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    Forensic Proteomics for the Evaluation of the post-Mortem Decay in Bones

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    Current methods for the evaluation of post-mortem interval (PMI) of skeletal remains suffer from poor accuracy, due to the great number of variables that affect the diagenetic process and to the lack of specific guidelines to address this issue. During decomposition, proteins can undergo cumulative decay over the time, resulting in a decrease in the range and abundance of proteins present (i.e., the proteome) in different tissues as well as in an increase of post-translational modifications occurring on these proteins. In this study, we evaluate the applicability of bone proteomic analyses to simulated forensic contexts, looking for specific biomarkers that may help the estimation of PMI and evaluating a previously discovered marker for the estimation of biological age. We noticed a reduction of specific plasma and muscle proteins with increasing PMIs, as well as an increased deamidation of biglycan, a protein with a role in modulating bone growth and mineralization, which may be developed further for the estimation of PMI from a molecular perspective. We also corroborated our previous results regarding the use of fetuin-A as a potential biomarker for the estimation of age-at-death, demonstrating the applicability and the great potential that proteomics may have towards forensic sciences. Significance: The estimation of the post-mortem interval has a key role in forensic investigations, however nowadays it still suffers from poor reliability, especially when bodies are heavily decomposed. Here we proposed for the first time the application of bone proteomics to the estimation of the time elapsed from death, and we found some new potential biomarkers to address this specific question. This study hence proves the applicability of proteomic analyses to forensic sciences, showing that proteomics may become an integrant discipline to answer unresolved forensic issues

    Application of accelerated time models to compare performance of two comorbidity -adjusting methods with APACHE II in predicting short-term mortality among the critically ill

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    Objective This study aimed to determine how the abilities of the Charlson Index and Elixhauser comorbidities compared with the chronic health components of the Acute Physiology and Chronic Health Evaluation (APACHE II) to predict in-hospital 30 day mortality among adult critically ill patients treated inside and outside of Intensive Care Unit (ICU). Methods A total of 701 critically ill patients, identified in a prevalence study design on four randomly selected days in five acute care hospitals, were followed up from the date of becoming critically ill for 30 days or until death, whichever occurred first. Multiple data sources including administrative, clinical, pathology, microbiology and laboratory patient records captured the presence of acute and chronic illnesses. The exponential, Gompertz, Weibull, and log-logistic distributions were assessed as candidate parametric distributions available for the modelling of survival data. Of these, the log-logistic distribution provided the best fit and was used to construct a series of parametric survival models. Results Of the 701 patients identified in the initial prevalence study, 637 (90.9%) had complete data for all fields used to calculate APACHE II score. Controlling for age, sex and Acute Physiology Score (APS), the chronic health components of the APACHE II score, as a group, were better predictors of survival than Elixhauser comorbidities and Charlson Index. Of the APACHE II chronic health components, only the relatively uncommon conditions of liver failure (3.4%) and immunodeficiency (9.6%) were statistically associated with inferior patient survival with acceleration factors of 0.35 (95% CI 0.17, 0.72) for liver failure, and 0.42 (95% CI 0.26, 0.72) for immunodeficiency. Sensitivity analyses on an imputed dataset that also included the 64 individuals with imputed APACHE II score showed identical results. Conclusion Our study suggests that, in acute critical illness, most co-existing comorbidities are not major determinants of short-term survival, indicating that observed variations in ICU patient 30-day mortality may not be confounded by lack of adjustment to pre-existing comorbidities

    Enhancing the dissolution of phenylbutazone using Syloid® based mesoporous silicas for oral equine applications

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    Three mesoporous silica excipients (Syloid® silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent, and rate, of drug release for all three forms of Syloid® silica at a 1:1 drug:silica ratio over a period of 30 minutes. An explanation for this increase was determined to be conversion to the amorphous form and an enhanced drug loading ability within the pores. Differences between the release profiles of the three silicas was concluded to be a consequence of the physicochemical differences between the three forms. Overall, this study confirms that Syloid® silica based excipients can be used to enhance dissolution, and potentially therefore bioavailability, for compounds with poor aqueous solubility, such as phenylbutazone. In addition, it has been confirmed that drug release can be carefully tailored based on the choice of Syloid® silica and desired release profile

    Dividend policy in Turkey: Survey evidence from Borsa Istanbul firms

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    This study investigates the views of managers of firms listed on the Borsa Istanbul (BIST) on dividend policy. The survey evidence provides general support for Lintner’s partial adjustment model, signaling theory, catering, firm life cycle, and bird-in-the-hand hypotheses for explaining cash dividends. The results do not support the agency cost theory, substitution model of dividends, tax-related explanations, transaction cost theory, and residual dividend policy. The findings suggest that after implementing major economic and structural reforms and abolishing a mandatory dividend payment requirement, BIST managers follow similar dividend policy factors and patterns of dividend policy as managers in more developed countries

    Corporate governance and audit features: SMEs evidence

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    Purpose The purpose of this paper is to investigate the effect of corporate governance factors on audit features, namely, audit fees and the selection of Big 4 audit firms within the UK SMEs context. Design/methodology/approach The author uses different regression models to investigate the impact of corporate governance characteristics on audit features, and employs cross-sectional time series models as well as two-stage least squares technique. In addition, the author has used logit analysis to examine the effect of corporate governance factors on the selection of Big 4 audit firms. Findings The author provides new evidence that governance mechanisms in SMEs affect different audit features. The results show that corporate governance mechanisms are important in determining audit fees. The author detects a positive impact of board independence, audit meeting and board size on audit fees. The author also reports evidence that governance factors determine the selection of Big 4 audit firms. In particular, the author reports that independent directors and audit diligence positively affect the decision to select Big 4 audit firms. Originality/value This paper investigates the under-researched relationship between audit features and corporate governance using UK SMEs. In so doing, the author aims to provide new insights into this relationship within the SMEs context

    A cost-effectiveness analysis of a hydration response technology dressing in the treatment of venous leg ulcers in the UK

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    Introduction: Venous leg ulceration causes significant pain and suffering for patients, additionally it places considerable financial and service burden on the National Health Service (NHS). A large proportion of venous leg ulceration do not heal within the standard time frames of 16 – 24 weeks, resulting in static wounds which commonly have issues with increasing exudate production. Static wounds can have significant negative impact on the patients quality of life, the wound bed and periwound skin, increased risk of infection all of which results in delayed wound healing and increased health service costs. As the NHS continues to face times of austerity, services need to find solutions to be able to reduce cost and release nursing time whilst maintaining standards of care. Cutimed® Sorbion® Sachet S is a treatment option for the management of patients with a venous leg ulceration. The objective of this study was to provide an update of the health economic analysis of Cutimed® Sorbion® Sachet S in comparison to relevant comparators in the UK with current cost data. Methods: Cutimed® Sorbion® Sachet S was compared against Zetuvit Plus, DryMax extra, KerraMax Care and Eclypse from a cost effectiveness perspective. Clinical data were derived from literature and expert opinion. Cost input was utilized based on publicly available data and literature. The average patient in the model is assumed to be 65 years with a diagnosed venous leg ulcer. It is assumed that patients in the different treatment arms have the same background mortality, hence the endpoint mortality is not included in the model. The analysis is based on a deterministic Markov model derived from Harding et al. with weekly cycles. The following assumptions are made: First, all patients start in a static health state with a non-healed but non-progressing venous leg ulcer. It is assumed in the model that patients can transition to a deteriorating health state where a wound is improving or the wound could progress. Additionally, venous leg ulcers could be healed from a progressed wound (i.e. improved wound), they could develop into a severe wound with complications (infections) to be treated in hospitals. The time frame for the analysis was fixed for one year and no re-occurence after healing was assumed to happen. Results: The cost-effectiveness analysis demonstrates health economic dominance of Cutimed® Sorbion® Sachet S being more effective and cost-saving against all analysed comparators. When using literature-based input values the incrementally higher healing rates for Cutimed® Sorbion® Sachet S are 11.04 months (versus Zetuvit Plus), 29.04 months (versus DryMax extra), 1.68 months (versus KerraMax Care) and 11.04 months (versus Eclypse). Cost savings per patient were 37.60£ (versus Zetuvit Plus), 171.68£ (versus DryMax extra), 3.13£ (versus KerraMax Care) and 43.63£ (versus Eclypse). Clinical benefits and cost savings are increasing when real life practice assumptions based on expert opinion are included. Conclusions: Based on the underlying health economic model, Cutimed® Sorbion® Sachet S is more effective and less costly than other comparative products in venous leg ulcers in the UK

    Moving forward :opportunities and challenges

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    SceneMaker: Creative Technology for Digital StoryTelling

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    We brought together the subject of computing with creative technologies, cinematic arts (film), drama, dance, music and design in terms of research and education and propose here the development of a flagship computer software platform, SceneMaker, acting as a digital laboratory workbench for integrating and experimenting with the computer processing of new theories and methods in these multidisciplinary fields. We discuss the architecture of SceneMaker and relevant technologies for processing within its component modules. SceneMaker will enable the automated production of multimodal animated scenes from film and drama scripts or screenplays. SceneMaker will highlight affective or emotional content in digital storytelling with particular focus on character body posture, facial expressions, speech, non-speech audio, scene composition, timing, lighting, music and cinematography. Applications of SceneMaker include automated simulation of productions and education and training of actors, screenwriters and directors

    Say yes to mess – why companies should embrace disorder

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    Beyond the “Code”: A Guide to the Description and Documentation of Biodiversity in Ciliated Protists (Alveolata, Ciliophora)

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    Recent advances in molecular technology have revolutionized research on allaspects of the biology of organisms, including ciliates, and created unprece-dented opportunities for pursuing a more integrative approach to investigationsof biodiversity. However, this goal is complicated by large gaps and inconsis-tencies that still exist in the foundation of basic information about biodiversityof ciliates. The present paper reviews issues relating to the taxonomy of cili-ates and presents specific recommendations for best practice in the observa-tion and documentation of their biodiversity. This effort stems from aworkshop that explored ways to implement six Grand Challenges proposed bythe International Research Coordination Network for Biodiversity of Ciliates(IRCN-BC). As part of its commitment to strengthening the knowledge basethat supports research on biodiversity of ciliates, the IRCN-BC proposes topopulate The Ciliate Guide, an online database, with biodiversity-related dataand metadata to create a resource that will facilitate accurate taxonomic identi-fications and promote sharing of data

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