Analyzing M-Service Quality Dimensions Using Multivariate Statistical Techniques

This paper continues previous work of the authors concerning the identification and statistical analysis of the quality dimensions in mobile services (m-services). In this work, the structure of mservice quality into dimensions and criteria, which these dimensions are further analyzed into, is examined and grounded through an empirical analysis. The use of multivariate statistical techniques is decomposed into two stages: in the first stage, Factor Analysis in order to explore the relationship between the examined items (quality criteria) and the constructs (dimensions) proposed through the study of the relevant literature. In the second stage, Cluster Analysis and Principal Component Analysis are employed in order to explore intra-construct relationships. The contribution of this paper lies on the fact that a mix of multivariate statistical techniques is all integrated in a single framework, so that information about the structure of m-service quality criteria and constructs is obtained. The findings of the study confirm the theoretical background and provide valuable managerial insights

Διερεύνηση της προγνωστικής αξίας του επιπέδου έκφρασης της πρωτεϊνης MCT4 στο στρώμα που περιβάλλει τα καρκινικά κύτταρα αδενοκαρκινωμάτων παχέος εντέρου και ορθοκολικών ηπατικών μεταστάσεων

Περίληψη Σκοπός Σκοπός της εργασίας αυτής είναι ο καθορισμός της προγνωστικής αξίας της μεμβρανικής πρωτεΐνης μεταφοράς μονοκαρβοξυλασών (MCT4) σε ασθενείς με καρκίνο παχέος εντέρου και ηπατικές μεταστάσεις (CRLM). Διερευνήσαμε τη συσχέτιση μεταξύ της έκφρασης της MCT4 στους ασθενείς με CRLM και της συνολικής επιβίωσης (overall survival-OS) καθώς επίσης και του διαστήματος ελευθέρου νόσου (Disease Free Survival – DFS). Η μελέτη της έκφρασης της MCT4 έγινε τόσο στα κύτταρα του στρώματος που περιβάλλουν τις ηπατικές μεταστάσεις και ειδικότερα στους ινοβλάστες που σχετίζονται με τον καρκίνο (CAFs) όσο και στα ίδια τα καρκινικά κύτταρα. Ο πληθυσμός της μελέτης αφορούσε ασθενείς με καρκίνο στο παχύ έντερο οι οποίοι είχαν μεταστατική νόσο μόνο στο ήπαρ χωρίς οποιαδήποτε άλλη εξωηπατική εντόπιση. Μέθοδος Πρόκειται για μια αναδρομική έρευνα κατά την οποία χρησιμοποιήθηκαν τα κλινικά αρχεία και τα ιστολογικά παρασκευάσματα 107 ασθενών με καρκίνο παχέος εντέρου και ηπατικές μεταστάσεις. Η ανίχνευση και καθορισμός της έκφρασης της MCT4 πραγματοποιήθηκε με τη χρήση ανοσοϊστοχημείας η οποία αξιολογήθηκε με ημιποσοτική μέθοδο. Δημιουργήθηκαν τελικά δύο ομάδες ασθενών προς σύγκριση της συνολικής τους επιβίωσης (OS) και του διαστήματος ελευθέρου νόσου (DFS). Η πρώτη ομάδα περιλάμβανε τους ασθενείς τους οποίους τα ιστολογικά παρασκευάσματα είχαν ασθενή χρώση για την MCT4 (weak MCT4 expression) και η δεύτερη ομάδα περιλάμβανε αυτούς που παρουσίαζαν ισχυρή χρώση για την MCT4 (strong MCT4 expression). Η στατιστική ανάλυση των αποτελεσμάτων για τη συνολική επιβίωση (OS) και το διάστημα ελεύθερο νόσου (DFS) περιλάμβανε τόσο τη μέθοδο Kaplan-Meier όσο και πολυπαραγοντικές μεθόδους ανάλυσης ( Cox-regression methods). Αποτελέσματα Τα ιστολογικά δείγματα από CLRΜ των 57 ασθενών (53,27%) παρουσίασαν ασθενή χρώση των κυττάρων του στρώματος ως προς την MCT4 σε αντίθεση με τα δείγματα 50 ασθενών (46,73%) τα οποία παρουσίασαν ισχυρή χρώση των κυττάρων του στρώματος για την MCT4. Από την στατιστική ανάλυση που ακολούθησε οι ασθενείς οι οποίοι εμφάνιζαν ισχυρή χρώση για την MCT4 είχαν μειωμένο διάστημα ελεύθερο νόσου - DFS (HR 1.79; 95%CI, 1.12-2.85; P=0,014) καθώς επίσης και μειωμένη συνολική πενταετή επιβίωση - OS (HR 3.81 95%CI, 1.88-7.72; P<0,001) στην μονοπαραγοντική ανάλυση διακύμανσης. Η συσχέτιση αυτή παρέμεινε στατιστικά σημαντική και κατά τη διενέργεια της πολυπαραγοντικής ανάλυσης για το διάστημα ελεύθερο νόσου – DFS και για τη συνολική πενταετή επιβίωση - OS (HR 1.95; 95% CI, 1.19-3.17; P=0.007, και HR 4.38; 95%CI, 2.15-8.92; P<0.001 αντίστοιχα). Το ποσοστό έκφρασης της MCT4 στα καρκινικά κύτταρα δεν συσχετίζεται με το διάστημα ελεύθερο νόσου – DFS και τη συνολική πενταετή επιβίωση - OS στους ασθενείς με CRLM. Το διάστημα ελεύθερο νόσου – DFS και η συνολική πενταετής επιβίωση - OS για τους ασθενείς με ασθενή χρώση στα κύτταρα του στρώματος για την MCT4 ήταν 43% και 78% ενώ τα αντίστοιχα ποσοστά για τους ασθενείς που εμφανίζαν ισχυρή χρώση για την MCT4 ήταν 15% and 37% αντίστοιχα. Συμπέρασμα Τα αποτελέσματα της παρούσας μελέτης συνδέουν την ισχυρή έκφραση της MCT4 στα κύτταρα του στρώματος (και ειδικότερα στους ινοβλάστες-CAFs) με χειρότερη συνολική επιβίωση και συχνότερες υποτροπές στους ασθενείς με καρκίνο παχέος εντέρου και ηπατικές μόνο μεταστάσεις. Τα αποτελέσματα αυτά πρέπει να επικυρωθούν και με άλλες μελέτες για να μπορέσει η MCT4 να καθιερωθεί ως προγνωστικός δείκτης στον CRLM και παράλληλα πρέπει να μελετηθεί η ανάπτυξη αναστολέων της MCT4 οι οποίοι θα μπορούσαν να χρησιμοποιηθούν συνεργικά με τα υπάρχοντα χημειοθεραπευτικά σχήματα για μείωση του κυτταρικού πολλαπλασιασμού και του μεταστατικού δυναμικού των καρκινικών κυττάρων. Η στοχοποίηση με μικρά μόρια-αναστολείς του κυτταρικού μεταβολισμού μπορεί να επιφέρει θετικά ευεργετικά αποτελέσματα στους ασθενείς με κακοήθεια.Abstract OBJECTIVE: To validate the prognostic significance of the expression of Monocarboxylate Transporter 4 (MCT4) in patients with colorectal liver metastases (CRLM). In this study, we investigated the correlation between MCT4 expression in stromal and tumor cells of colorectal liver metastases (CRLM) with disease free (DFS) and overall survival (OS) in liver-only colorectal metastases treated with liver resection following neoadjuvant chemotherapy. METHODS: This is a retrospective study, of 107 patients with colorectal liver metastases. MCT4 expression in both stromal and tumor cells was studied by immunohistochemistry. The staining was scored semiquantitatively as weak, or strong. DFS and OS were calculated using both Kaplan-Meier and multivariate Cox-regression methods RESULTS: Specimens from 57 patients (53,27%) showed weak levels of stromal MCT4 staining, whereas 50 patients (46,73%) showed strong levels of MCT4 staining. From the statistical analysis strong stromal MCT4 expression was associated with decreased DFS (HR 1.79; 95%CI, 1.12-2.85; P=0,014) and OS (HR 3.81 95%CI, 1.88-7.72; P<0,001) in univariate analysis. This finding remained significant in multivariate analysis for both DFS and OS (HR 1.95; 95%CI, 1.19-3.17; P=0.007, and HR 4.38; 95%CI, 2.15-8.92; P<0.001 respectively). Tumour MCT4 expression was not associated with DFS and OS. Five-years DFS and OS rates were 43% and 78% respectively in patients with weak and 15% and 37% respectively in patients with strong stromal MCT4 expression. CONCLUSION: Our results indicated that strong expression of stromal MCT4 in CRLM was associated with poor prognosis in patients who undergo liver resection for liver-only colorectal metastases. This finding could be further more validated in independed studies and MCT4 could be used as a new biomarker in CRLM and creates the possibility of new studies in targeted therapies. Keywords MCT4, CRLM, colorectal cancer prognosi

Frequency of pathogenic germline variants in BRCA1, BRCA2, PALB2, CHEK2 and TP53 in ductal carcinoma in situ diagnosed in women under the age of 50 years

a: TP53 pathogenic variants in cases. b: TP53 VUS in cases. (DOCX 20 kb

Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne

Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease. Likely causal variants disrupt the coding region of WNT10A and a P63 transcription factor binding site in SEMA4B. Risk alleles at the 1q25 locus are associated with increased expression of LAMC2, in which biallelic loss-of-function mutations cause the blistering skin disease epidermolysis bullosa. These findings indicate that variation affecting the structure and maintenance of the skin, in particular the pilosebaceous unit, is a critical aspect of the genetic predisposition to severe acne

Genetic predisposition to ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. RESULTS: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). CONCLUSION: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist

Genetic predisposition to ductal carcinoma in situ of the breast

Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10-8. Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist

Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes

Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk.

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis

cited By 0Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.Peer reviewe

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio