Emerging concepts in colorectal neoplasia

An understanding of the mechanisms that explain the initiation and early evolution of colorectal cancer should facilitate the development of new approaches to effective prevention and intervention. This review highlights deficiencies in the current model for colorectal neoplasia in which APC mutation is placed at the point of initiation. Other genes implicated in the regulation of apoptosis and DNA repair may underlie the early development of colorectal cancer. Inactivation of these genes may occur not by mutation or loss but through silencing mediated by methylation of the gene's promoter region. hMLH1 and MGMT are examples of DNA repair genes that are silenced by methylation. Loss of expression of hMLH1 and MGMT protein has been demonstrated immunohistochemically in serrated polyps. Multiple lines of evidence point to a serrated pathway of neoplasia that is driven by inhibition of apoptosis and the subsequent inactivation of DNA repair genes by promoter methylation. The earliest lesions in this pathway are aberrant crypt foci (ACF). These may develop Into hyperplastic polyps or transform while still of microscopic size into admixed polyps, serrated adenomas, or traditional adenomas. Cancers developing from these lesions may show high- or low-level microsatellite instability (MSI-H and MSI-L, respectively) or may be microsatellite stable (MSS). The suggested clinical model for this alternative pathway is the condition hyperplastic polyposis. If colorectal cancer is a heterogeneous disease comprising discrete subsets that evolve through different pathways, it is evident that these subsets will need to be studied individually in the future.

Drawing insight from pictures: The development of concepts of false drawing and false belief in children with deafness, normal hearing, and autism

Theory-of-mind concepts in children with deafness, autism, and normal development (N = 154) were examined in three experiments using a set of standard inferential false-belief tasks and matched sets of tasks involving false drawings. Results of all three experiments replicated previously published findings by showing that primary school children with deafness or autism, aged 6 to 13 years, scored significantly lower than normal-developing 4-year-old preschoolers on standard misleading-container and unseen-change tests of false-belief understanding. Furthermore, deaf and autistic children generally scored higher on drawing-based tests than on corresponding standard tests and, on the most challenging of the false-drawing tests in Experiment 2, they significantly outperformed the normal-developing preschoolers by clearly understanding their own false intentions and another person's false beliefs about an actively misleading drawing. In Experiment 3, preschoolers; outperformed older deaf and autistic children on standard tasks, but did less well on a task that required the drawing of a false belief. Methodological factors could not fully explain the findings, but early social and conversational experiences in the family were deemed likely contributors.

Current concepts in central nervous system regeneration

A dictum long-held has stated that the adult mammalian brain and spinal cord are not capable of regeneration after injury. Recent discoveries have, however, challenged this dogma. In particular, a more complete understanding of developmental neurobiology has provided an insight into possible ways in which neuronal regeneration in the central nervous system may be encouraged. Knowledge of the role of neurotrophic factors has provided one set of strategies which may be useful in enhancing CNS regeneration. These factors can now even be delivered to injury sites by transplantation of genetically modified cells. Another strategy showing great promise is the discovery and isolation of neural stem cells from adult CNS tissue. It may become possible to grow such cells in the laboratory and use these to replace injured or dead neurons. The biological and cellular basis of neural injury is of special importance to neurosurgery, particularly as therapeutic options to treat a variety of CNS diseases becomes greater. (C) 2002 Published by Elsevier Science Ltd.

Current concepts - Schistosomiasis

In 1851, Theodor Bilharz described a parasitic infection (bilharzia) that would later be termed schistosomiasis. Currently, 200 million people in 74 countries have this disease; 120 million of them have symptoms, and 20 million have severe illness.1 Schistosomiasis is caused by parasitic trematode worms (schistosomes) that reside in the abdominal veins of their vertebrate definitive hosts. The life cycle of the schistosome is depicted in Figure 1. Schistosomiasis is 1 of the 10 tropical diseases especially targeted for control by the Special Program for Research and Training in Tropical Diseases of the United Nations Development Program, the World Bank, . . . [Full Text of this Article]

A metalinguistic approach to deconstructing the concepts of 'face' and 'politeness' in Chinese, English and Japanese

In this paper we investigate the concepts of 'face' and 'politeness'. We introduce a metalanguage which we believe is a framework for simplifying the analysis of 'face' and 'politeness'. This metalanguage is based on the observation that both 'face' and 'politeness' involve external evaluations of people. This common element is represented in the metalanguage as B what A shows A thinks of B and what B thinks A thinks of B. The implications of the metalanguage for the analysis of Chinese mian and lion ('face') and English face are then discussed. This is followed by an analysis of examples of politeness in English and teineisa ('politeness') in Japanese. We conclude that the metalanguage may be further developed for use in comparisons of 'face' and 'politeness' across cultures. (C) 2003 Elsevier B.V. All rights reserved.

Current concepts of tumour metastasis

Background: Tumour metastasis remains the principal cause of treatment failure and poor prognosis in patients with cancer. Recent advances in our understanding of the biology of metastasis are providing novel potential targets for anti-cancer therapies. Aim: This paper reviews the current concepts in tumour metastasis. Methods: A review of Medline publications relating to the molecular biology and therapy of human tumour metastasis was conducted. Results and Discussion: Early metastasis models were based upon the premise of uninterrupted tumour growth, with the inevitable formation of distant metastases and eventual death of the patient. However, current research suggests that metastasis is an inefficient process governed by several rate-limiting steps, and that failure to negotiate these steps can lead to tumour dormancy. Successful metastatic tumour growth depends upon appropriate tumour-host microenvironment interactions and, ultimately, the development of vascularised metastases post-extravasation in the target organ. An understanding of the molecular mechanisms involved in this dynamic process will aid in the identification of therapeutic targets that may allow earlier diagnosis and more specific therapies for patients with metastasis.

Cross-cultural perceptions in the leadership process: Theoretical perspective on the influence of culture on self-concepts and manager worker attributions

This article examines the influence of culture on the way managers and workers perceive causes of success and failure in organizational tasks. The author argues that selfserving and actor-observer biases, as well as other attribution errors, will be moderated by culture. Specifically, managers and workers with a sociocentric self-concept from high-context cultures may be biased toward external attributions, while managers from low-context cultures with an idiocentric self-concept have a tendency to make more internal attributions. These variations in attributions have consequences that affect both managers and workers. Theoretical propositions and implications for international management practices are discussed. © 2005 Wiley Periodicals, Inc.

New concepts for distinguishing the hidden patterns of linkage disequilibrium which underlie association between genotypes and complex phenotypes

A disappointing feature of conventional methods for detecting association between DNA variation and a phenotype of interest is that they tell us little about the hidden pattern of linkage disequilibrium (LD) with the functional variant that is actually responsible for the association. This limitation applies to case-control studies and also to the transmission/disequilibrium test (TDT) and other family-based association methods. Here we present a fresh perspective on genetic association based on two novel concepts called 'LD squares' and 'equi-risk alleles'. These describe and characterize the different patterns of gametic LD which underlie genetic association. These concepts lead to a general principle - the Equi-Risk Allele Segregation Principle - which captures the way in which underlying LD patterns affect the transmission patterns of genetic variants associated with a phenotype. This provides a basis for distinguishing the hidden LD patterns and might help to locate the functional variants responsible for the association.

Mind and body: Concepts of human cognition, physiology and false belief in children with autism or typical development

This study examined theory of mind (ToM) and concepts of human biology (eyes, heart, brain, lungs and mind) in a sample of 67 children, including 25 high functioning children with autism (age 6-13), plus age-matched and preschool comparison groups. Contrary to Baron-Cohen [1989, Journal of Autism and Developmental Disorders, 19(4), 579-600], most children with autism correctly understood the functions of the brain (84%) and the mind (64%). Their explanations were predominantly mentalistic. They outperformed typically developing preschoolers in understanding inner physiological (heart, lungs) and cognitive (brain, mind) systems, and scored as high as age-matched typical children. Yet, in line with much previous ToM research, most children with autism (60%) failed false belief, and their ToM performance was unrelated to their understanding of. human biology. Results were discussed in relation to neurobiological and social-experiential accounts of the ToM deficit in autism.

Beyond the sphere of the English facial approximation literature: Ramifications of German papers on western method concepts

In the English literature, facial approximation methods have been commonly classified into three types: Russian, American, or Combination. These categorizations are based on the protocols used, for example, whether methods use average soft-tissue depths (American methods) or require face muscle construction (Russian methods). However, literature searches outside the usual realm of English publications reveal key papers that demonstrate that the Russian category above has been founded on distorted views. In reality, Russian methods are based on limited face muscle construction, with heavy reliance on modified average soft-tissue depths. A closer inspection of the American method also reveals inconsistencies with the recognized classification scheme. This investigation thus demonstrates that all major methods of facial approximation depend on both face anatomy and average soft-tissue depths, rendering common method classification schemes redundant. The best way forward appears to be for practitioners to describe the methods they use (including the weight each one gives to average soft-tissue depths and deep face tissue construction) without placing them in any categorical classificatory group or giving them an ambiguous name. The state of this situation may need to be reviewed in the future in light of new research results and paradigms.