Size Matters: Economies of Scale in European Payment Processing

This paper investigates the existence and extent of economies of scale in the European payment processing industry. It is expected that the creation of a Single European Payments Area (SEPA) will spur consolidations and mergers among European payment processors to more fully realize payment economies of scale. We find evidence for the existence of significant economies of scale using data of eight European payment processors during the years 1990-2005. The analysis also reveals that ownership structure is an important factor to explain cost differences across European ACHs.Payment Scale Economies, SEPA, ACHs, ownership

Comparing the old and new generation SELDI-TOF MS: implications for serum protein profiling

<p>Abstract</p> <p>Background</p> <p>Although the PBS-IIc SELDI-TOF MS apparatus has been extensively used in the search for better biomarkers, issues have been raised concerning the semi-quantitative nature of the technique and its reproducibility. To overcome these limitations, a new SELDI-TOF MS instrument has been introduced: the PCS 4000 series. Changes in this apparatus compared to the older one are a.o. an increased dynamic range of the detector, an adjusted configuration of the detector sensitivity, a raster scan that ensures more complete desorption coverage and an improved detector attenuation mechanism. In the current study, we evaluated the performance of the old PBS-IIc and new PCS 4000 series generation SELDI-TOF MS apparatus.</p> <p>Methods</p> <p>To this end, two different sample sets were profiled after which the same ProteinChip arrays were analysed successively by both instruments. Generated spectra were analysed by the associated software packages. The performance of both instruments was evaluated by assessment of the number of peaks detected in the two sample sets, the biomarker potential and reproducibility of generated peak clusters, and the number of peaks detected following serum fractionation.</p> <p>Results</p> <p>We could not confirm the claimed improved performance of the new PCS 4000 instrument, as assessed by the number of peaks detected, the biomarker potential and the reproducibility. However, the PCS 4000 instrument did prove to be of superior performance in peak detection following profiling of serum fractions.</p> <p>Conclusion</p> <p>As serum fractionation facilitates detection of low abundant proteins through reduction of the dynamic range of serum proteins, it is now increasingly applied in the search for new potential biomarkers. Hence, although the new PCS 4000 instrument did not differ from the old PBS-IIc apparatus in the analysis of crude serum, its superior performance after serum fractionation does hold promise for improved biomarker detection and identification.</p

Comparison of normalisation methods for surface-enhanced laser desorption and ionisation (SELDI) time-of-flight (TOF) mass spectrometry data

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry for biological data analysis is an active field of research, providing an efficient way of high-throughput proteome screening. A popular variant of mass spectrometry is SELDI, which is often used to measure sample populations with the goal of developing (clinical) classifiers. Unfortunately, not only is the data resulting from such measurements quite noisy, variance between replicate measurements of the same sample can be high as well. Normalisation of spectra can greatly reduce the effect of this technical variance and further improve the quality and interpretability of the data. However, it is unclear which normalisation method yields the most informative result.</p> <p>Results</p> <p>In this paper, we describe the first systematic comparison of a wide range of normalisation methods, using two objectives that should be met by a good method. These objectives are minimisation of inter-spectra variance and maximisation of signal with respect to class separation. The former is assessed using an estimation of the coefficient of variation, the latter using the classification performance of three types of classifiers on real-world datasets representing two-class diagnostic problems. To obtain a maximally robust evaluation of a normalisation method, both objectives are evaluated over multiple datasets and multiple configurations of baseline correction and peak detection methods. Results are assessed for statistical significance and visualised to reveal the performance of each normalisation method, in particular with respect to using no normalisation. The normalisation methods described have been implemented in the freely available MASDA R-package.</p> <p>Conclusion</p> <p>In the general case, normalisation of mass spectra is beneficial to the quality of data. The majority of methods we compared performed significantly better than the case in which no normalisation was used. We have shown that normalisation methods that scale spectra by a factor based on the dispersion (e.g., standard deviation) of the data clearly outperform those where a factor based on the central location (e.g., mean) is used. Additional improvements in performance are obtained when these factors are estimated locally, using a sliding window within spectra, instead of globally, over full spectra. The underperforming category of methods using a globally estimated factor based on the central location of the data includes the method used by the majority of SELDI users.</p

Validation of previously identified serum biomarkers for breast cancer with SELDI-TOF MS: a case control study

<p>Abstract</p> <p>Background</p> <p>Serum protein profiling seems promising for early detection of breast cancer. However, the approach is also criticized, partly because of difficulties in validating discriminatory proteins. This study's aim is to validate three proteins previously reported to be discriminative between breast cancer cases and healthy controls. These proteins had been identified as a fragment of inter-alpha trypsin inhibitor H4 (4.3 kDa), C-terminal-truncated form of C3a des arginine anaphylatoxin (8.1 kDa) and C3a des arginine anaphylatoxin (8.9 kDa).</p> <p>Methods</p> <p>Serum protein profiles of 48 breast cancer patients and 48 healthy controls were analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Differences in protein intensity between breast cancer cases and controls were measured with the Mann-Whitney U test and adjusted for confounding in a multivariate logistic regression model.</p> <p>Results</p> <p>Four peaks, with mass-to-charge ratio (<it>m/z</it>) 4276, 4292, 8129 and 8941, were found that were assumed to represent the previously reported proteins. <it>M/</it>z 4276 and 4292 were statistically significantly decreased in breast cancer cases compared to healthy controls (p < 0.001). M/<it>z </it>8941 was decreased in breast cancer cases (p < 0.001) and <it>m/z </it>8129 was not related with breast cancer (p = 0.87). Adjustment for sample preparation day, sample storage duration and age did not substantially alter results.</p> <p>Conclusion</p> <p><it>M/z </it>4276 and 4292 both represented the previously reported 4.3 kDa protein and were both decreased in breast cancer patients, which is in accordance with the results of most previous studies. <it>M/z </it>8129 was in contrast with previous studies not related with breast cancer. Remarkably, <it>m/z </it>8941 was decreased in breast cancer cases whereas in previous studies it was increased. Differences in patient populations and pre-analytical sample handling could have contributed to discrepancies. Further research is needed before we can conclude on the relevance of these proteins as breast cancer biomarkers.</p

Postoperative serum proteomic profiles may predict recurrence-free survival in high-risk primary breast cancer

Item does not contain fulltextPURPOSE: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective longitudinal study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence-free survival. METHODS: Sera of 82 breast cancer patients obtained after surgery, but prior to the administration of adjuvant therapy, were fractionated using anion-exchange chromatography, to facilitate the detection of the low-abundant serum peptides. Selected fractions were subsequently analysed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS), and the resulting protein profiles were searched for prognostic markers by appropriate bioinformatics tools. RESULTS: Four peak clusters (i.e. m/z 3073, m/z 3274, m/z 4405 and m/z 7973) were found to bear significant prognostic value (P </= 0.01). The m/z 3274 candidate marker was structurally identified as inter-alpha-trypsin inhibitor heavy chain 4 fragment(658-688) in serum. Except for the m/z 7973 peak cluster, these peaks remained independently associated with recurrence-free survival upon multivariate Cox regression analysis, including clinical parameters of known prognostic value in this study population. CONCLUSION: Investigation of the postoperative serum proteome by, e.g., anion-exchange fractionation followed by SELDI-TOF MS analysis is promising for the detection of novel prognostic factors. However, regarding the rather limited study population, validation of these results by analysis of independent study populations is warranted to assess the true clinical applicability of discovered prognostic markers. In addition, structural identification of the other markers will aid in elucidation of their role in breast cancer prognosis, as well as enable development of absolute quantitative assays

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

Contains fulltext : 70104tjan-heijnen.pdf (publisher's version ) (Open Access)BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis. RESULTS: In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 - 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 - 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. CONCLUSION: In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker

Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study

<p>Abstract</p> <p>Background</p> <p>Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected <it>at </it>or <it>after </it>diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort.</p> <p>Methods</p> <p>In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS).</p> <p>Results</p> <p>Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3a_desArg), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3a_desArgand ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer.</p> <p>Conclusions</p> <p>We show that serum protein profiles are already altered up to three years before breast cancer detection.</p

Size matters: Economies of scale in European payments processing

This paper investigates the existence and extent of economies of scale in the European payment processing industry. It is expected that the creation of a single European payments area (SEPA) will spur consolidations and mergers among European payment processors to more fully realize payment economies of scale. We find evidence for the existence of significant economies of scale using data of eight European payment processors during the years 1990-2005. The analysis also reveals that ownership structure is an important factor to explain cost differences across European processing centers

Size matters: economies of scale in European payments processing

This paper investigates the existence and extent of economies of scale in the European payment processing industry. It is expected that the creation of a Single European Payments Area (SEPA) will spur consolidations and mergers among European payment processors to more fully realize payment economies of scale. We find evidence for the existence of significant economies of scale using data of eight European payment processors during the year 1990-2005. The analysis also reveals that ownership structure is an important factor to explain cost differences across European ACHs.SEPA; payment scale economies; ACHs, ownership