30913 research outputs found
Sort by
Pharmacogenomics of CYP2C9: Functional and Clinical Considerations
Get PDF© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy. CYP2C9 substrate selectivity is detailed and, based on crystal structures for the enzyme, we describe how CYP2C9 catalyzes these reactions. Factors relevant to clinical response to CYP2C9 substrates including inhibition, induction and genetic polymorphism are discussed in detail. In particular, we consider the issue of ethnic variation in pattern and frequency of genetic polymorphisms and clinical implications. Warfarin is the most well studied CYP2C9 substrate; recent work on use of dosing algorithms that include CYP2C9 genotype to improve patient safety during initiation of warfarin dosing are reviewed and prospects for their clinical implementation considered. Finally, we discuss a novel approach to cataloging the functional capabilities of rare ‘variants of uncertain significance’, which are increasingly detected as more exome and genome sequencing of diverse populations is conducted
Cryptic lineage differentiation among Indo-Pacific bottlenose dolphins (Tursiops aduncus) in the northwest Indian Ocean
Get PDF© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/Phylogeography can provide insight into the potential for speciation and identify geographic regions and evolutionary processes associated with species richness and evolutionary endemism. In the marine environment, highly mobile species sometimes show structured patterns of diversity, but the processes isolating populations and promoting differentiation are often unclear. The Delphinidae (oceanic dolphins) are a striking case in point and, in particular, bottlenose dolphins (Tursiops spp.). Understanding the radiation of species in this genus is likely to provide broader inference about the processes that determine patterns of biogeography and speciation, because both fine-scale structure over a range of kilometers and relative panmixia over an oceanic range are known for Tursiops populations. In our study, novel Tursiops spp. sequences from the northwest Indian Ocean (including mitogenomes and two nuDNA loci) are included in a worldwide Tursiops spp. phylogeographic analysis. We discover a new ‘aduncus’ type lineage in the Arabian Sea (off India, Pakistan and Oman) that diverged from the Australasian lineage ∼261 Ka. Effective management of coastal dolphins in the region will need to consider this new lineage as an evolutionarily significant unit. We propose that the establishment of this lineage could have been in response to climate change during the Pleistocene and show data supporting hypotheses for multiple divergence events, including vicariance across the Indo-Pacific barrier and in the northwest Indian Ocean. These data provide valuable transferable inference on the potential mechanisms for population and species differentiation across this geographic range
A model to teach concomitant patient communication during psychomotor skill development
Get PDF© 2017 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license:http://creativecommons.org/licenses/by-nc-nd/4.0/Many health professionals use psychomotor or task-based skills in clinical practice that require concomitant communication with a conscious patient. Verbally engaging with the patient requires highly developed verbal communication skills, enabling the delivery of patient-centred care. Historically, priority has been given to learning the psychomotor skills essential to clinical practice. However, there has been a shift towards also ensuring competent communication with the patient during skill performance. While there is literature outlining the steps to teach and learn verbal communication skills, little is known about the most appropriate instructional approach to teach how to verbally engage with the patient when also learning to perform a task. A literature review was performed and it identified that there was no model or proven approach which could be used to integrate the learning of both psychomotor and communication skills. This paper reviews the steps to teach a communication skill and provides a suggested model to guide the acquisition and development of the concomitant -communication skills required with a patient at the time a psychomotor skill is performed
Building on solid foundations - the potential for social participation and procurement in South Australia
Get PDF© [2017] Flinders University / Australian Industrial Transformation InstituteGovernments around the world are seeking to leverage the local industry and employment generation potential of public procurement. South Australia has been a leader in this field through the introduction of legislation and policy requiring contractors to work with government to maximise local employment and industry participation in the delivery of publicly funded projects. This culminated in the establishment of the Office of the Industry Participation Advocate, a role that is seeking to increase the economic and social benefit to the State of public procurement through policy and program interventions. The focus of this report is on how public procurement undertaken by the South Australian Housing Trust (SAHT) and Housing SA might be leveraged for the benefit of Trust tenants through the creation of employment and training opportunities linked to this procurement
The Defence Dividend: Maximising spillovers from investment in maritime defence projects.
Get PDF© [2017] Flinders University / Australian Industrial Transformation InstituteThe suite of maritime defence projects is among the most sophisticated engineering endeavours ever undertaken in Australia. As well as providing highly desirable and strategically valuable opportunities for Australian industry participation, major defence projects demand highly skilled and qualified people. They also generate a range of spillovers, which are economic and social benefits that cannot be easily captured by the firms directly involved in the delivery of a major project. This includes knowledge, technologies, enterprise capabilities and workforce skills developed or applied during the course of a major defence project that have commercial application.
While the combined projects have the potential to accelerate industrial transformation and diversification efforts locally and
nationally, this cannot be taken for granted. Steps need be taken to optimise the outcome. The challenge facing industry,
government and the research community is to develop and successfully implement strategies capable of maximising the full
range of industry and employment opportunities that arise – a challenge that requires all key stakeholders being committed to leveraging the economic benefits that complex defence projects can generate. This briefing is designed to inform discussions on what the key ingredients of a successful strategy of spillover maximisation might be, recognising that a parallel discussion is underway on how to maximise Australian industry participation in defence projects
Editor's note and contents page for Volume 9, no. 2, May 2017
No full textEditor's note and contents page for Volume 9, no. 2, May 2017 of Transnational Literature
How do you spell bird? Effective parent programs to enhance 4-6 year old children's literacy development
No full textThis research examined the effectiveness of parent programs designed for families to support the literacy learning of their 4-6 year old children. The project began with a literature review analysing six established, effective parent programs that have been reported in the international and national research literature. An analysis of what made each of the programs effective entailed an analysis of the program's target population, the project inputs and activities and the initial, immediate and long term outcomes.
To explore further what local parents and families view as effective parent programs for 4-6 year old children the research explored individual site-specific parent programs in operation in South Australian childcare centres, preschools and schools in a range of diverse socioeconomic and geographic sites. Parents and teachers engaged in focus groups to describe ways the schools and centres sustain links between home and school learning.
To assess the elements of two existing parent programs to support children's early literacy development, parents and teachers participated in several focus groups. The two programs were the parent component of The Abecedarian Program (2001, 1979) developed in the United States and the South Australian Early Childhood Literacy Includes Parents Staff and Education ECLIPSE program (1997) developed by the South Australian Department of Education and Children's Services (DECS)
Supporting the Delivery of Total Knee Replacements Care for Both Patients and Their Clinicians With a Mobile App and Web-Based Tool: Randomized Controlled Trial Protocol
No full textOriginally published in JMIR Research Protocols (http://www.researchprotocols.org), 01.03.2017.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org, as well as this copyright and license information must be included.Background: Total knee replacement (TKR) surgeries have increased in recent years. Exercise programs and other interventions following surgery can facilitate the recovery process. With limited clinician contact time, patients with TKR have a substantial burden of self-management and limited communication with their care team, thus often fail to implement an effective rehabilitation plan.
Objective: We have developed a digital orthopedic rehabilitation platform that comprises a mobile phone app, wearable activity tracker, and clinical Web portal in order to engage patients with self-management tasks for surgical preparation and recovery, thus addressing the challenges of adherence to and completion of TKR rehabilitation. The study will determine the efficacy of the TKR platform in delivering information and assistance to patients in their preparation and recovery from TKR surgery and a Web portal for clinician care teams (ie, surgeons and physiotherapists) to remotely support and monitor patient progress.
Methods: The study will evaluate the TKR platform through a randomized controlled trial conducted at multiple sites (N=5) in a number of states in Australia with 320 patients undergoing TKR surgery; the trial will run for 13 months for each patient. Participants will be randomized to either a control group or an intervention group, both receiving usual care as provided by their hospital. The intervention group will receive the app and wearable activity tracker. Participants will be assessed at 4 different time points: 4 weeks before surgery, immediately before surgery, 12 weeks after surgery, and 52 weeks after surgery. The primary outcome measure is the Oxford Knee Score. Secondary outcome measures include quality of life (Short-Form Health Survey); depression, anxiety, and stress (Depression, Anxiety, and Stress Scales); self-motivation; self-determination; self-efficacy; and the level of satisfaction with the knee surgery and care delivery. The study will also collect quantitative usage data related to all components (app, activity tracker, and Web portal) of the TKR platform and qualitative data on the perceptions of the platform as a tool for patients, carers, and clinicians. Finally, an economic evaluation of the impact of the platform will be conducted.
Results: Development of the TKR platform has been completed and deployed for trial. The research protocol is approved by 2 human research ethics committees in Australia. A total of 5 hospitals in Australia (2 in New South Wales, 2 in Queensland, and 1 in South Australia) are expected to participate in the trial.
Conclusions: The TKR platform is designed to provide flexibility in care delivery and increased engagement with rehabilitation services. This trial will investigate the clinical and behavioral efficacy of the app and impact of the TKR platform in terms of service satisfaction, acceptance, and economic benefits of the provision of digital services
Examining the Effects of Ambient Temperature on Pre-Term Birth in Central Australia
No full textThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).Preterm birth (born before 37 completed weeks of gestation) is one of the leading causes of death among children under 5 years of age. Several recent studies have examined the association between extreme temperature and preterm births, but there have been almost no such studies in arid Australia. In this paper, we explore the potential association between exposures to extreme temperatures during the last 3 weeks of pregnancy in a Central Australian town. An immediate effect of temperature exposure is observed with an increased relative risk of 1%–2% when the maximum temperature exceeded the 90th percentile of the summer season maximum temperature data. Delayed effects are also observed closer to 3 weeks before delivery when the relative risks tend to increase exponentially. Immediate risks to preterm birth are also observed for cold temperature exposures (0 to –6 °C), with an increased relative risk of up to 10%. In the future, Central Australia will face more hot days and less cold days due to climate change and hence the risks posed by extreme heat is of particular relevance to the community and health practitioners
A novel strategy for clustering major depression individuals using whole-genome sequencing variant data
No full textThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Major depressive disorder (MDD) is highly prevalent, resulting in an exceedingly high disease burden. The identification of generic risk factors could lead to advance prevention and therapeutics. Current approaches examine genotyping data to identify specific variations between cases and controls. Compared to genotyping, whole-genome sequencing (WGS) allows for the detection of private mutations. In this proof-of-concept study, we establish a conceptually novel computational approach that clusters subjects based on the entirety of their WGS. Those clusters predicted MDD diagnosis. This strategy yielded encouraging results, showing that depressed Mexican-American participants were grouped closer; in contrast ethnically-matched controls grouped away from MDD patients. This implies that within the same ancestry, the WGS data of an individual can be used to check whether this individual is within or closer to MDD subjects or to controls. We propose a novel strategy to apply WGS data to clinical medicine by facilitating diagnosis through genetic clustering. Further studies utilising our method should examine larger WGS datasets on other ethnical groups