The effect of prebiotic fibre on the gut microbiome and surgical outcomes in patients with prosthetic joint infection (PENGUIN) - study protocol for a randomised, double-blind, placebo-controlled trial (ACTRN12623001273673).

Background: Prosthetic Joint Infection (PJI) is the most devastating complication of arthroplasty surgery and affects 1-5% of patients. Despite strict adherence to aseptic protocols and preventive measures, infection is the most common reason for revision arthroplasty, and the incidence is increasing. Treatment of PJI is challenging and often requires repeated major surgeries with sequentially poor results.

The effect of weight compared to BMI on patient reported outcomes at long term follow up of primary total hip arthroplasty.

Introduction: Obesity has been linked to the development of osteoarthritis meaning that a large portion of arthroplasty patients are overweight or obese. Whilst the short-term complications associated with obesity are well described there is a paucity of evidence on the effect of weight compared to BMI for long term functional outcomes of total hip replacements (THR). The aim of this study was to investigate the influence of BMI and weight on long-term patient reported outcome measures following primary THR.

RSA Measurements of Implant Instability in a Paprosky III Pelvic Defect with Discontinuity: A Case Report.

Case: We report a case of acetabular reconstruction for a large defect with pelvic discontinuity that underwent 4 revisions for dislocations over a 3-year period. This allowed assessment of implant stability both on imaging, using measurements on plain radiographs and radiostereometric analysis (RSA) against both ilium and ischium, and direct assessment during each surgery. Only implant stability measured with RSA correlated with intraoperative revision findings.

Efficacy of topical Calendula officinalis on prevalence of radiation-induced dermatitis: A randomised controlled trial.

Objectives: A randomised controlled trial was undertaken to compare the efficacy of topical Calendula officinalis (Calendula) versus standard of care (Sorbolene: 10% glycerine in cetomacragol cream) in reducing the prevalence of radiation-induced dermatitis in women undergoing breast cancer radiotherapy.

Methods: A total of 271 women were screened and 82 were randomised. The primary outcome was prevalence of acute radiation-induced dermatitis (RTOG grade 2+) assessed at multiple skin sites.

Managing the Risks Remotely Piloted Aircraft Operations Pose to People and Property on the Ground.

Worldwide there is much effort being directed towards the development of a framework of airworthiness regulations for remotely piloted aircraft systems (RPAS). It is now broadly accepted that regulations should have a strong foundation in, and traceability to, the management of the safety risks. Existing risk models for RPAS operations do not provide a simple means for incorporating the wide range of technical and operational controls into the risk analysis and evaluation processes.

Emulating avian orographic soaring with a small autonomous glider.

This paper explores a method by which an unpowered, fixed-wing micro air vehicle (MAV) may autonomously gain height by utilising orographic updrafts in urban environments. These updrafts are created when wind impinges on both man-made and natural obstacles, and are often highly turbulent and very localised. Thus in contrast to most previous autonomous soaring research, which have focused on large thermals and ridges, we use a technique inspired by kestrels known as 'wind-hovering', in order to maintain unpowered flight within small updrafts.

Non-animal Replacements for Acute Toxicity Testing.

Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data.

Risk Perception and the Public Acceptance of Drones.

Unmanned aircraft, or drones, are a rapidly emerging sector of the aviation industry. There has been limited substantive research, however, into the public perception and acceptance of drones. This article presents the results from two surveys of the Australian public designed to investigate (1) whether the public perceive drones to be riskier than existing manned aviation, (2) whether the terminology used to describe the technology influences public perception, and (3) what the broader concerns are that may influence public acceptance of the technology.

Analgesic use, pain and daytime sedation in people with and without dementia in aged care facilities: a cross-sectional, multisite, epidemiological study protocol.

Introduction: People living with dementia may experience and express pain in different ways to people without dementia. People with dementia are typically prescribed fewer analgesics than people without dementia indicating a potential difference in how pain is identified and treated in these populations. The objectives of this study are to (1) investigate the prevalence of analgesic load, pain and daytime sedation in people with and without dementia in Australian residential aged care facilities (RACFs), and (2) investigate the clinical and diagnostic associations between analgesic load, pain and daytime sedation in people with and without dementia in Australian RACFs.

Resistance to cancer in amphibians: a role for apoptosis?

The rarity of spontaneous cancer in amphibians, and the difficulty of inducing cancer in these lower vertebrates, suggest that they possess an effective system for resistance to the development of cancer. The first part of this narrative presents evidence for cancer resistance in amphibians, and then a variety of studies designed to help understand the physiological basis for this resistance are reviewed. Here, our emphasis is on evidence with regard to the role that apoptosis might play.

Comparative studies of apoptosis in Xenopus laevis and mouse thymoma cell lines.

With the use of in vitro methods and cell lines, functional aspects of apoptosis in the Xenopus laevis B3/B7 and mouse EL4 thymoma cell lines are revealed. Moreover, by using information gleaned from digital imaging and immunocytochemistry, changes in locations of key proteins implicated in apoptotic anti-cancer responses, e.g.

Comparative analysis of eight cytotoxicity assays evaluated within the ACuteTox Project.

A comparative analysis of eight cytotoxicity assays [the 3T3 and normal human keratinocytes Neutral Red Uptake (NRU) assay, the primary rat hepatocytes, human HepG2 and 3T3 MTT assay, and the human A.704, SH-SY5Y and HepG2 cells propidium iodide (PI) assay] included in several work packages of the EU Integrated Project ACuteTox, has been carried out. The aim was to evaluate whether cells originating from liver, kidney and brain provided different in vitro acute toxicity results, and the influence of primary liver cells versus cell lines originated from the same tissue.

The development and evaluation of in vitro alternative assays: a personal perspective.

Over the past 30 years, FRAME has actively participated in the development, evaluation and validation of in vitro alternative methods through the FRAME Alternatives Laboratory (FAL) in the University of Nottingham Medical School. Much has been learned through collaboration with industry (especially the cosmetics industry), other organisations (especially ECVAM), and certain individuals (notably Dr Björn Ekwall), particularly in relation to the need to use human cell cultures and to obtain, wherever possible, high-quality human data for use in in vivo/in vitro comparisons. Reference is made to the author's experience as Director of the FAL, notably in the development of in vitro assays for basal cytotoxicity, phototoxicity and the effects of repeated dosage.

A FRAME response to the Draft Report on Alternative (Non-animal) Methods for Cosmetics Testing: Current Status and Future Prospects--2010.

This response on behalf of FRAME to the European Commission's consultation on the five chapters of the Draft Report on Alternative (Non-animal) Methods for Cosmetics Testing: Current Status and Future Prospects--2010, is via a Comment in ATLA, rather than via the template supplied by the Commission. This is principally so that a number of general points about cosmetic ingredient testing can be made. It is concluded that the five draft chapters do not provide a credible basis for the Commission's forthcoming report to the European Parliament and the European Council on the five cosmetic ingredient safety issues for which the 7th Amendment to the Cosmetic Directive's ban on animal testing was postponed until 2013.

FRAME and the validation process.

FRAME's historical involvement in the development of the principles of validation, whereby the reliability and relevance of a procedure are established for a specific purpose, and in the practical application of the process, is summarised, and examples of participation in various validation studies on in vitro tests are reviewed. Emphasis is placed on the need for a parallel invalidation process, and on the role of ATLA as a forum for objective reporting and discussion on all aspects of the validation process.

An evaluation of the chick cardiomyocyte micromass system for identification of teratogens in a blind trial.

The chick micromass culture system has advantages over the validated rat system - ready availability and non-culling of the donor parent - but needs to give comparable results. This study confirmed comparability and the ability to extend the system to cover cardiac effects. It was also compared with the validated embryonic stem cell cardiomyocyte model.

A proposed eye irritation testing strategy to reduce and replace in vivo studies using Bottom-Up and Top-Down approaches.

In spite of over 20 years of effort, no single in vitro assay has been developed and validated as a full regulatory replacement for the Draize Eye Irritation test. However, companies have been using in vitro methods to screen new formulations and in some cases as their primary assessment of eye irritation potential for many years. The present report shows the outcome of an Expert Meeting convened by the European Centre for the Validation of Alternative Methods in February 2005 to identify test strategies for eye irritation.

The effects of terahertz radiation on human keratinocyte primary cultures and neural cell cultures.

Terahertz (THz) frequencies are found in a previously underexploited region of the radiation spectrum. This non-ionising energy is now being employed in medical imaging, so the possibility of adverse effects on human skin was evaluated. Primary cultures of normal human keratinocytes (NHKs) express adhesion molecules that comprise part of the natural barrier function of the skin.

A database of IC50 values and principal component analysis of results from six basal cytotoxicity assays, for use in the modelling of the in vivo and in vitro data of the EU ACuteTox project.

The main aim of the ACuteTox project (part of the EU 6th Framework programme) is to demonstrate that animal tests for acute systemic toxicity can be replaced by alternative in vitro assays. In this project, data for 97 reference chemicals were collected in the AcuBase database, designed to handle deposited in vitro and in vivo (human and animal) data. To demonstrate the applicability of in vitro basal cytotoxicity tests and in vitro-in vivo modelling, it was deemed necessary to obtain data that were generated via defined standard operating procedures.

Comparative evaluation of cytotoxicity and phototoxicity of mono and diacylglycerol amino acid-based surfactants.

Extensive efforts have been made, recently, to find surfactants with lower irritancy potential than those presently commercially employed in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of novel mono and diacylglycerol amino acid-based surfactants (glutamic acid, or arginine) were evaluated. All tested surfactants showed a clear concentration-response relationship to two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, demonstrated by and decrease of NR uptake.

Estimation of human blood LC50 values for use in modeling of in vitro-in vivo data of the ACuteTox project.

The main aim of the ACuteTox project, under EU 6th Framework programme, is to investigate whether animal toxicity tests for acute systemic toxicity could be replaced by a combination of alternative assays. Data for 97 reference chemicals was collected in the ACuteTox database (Acutoxbase), designed to handle invitro and invivo (human and animal) lodged data. The principal basis for demonstration of the applicability of invitro tests is the invitro-invivo modeling, by using statistical correlation between invitro IC50 molar values (the 50% inhibitory concentration for the endpoints measured) and human blood molar concentrations LC50 (50% lethal concentrations).

Phototoxicity and acute toxicity studies conducted by the FRAME Alternatives Laboratory: a brief review.

FRAME and the University of Nottingham have been in association for the past 25 years. During this time, the research in the FRAME Alternatives Laboratory (FAL) at the University of Nottingham, which is partly funded by FRAME and also, more recently, by ECVAM, has involved participation in a number of international validation studies. Validation has become a pre-requisite for the regulatory acceptance of in vitro alternative test procedures, and a number of key lessons have been learned from these studies.

An evaluation of a novel chick cardiomyocyte micromass culture assay with two teratogens/embryotoxins associated with heart defects.

This study was aimed at determining whether the chick cardiomyocyte micromass (MM) system could be employed to predict the teratogenicity/embryotoxicity of exogenous chemicals. Two documented teratogens/embryotoxins, sodium valproate (the sodium salt of valproic acid; VPA) and all-trans retinoic acid (tRA), were used in the initial phase of the study. White Leghorn 5-day-old embryo hearts were dissociated to produce a cardiomyocyte suspension in Dulbecco's Modified Eagle's Medium.