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Här redovisas den slutliga delrapporten i Trafikverkets Program för Elektrifiering av den tunga vägtrafiken på det statliga vägnätet (Elektrifieringsprogrammet) inom området Affärsmodeller – finansiering och organisering. Det är rapport nummer fem inom detta analysområde. Rapporten belyser övergripande de tre elektrifieringstekniker (elväg, stationär laddning och vätgas/bränsleceller) som analyserats inom Elektrifieringsprogrammet och mer specifikt deras olika karaktärsdrag och hur de skulle kunna samverka. Rapporten beskriver också den inledande analys som gjorts kring ett system med vätgas och bränsleceller, där ett arbete att ta fram en företagsekonomisk kalkylmodell för ett vätgassystem påbörjats.

This investigation follows four previous phases of studies into business models for electrification of heavy road traffic. The study includes (i) a description of electrification technologies and their systems, focusing on fuel cells as a heavy transport electrification technology and the fuel cell calculation model developed during the assignment, (ii) a comparison between the different electrification technologies and their characteristics, (iii) an analysis of possible combinations between electrification technologies, with a focus on electric road systems (ERS) and stationary charging, and (iv) conclusions and suggestions for further analysis.

En företagsekonomisk kalkylmodell med tillhörande manual har tagits fram inom Trafikverkets arbete med affärsmodeller och organisering vid elektrifiering av tunga transporter. Kalkylmodellen för stationär laddning är ett verktyg som syftar till att skapa en fördjupad förståelse kring finansiella konsekvenser för olika aktörer i ett system med stationär laddinfrastruktur. Modellen utgår från ett företagsekonomiskt resultaträkningsperspektiv och resultatet från kalkylmodellen ger en ögonblicksbild givet vald indata. Kalkylmodellen kan användas som diskussionsunderlag för att hjälpa till att skapa en förståelse för vad olika förutsättningar innebär aktörer i systemet.

En företagsekonomisk kalkylmodell med tillhörande manual har tagits fram inom Trafikverkets arbete med affärsmodeller och organisering vid elektrifiering av tunga transporter. Kalkylmodellen är ett verktyg som syftar till att skapa en fördjupad förståelse för olika aktörers förutsättningar i ett elvägssystem på en helhet utifrån ett företagsekonomiskt resultaträkningsperspektiv. Resultatet från kalkylen ger en ögonblicksbild för ett år och tar ej hänsyn till eventuell upprampningsperiod. Kalkylmodellen kan med fördel användas som diskussionsunderlag för att hjälpa till att skapa en förståelse för vad olika förutsättningar innebär för aktörer i ett elvägssystem.

Enteric (or typhoid) fever is a systemic infection mainly caused by Salmonella Typhi and Salmonella Paratyphi A. The disease is common in areas with poor water quality and insufficient sanitation. Humans are the only reservoir for transmission of the disease. The presence of asymptomatic chronic carriers is a complicating factor for the transmission. There are major limitations regarding the current diagnostic methods both for acute infection and chronic carriage. Metabolomics is a methodology studying metabolites in biological systems under influence of environmental or physiological perturbations. It has been applied to study several infectious diseases, with the goal of detecting diagnostic biomarkers. In this thesis, a mass spectrometry-based metabolomics approach, including chemometric bioinformatics techniques for data analysis, has been used to evaluate the potential of metabolite biomarker patterns for diagnosis of enteric fever at different stages of the disease. In Paper I, metabolite patterns related to acute enteric fever were investigated. Human plasma samples from patients in Nepal with culture-confirmed S. Typhi or S. Paratyphi A infection were compared to afebrile controls. A metabolite pattern discriminating between acute enteric fever and afebrile controls, as well as between the two causative agents of enteric fever was detected. The strength of using a panel of metabolites instead of single metabolites as biomarkers was also highlighted. In Paper II, metabolite patterns for acute enteric fever, this time focusing only on S. Typhi infections, were investigated. Human plasma from patients in Bangladesh with culture-positive or -negative but clinically suspected S. Typhi infection were compared to febrile controls. Differences were found in metabolite patterns between the culture-positive S. Typhi group and the febrile controls with a heterogeneity among the suspected S. Typhi samples. Consistencies in metabolite patterns were found to the results from Paper I. In addition, a validation cohort with culture-positive S. Typhi samples and a control group including patients with malaria and infections caused by other pathogens was analysed. Differences in metabolite patterns were detected between S. Typhi samples and all controls as well as between S. Typhi and malaria. Consistencies in metabolite patterns were found to the primary Bangladeshi cohort and the Nepali cohort from Paper I. Paper III focused on chronic Salmonella carriers. Human plasma samples from patients in Nepal undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage were compared to non-carriage controls. The Salmonella carriage samples were distinguished from the non-carriage controls and differential signatures were also found between the S. Typhi and S. Paratyphi A carriage samples. Comparing metabolites found during chronic carriage and acute enteric fever (in Paper I) resulted in a panel of metabolites significant only during chronic carriage. This work has contributed to highlight the potential of using metabolomics as a tool to find diagnostic biomarker patterns associated with different stages of enteric fever.

Pyrolysis is the process of molecular decomposition in an inert environment using heat. It is possible to fragment large molecules, such as polymers, by pyrolysis and separate the fragments directly in a GC. This makes it possible to form complex sample fingerprints that can be used in various applications, for example in forensic science. In this project, a malfunctioning Pyrola 85 pyrolysis unit was fixed by measuring the voltage signals from the photo diode during pyrolysis in a Labview program. With the Labview program, a partly manual filament temperature calibration procedure was developed, as replacement for the non-working automatic calibration procedure. The functioning pyrolysis unit was then installed on a GC/MS in the National University of Science, Ho Chi Minh City, Vietnam. Plant samples were analysed with the Pyrolysis-GC/MS system as a test of the system, resulting in pyrograms with a few identifiable peaks. However, both pyrolysis and GC/MS settings needs further investigation to optimize the analysis. In Sweden, a Labview controlled Pyrolysis unit was constructed to investigate the possibility of improving certain functions of the original control unit. A proposed Labview program and circuit boards were constructed and partially evaluated. The accuracy and precision of the pulses from the Labview program was

Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.

BACKGROUND: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder. METHODOLOGY/PRINCIPAL FINDINGS: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers. CONCLUSIONS/SIGNIFICANCE: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings.

Background Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder. Methodology/Principal findings Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers. Conclusions/Significance Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings., Author summary Enteric fever, caused by typhoidal Salmonella serovars, remains a substantial public health problem in many low- and middle-income countries. The human-restricted nature of these organisms combined with the development of new vaccines suggests that regional elimination of enteric fever should be possible. However, individuals that chronically carry Salmonella in their gallbladder, such as the notorious Typhoid Mary, complicates enteric fever transmission and maintain circulation of the organisms. The prospective detection of chronic Salmonella carriers is therefore a critical step for regional enteric fever elimination. However, there are currently no diagnostic methods routinely in use for this purpose. Here, we used a novel method for identifying chronic Salmonella carriers by comparing metabolite patterns in plasma samples from patients with chronic Salmonella carriage against non-carriage controls. We could significantly distinguish Salmonella carriers from non-carriers based on a large set of metabolites. Five metabolites were then highlighted, after comparing metabolite patterns obtained during chronic Salmonella carriage and acute enteric fever respectively, which could significantly distinguish Salmonella carriers from non-carriers. These potential biomarkers require further evaluation in epidemiological investigations of enteric fever in alternative endemic settings but this study provides a first step towards improved detection of Salmonella carriers.