Application of Confocal Laser Scanning Microscopy to Cytocompatibility Testing of Potential Orthopaedic Materials in Immortalised Osteoblast-Like Cell Lines

Confocal laser scanning microscopy (CLSM) was used in conjunction with in vitro cell culture to investigate cellular interactions with orthopaedic biomaterials. Transfected rat and human osteoblasts were seeded on two potential isoelastic hip prosthesis materials, carbon fibre reinforced polyetheretherketone (PEEK) and epoxy. Titanium 318 alloy was employed as a control. Determination of the material surface contour, an important factor influencing cellular adhesion, proliferation and function, was performed using the industry standard Talysurf® and compared to analogous results obtained using the CLSM. The latter technique consistently gave higher values of material roughness but offers the advantage that it can be used to correlate roughness with cell distribution on the same samples, whereas Talysurf® measurement of roughness requires clean rigid samples. Image analysis and processing, performed on cells after attachment and culture on the materials for 48 hours, provided cell morphology data. Cells cultured on titanium were larger, with a higher percentage of cytoplasm, than those grown on either of the other materials. The macroscopic surface of epoxy resulted in smaller cells with altered morphology, which orientated themselves along carbon fibres. In conclusion, we believe CLSM offers great potential for investigating the cellular interactions of biomaterials involving minimal sample preparation, non-invasive optical sectioning of samples and minimal opportunity for generation of cellular deformation and sample preparation artefacts

The Causal Structure of Emotions in Aristotle: Hylomorphism, Causal Interaction between Mind and Body, and Intentionality

Recently, a strong hylomorphic reading of Aristotelian emotions has been put forward, one that allegedly eliminates the problem of causal interaction between soul and body. Taking the presentation of emotions in de An. I 1 as a starting point and basic thread, but relying also on the discussion of Rh. II, I will argue that this reading only takes into account two of the four causes of emotions, and that, if all four of them are included into the picture, then a causal interaction of mind and body remains within Aristotelian emotions, independent of how strongly their hylomorphism is understood. Beyond the discussion with this recent reading, the analysis proposed of the fourfold causal structure of emotions is also intended as a hermeneutical starting point for a comprehensive analysis of particular emotions in Aristotle. Through the different causes Aristotle seems to account for many aspects of the complex phenomenon of emotion, including its physiological causes, its mental causes, and its intentional object

Convergence to stable laws for multidimensional stochastic recursions: the case of regular matrices

Given a sequence $(M_{n},Q_{n})_{n\ge 1}$ of i.i.d.\ random variables with generic copy $(M,Q) \in GL(d, \R) \times \R^d$, we consider the random difference equation (RDE) $$R_{n}=M_{n}R_{n-1}+Q_{n},$$ $n\ge 1$, and assume the existence of $\kappa >0$ such that \lim_{n \to \infty}(\E{\norm{M_1 ... M_n}^\kappa})^{\frac{1}{n}} = 1 . We prove, under suitable assumptions, that the sequence $S_n = R_1 + ... + R_n$, appropriately normalized, converges in law to a multidimensional stable distribution with index $\kappa$. As a by-product, we show that the unique stationary solution $R$ of the RDE is regularly varying with index $\kappa$, and give a precise description of its tail measure. This extends the prior work http://arxiv.org/abs/1009.1728v3 .Comment: 15 page

Potential Impact of Antiretroviral Therapy and Screening on Cervical Cancer Mortality in HIV-Positive Women in Sub-Saharan Africa: A Simulation

Despite having high cervical cancer incidence and mortality rates, screening for cervical precancerous lesions remains infrequent in sub-Saharan Africa. The need to screen HIV-positive women because of the higher prevalence and faster progression of cervical precancerous lesions may be heightened by the increased access to highly-active antiretroviral therapy (HAART). Policymakers need quantitative data on the effect of HAART and screening to better allocate limited resources. Our aim was to quantify the potential effect of these interventions on cervical cancer mortality.We constructed a Markov state-transition model of a cohort of HIV-positive women in Cameroon. Published data on the prevalence, progression and regression of lesions as well as mortality rates from HIV, cervical cancer and other causes were incorporated into the model. We examined the potential impact, on cumulative cervical cancer mortality, of four possible scenarios: no HAART and no screening (NHNS), HAART and no screening (HNS), HAART and screening once on HAART initiation (HSHI), and HAART and screening once at age 35 (HS35). Our model projected that, compared to NHNS, lifetime cumulative cervical cancer mortality approximately doubled with HNS. It will require 262 women being screened at HAART initiation to prevent one cervical cancer death amongst women on HAART. The magnitudes of these effects were most sensitive to the rate of progression of precancerous lesions.Screening, even when done once, has the potential of reducing cervical cancer mortality among HIV-positive women in Africa. The most feasible and cost-effective screening strategy needs to be determined in each setting

Block sequential adriamycin CMF – optimal non-myeloablative chemotherapy for high risk adjuvant breast cancer?

After the publication of the 10-year survival data from Milan on the adjuvant use of the block sequential regimen consisting of four cycles of adriamycin followed by eight cycles of intravenous CMF, many centres adopted this as standard of care for high risk, multiple node-positive breast cancer. For this reason it was identified as the standard arm for the Anglo-Celtic adjuvant high-dose chemotherapy trial. This study reports on the experience of this regimen in 329 women with early breast cancer involving at least four axillary nodes, who were treated outside any adjuvant chemotherapy trial. At a median follow-up of 3 years, the overall 5-year disease-free survival is 61%, and the overall survival is 70%. These data confirm the efficacy of this regimen in non-trial patients, and, for the same high risk subgroup, indicate that this approach offers an outcome at least as good as that seen in the CALGB 9344 AC-Taxol arm, and the NCIC days 1 and 8 CEF

Cancer-selective, single agent chemoradiosensitising gold nanoparticles

Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics

The formation of professional identity in medical students: considerations for educators

<b>Context</b> Medical education is about more than acquiring an appropriate level of knowledge and developing relevant skills. To practice medicine students need to develop a professional identity – ways of being and relating in professional contexts.<p></p> <b>Objectives</b> This article conceptualises the processes underlying the formation and maintenance of medical students’ professional identity drawing on concepts from social psychology.<p></p> <b>Implications</b> A multi-dimensional model of identity and identity formation, along with the concepts of identity capital and multiple identities, are presented. The implications for educators are discussed.<p></p> <b>Conclusions</b> Identity formation is mainly social and relational in nature. Educators, and the wider medical society, need to utilise and maximise the opportunities that exist in the various relational settings students experience. Education in its broadest sense is about the transformation of the self into new ways of thinking and relating. Helping students form, and successfully integrate their professional selves into their multiple identities, is a fundamental of medical education

Amenability of groups and GG-sets

This text surveys classical and recent results in the field of amenability of groups, from a combinatorial standpoint. It has served as the support of courses at the University of G\"ottingen and the \'Ecole Normale Sup\'erieure. The goals of the text are (1) to be as self-contained as possible, so as to serve as a good introduction for newcomers to the field; (2) to stress the use of combinatorial tools, in collaboration with functional analysis, probability etc., with discrete groups in focus; (3) to consider from the beginning the more general notion of amenable actions; (4) to describe recent classes of examples, and in particular groups acting on Cantor sets and topological full groups

Determinants of impact : towards a better understanding of encounters with the arts

The article argues that current methods for assessing the impact of the arts are largely based on a fragmented and incomplete understanding of the cognitive, psychological and socio-cultural dynamics that govern the aesthetic experience. It postulates that a better grasp of the interaction between the individual and the work of art is the necessary foundation for a genuine understanding of how the arts can affect people. Through a critique of philosophical and empirical attempts to capture the main features of the aesthetic encounter, the article draws attention to the gaps in our current understanding of the responses to art. It proposes a classification and exploration of the factors—social, cultural and psychological—that contribute to shaping the aesthetic experience, thus determining the possibility of impact. The ‘determinants of impact’ identified are distinguished into three groups: those that are inherent to the individual who interacts with the artwork; those that are inherent to the artwork; and ‘environmental factors’, which are extrinsic to both the individual and the artwork. The article concludes that any meaningful attempt to assess the impact of the arts would need to take these ‘determinants of impact’ into account, in order to capture the multidimensional and subjective nature of the aesthetic experience