Multilocus sequence typing (MLST) and Random Polymorphic DNA (RAPD) comparisons of geographic isolates of Neoparamoeba perurans, the causative agent of Amoebic Gill Disease

Neoparamoba perurans, is the aetiological agent of amoebic gill disease (AGD), a disease that affects farmed Atlantic salmon worldwide. Multilocus sequence typing (MLST) and Random Amplified Polymorphic DNA (RAPD) are PCR-based typing methods that allow for the highly reproducible genetic analysis of population structure within microbial species. To the best of our knowledge, this study represents the first use of these typing methods applied to N. perurans with the objective of distinguishing geographical isolates. These analyses were applied to a total of 16 isolates from Australia, Canada, Ireland, Scotland, Norway, and the USA. All the samples from Australia came from farm sites on the island state of Tasmania. Genetic polymorphism among isolates was more evident from the RAPD analysis compared to the MLST that used conserved housekeeping genes. Both techniques consistently identified that isolates of N. perurans from Tasmania, Australia were more similar to each other than to the isolates from other countries. While genetic differences were identified between geographical isolates, a BURST analysis provided no evidence of a founder genotype. This suggests that emerging outbreaks of AGD are not due to rapid translocation of this important salmonid pathogen from the same area

The Origin of Black Hole Entropy in String Theory

I review some recent work in which the quantum states of string theory which are associated with certain black holes have been identified and counted. For large black holes, the number of states turns out to be precisely the exponential of the Bekenstein-Hawking entropy. This provides a statistical origin for black hole thermodynamics in the context of a potential quantum theory of gravity.Comment: 18 pages (To appear in the proceedings of the Pacific Conference on Gravitation and Cosmology, Seoul, Korea, February 1-6, 1996.

Discovering duplicate tasks in transition systems for the simplification of process models

This work presents a set of methods to improve the understandability of process models. Traditionally, simplification methods trade off quality metrics, such as fitness or precision. Conversely, the methods proposed in this paper produce simplified models while preserving or even increasing fidelity metrics. The first problem addressed in the paper is the discovery of duplicate tasks. A new method is proposed that avoids overfitting by working on the transition system generated by the log. The method is able to discover duplicate tasks even in the presence of concurrency and choice. The second problem is the structural simplification of the model by identifying optional and repetitive tasks. The tasks are substituted by annotated events that allow the removal of silent tasks and reduce the complexity of the model. An important feature of the methods proposed in this paper is that they are independent from the actual miner used for process discovery.Peer ReviewedPostprint (author's final draft

CSF metabolites associate with CSF tau and improve prediction of Alzheimer's disease status

Introduction: Cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) are biomarkers of Alzheimer's disease (AD), yet much is unknown about AD-associated changes in tau metabolism and tau tangle etiology. Methods: We assessed the variation of t-tau and p-tau explained by 38 previously identified CSF metabolites using linear regression models in middle-age controls from the Wisconsin Alzheimer's Disease Research Center, and predicted AD/mild cognitive impairment (MCI) versus an independent set of older controls using metabolites selected by the least absolute shrinkage and selection operator (LASSO). Results: The 38 CSF metabolites explained 70.3% and 75.7% of the variance in t-tau and p-tau, respectively. Of these, seven LASSO-selected metabolites improved the prediction ability of AD/MCI versus older controls (area under the curve score increased from 0.92 to 0.97 and 0.78 to 0.93) compared to the base model. Discussion: These tau-correlated CSF metabolites increase AD/MCI prediction accuracy and may provide insight into tau tangle etiology

Learning at large conferences:from the 'sage on the stage' to contemporary models of learning

AimTo explore and evaluate the affordances of a flipped classroom model applied to a research paper session within the professional development opportunity of a large conference setting.MethodAuthors were invited to present their research papers in a flipped classroom presentation format at two large, multi-national conferences. Before the session, authors and moderators met online to clarify features of the session, and preparation of the material. The research material was then posted online before the conference, to allow access by meeting attendees. During the sessions, moderators encouraged the audience to actively participate. An evaluation form was collected from the audience at the end of each session.ResultsParticipants found the session valuable, and appreciated the opportunity to engage in a meaningful dialogue with colleagues. However, the majority of the audience did not access the materials in advance. Lack of time, or technology-related issues were mentioned as potential challenges to such format.ConclusionIn the context of a large conference, a 'flipped session' format can facilitate active learning and a participatory culture of inquiry. However, to change the nature of how individuals learn collaboratively at large conferences means a change in the culture of continuous professional learning

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update

This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry

Reasoning deficits among illicit drug users are associated with aspects of cannabis use

Background. Deficits in deductive reasoning have been observed among ecstasy/polydrug users. The present study seeks to investigate dose-related effects of specific drugs and whether these vary with the cognitive demands of the task. Methods. One hundred and five participants (mean age 21.33, S.D. 3.14; 77 females, 28 males) attempted to generate solutions for eight one-model syllogisms and one syllogism for which there was no valid conclusion (NVC). All of the one model syllogisms generated at least one valid conclusion and six generated two valid conclusions. In these six cases one of the conclusions was classified as common and the other as non-common. Results. The number of valid common inferences was negatively associated with aspects of short term cannabis use and with measures of IQ. The outcomes observed were more than simple post intoxication effects since cannabis use in the 10 days immediately before testing was unrelated to reasoning performance. Following adjustment for multiple comparisons, the number of non-common valid inferences was not significantly associated with any of the drug use measures. Conclusions. Recent cannabis use appears to impair the processes associated with generating valid common inferences while not affecting the production of non-common inferences. It is possible, therefore, that the two types of inference may recruit different executive resources which may differ in their susceptibility to cannabis-related effects

The use of routine outcome measures in two child and adolescent mental health services: a completed audit cycle

Background: Routine outcome measurement (ROM) is important for assessing the clinical effectiveness of health services and for monitoring patient outcomes. Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption of ROM in CAMHS has been supported by both national and local initiatives (such as government strategies, local commissioning policy, and research). Methods: With the aim of assessing how these policies and initiatives may have influenced the uptake of ROM within two different CAMHS we report the findings of two case-note audits: a baseline audit conducted in January 2011 and a re-audit conducted two years later in December 2012-February 2013. Results: The findings show an increase in both the single and repeated use of outcome measures from the time of the original audit, with repeated use (baseline and follow-up) of the Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing from 10% to 50% of cases. Re-audited case-notes contained more combined use of different outcome measures, with greater consensus on which measures to use. Outcome measures that were applicable across a wide range of clinical conditions were more likely to be used than symptom-specific measures, and measures that were completed by the clinician were found more often than measures completed by the service user. Conclusions: The findings show a substantial improvement in the use of outcome measures within CAMHS. These increases in use were found across different service organisations which were subject to different types of local service priorities and drivers

Effectiveness, cost-effectiveness and cost-benefit of a single annual professional intervention for the prevention of childhood dental caries in a remote rural Indigenous community

Background The aim of the study is to reduce the high prevalence of tooth decay in children in a remote, rural Indigenous community in Australia, by application of a single annual dental preventive intervention. The study seeks to (1) assess the effectiveness of an annual oral health preventive intervention in slowing the incidence of dental caries in children in this community, (2) identify the mediating role of known risk factors for dental caries and (3) assess the cost-effectiveness and cost-benefit of the intervention. Methods/design The intervention is novel in that most dental preventive interventions require regular re-application, which is not possible in resource constrained communities. While tooth decay is preventable, self-care and healthy habits are lacking in these communities, placing more emphasis on health services to deliver an effective dental preventive intervention. Importantly, the study will assess cost-benefit and cost-effectiveness for broader implementation across similar communities in Australia and internationally. Discussion There is an urgent need to reduce the burden of dental decay in these communities, by implementing effective, cost-effective, feasible and sustainable dental prevention programs. Expected outcomes of this study include improved oral and general health of children within the community; an understanding of the costs associated with the intervention provided, and its comparison with the costs of allowing new lesions to develop, with associated treatment costs. Findings should be generalisable to similar communities around the world. The research is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12615000693527; date of registration: 3rd July 2015