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Road agencies employ different criteria and methods to compare treatment alternatives and develop maintenance and rehabilitation (M&R) programmes for their networks. The maximisation of benefits has been integrated in several leading pavement management systems and used for network-level programming since the 1980s. The approach defines benefit as the area between the performance curves with and without M&R actions based on an aggregated index, representing the overall pavement condition. Further simplifications like the screening of solutions using an efficiency frontier and the incremental benefit–cost technique have made it possible to apply the method with the available computing power at the time. Based on a case study of 1000 road sections, this paper analyses the effect of benefit maximisation on annual budget, network condition, treatment selection, trigger values and remaining life. M&R programmes minimising costs and maximising benefits are compared at the project and network level for various budget scenarios. The results show that the maximisation of benefits based on an aggregated condition index leads to substantially higher agency costs and favours the selection of expensive treatments with earlier timing, irrespective of actual failure causes. The conclusions of this work may be useful to road agencies in developing more efficient budget-allocation polices. [ABSTRACT FROM AUTHOR]

A common feature of most pavement management systems is the aggregation of condition data collected from periodic surveys to appropriate long homogeneous sections, aiming to reduce the amount of data to be analysed. It can be shown that regardless of the methods used for sectioning and prediction, homogeneous sections cannot describe the true variation in condition and failure time, leading to either over- or underestimation of service life and hence suboptimal selection of timing and type of maintenance and rehabilitation (M&R) treatments. Furthermore, the generation of homogeneous sections hinders the derivation of project-level performance models from historical condition surveys due to shifting of sections and greatly reduces the number of possible work-zone solutions in the optimisation. This paper illustrates the deviations resulting from different levels of data aggregation based on a case study of 1000 road sections. The results of common sectioning algorithms are then compared to those derived from a LCC-optimisation approach based on accurate condition predictions on short survey sections and work-zones based on economies of scale. The conclusions of this work may be useful to road agencies in avoiding substantial drawbacks of data aggregation and improving project-level M&R treatment recommendations based on the same input condition data. [ABSTRACT FROM AUTHOR]

Existing pavement management systems (PMSs) aggregate short survey sections into long homogeneous sections (typically 1–5 km), aiming to reduce the amount of data and formulate a tractable optimisation problem. However, assuming that sections in a similar condition will undergo a similar deterioration of this condition is incorrect, resulting in imprecise predictions and violations of thresholds. Thus, any maintenance and rehabilitation (M&R) optimisation approach based on long road sections and a single condition indicator (aggregated or not) cannot provide applicable results at the project level. This paper provides a holistic model framework and consistent methodology for a new PMS, abolishing the need for composite condition indices, data aggregation and homogeneous sections in the M&R optimisation process. The proposed bottom-up optimisation is based on short survey sections (25–50m) and solves for optimal treatment type, timing, work-zone length and layout, minimising agency, road user and environmental life cycle costs. Instead of using just one condition indicator, the method models the effects of each treatment on multiple distress types and their combinations. Moreover, the short survey sections are grouped into larger work zones based on purely economic criteria (i.e. economies-of-scale costs). Treatment cost, temporary traffic control cost, and work-zone user cost models are derived as a function of the project size and calibrated for actual prices in Austria. Genetic algorithms are employed as a part of the solution algorithm, being capable of handling an unlimited number of road sections. Furthermore, the approach can be extended to account for budget restrictions, risk and cross-asset allocation of funds for any aging repairable infrastructure system. [ABSTRACT FROM AUTHOR]

An accurate estimation of service life is of primary interest in pavement management systems limiting the time frame for maintenance and rehabilitation (M&R) treatments. Common condition prediction models are derived by regression analysis at the road network level based on empirical data from periodic condition surveys. If a particular section has not failed prior to the last survey or the condition has improved (e.g. due to treatment), it is considered as censored. If censoring is neglected the performance functions, service lives and estimated costs may show substantial bias. The authors who acknowledge this problem have used standard statistical (survival analysis) techniques accounting for censoring. However, any road section may fail due to different but dependent competing failure causes (risks), each leading to treatments. This constitutes a special type of censoring that cannot be addressed with traditional survival analysis methods relying on the assumption of independent censoring. As the number of failure causes usually exceeds one (e.g. fatigue, permanent deformation, thermal cracking), this case is quite common. Moreover, the time until a first failure depends on the sign and degree of correlation between present failure types being modelled by the overall survival function. This paper presents a critical review and comparison of common regression, Markov chain and survival analysis models with and without correlated competing risks based on computer-generated data. Using performance history and distress progression models at the section level in combination with survival analysis improves the accuracy of predictions in comparison. Furthermore, the paper proposes a simultaneous modelling of joint and marginal service life distributions based on copula functions as generalised solution accounting for dependence between competing risks. As the focus of this paper is on condition prediction with censored data, the distress-specific planning and optimisation of treatments will be covered in forthcoming papers. [ABSTRACT FROM AUTHOR]

Periodic condition assessments of pavements together with condition predictions are the basis for investment decisions in every pavement management system (PMS). Typical approaches include surveys of distress types every 3–6 years with analysis rating and calculation of condition indices for road safety and/or structural health. Furthermore, advanced PMS prediction models allow a comparison of maintenance alternatives and an optimisation of investment strategies. This paper presents an overview of current survey and rating approaches in Germany, Switzerland and Austria, together with an impact analysis of different methods, utilised deterministic performance functions and condition threshold (trigger) values for all major distress types. The core of this paper is a comparison of common deterministic condition prediction models with discrete stochastic approaches and prediction models based on advanced regression techniques mainly from scientific literature and an innovative stochastic continuous time and continuous state space process (HOFFMANN – Process). All prediction models are applied to real-world data from condition surveys in Austria and the long-term pavement performance Database (USA) at single-section and network level. The paper provides evidence why deterministic prediction approaches are leading to substantial bias in condition distribution and remaining service life as they do not account for the stochastic nature of pavements. Classic Markov-chain approaches do not account for censoring of survey data and neglect changes in transition probabilities with increasing age. Applying common bivariate and multiple regression techniques may also lead to certain bias due to collinearity effects and specification bias. The paper provides mathematical evidence on ways to avoid these shortcomings based on the presented innovative stochastic process leading to a higher reliability in condition assessment, rating and accuracy of condition predictions. The aspects of censoring, distress-specific assignment and optimisation of treatments with this new HOFFMANN-process will be covered in forthcoming papers. [ABSTRACT FROM PUBLISHER]

Conclusion The results of this study corroborate earlier findings that human papillomavirus (HPV)16 is the most prevalent type of HPV in squamous cell carcinomas of the head and neck (SCCHNs) and reinforce a possible influence of HPV on SCCHN progression by showing that the majority of HPV-positive patients harbor HPV16 (or HPV33) both in their primary tumors and in lymph node neck metastases (LNNMs).Objective HPVs are causally associated with carcinomas of the uterine cervix and have also been linked to a subset of SCCHNs. In order to further investigate the predicted causative role of HPV in SCCHNs, we analyzed pairs of primary tumors and LNNMs or LNNMs alone for the presence of HPV DNA using polymerase chain reaction (PCR).Material and methods DNA was extracted from fresh frozen tissue samples of primary tumors and the corresponding LNNMs of 18 patients and from LNNMs alone in 17 patients. For the detection and typing of HPV, PCR was performed using both type-specific and consensus primer pairs, followed by Southern hybridization and, in selected cases, sequencing of the PCR products.Results Of the 35 patients investigated, 22 (63%) were found to have HPV DNA in their tumors: HPV16 DNA in 21 cases and HPV33 in 1. The highest HPV prevalence was detected in tumors of Waldeyer's tonsillar ring (8/9 patients; 89%). Of the 18 patients in whom primary tumors and LNNMs were analyzed, 7 (39%) were HPV-positive in both samples (HPV16, n=6; HPV33, n=1), in 3 (17%) the primary tumors were HPV-negative and the LNNMs HPV16-positive and in 1 (5.5%) the primary tumor contained HPV16 and the LNNM was negative. Interestingly, of the 7 patients in whom LNNMs had been detected only several months after diagnosis and treatment of the primary tumors, only 1 showed infection with HPV (HPV33). [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infections are related to the genesis of various benign and malignant human neoplasias. The HPV types 16 and 18 seem to be causally related to the development of most squamous cell carcinoma of the anogenital tract and a proportion of carcinomas of the upper aerodigestive tract. The near 100% positivity of the HPV types 6 and 11 in laryngeal papillomatosis is well established. We investigated whether HPV also plays a role in non-neoplastic mucosal entities such as sinunasal polyposis, the genesis of which has been discussed as being triggered by viral infections. On DNA from 39 sinunasal polyps (33 patients), polymerase chain reaction (PCR) was performed using b-globin primers for demonstration of amplifiable DNA in the tissue extracts. Consensus primers for the detection of several different HPV types were applied to the β-globin-positive samples. The results were confirmed by Southern blot hybridization using consensus probes. Cycle sequencing was performed on the positive cases. All 39 samples showed positive signals for β-globin. HPV-DNA investigations showed a slight positive signal in only 1 of the 39 investigated cases (2.6%). Further molecular investigations of this sample, including cycle sequencing, could not confirm this result. All the other tissue samples remained HPV-DNA-negative. Therefore, those HPV types readily detectable with the PCR primers and probes used are not frequently associated with sinunasal polyposis. The data confirm the hypothesis that HPV is correlated to a lesser extent to infectious mucosal lesions than to proliferative lesions. Furthermore, the results emphasize that the presence of HPV in specific lesions does not occur by chance, but represents a specific infection of the mucosa leading to proliferation and even to malignancy. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPV) are discussed as cofactors in the carcinogenesis of squamous cell carcinoma of the head and neck (SCCHN). The prevalence of HPV infection in SCCHN is the subject of controversy since reported HPV prevalences range from less than 10% to almost 100%, depending mainly on the detection method employed. This study presents a realistic approximation to the real prevalence of HPV in SSCHN by applying polymerase chain reaction (PCR) and Southern blot hybridization (SBH), which are the most sensitive and specific HPV detection methods. Diagnostic procedures were optimized by applying a ''hot-start'' PCR protocol followed by a confirmatory SBH of the PCR products to reactions using both type-specific and consensus primers and probes. DNA of 75 tumour samples and 22 normal mucosa samples of the same patients were investigated. In 14 cases genomic SBH using complete HPV genomes as probes was performed additionally. HPV DNA was detected in 17/75 (22.7%) SCCHN specimens. HPV 16 was identified in four cases, HPV 45 in three cases, and HPV 6 and 18 in one case each. Hot-start PCR and SBH are the most reliable HPV detection methods, as they minimize both false-positive and false-negative results. With these methods, a HPV prevalence of 23% was achieved, which can be assumed to be representative for comparable study populations. The significant number of positives detected only by consensus primer PCR, along with the identification of HPV 45, indicate that further HPV types may play an important role in the genesis of SCCHN. [ABSTRACT FROM AUTHOR]

Objective: Investigate the involvement of the fatty acids receptor GPR40 in the assembly and activation of NADPH oxidase and the implications on pancreatic β-cell function. Methods: BRIN-BD11 β-cells were exposed to GPR40 agonist (GW9508) or linoleic acid in different glucose concentrations. Superoxide and H2O2 were analyzed, respectively, by DHE fluorescence and by fluorescence of the H2O2 sensor, roGFP2-Orp1. Protein contents of p47phox in plasma membrane and cytosol were analyzed by western blot. NADPH oxidase role was evaluated by p22phox siRNA or by pharmacological inhibition with VAS2870. NOX2 KO islets were used to measure total cytosolic calcium and insulin secretion. Results: GW9508 and linoleic acid increased superoxide and H2O2 contents at 5.6 and 8.3 mM of glucose. In addition, in 5.6 mM, but not at 16.7 mM of glucose, activation of GPR40 led to the translocation of p47phox to the plasma membrane. Knockdown of p22phox abolished the increase in superoxide after GW9508 and linoleic acid. No differences in insulin secretion were found between wild type and NOX2 KO islets treated with GW9508 or linoleic acid. Discussion: We report for the first time that acute activation of GPR40 leads to NADPH oxidase activation in pancreatic β-cells, without impact on insulin secretion. [ABSTRACT FROM AUTHOR]

Hydrocarbon oils such as pristane or hexadecane induce arthritis and lupus in rodents sharing clinical and pathological features with the human diseases rheumatoid arthritis and systemic lupus erythematosus, respectively. In pristane-induced lupus in the mouse induction of apoptosis and augmentation of type-I Interferon signalling by pristane have been suggested to contribute to pathology, whereas in pristane-induced arthritis (PIA) in the rat the pathological mechanisms are still elusive. Here we show that pristane induces cell death in rat and human cells. Increased numbers of apoptotic cells were found in draining lymph nodes of pristane-injected rats and increased percentages of apoptotic and necrotic cells were observed in peripheral blood. In addition, neutrophil extracellular trap formation was triggered by pristane and hexadecane in neutrophils. Because levels of interleukin (IL)-1β were elevated in sera of pristane-injected rats, with levels mirroring the course of PIA, we examined the effect of pristane at single cell level in vitro, using rat splenocytes and the human monocytic cell line THP-1. Pristane and other hydrocarbon oils induced IL-1β secretion in THP-1 cells as well as in rat splenocytes. The potassium channel inhibitor glibenclamide partly inhibited IL-1β induction, suggesting involvement of the inflammasome. Elevated levels of IL-1α were also found in supernatants of cells treated with pristane and hexadecane. In conclusion, autoimmunogenic hydrocarbon oils induce various forms of cell death in rat and human cells. The higher serum IL-1β levels in pristane-injected animals might be caused by both inflammasome-dependent and -independent mechanisms, such as passive release from dying-cells and probably extracellular maturation of pro-IL-1β. [ABSTRACT FROM AUTHOR]