The dwelling house

Why she returned she did not kno

Do we weep for Cordelia?

Much of the contemporary debate concerning the nature and role of fictive emotions has argued that we do feel garden-variety emotions for fictional characters; the puzzle has been to account for this, given our knowledge of their fictional status. In this paper I argue that many of the emotional responses we have towards fictional characters are nothing like the emotions we feel in ordinary life. The implications for our engagement with literary fictions are subsequently examined

Harnessing the Imagination: The Asymmetry of Belief and Make-Believe

Contemporary philosophical discussion on the nature of the imagination has been influenced by recent empirical work in cognitive science. Our imaginative and emotional engagement with works of fiction has been explained by appealing to the similarities between our ordinary cognitive functioning and the workings of our imagination. Believing and imagining, it is argued, are governed by a “single code.” I argue against this claim, and suggest that our imagination – and in particular our literary imagination – in many respects functions very differently from ordinary cognition

Validation of numerical prediction of bone ingrowth into cementless implants

Total joint replacement was pioneered by John Charnley in the late 1950's, and has since revolutionised the management of arthritis sufferers. By 1991, an estimated 5 million people had undergone hip replacements. Although relatively successful, the cemented components had some problems, and this led to the development of cementless implants. These implants depend on the ingrowth of bone into a porous coating, to produce a durable method of implant fixation which the normal bone turnover process will maintain. One of the problems with cementless implants is that the type and extent of tissue ingrowth into the porous coating is unpredictable. Movement of the implant relative to the surrounding bone may result in the formation of an interfacial fibrous tissue layer. Hence, numerical modelling has been used to predict tissue ingrowth into such implants. Numerical simulation has the advantage that comprehensive data can be extracted relatively quickly. The finite element method is a powerful tool that has become the preferred method of analysis, and takes into account critical factors such as implant design, bone properties, and loading conditions. However, these models have not been tested extensively. Little attention has been given to comparing numerical models with the actual findings of retrieval studies or radiological imaging studies. This study thus evaluates the potential of one such numerical model. Most numerical models analyse the stress patterns of a particular state of bone ingrowth (i.e. a static case). This model considered the development of the ingrowing material - a dynamic analysis of tissue changes over a period of time. A 2-dimensional, plane stress finite element model was used to predict the ingrowth of bone into the porous coating of the femoral stem of a hip implant. A side plate was incorporated to mimic 3-dimensional characteristics. The evaluation was achieved by comparing the predictions of the numerical model with plane X-ray images of seven patients with Zimmer Anatomic cementless hip implants. The X-rays were scanned at a high resolution, so as to be able to "magnify" the regions to be examined. Several algorithms were developed to analyse the images, and provide a quantitative assessment of the X-ray images. The algorithms were designed to identify regions of bony and fibrous tissue. This involved the identification of the interface between the implant and the surrounding bone, and the extraction of the grayscale values of the X-rays at this interface. Thereafter, various radiographic signs that indicate the presence of fibrous tissue or bony tissue were identified, and these were used to enhance the original grayscale plot. The resulting graph was then modified slightly so as to make its presentation comparable with the numerical model. Plane X-rays proved to be suitable for the task of identifying tissue types. These data were then compared with the predictions of the numerical model. A qualitative correlation was used, as this was deemed to be most appropriate. Several authors in the literature also found a quantitative approach to have limitations. Some agreement between the experimental findings and the numerical simulation was found to exist, although this was limited. The agreement was judged to be less than the "reasonable agreement'' that several studies in the literature concluded. The correlation is better described by "some agreement". Nevertheless, the finite element method was assessed as being a tool with great potential, and modifications to the present model may provide more reliable results. A time study was also undertaken, whereby the tissue density was evaluated at various periods after the operation. The study provided insight into the evolution of the implant-bone interface after surgery, and correlated well with the literature. The phases of repair and remodelling were evident, and it was assessed as being a valuable contribution to this work. The time study may prove to be a more useful method than those used in assessing the "static" images, and could even provide a prognostic tool in assessing implant stability over time

A clinical and laboratory investigation of synthetic materials to enhance healing and aid regenerative procedures in periodontal surgery

This study investigated the use of synthetic materials to enhance healing and to encourage regeneration of periodontal tissues after surgical therapy. The study was in two parts, a clinical investigation of the use of hydroxy-apatite implant material, and a laboratory investigation of biodegradable polymer membranes being developed for use as barrier membranes in the technique known as guided tissue regeneration. The aim of this study was to evaluate the efficacy of these materials in surgical wounds, to observe their limitations and to establish their potential to enhance regeneration of tissues. The hydroxy-apatite material was well tolerated by the tissues, but clinically significant benefits could not be established. Radiographically significantly more infill occurred in the sites which received the implant material, with some evidence of the material being modified with time so that the density and structure became more similar to that of the approximating host bone. Histological assessment of specimens from three individuals who were not in the clinical trial demonstrated resorption and osteoid formation over a longer time period. Both the radiographic and histological investigations indicated that there was a wide variation in the tissue responses to this material. The membrane materials were also well tolerated by the tissues, but a highly variable tissue response to them was also noted. Absorption of the biodegradable materials was irregular and unpredictable. The non-degradable Gore-Tex material was associated with prolonged inflammation, poor wound healing and epithelial downgrowth. It was therefore concluded that variable and unpredictable tissue responses occur in relation to these materials. The variations described were attributed to localised tissue responses, and individual site and host variations, rather than to the materials themselves. Other factors like the surface roughness, hydrophobicity or electrostatic surface changes of the materials may also be of importance. Although in general, for the clinical study, results were found to be equal to, or marginally better than control procedures, the enhancement of tissue regeneration using the synthetic implant materials or barrier membranes employed in this study to augment periodontal surgery is not entirely predictable

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms and here, we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure / function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era

Design and characterization of a biodegradable double-layer scaffold aimed at periodontal tissue-engineering applications

First published: 1 September 2013The inefficacy of the currently used therapies in achieving the regeneration ad integrum of the periodontium stimulates the search for alternative approaches, such as tissue-engineering strategies. Therefore, the core objective of this study was to develop a biodegradable double-layer scaffold for periodontal tissue engineering. The design philosophy was based on a double-layered construct obtained from a blend of starch and poly-ε-caprolactone (30:70 wt%; SPCL). A SPCL fibre mesh functionalized with silanol groups to promote osteogenesis was combined with a SPCL solvent casting membrane aiming at acting as a barrier against the migration of gingival epithelium into the periodontal defect. Each layer of the double-layer scaffolds was characterized in terms of morphology, surface chemical composition, degradation behaviour and mechanical properties. Moreover, the behaviour of seeded/cultured canine adipose-derived stem cells (cASCs) was assessed. In general, the developed double-layered scaffolds demonstrated adequate degradation and mechanical behaviour for the target application. Furthermore, the biological assays revealed that both layers of the scaffold allow adhesion and proliferation of the seeded undifferentiated cASCs, and the incorporation of silanol groups into the fibre-mesh layer enhance the expression of a typical osteogenic marker. This study allowed an innovative construct to be developed, combining a three-dimensional (3D) scaffold with osteoconductive properties and with potential to assist periodontal regeneration, carrying new possible solutions to current clinical needs .The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013; under Grant Agreement No. REGPOT-CT2012-316331-POLARIS) and from the Portuguese Foundation for Science and Technology (FCT; Grant No, MIT/ECE/0047/2009). Joao Requicha acknowledges the FCT for his PhD scholarship ( Grant No. SFRH/BD/44143/2008)