Cell migration leads to spatially distinct but clonally related airway cancer precursors

Background Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related. Methods Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship. Results We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12 years. Conclusions Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree

Eyewitness Testimony in Autism Spectrum Disorder: A Review

Autism spectrum disorder (ASD) is estimated to affect around 1% of the population, and is characterised by impairments in social interaction, communication, and behavioural flexibility. A number of risk factors indicate that individuals with ASD may become victims or witnesses of crimes. In addition to their social and communication deficits, people with ASD also have very specific memory problems, which impacts on their abilities to recall eyewitnessed events. We begin this review with an overview of the memory difficulties that are experienced by individuals with ASD, before discussing the studies that have specifically examined eyewitness testimony in this group and the implications for investigative practice. Finally, we outline related areas that would be particularly fruitful for future research to explore

Claudins in lung diseases

Tight junctions are the most apically localized part of the epithelial junctional complex. They regulate the permeability and polarity of cell layers and create compartments in cell membranes. Claudins are structural molecules of tight junctions. There are 27 claudins known, and expression of different claudins is responsible for changes in the electrolyte and solute permeability in cells layers. Studies have shown that claudins and tight junctions also protect multicellular organisms from infections and that some infectious agents may use claudins as targets to invade and weaken the host's defense. In neoplastic diseases, claudin expression may be up- or downregulated. Since their expression is associated with specific tumor types or with specific locations of tumors to a certain degree, they can, in a restricted sense, also be used as tumor markers. However, the regulation of claudin expression is complex involving growth factors and integrins, protein kinases, proto-oncogens and transcription factors. In this review, the significance of claudins is discussed in lung disease and development

Empirical legitimacy and normative compliance with the law

This entry considers the role that legitimacy plays in motivating people to comply with the law. The first section distinguishes between normative and empirical concepts of legitimacy. The second section discusses the preconditions of empirical legitimacy. The third section reviews the motivational influence of legitimacy. Attention is given to (a) the sanction-independent and content-independent qualities of legitimacy and (b) some ways to broaden the motivational scope

Communicating security? Policing urban spaces and control signals

The rise of reassurance policing in the UK, informed by ideas drawn from a Signal Crimes Perspective, replaced a narrow focus on controlling crime with a broader emphasis on communicating security. This paper provides a sympathetic critique of dominant assumptions implied in this policy shift concerning the reassurance function of policing. Important in these theoretically informed policy debates is the idea that the police and their partners, through symbolic communications, can influence the extent to which individuals perceive that order and security exist within urban spaces. The paper draws on research findings to illustrate the contrasting ways visible signifiers of crime and formal controls are received and interpreted by diverse audiences. It challenges assumptions about the impact of criminal activities upon perceptions of safety and contributes insights into the unintended effects of formal controls that have implications for our understanding of local social order