (MnB). Being a welder or suffering from PD or HC elicited no additional group effect on R1 or R2* beyond the effects of MnB and SF. In active welders, shift concentrations of respirable Mn > 100 μg/m3 were associated with stronger R1 signals in the GP. In addition to the effects of MnB and SF, the welding technique had no further influence on R1. Conclusions MnB and SF were significant predictors of R1 but not of R2*, indicative of metal accumulation, especially in the GP. Also, high airborne Mn concentration was associated with higher R1 signals in this brain region. The negative results obtained for being a welder or for the techniques with higher exposure to ultrafine particles when the blood-borne concentration was included into the models indicate that airborne exposure to Mn may act mainly through MnB.