Accuracy of rate estimation using relaxed-clock models with a critical focus on the early metazoan radiation

In recent years, a number of phylogenetic methods have been developed for estimating molecular rates and divergence dates under models that relax the molecular clock constraint by allowing rate change throughout the tree. These methods are being used with increasing frequency, but there have been few studies into their accuracy. We tested the accuracy of several relaxed-clock methods (penalized likelihood and Bayesian inference using various models of rate change) using nucleotide sequences simulated on a nine-taxon tree. When the sequences evolved with a constant rate, the methods were able to infer rates accurately, but estimates were more precise when a molecular clock was assumed. When the sequences evolved under a model of autocorrelated rate change, rates were accurately estimated using penalized likelihood and by Bayesian inference using lognormal and exponential models of rate change, while other models did not perform as well. When the sequences evolved under a model of uncorrelated rate change, only Bayesian inference using an exponential rate model performed well. Collectively, the results provide a strong recommendation for using the exponential model of rate change if a conservative approach to divergence time estimation is required. A case study is presented in which we use a simulation-based approach to examine the hypothesis of elevated rates in the Cambrian period, and it is found that these high rate estimates might be an artifact of the rate estimation method. If this bias is present, then the ages of metazoan divergences would be systematically underestimated. The results of this study have implications for studies of molecular rates and divergence dates.

The Prehistory of Potyviruses: Their Initial Radiation Was during the Dawn of Agriculture

Background: Potyviruses are found world wide, are spread by probing aphids and cause considerable crop damage. Potyvirus is one of the two largest plant virus genera and contains about 15% of all named plant virus species. When and why did the potyviruses become so numerous? Here we answer the first question and discuss the other. Methods and Findings: We have inferred the phylogenies of the partial coat protein gene sequences of about 50 potyviruses, and studied in detail the phylogenies of some using various methods and evolutionary models. Their phylogenies have been calibrated using historical isolation and outbreak events: the plum pox virus epidemic which swept through Europe in the 20th century, incursions of potyviruses into Australia after agriculture was established by European colonists, the likely transport of cowpea aphid-borne mosaic virus in cowpea seed from Africa to the Americas with the 16th century slave trade and the similar transport of papaya ringspot virus from India to the Americas. Conclusions/Significance: Our studies indicate that the partial coat protein genes of potyviruses have an evolutionary rate of about 1.1561024 nucleotide substitutions/site/year, and the initial radiation of the potyviruses occurred only about 6,600 years ago, and hence coincided with the dawn of agriculture. We discuss the ways in which agriculture may have triggered the prehistoric emergence of potyviruses and fostered their speciation.

A tan in a test tube -in vitro models for investigating ultraviolet radiation-induced damage in skin

Presently, global rates of skin cancers induced by ultraviolet radiation (UVR) exposure are on the rise. In view of this, current knowledge gaps in the biology of photocarcinogenesis and skin cancer progression urgently need to be addressed. One factor that has limited skin cancer research has been the need for a reproducible and physiologically-relevant model able to represent the complexity of human skin. This review outlines the main currently-used in vitro models of UVR-induced skin damage. This includes the use of conventional two-dimensional cell culture techniques and the major animal models that have been employed in photobiology and photocarcinogenesis research. Additionally, the progression towards the use of cultured skin explants and tissue-engineered skin constructs, and their utility as models of native skin's responses to UVR are described. The inherent advantages and disadvantages of these in vitro systems are also discussed.

A risk simulation framework for information infrastructure protection

Information communication and technology (ICT) systems are almost ubiquitous in the modern world. It is hard to identify any industry, or for that matter any part of society, that is not in some way dependent on these systems and their continued secure operation. Therefore the security of information infrastructures, both on an organisational and societal level, is of critical importance. Information security risk assessment is an essential part of ensuring that these systems are appropriately protected and positioned to deal with a rapidly changing threat environment. The complexity of these systems and their inter-dependencies however, introduces a similar complexity to the information security risk assessment task. This complexity suggests that information security risk assessment cannot, optimally, be undertaken manually. Information security risk assessment for individual components of the information infrastructure can be aided by the use of a software tool, a type of simulation, which concentrates on modelling failure rather than normal operational simulation. Avoiding the modelling of the operational system will once again reduce the level of complexity of the assessment task. The use of such a tool provides the opportunity to reuse information in many different ways by developing a repository of relevant information to aid in both risk assessment and management and governance and compliance activities. Widespread use of such a tool allows the opportunity for the risk models developed for individual information infrastructure components to be connected in order to develop a model of information security exposures across the entire information infrastructure. In this thesis conceptual and practical aspects of risk and its underlying epistemology are analysed to produce a model suitable for application to information security risk assessment. Based on this work prototype software has been developed to explore these concepts for information security risk assessment. Initial work has been carried out to investigate the use of this software for information security compliance and governance activities. Finally, an initial concept for extending the use of this approach across an information infrastructure is presented.

Re-examining the evidence in radiation dermatitis management literature : an overview and a critical appraisal of systematic reviews

Purpose: To provide an overview and a critical appraisal of systematic reviews (SRs) of published interventions for the prevention/management of radiation dermatitis. Methods and Materials: We searched Medline, CINAHL, Embase, and the Cochrane Library. We also manually searched through individual reference lists of potentially eligible articles and a number of key journals in the topic area. Two authors screened all potential articles and included eligible SRs. Two authors critically appraised and extracted key findings from the included reviews using AMSTAR (the measurement tool for “assessment of multiple systematic reviews”). Results: Of 1837 potential titles, 6 SRs were included. A number of interventions have been reported to be potentially beneficial for managing radiation dermatitis. Interventions evaluated in these reviews included skin care advice, steroidal/nonsteroidal topical agents, systemic therapies, modes of radiation delivery, and dressings. However, all the included SRs reported that there is insufficient evidence supporting any single effective intervention. The methodological quality of the included studies varied, and methodological shortfalls in these reviews might create biases to the overall results or recommendations for clinical practice. Conclusions: An up-to-date high-quality SR in the prevention/management of radiation dermatitis is needed to guide practice and direction for future research. We recommend that clinicians or guideline developers critically evaluate the information of SRs in their decision making.

Rethinking Youth Prostitution: National Provision at the Margins of Child Protection and Youth Justice

In March 2000, the Department of Health and the Home Office issued guidance fundamentally altering policy and practice with regard to young people in prostitution. 1 Instead of being arrested and punished for prostitution-related offences, those under 18 years old were to be thought of as children ‘in need’ and offered welfare-based interventions. The practice that has developed in the last three years has offered interventions that are located within both child protection and youth justice work. This article examines these changes in order to generate insights about the changing nature of youth justice. In particular, it is argued that the drive to manage the risks posed by young people in prostitution to specific organisations, takes precedence over either the desire to care for, or the demand to punish them. Through an analysis of how practitioners and policy makers responsible for implementing this new approach to youth prostitution talk about ‘risk’ and ‘responsibility’, ‘liability’, ‘protection’ and ‘punishment’, the article argues that the contradiction between care and control has been re-interpreted, such that there is noticeable blurring of the boundaries between welfare and punishment at the margins of youth justice work.

Evaluation of an inactivated Ross River virus vaccine in active and passive mouse immunization models and establishment of a correlate of protection

Ross River Virus has caused reported outbreaks of epidemic polyarthritis, a chronic debilitating disease associated with significant long-term morbidity in Australia and the Pacific region since the 1920s. To address this public health concern, a formalin- and UV-inactivated whole virus vaccine grown in animal protein-free cell culture was developed and tested in preclinical studies to evaluate immunogenicity and efficacy in animal models. After active immunizations, the vaccine dose-dependently induced antibodies and protected adult mice from viremia and interferon α/β receptor knock-out (IFN-α/βR(-/-)) mice from death and disease. In passive transfer studies, administration of human vaccinee sera followed by RRV challenge protected adult mice from viremia and young mice from development of arthritic signs similar to human RRV-induced disease. Based on the good correlation between antibody titers in human sera and protection of animals, a correlate of protection was defined. This is of particular importance for the evaluation of the vaccine because of the comparatively low annual incidence of RRV disease, which renders a classical efficacy trial impractical. Antibody-dependent enhancement of infection, did not occur in mice even at low to undetectable concentrations of vaccine-induced antibodies. Also, RRV vaccine-induced antibodies were partially cross-protective against infection with a related alphavirus, Chikungunya virus, and did not enhance infection. Based on these findings, the inactivated RRV vaccine is expected to be efficacious and protect humans from RRV disease

A double-blind randomised controlled trial of a natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer

Background: Radiation-induced skin reaction (RISR) is one of the most common and distressing side effects of radiotherapy in patients with cancer. It is featured with swelling, redness, itching, pain, breaks in skin, discomfort, and a burning sensation. There is a lack of convincing evidence supporting any single practice in the prevention or management of RISR. Methods/Designs: This double-blinded randomised controlled trial aims to investigate the effects of a natural oil-based emulsion containing allantoin (as known as Moogoo Udder Cream®) versus aqueous cream in reducing RISR, improving pain, itching and quality of life in this patient group. One group will receive Moogoo Udder Cream®. Another group will receive aqueous cream. Outcome measures will be collected using patient self-administered questionnaire, interviewer administered questionnaire and clinician assessment at commencement of radiotherapy, weekly during radiotherapy, and four weeks after the completion of radiotherapy. Discussion: Despite advances of radiologic advances and supportive care, RISR are still not well managed. There is a lack of efficacious interventions in managing RISR. While anecdotal evidence suggests that Moogoo Udder Cream® may be effective in managing RISR, research is needed to substantiate this claim. This paper presents the design of a double blind randomised controlled trial that will evaluate the effects of Moogoo Udder Cream® versus aqueous cream for managing in RISR in patients with cancer. Trial registration: ACTRN 12612000568819

Folate degradation due to ultraviolet radiation : possible implications for human health and nutrition

Folate is essential for human health in the prevention of megaloblastic anaemia and neural tube birth defects as well as roles in cardiovascular disease and cancer. Therefore research into environmental factors that may impact folate status, such as solar ultraviolet radiation, is of great health significance. In vitro studies have shown that ultraviolet (UV) radiation can degrade folate and folic acid in human blood and this has been confirmed in several human studies. Despite these findings, there is a dearth of epidemiological research into investigating the relationship between folate status and the links to solar UV exposure.

Integrity, attribution, and exploitation : contractual and normative moral rights protection in open licensing

Over the last twenty years, the use of open content licenses has become increasingly and surprisingly popular. The use of such licences challenges the traditional incentive-based model of exclusive rights under copyright. Instead of providing a means to charge for the use of particular works, what seems important is mitigating against potential personal harm to the author and, in some cases, preventing non-consensual commercial exploitation. It is interesting in this context to observe the primacy of what are essentially moral rights over the exclusionary economic rights. The core elements of common open content licences map somewhat closely to continental conceptions of the moral rights of authorship. Most obviously, almost all free software and free culture licences require attribution of authorship. More interestingly, there is a tension between social norms developed in free software communities and those that have emerged in the creative arts over integrity and commercial exploitation. For programmers interested in free software, licence terms that prohibit commercial use or modification are almost completely inconsistent with the ideological and utilitarian values that underpin the movement. For those in the creative industries, on the other hand, non-commercial terms and, to a lesser extent, terms that prohibit all but verbatim distribution continue to play an extremely important role in the sharing of copyright material. While prohibitions on commercial use often serve an economic imperative, there is also a certain personal interest for many creators in avoiding harmful exploitation of their expression – an interest that has sometimes been recognised as forming a component of the moral right of integrity. One particular continental moral right – the right of withdrawal – is present neither in Australian law or in any of the common open content licences. Despite some marked differences, both free software and free culture participants are using contractual methods to articulate the norms of permissible sharing. Legal enforcement is rare and often prohibitively expensive, and the various communities accordingly rely upon shared understandings of acceptable behaviour. The licences that are commonly used represent a formalised expression of these community norms and provide the theoretically enforceable legal baseline that lends them legitimacy. The core terms of these licences are designed primarily to alleviate risk in sharing and minimise transaction costs in sharing and using copyright expression. Importantly, however, the range of available licences reflect different optional balances in the norms of creating and sharing material. Generally, it is possible to see that, stemming particularly from the US, open content licences are fundamentally important in providing a set of normatively accepted copyright balances that reflect the interests sought to be protected through moral rights regimes. As the cost of creation, distribution, storage, and processing of expression continues to fall towards zero, there are increasing incentives to adopt open content licences to facilitate wide distribution and reuse of creative expression. Thinking of these protocols not only as reducing transaction costs but of setting normative principles of participation assists in conceptualising the role of open content licences and the continuing tensions that permeate modern copyright law.

Does the protection of vulnerable children require a system of mandatory reporting of abuse and neglect? [An issues paper for the New Zealand Government Green Paper for vulnerable children]

In this Issues Paper, I raise some key points relevant for any government which is considering its child protection and family welfare policy. In particular, I will raise questions about whether a form of legislative reporting duty is required, and if so, what consequences this has for child protection. The context of child maltreatment - and each form of maltreatment: physical abuse, sexual abuse, psychological or emotional abuse, and neglect - is extremely complex, and the overarching question of how to deal with these phenomena involve challenging normative, economic and practical questions. There are no easy or perfect solutions. Nor, often, is there the amount and quality of evidence available on which public policy approaches should be devised. However, from the best evidence about the history of this context, from research conducted in this field, and from the best evidence available about the nature, incidence and effects of different subtypes of maltreatment, some observations can be made which may help to inform deliberations. I outline 10 key issues related to mandatory reporting legislation while being mindful of the New Zealand context. My view, based on both research evidence and a concern to protect and promote children’s interests, and society’s interests, is that reporting laws in some form are necessary and can contribute substantially to child protection and enhancing family and community health and wellbeing. However, they are only one necessary part of a sound child protection system, being a method of tertiary and secondary prevention, and primary prevention efforts must also be prioritised. Moreover, it is essential that if a legislative reporting duty is enacted, it must be designed carefully and implemented soundly, and it must be integrated within a properly resourced child protection and family welfare system.

Evaluation of coronary angiographic projections to balance the clinical yield with the radiation risk

Objective: Radiation safety principles dictate that imaging procedures should minimise the radiation risks involved, without compromising diagnostic performance. This study aims to define a core set of views that maximises clinical information yield for minimum radiation risk. Angiographers would supplement these views as clinically indicated. Methods: An algorithm was developed to combine published data detailing the quality of information derived for the major coronary artery segments through the use of a common set of views in angiography with data relating to the dose–area product and scatter radiation associated with these views. Results: The optimum view set for the left coronary system comprised four views: left anterior oblique (LAO) with cranial (Cr) tilt, shallow right anterior oblique (AP-RAO) with caudal (Ca) tilt, RAO with Ca tilt and AP-RAO with Cr tilt. For the right coronary system three views were identified: LAO with Cr tilt, RAO and AP-RAO with Cr tilt. An alternative left coronary view set including a left lateral achieved minimally superior efficiency (,5%), but with an ,8% higher radiation dose to the patient and 40% higher cardiologist dose. Conclusion: This algorithm identifies a core set of angiographic views that optimises the information yield and minimises radiation risk. This basic data set would be supplemented by additional clinically determined views selected by the angiographer for each case. The decision to use additional views for diagnostic angiography and interventions would be assisted by referencing a table of relative radiation doses for the views being considered.