A two-arm cluster randomized control trial to determine the effectiveness of a pressure ulcer prevention bundle for critically ill patients

Purpose This study tested the effectiveness of a pressure ulcer (PU) prevention bundle in reducing the incidence of PUs in critically ill patients in two Saudi intensive care units (ICUs). Design A two-arm cluster randomized experimental control trial. Methods Participants in the intervention group received the PU prevention bundle, while the control group received standard skin care as per the local ICU policies. Data collected included demographic variables (age, diagnosis, comorbidities, admission trajectory, length of stay) and clinical variables (Braden Scale score, severity of organ function score, mechanical ventilation, PU presence, and staging). All patients were followed every two days from admission through to discharge, death, or up to a maximum of 28 days. Data were analyzed with descriptive correlation statistics, Kaplan-Meier survival analysis, and Poisson regression. Findings The total number of participants recruited was 140: 70 control participants (with a total of 728 days of observation) and 70 intervention participants (784 days of observation). PU cumulative incidence was significantly lower in the intervention group (7.14%) compared to the control group (32.86%). Poisson regression revealed the likelihood of PU development was 70% lower in the intervention group. The intervention group had significantly less Stage I (p = 002) and Stage II PU development (p = 026). Conclusions Significant improvements were observed in PU-related outcomes with the implementation of the PU prevention bundle in the ICU; PU incidence, severity, and total number of PUs per patient were reduced. Clinical Relevance Utilizing a bundle approach and standardized nursing language through skin assessment and translation of the knowledge to practice has the potential to impact positively on the quality of care and patient outcome.

An upstream open reading frame is essential for feedback regulation of ascorbate biosynthesis in arabidopsis

Ascorbate (vitamin C) is an essential antioxidant and enzyme cofactor in both plants and animals. Ascorbate concentration is tightly regulated in plants, partly to respond to stress. Here, we demonstrate that ascorbate concentrations are determined via the posttranscriptional repression of GDP-l-galactose phosphorylase (GGP), a major control enzyme in the ascorbate biosynthesis pathway. This regulation requires a cis-acting upstream open reading frame (uORF) that represses the translation of the downstream GGP open reading frame under high ascorbate concentration. Disruption of this uORF stops the ascorbate feedback regulation of translation and results in increased ascorbate concentrations in leaves. The uORF is predicted to initiate at a noncanonical codon (ACG rather than AUG) and encode a 60- to 65-residue peptide. Analysis of ribosome protection data from Arabidopsis thaliana showed colocation of high levels of ribosomes with both the uORF and the main coding sequence of GGP. Together, our data indicate that the noncanonical uORF is translated and encodes a peptide that functions in the ascorbate inhibition of translation. This posttranslational regulation of ascorbate is likely an ancient mechanism of control as the uORF is conserved in GGP genes from mosses to angiosperms.

The role of DNA repair pathways in cisplatin resistant lung cancer

Platinum chemotherapeutic agents such as cisplatin are currently used in the treatment of various malignancies such as lung cancer. However, their efficacy is significantly hindered by the development of resistance during treatment. While a number of factors have been reported that contribute to the onset of this resistance phenotype, alterations in the DNA repair capacity of damaged cells is now recognised as an important factor in mediating this phenomenon. The mode of action of cisplatin has been linked to its ability to crosslink purine bases on the DNA, thereby interfering with DNA repair mechanisms and inducing DNA damage. Following DNA damage, cells respond by activating a DNA-damage response that either leads to repair of the lesion by the cell thereby promoting resistance to the drug, or cell death via activation of the apoptotic response. Therefore, DNA repair is a vital target to improving cancer therapy and reduce the resistance of tumour cells to DNA damaging agents currently used in the treatment of cancer patients. To date, despite the numerous findings that differential expression of components of the various DNA repair pathways correlate with response to cisplatin, translation of such findings in the clinical setting are still warranted. The identification of alterations in specific proteins and pathways that contribute to these unique DNA repair pathways in cisplatin resistant cancer cells may potentially lead to a renewed interest in the development of rational novel therapies for cisplatin resistant cancers, in particular, lung cancer.

Research around practice partnerships: An example of building partnerships to address overweight and obesity in children

Prevention and management of childhood overweight and obesity is a health priority for governments and communities throughout the developed world. A conceptual model, Research around Practice in Childhood Obesity (RAPICO), has been developed to guide capacity building in a coordinated 'bench to fieldwork' initiative to address this public health problem. Translation of research findings into sustainable responses with optimal fit requires consideration of context-specific relevance, cost-effectiveness, feasibility and levels of available support. The RAPICO model uses program theory to describe a framework for progressing practitionercommunityresearch partnerships to address low, medium and high levels of risk for childhood overweight and obesity within community settings. A case study describing the development of a logic model to inform risk-linked responses to childhood overweight and obesity is presented for the Ipswich community in south-east Queensland.

Submission to: Strategic Review of Health and Medical Research (Australia) otherwise known as the McKeon Review

Public submission # 247 to the McKeon Review. The submission addresses the terms of reference on: How can we optimise translation of health and medical research into better health and wellbeing? (Terms of Reference 4, 8, 9, 10 and 11)

May the best Tweeter win : The Twitter strategies of key campaign accounts in the 2012 US election

The 2008 US election has been heralded as the first presidential election of the social media era, but took place at a time when social media were still in a state of comparative infancy; so much so that the most important platform was not Facebook or Twitter, but the purpose-built campaign site my.barackobama.com, which became the central vehicle for the most successful electoral fundraising campaign in American history. By 2012, the social media landscape had changed: Facebook and, to a somewhat lesser extent, Twitter are now well-established as the leading social media platforms in the United States, and were used extensively by the campaign organisations of both candidates. As third-party spaces controlled by independent commercial entities, however, their use necessarily differs from that of home-grown, party-controlled sites: from the point of view of the platform itself, a @BarackObama or @MittRomney is technically no different from any other account, except for the very high follower count and an exceptional volume of @mentions. In spite of the significant social media experience which Democrat and Republican campaign strategists had already accumulated during the 2008 campaign, therefore, the translation of such experience to the use of Facebook and Twitter in their 2012 incarnations still required a substantial amount of new work, experimentation, and evaluation. This chapter examines the Twitter strategies of the leading accounts operated by both campaign headquarters: the ‘personal’ candidate accounts @BarackObama and @MittRomney as well as @JoeBiden and @PaulRyanVP, and the campaign accounts @Obama2012 and @TeamRomney. Drawing on datasets which capture all tweets from and at these accounts during the final months of the campaign (from early September 2012 to the immediate aftermath of the election night), we reconstruct the campaigns’ approaches to using Twitter for electioneering from the quantitative and qualitative patterns of their activities, and explore the resonance which these accounts have found with the wider Twitter userbase. A particular focus of our investigation in this context will be on the tweeting styles of these accounts: the mixture of original messages, @replies, and retweets, and the level and nature of engagement with everyday Twitter followers. We will examine whether the accounts chose to respond (by @replying) to the messages of support or criticism which were directed at them, whether they retweeted any such messages (and whether there was any preferential retweeting of influential or – alternatively – demonstratively ordinary users), and/or whether they were used mainly to broadcast and disseminate prepared campaign messages. Our analysis will highlight any significant differences between the accounts we examine, trace changes in style over the course of the final campaign months, and correlate such stylistic differences with the respective electoral positioning of the candidates. Further, we examine the use of these accounts during moments of heightened attention (such as the presidential and vice-presidential debates, or in the context of controversies such as that caused by the publication of the Romney “47%” video; additional case studies may emerge over the remainder of the campaign) to explore how they were used to present or defend key talking points, and exploit or avert damage from campaign gaffes. A complementary analysis of the messages directed at the campaign accounts (in the form of @replies or retweets) will also provide further evidence for the extent to which these talking points were picked up and disseminated by the wider Twitter population. Finally, we also explore the use of external materials (links to articles, images, videos, and other content on the campaign sites themselves, in the mainstream media, or on other platforms) by the campaign accounts, and the resonance which these materials had with the wider follower base of these accounts. This provides an indication of the integration of Twitter into the overall campaigning process, by highlighting how the platform was used as a means of encouraging the viral spread of campaign propaganda (such as advertising materials) or of directing user attention towards favourable media coverage. By building on comprehensive, large datasets of Twitter activity (as of early October, our combined datasets comprise some 3.8 million tweets) which we process and analyse using custom-designed social media analytics tools, and by using our initial quantitative analysis to guide further qualitative evaluation of Twitter activity around these campaign accounts, we are able to provide an in-depth picture of the use of Twitter in political campaigning during the 2012 US election which will provide detailed new insights social media use in contemporary elections. This analysis will then also be able to serve as a touchstone for the analysis of social media use in subsequent elections, in the USA as well as in other developed nations where Twitter and other social media platforms are utilised in electioneering.

A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications

BACKGROUND Given moderately strong genetic contributions to variation in alcoholism and heaviness of drinking (50% to 60% heritability) with high correlation of genetic influences, we have conducted a quantitative trait genome-wide association study (GWAS) for phenotypes related to alcohol use and dependence. METHODS Diagnostic interview and blood/buccal samples were obtained from sibships ascertained through the Australian Twin Registry. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed with 8754 individuals (2062 alcohol-dependent cases) selected for informativeness for alcohol use disorder and associated quantitative traits. Family-based association tests were performed for alcohol dependence, dependence factor score, and heaviness of drinking factor score, with confirmatory case-population control comparisons using an unassessed population control series of 3393 Australians with genome-wide SNP data. RESULTS No findings reached genome-wide significance (p = 8.4 x 10(-8) for this study), with lowest p value for primary phenotypes of 1.2 x 10(-7). Convergent findings for quantitative consumption and diagnostic and quantitative dependence measures suggest possible roles for a transmembrane protein gene (TMEM108) and for ANKS1A. The major finding, however, was small effect sizes estimated for individual SNPs, suggesting that hundreds of genetic variants make modest contributions (1/4% of variance or less) to alcohol dependence risk. CONCLUSIONS We conclude that: - 1) meta-analyses of consumption data may contribute usefully to gene discovery; - 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging, and; - 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies).

Coping with information silos: An examination of the medication management process in residential aged care facilities (RACFs)

The aim of this study was to examine the actions of geographically dispersed process stakeholders (doctors, community pharmacists and RACFs) in order to cope with the information silos that exist within and across different settings. The study setting involved three metropolitan RACFs in Sydney, Australia and employed a qualitative approach using semi-structured interviews, non-participant observations and artefact analysis. Findings showed that medication information was stored in silos which required specific actions by each setting to translate this information to fit their local requirements. A salient example of this was the way in which community pharmacists used the RACF medication charts to prepare residents' pharmaceutical records. This translation of medication information across settings was often accompanied by telephone or face-to-face conversations to cross-check, validate or obtain new information. Findings highlighted that technological interventions that work in silos can negatively impact the quality of medication management processes in RACF settings. The implementation of commercial software applications like electronic medication charts need to be appropriately integrated to satisfy the collaborative information requirements of the RACF medication process.

The research capacity and culture of Australian podiatrists

Background Best practice clinical health care is widely recognised to be founded on evidence based practice. Enhancing evidence based practice via the rapid translation of new evidence into every day clinical practice is fundamental to the success of health care and in turn health care professions. There is little known about the collective research capacity and culture of the podiatry profession across Australia. Thus, the aim of this study was to investigate the research capacity and culture of the podiatry profession within Australia and determine if there were any differences between podiatrists working in different health sectors and workplaces. Method All registered podiatrists were eligible to participate in a cross-sectional online survey. The Australian Podiatry Associations disseminated the survey and all podiatrists were encouraged to distribute it to colleagues. The Research Capacity and Culture (RCC) tool was used to collect all research capacity and culture item variables using a 10-point scale (1 = lowest; 10 = highest). Additional demographic, workplace and health sector data variables were also collected. Mann–Whitney-U, Kruskal–Wallis and logistic regression analyses were used to determine any difference between health sectors and workplaces. Word cloud analysis was used for qualitative responses of individual motivators and barriers to research culture. Results There were 232 fully completed surveys (6% of Australian registered podiatrists). Overall respondents reported low success or skills (Median rating < 4) on the majority of individual success or skill items. Podiatrists working in multi-practitioner workplaces reported higher individual success or skills in the majority of items compared with sole practitioners (p < 0.05). Non-clinical and public health sector podiatrists reported significantly higher post-graduate study enrolment or completion, research activity participation, provisions to undertake research and individual success or skill than those working privately. Conclusions This study suggests that podiatrists in Australia report similar low levels of research success or skill to those reported in other allied health professions. The workplace setting and health sector seem to play key roles in self reported research success and skills. This is important knowledge for podiatrists and researchers aiming to translate research evidence into clinical practice.

Concise review: Humanized models of tumor immunology in the 21st century: Convergence of cancer research and tissue engineering

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to “make the model organism mouse more human.” To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.