An Investigation of the Role of Cholesteryl Ester Transfer Protein in Lipid Metabolism

The investigation of the role of cholesteryl ester transfer protein (CETP) in lipid metabolism was divided into five main areas. These included the development of a reliable and reproducible assay for CETP activity, the development of polyclonal and monoclonal antibodies to CETP, studying the effect of various drugs on plasma CETP activity in several animal species, looking at the control of CETP secretion by different cell lines and analysing the relationship between restriction fragment length polymorphisms (RFLPs) of the CETP gene and various plasma lipid parameters in a population of 56 individuals

Molecular basis of gap junctional communication in the CNS of the leech Hirudo medicinalis

Gap junctions are intercellular channels that allow the passage of ions and small molecules between cells. In the nervous system, gap junctions mediate electrical coupling between neurons. Despite sharing a common topology and similar physiology, two unrelated gap junction protein families exist in the animal kingdom. Vertebrate gap junctions are formed by members of the connexin family, whereas invertebrate gap junctions are composed of innexin proteins. Here we report the cloning of two innexins from the leech Hirudo medicinalis. These innexins show a differential expression in the leech CNS: Hm-inx1 is expressed by every neuron in the CNS but not in glia, whereas Hm-inx2 is expressed in glia but not neurons. Heterologous expression in the paired Xenopus oocyte system demonstrated that both innexins are able to form functional homotypic gap junctions. Hm-inx1 forms channels that are not strongly gated. In contrast, Hm-inx2 forms channels that are highly voltage-dependent; these channels demonstrate properties resembling those of a double rectifier. In addition, Hm-inx1 and Hm-inx2 are able to cooperate to form heterotypic gap junctions in Xenopus oocytes. The behavior of these channels is primarily that predicted from the properties of the constituent hemichannels but also demonstrates evidence of an interaction between the two. This work represents the first demonstration of a functional gap junction protein from a Lophotrochozoan animal and supports the hypothesis that connexin-based communication is restricted to the deuterostome clade

Familiars: representing Facebook users’ social behaviour through a reflective playful experience

In this paper, we describe the design and development of a social game called Familiars. Inspired by the daemons in Pullman’s “Dark Material” trilogy, Familiars are animal companions that sit on your Facebook profile and change into different animal forms based on your social activity within the social network of Facebook. . Familiars takes advantage of the powerful capabilities of the developers platform of Facebook to build a multi-dimensional picture of a player’s state based on social activity, facial expression analysis on photographs and suggestions from friends. This rich information is then distilled and presented to the player in the form of animal that the familiar chooses to take. We show how the types of animals and personalities were associated in a cross-cultural user study, and present quantitative results from the social behaviours of the players within the game in addition to qualitative data gathered from questionnaire responses

Streaming primary urgent care: a prospective approach

Aim: To identify the appropriate service provider attendees of emergency departments (EDs) and walk-in centres (WiCs) in North East London and to match this to local service provision and patient choice. Design: An anonymous patient survey and a retrospective analysis of a random sample of patient records were performed. A nurse consultant, general practitioner (GP) and pharmacist used the presenting complaints in the patients’ records to independently stream the patient to primary care services, non-National Health Services or ED. Statistical analysis of level of agreement was undertaken. A stakeholder focus group reviewed the results. Subjects and setting Adult health consumers attending ED and urgent care services in North East London. Results The health user survey identified younger rather than older users (mean age of 35.6 years – SD 15.5), where 50% had not seen a health professional about their concern, with over 40% unable to obtain a convenient or emergency appointment with their GP. Over a third of the attendees were already receiving treatment and over 40% of these saw their complaint as an emergency. Over half of respondents expected to see a doctor, one-quarter expected to see a nurse and only 1% expected to see a pharmacist across both services, although WiCs are nurse-led services. More respondents expected a prescription from a visit to a WiC, whereas in the ED a third of respondents sought health advice or reassurance. Conclusion: A number of unscheduled care strategies are, or have just been, developed with the emphasis on moving demand into community-based services. Plurality of services provides service users with a range of alternative access points but can cause duplication of services and repeat attendance. Managing continued increase in emergency and unscheduled care is a challenge. The uncertainties in prospective decision making could be used to inform service development and delivery

The Protectors and the Protected: What Regulators and Researchers Can Learn from IRB Members and Subjects

Clinical research is increasingly conducted in settings that include private physicians’ offices, clinics, community hospitals, local institutes, and independent research centers. The migration of such research into this new, non–academic environment has brought new cadres of researchers into the clinical research enterprise and also broadened the pool of potential research participants. Regulatory approaches for protecting human subjects who participate in research have also evolved. Some institutions retain their own Institutional Review Boards (IRBs), but Independent IRBs, community hospital IRBs and community–based IRBs also fulfill oversight responsibilities. This article sheds light on this evolving world by discussing the findings gleaned from two studies: a study of the decision making processes used by members who serve on different kinds of IRBs and a study of the decision making processes employed by research participants. The article then discusses how the key findings may inform proposed revisions to the Common Rule

Development and validation of a chemostat gut model to study both planktonic and biofilm modes of growth of Clostridium difficile and human microbiota

Copyright: 2014 Crowther et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The human gastrointestinal tract harbours a complex microbial community which exist in planktonic and sessile form. The degree to which composition and function of faecal and mucosal microbiota differ remains unclear. We describe the development and characterisation of an in vitro human gut model, which can be used to facilitate the formation and longitudinal analysis of mature mixed species biofilms. This enables the investigation of the role of biofilms in Clostridium difficile infection (CDI). A well established and validated human gut model of simulated CDI was adapted to incorporate glass rods that create a solid-gaseous-liquid interface for biofilm formation. The continuous chemostat model was inoculated with a pooled human faecal emulsion and controlled to mimic colonic conditions in vivo. Planktonic and sessile bacterial populations were enumerated for up to 46 days. Biofilm consistently formed macroscopic structures on all glass rods over extended periods of time, providing a framework to sample and analyse biofilm structures independently. Whilst variation in biofilm biomass is evident between rods, populations of sessile bacterial groups (log10 cfu/g of biofilm) remain relatively consistent between rods at each sampling point. All bacterial groups enumerated within the planktonic communities were also present within biofilm structures. The planktonic mode of growth of C. difficile and gut microbiota closely reflected observations within the original gut model. However, distinct differences were observed in the behaviour of sessile and planktonic C. difficile populations, with C. difficile spores preferentially persisting within biofilm structures. The redesigned biofilm chemostat model has been validated for reproducible and consistent formation of mixed species intestinal biofilms. This model can be utilised for the analysis of sessile mixed species communities longitudinally, potentially providing information of the role of biofilms in CDI.Peer reviewe

A Cross-Media Presence Questionnaire: The ITC-Sense of Presence Inventory

The presence research community would benefit from a reliable and valid cross-media presence measure that allows results from different laboratories to be compared and a more comprehensive knowledge base to be developed. The ITC-Sense of Presence Inventory (ITC-SOPI) is a new state questionnaire measure whose development has been informed by previous research on the determinants of presence and current self-report measures. It focuses on users' experiences of media, with no reference to objective system parameters. More than 600 people completed the ITC-SOPI following an experience with one of a range of noninteractive and interactive media. Exploratory analysis (principal axis factoring) revealed four factors: Sense of Physical Space, Engagement, Ecological Validity, and Negative Effects. Relations between the factors and the consistency of the factor structure with others reported in the literature are discussed. Preliminary analyses described here demonstrate that the ITC-SOPI is reliable and valid, but more rigorous testing of its psychometric properties and applicability to interactive virtual environments is required. Subject to satisfactory confirmatory analyses, the ITC-SOPI will offer researchers using a range of media systems a tool with which to measure four facets of a media experience that are putatively related to presence

Ethical Problems in Performing Research on Individuals With Compromised Autonomy: Children, the Elderly, and the Mentally Ill

In this thesis, I explore the range of ethical problems that are seen in research generally, and in research involving individuals with compromised autonomy more specifically - that is, children, the elderly, and the mentally ill. Chapter 1 deals with reasons why ethical issues surrounding research are becoming more important, and the focus society has on rights, autonomy, and consent. Problems with consent (definition, amount of information to disclose, communication difficulties, and risk-benefit analysis) are explored. The ethical implications of research versus experimentation, and clinical versus non-clinical research are analysed. Problems with clinical research (such as involvement of ill people and conflict or interest) are assessed, as are the problems of non-therapeutic research (use of well people, motivation to participate, and the role of patient consent). This forms the background for an analysis of research on those who have compromised autonomy - children, the elderly, and the mentally ill. Chapter 2 relates to problems with research on children, assessing the role of parental consent and its advantages (preservation of family relationships and access to benefits of trial) and disadvantages (problems with parental understanding, and the idea that it represents necessarily the views and best interests of the child). The autonomy of the child is also assessed, and seen to be limited by balance of power, difficulties ensuring understanding and voluntary consent, and problems specific to adolescents. Psychosocial research is also analysed, as is the conflict of the doctor's involvement in paediatric research. Chapter 3 relates to research involving the elderly and why this is important. Autonomy of the elderly may be compromised by a number of factors, such as ambiguity in terminology applied to the elderly, stereotype, extrinsic factors such as poverty and family relationships, and intrinsic factors, such as cognitive impairment, deafness, blindness, and so forth. Problems obtaining consent relate to the above factors, as well as institutionalisation and the pressures from family. However, research in this group is also important as they have problems which cannot be researched in other groups. Chapter 4 assesses problems in performing research on the mentally ill, which are particularly highlighted through past exploitation of psychiatric patients. Autonomy in the mentally ill is threatened by a number of factors, such as the wide range of capabilities the mentally ill have; stigmatisation; communication, reasoning, and assessment problems; involuntary hospitalisation and treatment, and the use of psychotropic medications; and deranged interpersonal relationships. Children and the elderly who also have mental illness have extra problems and need careful handling for research. The doctor-patient relationship may also be jeopardised, which is even more significant in a group with fewer social supports. In summary, there may be seen to be a number of factors which compromise the autonomy of children, the mentally ill, and the elderly. A recognition of these factors, coupled with practical measures to optimise consent and the acceptability of research, can help make such research more ethical. It is important to perform such research, in order to maximise the happiness and well-being of these individuals