In spite of the great weight of theory and speculation they contain, Piaget's books are all founded essentially on experimental work with children, and the purpose of this study was to repeat some of the experiments which Piaget has outlined in the book on number. Piaget has been criticized for not stating the number of subjects who took part in a given experiment from which he has drawn a specific conclusion: for not giving precisely the age range of the subjects, and for not relating their performance to mental age as well as to the chronological age. The aim of this study therefore was to determine whether (a) a group of normal English speaking children, and (b) a sample of mentally retarded children and adults, would show the same general trends in development of pre‐number concepts as Piaget's subjects. The factors of mental and chronological age were also considered, as well as the relation of stage of development to ability in arithmetic.
Background
To understand the relationship between key non-canonical NF-κB kinase IKK-alpha(α), tumour mutational profile and survival in primary colorectal cancer.
Methods
Immunohistochemical expression of IKKα was assessed in a cohort of 1030 patients who had undergone surgery for colorectal cancer using immunohistochemistry. Mutational tumour profile was examined using a customised gene panel. Immunofluorescence was used to identify the cellular location of punctate IKKα expression.
Results
Two patterns of IKKα expression were observed; firstly, in the tumour cell cytoplasm and secondly as discrete ‘punctate’ areas in a juxtanuclear position. Although cytoplasmic expression of IKKα was not associated with survival, high ‘punctate’ IKKα expression was associated with significantly reduced cancer-specific survival on multivariate analysis. High punctate expression of IKKα was associated with mutations in KRAS and PDGFRA. Dual immunofluorescence suggested punctate IKKα expression was co-located with the Golgi apparatus.
Conclusions
These results suggest the spatial expression of IKKα is a potential biomarker in colorectal cancer. This is associated with a differential mutational profile highlighting possible distinct signalling roles for IKKα in the context of colorectal cancer as well as potential implications for future treatment strategies using IKKα inhibitors.
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