Using decision trees to understand structure in missing data

Objectives Demonstrate the application of decision trees – classification and regression trees (CARTs), and their cousins, boosted regression trees (BRTs) – to understand structure in missing data. Setting Data taken from employees at three different industry sites in Australia. Participants 7915 observations were included. Materials and Methods The approach was evaluated using an occupational health dataset comprising results of questionnaires, medical tests, and environmental monitoring. Statistical methods included standard statistical tests and the ‘rpart’ and ‘gbm’ packages for CART and BRT analyses, respectively, from the statistical software ‘R’. A simulation study was conducted to explore the capability of decision tree models in describing data with missingness artificially introduced. Results CART and BRT models were effective in highlighting a missingness structure in the data, related to the Type of data (medical or environmental), the site in which it was collected, the number of visits and the presence of extreme values. The simulation study revealed that CART models were able to identify variables and values responsible for inducing missingness. There was greater variation in variable importance for unstructured compared to structured missingness. Discussion Both CART and BRT models were effective in describing structural missingness in data. CART models may be preferred over BRT models for exploratory analysis of missing data, and selecting variables important for predicting missingness. BRT models can show how values of other variables influence missingness, which may prove useful for researchers. Conclusion Researchers are encouraged to use CART and BRT models to explore and understand missing data.

Using simplified peer review processes to fund research: A prospective study

Objective: To prospectively test two simplified peer review processes, estimate the agreement between the simplified and official processes, and compare the costs of peer review. Design, participants and setting: A prospective parallel study of Project Grant proposals submitted in 2013 to the National Health and Medical Research Council (NHMRC) of Australia. The official funding outcomes were compared with two simplified processes using proposals in Public Health and Basic Science. The two simplified processes were: panels of 7 reviewers who met face-to-face and reviewed only the nine-page research proposal and track record (simplified panel); and 2 reviewers who independently reviewed only the nine-page research proposal (journal panel). The official process used panels of 12 reviewers who met face-to-face and reviewed longer proposals of around 100 pages. We compared the funding outcomes of 72 proposals that were peer reviewed by the simplified and official processes. Main outcome measures: Agreement in funding outcomes; costs of peer review based on reviewers’ time and travel costs. Results: The agreement between the simplified and official panels (72%, 95% CI 61% to 82%), and the journal and official panels (74%, 62% to 83%), was just below the acceptable threshold of 75%. Using the simplified processes would save $A2.1–$A4.9 million per year in peer review costs. Conclusions: Using shorter applications and simpler peer review processes gave reasonable agreement with the more complex official process. Simplified processes save time and money that could be reallocated to actual research. Funding agencies should consider streamlining their application processes.

Intravascular device administration sets: Replacement after standard versus prolonged use in hospitalised patients--a study protocol for a randomised controlled trial (The RSVP Trial)

Introduction Vascular access devices (VADs), such as peripheral or central venous catheters, are vital across all medical and surgical specialties. To allow therapy or haemodynamic monitoring, VADs frequently require administration sets (AS) composed of infusion tubing, fluid containers, pressure-monitoring transducers and/or burettes. While VADs are replaced only when necessary, AS are routinely replaced every 3–4 days in the belief that this reduces infectious complications. Strong evidence supports AS use up to 4 days, but there is less evidence for AS use beyond 4 days. AS replacement twice weekly increases hospital costs and workload. Methods and analysis This is a pragmatic, multicentre, randomised controlled trial (RCT) of equivalence design comparing AS replacement at 4 (control) versus 7 (experimental) days. Randomisation is stratified by site and device, centrally allocated and concealed until enrolment. 6554 adult/paediatric patients with a central venous catheter, peripherally inserted central catheter or peripheral arterial catheter will be enrolled over 4 years. The primary outcome is VAD-related bloodstream infection (BSI) and secondary outcomes are VAD colonisation, AS colonisation, all-cause BSI, all-cause mortality, number of AS per patient, VAD time in situ and costs. Relative incidence rates of VAD-BSI per 100 devices and hazard rates per 1000 device days (95% CIs) will summarise the impact of 7-day relative to 4-day AS use and test equivalence. Kaplan-Meier survival curves (with log rank Mantel-Cox test) will compare VAD-BSI over time. Appropriate parametric or non-parametric techniques will be used to compare secondary end points. p Values of <0.05 will be considered significant.

Bloomsday: Copyright estates and cultural festivals

Copyright estates have been unduly empowered by the extension of the term of copyright protection in Europe, the United States, Australia and elsewhere. The Estate of the Irish novelist, James Joyce, has been particularly aggressive in policing his revived copyrights. The "keepers of the flame" have relied upon threats of legal action to discourage the production of derivative works based upon the canonical texts of the novelist. The Estate has also jealously guarded the reputation of the author by vetoing the use of his work in various scholarly productions. Most radically of all, the grandson Stephen Joyce threatened to take legal action to prevent the staging of "Rejoyce Dublin 2004", a festival celebrating the centenary of Bloomsday. In response, the Irish Parliament rushed through emergency legislation, entitled the Copyright and Related Rights (Amendment) Act 2004 (Ireland) to safeguard the celebrations. The legislation clarified that a person could place literary and artistic works on public exhibition, without breaching the copyright vested in such cultural texts. Arguably, though, the ad hoc legislation passed by the Irish Parliament is inadequate. The Estate of James Joyce remains free to exercise its suite of economic and moral rights to control the use and adaptation of works of the Irish novelist. It is contended that copyright law needs to be revised to promote the interests of libraries and other cultural institutions. Most notably, the defence of fair dealing should be expanded to allow for the transformative use of copyright works, particularly in respect of adaptations and derived works. There should be greater scope for compulsory licensing and crown acquisition of revived copyrights.

Simultaneous enhancement of brightness, efficiency, and switching in RGB organic light emitting transistors

An innovative design strategy for light emitting field effect transistors (LEFETs) to harvest higher luminance and switching is presented. The strategy uses a non-planar electrode geometry in tri-layer LEFETs for simultaneous enhancement of the key parameters of quantum efficiency, brightness, switching, and mobility across the RGB color gamut.

Systematic review: Unmet supportive care needs in people diagnosed with chronic liver disease

Objective People with chronic liver disease, particularly those with decompensated cirrhosis, experience several potentially debilitating complications that can have a significant impact on activities of daily living and quality of life. These impairments combined with the associated complex treatment mean that they are faced with specific and high levels of supportive care needs. We aimed to review reported perspectives, experiences and concerns of people with chronic liver disease worldwide. This information is necessary to guide development of policies around supportive needs screening tools and to enable prioritisation of support services for these patients. Design Systematic searches of PubMed, MEDLINE, CINAHL and PsycINFO from the earliest records until 19 September 2014. Data were extracted using standardised forms. A qualitative, descriptive approach was utilised to analyse and synthesise data. Results The initial search yielded 2598 reports: 26 studies reporting supportive care needs among patients with chronic liver disease were included, but few of them were patient-reported needs, none used a validated liver disease-specific supportive care need assessment instrument, and only three included patients with cirrhosis. Five key domains of supportive care needs were identified: informational or educational (eg, educational material, educational sessions), practical (eg, daily living), physical (eg, controlling pruritus and fatigue), patient care and support (eg, support groups), and psychological (eg, anxiety, sadness). Conclusions While several key domains of supportive care needs were identified, most studies included hepatitis patients. There is a paucity of literature describing the supportive care needs of the chronic liver disease population likely to have the most needs—namely those with cirrhosis. Assessing the supportive care needs of people with chronic liver disease have potential utility in clinical practice for facilitating timely referrals to support services.

Dynamic pattern of suicide in Australia, 1986-2005: A descriptive-analytic study

Objective This study explores the spatiotemporal variations of suicide across Australia from 1986 to 2005, discusses the reasons for dynamic changes, and considers future suicide research and prevention strategies. Design Suicide (1986–2005) and population data were obtained from the Australian Bureau of Statistics. A series of analyses were conducted to examine the suicide pattern by sex, method and age group over time and geography. Results Differences in suicide rates across sex, age groups and suicide methods were found across geographical areas. Male suicides were mainly completed by hanging, firearms, gases and self-poisoning. Female suicides were primarily completed by hanging and self-poisoning. Suicide rates were higher in rural areas than in urban areas (capital cities and regional centres). Suicide rates by firearms were higher in rural areas than in urban areas, while the pattern for self-poisoning showed the reverse trend. Suicide rates had relatively stable trend for the total population and those aged between 15 and 54, while suicide decreased among 55 years and over during the study period. There was a decrease in suicides by firearms during the study period especially after 1996 when a new firearm control law was implemented, while suicide by hanging continued to increase. Areas with a high proportion of indigenous population (eg, northwest of Queensland and top north of the Northern Territory) had shown a substantial increase in suicide incidence after 1995. Conclusions Suicide rates varied over time and space and across sexes, age groups and suicide methods. This study provides detailed patterns of suicide to inform suicide control and prevention strategies for specific subgroups and areas of high and increased risk.

Numerical analysis of a new space-time variable fractional order advection-dispersion equation

Many physical processes appear to exhibit fractional order behavior that may vary with time and/or space. The continuum of order in the fractional calculus allows the order of the fractional operator to be considered as a variable. In this paper, we consider a new space–time variable fractional order advection–dispersion equation on a finite domain. The equation is obtained from the standard advection–dispersion equation by replacing the first-order time derivative by Coimbra’s variable fractional derivative of order α(x)∈(0,1]α(x)∈(0,1], and the first-order and second-order space derivatives by the Riemann–Liouville derivatives of order γ(x,t)∈(0,1]γ(x,t)∈(0,1] and β(x,t)∈(1,2]β(x,t)∈(1,2], respectively. We propose an implicit Euler approximation for the equation and investigate the stability and convergence of the approximation. Finally, numerical examples are provided to show that the implicit Euler approximation is computationally efficient.

Risedronate in adults with osteogenesis imperfecta type I: Increased bone mineral density and decreased bone turnover, but high fracture rate persists

Summary Bisphosphonates can increase bone mineral density (BMD) in children with osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate increased BMD at lumbar spine (but not total hip) and decreased bone turnover. However, the fracture rate in these patients remained high. Introduction Intravenous bisphosphonates given to children with OI can increase BMD and reduce fracture incidence. Oral and/or intravenous bisphosphonates may have similar effects in adults with OI. We completed an observational study of the effect of risedronate in adults with OI type I. Methods Thirty-two adults (mean age, 39 years) with OI type I were treated with risedronate (total dose, 35 mg weekly) for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and total hip (TH). Secondary outcome measures were fracture incidence, bone pain, and change in bone turnover markers (serum procollagen type I aminopropeptide (P1NP) and bone ALP). A meta-analysis of published studies of oral bisphosphonates in adults and children with OI was performed. Results Twenty-seven participants (ten males and seventeen females) completed the study. BMD increased at LS by 3.9% (0.815 vs. 0.846 g/cm 2, p=0.007; mean Z-score, -1.93 vs. -1.58, p=0.002), with no significant change at TH. P1NP fell by 37% (p=0.00041), with no significant change in bone ALP (p=0.15). Bone pain did not change significantly (p=0.6). Fracture incidence remained high, with 25 clinical fractures and 10 major fractures in fourteen participants (0.18 major fractures per person per year), with historical data of 0.12 fractures per person per year. The meta-analysis did not demonstrate a significant difference in fracture incidence in patients with OI treated with oral bisphosphonates. Conclusions Risedronate in adults with OI type I results in modest but significant increases in BMD at LS, and decreased bone turnover. However, this may be insufficient to make a clinically significant difference to fracture incidence.

Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene

Ankylosing spondylitis (AS) is polygenic with contributions from the immunologically relevant genes HLA-B27, ERAP1 and IL23R. A recent genome-wide association screen (GWAS) identified associations (P0.005) with the non-synonymous single-nucleotide polymorphisms (nsSNPs), rs4077515 and rs3812571, in caspase recruitment domain-containing protein 9 (CARD9) and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) on chromosome 9q that had previously been linked to AS. We replicated these associations in a study of 730 AS patients compared with 2879 historic disease controls (rs4077515 P0.0004, odds ratio (OR)1.2, 95% confidence interval (CI)1.1-1.4; rs3812571 P0.0003, OR1.2, 95% CI1.1-1.4). Meta-analysis revealed strong associations of both SNPs with AS, rs4077515 P0.000005, OR1.2, 95% CI1.1-1.3 and rs3812571 P0.000006, OR1.2, 95% CI1.1-1.3. We then typed 1604 AS cases and 1020 controls for 13 tagging SNPs; 6 showed at least nominal association, 5 of which were in CARD9. We imputed genotypes for 13 additional SNPs but none was more strongly associated with AS than the tagging SNPs. Finally, interrogation of an mRNA expression database revealed that the SNPs most strongly associated with AS (or in strong linkage disequilibrium) were those most associated with CARD9 expression. CARD9 is a plausible candidate for AS given its central role in the innate immune response.

Genetic analyses in a sample of individuals with high or low BMD shows association with multiple Wnt pathway genes

INTRODUCTION Although the high heritability of BMD variation has long been established, few genes have been conclusively shown to affect the variation of BMD in the general population. Extreme truncate selection has been proposed as a more powerful alternative to unselected cohort designs in quantitative trait association studies. We sought to test these theoretical predictions in studies of the bone densitometry measures BMD, BMC, and femoral neck area, by investigating their association with members of the Wnt pathway, some of which have previously been shown to be associated with BMD in much larger cohorts, in a moderate-sized extreme truncate selected cohort (absolute value BMD Z-scores = 1.5-4.0; n = 344). MATERIALS AND METHODS Ninety-six tag-single nucleotide polymorphism (SNPs) lying in 13 Wnt signaling pathway genes were selected to tag common genetic variation (minor allele frequency [MAF] > 5% with an r(2) > 0.8) within 5 kb of all exons of 13 Wnt signaling pathway genes. The genes studied included LRP1, LRP5, LRP6, Wnt3a, Wnt7b, Wnt10b, SFRP1, SFRP2, DKK1, DKK2, FZD7, WISP3, and SOST. Three hundred forty-four cases with either high or low BMD were genotyped by Illumina Goldengate microarray SNP genotyping methods. Association was tested either by Cochrane-Armitage test for dichotomous variables or by linear regression for quantitative traits. RESULTS Strong association was shown with LRP5, polymorphisms of which have previously been shown to influence total hip BMD (minimum p = 0.0006). In addition, polymorphisms of the Wnt antagonist, SFRP1, were significantly associated with BMD and BMC (minimum p = 0.00042). Previously reported associations of LRP1, LRP6, and SOST with BMD were confirmed. Two other Wnt pathway genes, Wnt3a and DKK2, also showed nominal association with BMD. CONCLUSIONS This study shows that polymorphisms of multiple members of the Wnt pathway are associated with BMD variation. Furthermore, this study shows in a practical trial that study designs involving extreme truncate selection and moderate sample sizes can robustly identify genes of relevant effect sizes involved in BMD variation in the general population. This has implications for the design of future genome-wide studies of quantitative bone phenotypes relevant to osteoporosis.

Evidence-based recommendations for the monitoring and treatment of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

Aim: To develop a set of Australian recommendations for the monitoring and treatment of ankylosing spondylitis (AS) through systematic literature review combined with the opinion of practicing rheumatologists. Methods: A set of eight questions, four in each domain of monitoring and treatment, were formulated by voting and the Delphi method. The results of a systematic literature review addressing each question were presented to the 23 participants of the Australian 3E meeting. All participants were clinical rheumatologists experienced in the daily management of AS. Results: After three rounds of breakout sessions to discuss the findings of the literature review, a set of recommendations was finalized after discussion and voting. The category of evidence and strength of recommendation were determined for each proposal. The level of agreement among participants was excellent (mean 84%, range 64-100%). Conclusions: The 12 recommendations developed from evidence and expert opinion provide guidance for the daily management of AS patients. For most recommendations, we found a paucity of supportive evidence in the literature highlighting the need for additional clinical studies.

Pacific Journalism Review : Twenty years on the front line of regional identity and freedom

Pacific Journalism Review has consistently, at a good standard, honoured its 1994 founding goal: to be a credible peer-reviewed journal in the Asia-Pacific region, probing developments in journalism and media, and supporting journalism education. Global, it considers new media and social movements; ‘regional’, it promotes vernacular media, human freedoms and sustainable development. Asking how it developed, the method for this article was to research the archive, noting authors, subject matter, themes. The article concludes that one answer is the journal’s collegiate approach; hundreds of academics, journalists and others, have been invited to contribute. Second has been the dedication of its one principal editor, Professor David Robie, always somehow providing resources—at Port Moresby, Suva, and now Auckland—with a consistent editorial stance. Eclectic, not partisan, it has nevertheless been vigilant over rights, such as monitoring the Fiji coups d’etat. Watching through a media lens, it follows a ‘Pacific way’, handling hard information through understanding and consensus. It has 237 subscriptions indexed to seven databases. Open source, it receives more than 1000 site visits weekly. With ‘clientele’ mostly in Australia, New Zealand and ‘Oceania’, it extends much further afield. From 1994 to 2014, 701 articles and reviews were published, now more than 24 scholarly articles each year.

The use of a synthetic prostaglandin e1 analogue (misoprostol) as an adjunct to pancreatic enzyme replacement in cystic fibrosis

Eleven cystic fibrosis children (mean age, 9.6 years) were chosen at random to participate in a study to observe the effects of concurrently stimulating gastric/duodenal bicarbonate secretion and inhibiting gastric acid secretion, using a methylated prostaglandin E1 analogue in patients with pancreatic insufficiency and taking pancreatic enzymes. Percentage fat absorption in 3-day stool collections were calculated before and after commencing therapy with misoprostol, 400 μg/day in divided doses. We found a significant reduction in fat output (14.7 ± 11.7 versus 7.5 ± 3.5 g/day, p < 0.05) in the study group as a whole and a significant reduction in steatorrhoeic level as a percentage of fat intake in all of the patients with abnormal base-line collections (23.1% versus 9.2% p < 0.002). We conclude that misoprostol should be considered in cystic fibrosis patients with steatorrhoea as a means of improving nutrient absorption. © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Land grabs, bio-piracy and the inversion of justice in Colombia

The possibility of commercially exploiting plant, animal and human genetic resources unlocked by biotechnology has given rise to a wide range of cultural, environmental, ethical and economic conflicts. While supporters describe this activity as bioprospecting, critics refer to it as biopiracy. According to this latter view, international legal agreements and treaties have disregarded opposition and legalized the possibility of appropriating genetic resources and their derivative products through the use of patents. The legal framework that permits the appropriation of natural genetic products in Colombia also criminalizes aspects of traditional ways of life and enables a legally approved but socially harmful land-grabbing process. The article describes these processes and impact in terms of the inversion of justice and the erosion of environmental sustainability.