The phase III CRYSTAL study demonstrated that addition of cetuximab to fluorouracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival, progression-free survival, and ...objective response in the first-line treatment of patients with KRAS codon 12/13 (exon 2) wild-type metastatic colorectal cancer (mCRC). Outcome was reassessed in subgroups defined by extended RAS mutation testing.
Existing DNA samples from KRAS exon 2 wild-type tumors from CRYSTAL study patients were reanalyzed for other RAS mutations in four additional KRAS codons (exons 3 and 4) and six NRAS codons (exons 2, 3, and 4) using beads, emulsion, amplification, and magnetics technology. No tissue microdissection was performed. A ≥ 5% mutant allele cutoff was used to call mutations.
Mutation status was evaluable in 430 (64.6%) of 666 patients with KRAS exon 2 wild-type tumors. Other RAS mutations were detected in 63 (14.7%) of 430 patients. In those with RAS wild-type tumors, a significant benefit across all efficacy end points was associated with the addition of cetuximab to FOLFIRI. In patients with other RAS tumor mutations, no difference in efficacy outcomes between treatment groups was seen. The safety profile in RAS subgroups was similar and in line with expectations.
In the first-line treatment of mCRC, patients with RAS wild-type tumors derived a significant benefit from the addition of cetuximab to FOLFIRI; patients with RAS tumor mutations did not. Molecular testing of tumors for all activating RAS mutations is essential before considering anti-epidermal growth factor receptor therapy, thereby allowing the further tailoring of cetuximab administration to maximize patient benefit.
In this paper, we propose a new spatio-temporal gait representation, called Gait Energy Image (GEI), to characterize human walking properties for individual recognition by gait. To address the ...problem of the lack of training templates, we also propose a novel approach for human recognition by combining statistical gait features from real and synthetic templates. We directly compute the real templates from training silhouette sequences, while we generate the synthetic templates from training sequences by simulating silhouette distortion. We use a statistical approach for learning effective features from real and synthetic templates. We compare the proposed GEI-based gait recognition approach with other gait recognition approaches on USF HumanID Database. Experimental results show that the proposed GEI is an effective and efficient gait representation for individual recognition, and the proposed approach achieves highly competitive performance with respect to the published gait recognition approaches
ABSTRACT Accurately determining the mass of galaxy clusters is fundamental for many studies of cosmology and galaxy evolution. We collect and rescale the cluster masses of 1191 clusters of estimated ...by X-ray or Sunyaev-Zeldovich measurements and use them to calibrate the optical mass proxy. The total r-band luminosity (in units of ) of these clusters is obtained by using spectroscopic and photometric data of the Sloan Digital Sky Survey (SDSS). We find that the correlation between the cluster mass and total r-band luminosity significantly evolves with redshift. After correcting for the evolution, we define a new cluster richness as the optical mass proxy. By using this newly defined richness and the recently released SDSS DR12 spectroscopic data, we update the WHL12 cluster catalog and identify 25,419 new rich clusters at high redshift. In the SDSS spectroscopic survey region, about 89% of galaxy clusters have spectroscopic redshifts. The mass can be estimated with a scatter of 0.17 dex for the clusters in the updated catalog.
The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, ...plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients. Contingency tables were constructed and a χ2 test was used to test for statistical significance. Odds ratios with 95% confidence intervals were calculated. The presence of tumor infiltrating lymphocytes and a mucinous phenotype (>50% mucinous surface area) were strongly correlated with CMS1 (p < 0.001 and p = 0.008) and CRIS-A (p = 0.006 and p < 0.001). The presence of mucus (≥ 10%) was associated with CMS3: mucus was present in 64.1% of all CMS3 tumors (p < 0.001). Although a clear association between tumor-stroma ratio and CMS4 was established in this study (p = 0.006), still 32 out of 61 (52.5%) CMS4 tumors were scored as stroma-low, indicating that CMS4 tumors cannot be identified solely based on stromal content. Higher budding counts were seen in CMS4 and CRIS-B tumors (p = 0.045 and p = 0.046). No other associations of the measured parameters were seen for any of the other CRIS subtypes. Our analysis revealed clear associations between histopathologic features and CMS or CRIS subtypes. However, identification of distinct molecular subtypes solely based on histopathology proved to be infeasible. Combining both molecular and morphologic features could potentially improve patient stratification.
The diagnosis of nodal marginal zone lymphoma is one of the remaining problem areas in hematopathology. Because no established positive markers exist for this lymphoma, it is frequently a diagnosis ...of exclusion, making distinction from other low-grade B-cell lymphomas difficult or even impossible. This systematic review summarizes and discusses the current knowledge on nodal marginal zone lymphoma, including clinical features, epidemiology and etiology, histology, and cytogenetic and molecular features. In particular, recent advances in diagnostics and pathogenesis are discussed. New immunohistochemical markers have become available that could be used as positive markers for nodal marginal zone lymphoma. These markers could be used to ensure more homogeneous study groups in future research. Also, recent gene expression studies and studies describing specific gene mutations have provided clues to the pathogenesis of nodal marginal zone lymphoma, suggesting deregulation of the nuclear factor kappa B pathway. Nevertheless, nodal marginal zone lymphoma remains an enigmatic entity, requiring further study to define its pathogenesis to allow an accurate diagnosis and tailored treatment. However, recent data indicate that it is not related to splenic or extranodal lymphoma, and that it is also not related to lymphoplasmacytic lymphoma. Thus, even though the diagnosis is not always easy, it is clearly a separate entity.
Dynamical state of galaxy clusters is closely related to their observational properties in X-ray, optical and radio wavelengths. We develop a method to diagnose the substructure and dynamical state ...of galaxy clusters by using photometric data of Sloan Digital Sky Survey (SDSS). To trace mass distribution, the brightness distribution of member galaxies is smoothed by using a Gaussian kernel with a weight of their optical luminosities. After deriving the asymmetry, the ridge flatness and the normalized deviation of the smoothed optical map, we define a relaxation parameter, Γ, to quantify dynamical state of clusters. This method is applied to a test sample of 98 clusters of 0.05 < z 0.42 collected from literature with known dynamical states and can recognize dynamical state for relaxed (Γ ≥ 0) and unrelaxed (Γ < 0) clusters with a success rate of 94 per cent. We then calculate relaxation parameters of 2092 rich clusters previously identified from the SDSS, of which 28 per cent clusters are dynamically relaxed with Γ ≥ 0. We find that the dominance and absolute magnitude of the brightest cluster galaxies closely correlate with dynamical states of clusters. The emission power of radio haloes is quantitatively related to cluster dynamical state, beside the known dependence on the X-ray luminosity.
Many psychology studies are statistically underpowered. In part, this may be because many researchers rely on intuition, rules of thumb, and prior practice (along with practical considerations) to ...determine the number of subjects to test. In Study 1, we surveyed 291 published research psychologists and found large discrepancies between their reports of their preferred amount of power and the actual power of their studies (calculated from their reported typical cell size, typical effect size, and acceptable alpha). Furthermore, in Study 2, 89% of the 214 respondents overestimated the power of specific research designs with a small expected effect size, and 95% underestimated the sample size needed to obtain .80 power for detecting a small effect. Neither researchers' experience nor their knowledge predicted the bias in their self-reported power intuitions. Because many respondents reported that they based their sample sizes on rules of thumb or common practice in the field, we recommend that researchers conduct and report formal power analyses for their studies.
The identification of patients with high-risk stage II colon cancer who may benefit from adjuvant therapy may allow the clinical approach to be tailored for these patients based on an understanding ...of tumour biology. MicroRNAs have been proposed as markers of the prognosis or treatment response in colorectal cancer. Recently, a 2-microRNA signature (let-7i and miR-10b) was proposed to identify colorectal cancer patients at risk of developing distant metastasis. We assessed the prognostic value of this signature and additional candidate microRNAs in an independent, clinically well-defined, prospectively collected cohort of primary colon cancer patients including stage I-II colon cancer without and stage III colon cancer with adjuvant treatment. The 2-microRNA signature specifically predicted hepatic recurrence in the stage I-II group, but not the overall ability to develop distant metastasis. The addition of miR-30b to the 2-microRNA signature allowed the prediction of both distant metastasis and hepatic recurrence in patients with stage I-II colon cancer who did not receive adjuvant chemotherapy. Available gene expression data allowed us to associate miR-30b expression with axon guidance and let-7i expression with cell adhesion, migration, and motility.
Clonality analysis in classic Hodgkin lymphoma (cHL) is of added value for correctly diagnosing patients with atypical presentation or histology reminiscent of T cell lymphoma, and for establishing ...the clonal relationship in patients with recurrent disease. However, such analysis has been hampered by the sparsity of malignant Hodgkin and Reed-Sternberg (HRS) cells in a background of reactive immune cells. Recently, the EuroClonality-NGS Working Group developed a novel next-generation sequencing (NGS)-based assay and bioinformatics platform (ARResT/Interrogate) to detect immunoglobulin (IG) gene rearrangements for clonality testing in B-cell lymphoproliferations. Here, we demonstrate the improved performance of IG-NGS compared to conventional BIOMED-2/EuroClonality analysis to detect clonal gene rearrangements in 16 well-characterized primary cHL cases within the IG heavy chain (IGH) and kappa light chain (IGK) loci. This was most obvious in formalin-fixed paraffin-embedded (FFPE) tissue specimens, where three times more clonal cases were detected with IG-NGS (9 cases) compared to BIOMED-2 (3 cases). In total, almost four times more clonal rearrangements were detected in FFPE with IG-NGS (N = 23) as compared to BIOMED-2/EuroClonality (N = 6) as judged on identical IGH and IGK targets. The same clonal rearrangements were also identified in paired fresh frozen cHL samples. To validate the neoplastic origin of the detected clonotypes, IG-NGS clonality analysis was performed on isolated HRS cells, demonstrating identical clonotypes as detected in cHL whole-tissue specimens. Interestingly, IG-NGS and HRS single-cell analysis after DEPArray™ digital sorting revealed rearrangement patterns and copy number variation profiles indicating clonal diversity and intratumoral heterogeneity in cHL. Our data demonstrate improved performance of NGS-based detection of IG gene rearrangements in cHL whole-tissue specimens, providing a sensitive molecular diagnostic assay for clonality assessment in Hodgkin lymphoma.
This paper introduces a Malmquist CO
2 emission performance index (MCPI) for measuring changes in total factor carbon emission performance over time. The MCPI is derived by solving several data ...envelopment analysis models. Bootstrapping MCPI is proposed to perform statistical inferences on the MCPI results. Using the index the emission performance of the world's 18 top CO
2 emitters from 1997 to 2004 is studied. The results obtained show that the total factor carbon emission performance of the countries as a whole improved by 24% over the period and this was mainly driven by technological progress. The results of a cross-country regression analysis to investigate the determinants of the resulting MCPI are presented.
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