An early assessment of silicone hydrogel safety : pearls and pitfalls, and current status

The contact lens industry has evolved and now provides many choices, including continuous wear, overnight orthokeratology, frequent-replacement lenses, daily-disposable lenses, and many alternatives in systems of care and maintenance. Epidemiologic studies to date have shown that how a lens is worn, particularly if worn overnight, can increase the risk of microbial keratitis. However, the risk of silicone hydrogel contact lenses worn on a continuous-wear basis has been evaluated only recently. This article summarizes the recent research data on extended-wear silicone hydrogel lenses and discusses the challenges of early evaluations of silicone hydrogel lens safety. Finally, the relevance of this information is discussed to practitioners and contact lens wearers making choices about the risks and benefits of different products and how they are used.

Conflicting notions of risk : the chasm of conflict between institutions and the public

The trust and credibility gap between institutional regulators and the public is based on fundamental social and cultural differences related to power and authority. It is also associated with the 'distance' of a bureaucracies from those whom they serve. The nature of public concern about risk may be investigated by considering specific cognitive decision making 'rules' such as 'familiarity' of a hazard or 'voluntariness' of exposure. A more complete appreciation of the 'how' and 'why' of public response to danger from industrial hazards can be gained by appreciating these 'rules' within the broader context of mis-communication between 'elite' regulators and a highly diverse public. If the results of risk assessments are expressed in technical terms alone, it is unlikely that any real communication will occur. Further, if issues related to the 'remote' nature of much institutional decision making are not addressed, closure of the 'gap' may be difficult to bring about.

Risk-management of UAS robust autonomy for its integration into civil aviation safety frameworks

This paper discusses a model of the civil aviation reg- ulation framework and shows how the current assess- ment of reliability and risk for piloted aircraft has limited applicability for Unmanned Aircraft Systems (UAS) with high levels of autonomous decision mak- ing. Then, a new framework for risk management of robust autonomy is proposed, which arises from combining quantified measures of risk with normative decision making. The term Robust Autonomy de- scribes the ability of an autonomous system to either continue or abort its operation whilst not breaching a minimum level of acceptable safety in the presence of anomalous conditions. The decision making associ- ated with risk management requires quantifying prob- abilities associated with the measures of risk and also consequences of outcomes related to the behaviour of autonomy. The probabilities are computed from an assessment under both nominal and anomalous sce- narios described by faults, which can be associated with the aircraft’s actuators, sensors, communication link, changes in dynamics, and the presence of other aircraft in the operational space. The consequences of outcomes are characterised by a loss function which rewards the certification decision

Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden

Over 80% of women diagnosed with advanced-stage ovarian cancer die as a result of disease recurrence due to failure of chemotherapy treatment. In this study, using two distinct ovarian cancer cell lines (epithelial OVCA 433 and mesenchymal HEY) we demonstrate enrichment in a population of cells with high expression of CSC markers at the protein and mRNA levels in response to cisplatin, paclitaxel and the combination of both. We also demonstrate a significant enhancement in the sphere forming abilities of ovarian cancer cells in response to chemotherapy drugs. The results of these in vitro findings are supported by in vivo mouse xenograft models in which intraperitoneal transplantation of cisplatin or paclitaxel-treated residual HEY cells generated significantly higher tumor burden compared to control untreated cells. Both the treated and untreated cells infiltrated the organs of the abdominal cavity. In addition, immunohistochemical studies on mouse tumors injected with cisplatin or paclitaxel treated residual cells displayed higher staining for the proliferative antigen Ki67, oncogeneic CA125, epithelial E-cadherin as well as cancer stem cell markers such as Oct4 and CD117, compared to mice injected with control untreated cells. These results suggest that a short-term single treatment of chemotherapy leaves residual cells that are enriched in CSC-like traits, resulting in an increased metastatic potential. The novel findings in this study are important in understanding the early molecular mechanisms by which chemoresistance and subsequent relapse may be triggered after the first line of chemotherapy treatment.