| 1. |
- Birgisson, H, et al.
(författare)
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Plasma Protein Profiling Reveal Osteoprotegerin as a Marker of Prognostic Impact for Colorectal Cancer
- 2018
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Ingår i: Translational Oncology. - : ELSEVIER SCIENCE INC. - 1944-7124 .- 1936-5233. ; 11:4, s. 1034-1043
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Due to difficulties in predicting recurrences in colorectal cancer stages II and III, reliable prognostic biomarkers could be a breakthrough for individualized treatment and follow-up. OBJECTIVE: To find potential prognostic protein biomarkers in colorectal cancer, using the proximity extension assays. METHODS: A panel of 92 oncology-related proteins was analyzed with proximity extension assays, in plasma from a cohort of 261 colorectal cancer patients with stage II-IV. The survival analyses were corrected for disease stage and age, and the recurrence analyses were corrected for disease stage. The significance threshold was adjusted for multiple comparisons. RESULTS: The plasma proteins expression levels had a greater prognostic relevance in disease stage III colorectal cancer than in disease stage II, and for overall survival than for time to recurrence. Osteoprotegerin was the only biomarker candidate in the protein panel that had a statistical significant association with overall survival (P = .00029). None of the proteins were statistically significantly associated with time to recurrence. CONCLUSIONS: Of the 92 analyzed plasma proteins, osteoprotegerin showed the strongest prognostic impact in patients with colorectal cancer, and therefore osteoprotegerin is a potential predictive marker, and it also could be a target for treatments.
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| 2. |
- Dinegdae, Yared H., et al.
(författare)
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Design inputs variabilities influence on pavement performance reliability
- 2016
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Ingår i: Functional Pavement Design. - : CRC Press. ; , s. 741-750
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Konferensbidrag (refereegranskat)abstract
- Pavement design is a probabilistic process as it involves many random variables.Through the incorporation of reliability, pavement design methods consider inputparameters variabilities effect on pavement performance. Load and Resistance Factor Design(LRFD) is a typical example of reliability-based design procedure. In LRFD, a set of partialsafety factors are developed by modelling input parameters variabilities with representativeaverage conditions. This paper evaluates the impact input parameters variabilities have onestimated target reliability in the case when actual variabilities are different from assumedconditions. This was achieved by evaluating a field pavement section with various combinationsof input parameters variabilities. The optimized section for a given target reliability wasachieved through the mechanics-based LRFD procedure and the actual reliabilities of thevarious cases were obtained using a methodology that uses response surface approach andfirst order reliability method (FORM). The results have shown that the level of input parametersvariabilities used affect the target reliability considerably.
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| 3. |
- Dinegdae, Yared H., et al.
(författare)
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Effect of heavy traffic loading on predicted pavement fatigue life
- 2016
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Ingår i: RILEM Bookseries. - Dordrecht : Springer Netherlands. ; , s. 389-395
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Konferensbidrag (refereegranskat)abstract
- Fatigue cracking is one of the dominant failure modes of asphalt concrete pavements. There are a number of analysis and design methods that can be used to optimize pavement sections for this kind of distress. Most of these methods incorporate advanced material property predictive models. However, traffic loading, which has been identified as a primary contributing factor in causing fatigue cracking, is characterized relatively simplistically. There is a concern in light of recent advancement in traffic characterization, and tire inflation pressure surveys that existing methods might not be adequate. The objective of this paper is to evaluate and quantify the effects of truck traffic characterization in axle load spectra and high tire inflation pressure levels on predicted fatigue cracking performance. This was achieved by evaluating a number of pavement sections using the mechanics-based fatigue cracking analysis framework. The studied traffic characterization approaches are ESALs, axle load spectra with and without traffic seasonal variations and three levels of tire inflation pressures. It is evident from the result that higher tire inflation pressure and traffic characterization using axle load spectra induce more damage and subsequently early crack initiation time.
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| 4. |
- Dinegdae, Yared H., et al.
(författare)
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Effects of truck traffic on top-down fatigue cracking performance of flexible pavements using a new mechanics-based analysis framework
- 2018
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Ingår i: International Journal on Road Materials and Pavement Design. - : Taylor & Francis. - 1468-0629 .- 2164-7402. ; 19:1, s. 182-200
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Tidskriftsartikel (refereegranskat)abstract
- The mechanics-based analysis framework predicts top-down fatigue cracking initiation timein asphalt concrete pavements by utilising fracture mechanics and mixture morphology-basedproperty. To reduce the level of complexity involved, traffic data were characterised and incorporatedinto the framework using the equivalent single axle load (ESAL) approach. There isa concern that this kind of simplistic traffic characterisation might result in erroneous performancepredictions and pavement structural designs. This paper integrates axle load spectraand other traffic characterisation parameters into the mechanics-based analysis framework andstudies the impact these traffic characterisation parameters have on predicted fatigue crackingperformance. The traffic characterisation inputs studied are traffic growth rate, axle load spectra,lateral wheel wander and volume adjustment factors. For this purpose, a traffic integrationapproach which incorporates Monte Carlo simulation and representative traffic characterisationinputs was developed. The significance of these traffic characterisation parameters wasestablished by evaluating a number of field pavement sections. It is evident from the resultsthat all the traffic characterisation parameters except truck wheel wander have been observedto have significant influence on predicted top-down fatigue cracking performance.
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| 5. |
- Dinegdae, Yared H.
(författare)
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Mechanics-based Design Framework for Flexible Pavements
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Load induced top-down fatigue cracking has been recognized recently as a major distress phenomenon in asphalt pavements. This paper presents a mechanics-based design framework in load and resistance factor design (LRFD) format for the top-down fatigue cracking performance evaluation of flexible pavements. This was achieved by enhancing further the hot mix asphalt fracture mechanics (HMA-FM) model through the incorporation of mixture morphology influence on key fracture properties, and incorporating partial safety factors to account for variabilities and uncertainties. The analysis framework was calibrated and validated using pavement sections that have high quality laboratory data and well documented field performance histories. Moreover, as traffic volume was identified in having a dominant influence on predicted performance, a further investigation was performed to establish and evaluate truck traffic characterization parameters effect on predicted results.A two-component reliability analysis methodology, which uses central composite design (CCD) based response surface approach for surrogate model generation and the first order reliability method (FORM) for reliability estimation was used for the development of the LRFD mechanics-based design framework. The effectiveness of the design framework was investigated through design examples, and the results have shown that the formulated partial safety factors have accounted effectively the variabilities involved in the design process. Further investigation was performed to establish the influence design inputs variabilities have on target reliabilities through case studies that combine input variabilities in a systematic way. It was observed from the results that the coefficient of variation (COV) level of the variability irrespective of the distribution type used have a significant influence on estimated target reliability.
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| 6. |
- Dinegdae, Yared H., et al.
(författare)
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Mechanics-based Topdown Fatigue Cracking Initiation Prediction Framework for Asphaltic Pavements
- 2015
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Ingår i: International Journal on Road Materials and Pavement Design. - : Taylor & Francis. - 1468-0629 .- 2164-7402. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a new mechanics-based top-down fatigue cracking analysis framework is presented for asphalt pavements. A new mixture morphology-based set of material sub-models is presented for characterising key mixture properties and their change over time. Predicting the load induced top-down fatigue crack initiation (CI) time by utilising comprehensive mixture properties creates the possibility of optimising the mixture morphology while taking into account its subsequent effect on long-term pavement performance. The new framework was calibrated and subsequently validated against a number of field pavement sections with varying traffic levels that are representative for current practices and which have a wide range in material properties. The framework accounts the change in key mixture properties due to ageing and mixture-healing effect on damage accumulation while determining the overall effect of design inputs on cracking performance. Model calibration and validation were achieved based on the healing potential of the asphalt mixture. It was found out that the CI predictions for all the sections are in general agreement with the observed performance in the field, thus giving credibility for the framework.
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| 7. |
- Dinegdae, Yared H., et al.
(författare)
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Reliability-Based Design Procedure for Fatigue Cracking in Asphalt Pavements
- 2016
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Ingår i: Transportation Research Record. - : NATL ACAD SCIENCES. - 0361-1981 .- 2169-4052. ; :2583, s. 127-133
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Tidskriftsartikel (refereegranskat)abstract
- The need to account for the effect of design input variabilities on predicted performance has led to many design procedures that address reliability for pavement applications. The Florida cracking model uses empirically derived reliability for fatigue cracking design of asphalt pavements. A reliability approach, which is based on probabilistic uncertainty quantification, is necessary to account properly and effectively for the contribution of the variability in each parameter to the overall variance. This paper presents a load and resistance factor design (LRFD) procedure for the Florida cracking model. By delivering designs of uniform reliability, LRFD provides the basis for developing quality control and quality assurance standards. A first-order reliability method that incorporates a surrogate model based on central composite design was used to compute the reliability and formulate the partial safety factors. The reliability calibration was based on field pavement sections that had a wide range of design inputs and target reliability. Illustrative designs based on the developed LRFD procedure show the effectiveness of the partial safety factors and further confirm the credibility of the reliability analysis methodology.
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| 8. |
- Enblad, Malin, et al.
(författare)
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Increased incidence of bowel cancer after non-surgical treatment of appendicitis
- 2017
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 43:11, s. 2067-2075
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is an ongoing debate on the use of antibiotics instead of appendectomy for treating appendicitis but diagnostic difficulties and longstanding inflammation might lead to increased incidence of bowel cancer in these patients. The aim of this population-based study was to investigate the incidence of bowel cancer after non-surgical treatment of appendicitis.PATIENTS AND METHODS: Patients diagnosed with appendicitis but lacking the surgical procedure code for appendix removal were retrieved from the Swedish National Inpatient Register 1987-2013. The cohort was matched with the Swedish Cancer Registry and the standardised incidence ratios (SIR) with 95% confidence interval (95% CI) for appendiceal, colorectal and small bowel cancers were calculated.RESULTS: Of 13 595 patients with non-surgical treatment of appendicitis, 352 (2.6%) were diagnosed with appendiceal, colorectal or small bowel cancer (SIR 4.1, 95% CI 3.7-4.6). The largest incidence increase was found for appendiceal (SIR 35, 95% CI 26-46) and right-sided colon cancer (SIR 7.5, 95% CI 6.6-8.6). SIR was still elevated when excluding patients with less than 12 months since appendicitis and the incidence of right-sided colon cancer was elevated five years after appendicitis (SIR 3.5, 95% CI 2.1-5.4). An increased incidence of bowel cancer was found after appendicitis with abscess (SIR 4.6, 95% CI 4.0-5.2), and without abscess (SIR 3.5, 95% CI 2.9-4.1).CONCLUSION: Patients with non-surgical treatment of appendicitis have an increased short and long-term incidence of bowel cancer. This should be considered in the discussion about optimal management of patients with appendicitis.
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| 9. |
- Ghanipour, Lana, et al.
(författare)
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Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer
- 2017
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 43:2, s. 311-321
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Tidskriftsartikel (refereegranskat)abstract
- Background Microsatellite instability arises due to defect mismatch repair (MMR) and occurs in 10–20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives. Material and methods Tumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases. Results Forty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p = 0.789). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p = 0.006) and prolonged time to recurrence (p = 0.037). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 4.32; CI, 1.46–12.78). The same prognostic information was also seen in distal colon cancer; no recurrences seen in the eight patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant. Conclusion No correlation between MSI and heredity for colorectal cancer in first-degree relatives was seen. Patients with MSI tumours had improved survival.
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| 10. |
- Glimelius, Bengt, et al.
(författare)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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