Impact of malnutrition on 12-month mortality following acute hip fracture

Background Studies investigating the relationship between malnutrition and post-discharge mortality following acute hip fracture yield conflicting results. This study aimed to determine whether malnutrition independently predicted 12-month post-fracture mortality after adjusting for clinically relevant covariates. Methods An ethics approved, prospective, consecutive audit was undertaken for all surgically treated hip fracture inpatients admitted to a dedicated orthogeriatric unit (November 2010–October 2011). The 12-month mortality data were obtained by a dual search of the mortality registry and Queensland Health database. Malnutrition was evaluated using the Subjective Global Assessment. Demographic (age, gender, admission residence) and clinical covariates included fracture type, time to surgery, anaesthesia type, type of surgery, post-surgery time to mobilize and post-operative complications (delirium, pulmonary and deep vein thrombosis, cardiac complications, infections). The Charlson Comorbidity Index was retrospectively applied. All diagnoses were confirmed by the treating orthogeriatrician. Results A total of 322 of 346 patients were available for audit. Increased age (P = 0.004), admission from residential care (P < 0.001), Charlson Comorbidity Index (P = 0.007), malnutrition (P < 0.001), time to mobilize >48 h (P < 0.001), delirium (P = 0.003), pulmonary embolism (P = 0.029) and cardiovascular complication (P = 0.04) were associated with 12-month mortality. Logistic regression analysis demonstrated that malnutrition (odds ratio (OR) 2.4 (95% confidence interval (CI) 1.3–4.7, P = 0.007)), in addition to admission from residential care (OR 2.6 (95% CI 1.3–5.3, P = 0.005)) and pulmonary embolism (OR 11.0 (95% CI 1.5–78.7, P = 0.017)), independently predicted 12-month mortality. Conclusions Findings substantiate malnutrition as an independent predictor of 12-month mortality in a representative sample of hip fracture inpatients. Effective strategies to identify and treat malnutrition in hip fracture should be prioritized.

Clinical investigation of asmofilcon A silicone hydrogel lenses

Purpose. To investigate the clinical and subjective performance of asmofilcon A, a new third generation silicone hydrogel contact lens during 6-night extended wear (EW) over 6 months. Methods. A prospective, randomized, single-masked study was conducted. Sixty experienced daily wear soft contact lens wearers were randomly assigned to wear either asmofilcon A or senofilcon A contact lenses bilaterally for 6 months on an EW basis. Evaluations were conducted at contact lens delivery and after 1 week, 4 weeks, 3 and 6 months of EW. Results. Fifty subjects (83%) successfully completed the study. Two subjects experienced adverse events; one unilateral red eye with asmofilcon A and one asymptomatic infiltrate with senofilcon A. There were no significant differences in high or low contrast distance visual acuity between asmofilcon A and senofilcon A; however, low contrast distance visual acuity decreased significantly over time with both contact lens types (p < 0.05). The two lens types did not vary significantly with respect to any of the objective and subjective measures assessed (p > 0.05). Superior palpebral conjunctival injection showed a statistically significant increase over time with both lens types (p < 0.05). Both lens types were rated highly with respect to overall comfort, with subjects reporting 14 or 15 h of comfortable lens wearing time per day at each of the study visits (p > 0.05). Overall satisfaction ratings were also very high at all visits, with median scores of 95 (86 to 99) for asmofilcon A and 90 (85 to 96) for senofilcon A at 6 months (p > 0.05). Conclusions. Over 6 months of EW, the asmofilcon A contact lens performed in a similar manner to senofilcon A with respect to visual acuity, ocular health, and contact lens performance measures. Longer-term EW studies are required to investigate the changes over time observed with both lens types.

Pathways for developing a 'smart' workforce : does the achievement of formal workplace qualifications encourage participation in higher education?

The purpose of this paper is to investigate a public workforce education initiative in the context of State and agency policies designed to enhance employee capabilities to adapt to a volatile and changing environment. In particular, we are concerned with public employees’ experience of a higher educational pathway that resulted in their obtaining a Diploma level qualification. In addition to understanding the employees’ experience of this pathway we were interested in whether the experience contributed to their openness to the prospect of university level education. We conducted telephone interviews with a sample of participants from the program. Employees reported very positive experience of the program; in particular employees reported enhanced efficacy beliefs, a strong sense of achievement, and a feeling of recognition. This experience is explained by four main factors; (1) a program design that was well aligned with the employees learning needs, (2) strong support by organisational staff who delivered and assessed participants on capability criteria, (3) strong management support for employees’ participation, (4) an academic ceremony that provided participants with public recognition of their achievement by valued others. Participants’ motivation to participate was primarily intrinsic rather than extrinsic. Participants in the study reported that their experience in this educational pathway gave them the confidence to consider the possibility of university level education. The paper also discusses the practitioner-academic collaboration that led to the development of this paper.

Contractual relationships for better stewardship of privatised critical infrastructures

Governments increasingly rely on forms of privatisation to provide critical public infrastructure yet when those infrastructures fail to meet community expectations government bears the political and economic risks, being held accountable by the public as steward for those infrastructures. Reconfiguration of the contractual relationships may achieve better stewardship. Many of the forms of privatization rely on Agency theory prescriptions, conceptualizing organisations and individuals as motivated solely by self-interest. Stewardship theory (Van Slyke 2007) has developed as a complement to Agency theory offering the possibility of contractual relationships which maximize stewardship outcome. Stewardship theory asserts that pro-stewardship factors cause the agent/steward to act in the interests of the principal. This research has interrogated the literature finding that of the pro-stewardship factors, sense of responsibility is pre-eminent and has a significant link to the agent acting as a steward. The research has explored how important it is that the steward feel sense of responsibility and the actions that sense of responsibility. Case studies of privatized core elements of urban water systems infrastructure were explored. Data has been gathered primarily from archival sources and individual interviews of government and private sector executives key to those systems. This paper reports the findings as to the extent of stewardship, how important it is that the steward acts in the interests of the principal, even to the steward’s detriment and the importance of the steward feeling a sense of responsibility. The actions which increase that sense of responsibility will be assembled to position the research to better proceed with the analysis of the data as to these actions.

Isolation of two phenylethanoid glycosides from Eremophila gilesii

The leaves of Eremophila gilesii have been used traditionally to treat colds, headaches, sores, and chest pains. Our previous screening of Australian native plants showed that the methanol extract of the aerial parts of E. gilesii demonstrated notable inhibition of ADP-induced human platelet aggregation and serotonin release. Subsequent fractionation on the methanol extract led to the isolation of two phenylethanoid glycosides, verbascoside (1) and poliumoside (2). This is the first study reporting the presence of phenylethanoid glycosides in E. gilesii.

Progression of human breast cancer cells from hormone-dependent to hormone-independent growth both in vitro and in vivo

We have isolated a series of sublines of the hormone-dependent MCF-7 human breast cancer cell line after selection both in vivo and in vitro for growth in the presence of subphysiological concentrations of estrogens. These sublines represent a model system for study of the processes leading to hormonal autonomy. The cells form growing tumors in ovariectomized athymic nude mice in the absence of estrogen supplementation but retain some responsivity to estrogen as determined by stimulation of the rate of tumor growth in vivo and by induction of progesterone receptor. An ovarian-independent but hormone-responsive phenotype may occur early in the natural progression to hormone-independent and unresponsive growth in breast cancer. We observed no change in the affinity or decrease in the level of expression of estrogen receptors and progesterone receptors among the sublines and the parental cells. Epidermal growth factor receptors are not overexpressed in ovarian-independent cells. Thus, altered hormone receptor expression may be a late event in the acquisition of a hormone-independent and unresponsive phenotype. Sublines isolated by in vivo but not in vitro selection are more invasive than the parental cells both in vivo and across an artificial basement membrane in vitro. Thus, as yet unknown tumor-host interactions may be important in the development of an invasive phenotype. Furthermore, acquisition of the ovarian-independent and invasive phenotypes can occur independently.

Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell lung cancer

INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of >/=200; scale 0-300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of >/=200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non-small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Human vs. machine : identification of bat species from their echolocation calls by humans and by artificial neural networks

Automated remote ultrasound detectors allow large amounts of data on bat presence and activity to be collected. Processing of such data involves identifying bat species from their echolocation calls. Automated species identification has the potential to provide more consistent, predictable, and potentially higher levels of accuracy than identification by humans. In contrast, identification by humans permits flexibility and intelligence in identification, as well as the incorporation of features and patterns that may be difficult to quantify. We compared humans with artificial neural networks (ANNs) in their ability to classify short recordings of bat echolocation calls of variable signal to noise ratios; these sequences are typical of those obtained from remote automated recording systems that are often used in large-scale ecological studies. We presented 45 recordings (1–4 calls) produced by known species of bats to ANNs and to 26 human participants with 1 month to 23 years of experience in acoustic identification of bats. Humans correctly classified 86% of recordings to genus and 56% to species; ANNs correctly identified 92% and 62%, respectively. There was no significant difference between the performance of ANNs and that of humans, but ANNs performed better than about 75% of humans. There was little relationship between the experience of the human participants and their classification rate. However, humans with <1 year of experience performed worse than others. Currently, identification of bat echolocation calls by humans is suitable for ecological research, after careful consideration of biases. However, improvements to ANNs and the data that they are trained on may in future increase their performance to beyond those demonstrated by humans.

The empire of cancer: Gene patents and cancer voices

In his book, The Emperor of All Maladies, Siddhartha Mukherjee writes a history of cancer — "It is a chronicle of an ancient disease — once a clandestine, 'whispered-about' illness — that has metamorphosed into a lethal shape-shifting entity imbued with such penetrating metaphorical, medical, scientific, and political potency that cancer is often described as the defining plague of our generation." Increasingly, an important theme in the history of cancer is the role of law, particularly in the field of intellectual property law. It is striking that a number of contemporary policy debates over intellectual property and public health have concerned cancer research, diagnosis, and treatment. In the area of access to essential medicines, there has been much debate over Novartis’ patent application in respect of Glivec, a treatment for leukaemia. India’s Supreme Court held that the Swiss company’s patent application violated a safeguard provision in India’s patent law designed to stop evergreening. In the field of tobacco control, the Australian Government introduced plain packaging for tobacco products in order to address the health burdens associated with the tobacco epidemic. This regime was successfully defended in the High Court of Australia. In the area of intellectual property and biotechnology, there have been significant disputes over the Utah biotechnology company Myriad Genetics and its patents in respect of genetic testing for BRCA1 and BRCA2, which are related to breast cancer and ovarian cancer. The Federal Court of Australia handed down a decision on the validity of Myriad Genetics’ patent in respect of genetic testing for BRCA1 in February 2013. The Supreme Court of the United States heard a challenge to the validity of Myriad Genetics’ patents in this area in April 2013, and handed down a judgment in July 2013. Such disputes have involved tensions between intellectual property rights, and public health. This article focuses upon one of these important test cases involving intellectual property, public health, and cancer research. In June 2010, Cancer Voices Australia and Yvonne D’Arcy brought an action in the Federal Court of Australia against the validity of a BRCA1 patent — held by Myriad Genetics Inc, the Centre de Recherche du Chul, the Cancer Institute of Japan and Genetic Technologies Limited. Yvonne D’Arcy — a Brisbane woman who has had treatment for breast cancer — maintained: "I believe that what they are doing is morally and ethically corrupt and that big companies should not control any parts of the human body." She observed: "For my daughter, I've had her have [sic] mammograms, etc, because of me but I would still like her to be able to have the test to see if the mutation gene is in there from me." The applicants made the following arguments: "Genes and the information represented by human gene sequences are products of nature universally present in each individual, and the information content of a human gene sequence is fixed. Genetic variations or mutations are products of nature. The isolation of the BRCA1 gene mutation from the human body constitutes no more than a medical or scientific discovery of a naturally occurring phenomenon and does not give rise to a patentable invention." The applicants also argued that "the alleged invention is not a patentable invention in that, so far as claimed in claims 1–3, it is not a manner of manufacture within the meaning of s 6 of the Statute of Monopolies". The applicants suggested that "the alleged invention is a mere discovery". Moreover, the applicants contended that "the alleged invention of each of claims 1-3 is not a patentable invention because they are claims for biological processes for the generation of human beings". The applicants, though, later dropped the argument that the patent claims related to biological processes for the generation of human beings. In February 2013, Nicholas J of the Federal Court of Australia considered the case brought by Cancer Voices Australia and Yvonne D’Arcy against Myriad Genetics. The judge presented the issues in the case, as follows: "The issue that arises in this case is of considerable importance. It relates to the patentability of genes, or gene sequences, and the practice of 'gene patenting'. Briefly stated, the issue to be decided is whether under the Patents Act 1990 (Cth) a valid patent may be granted for a claim that covers naturally occurring nucleic acid — either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) — that has been 'isolated'". In this context, the word "isolated" implies that naturally occurring nucleic acid found in the cells of the human body, whether it be DNA or RNA, has been removed from the cellular environment in which it naturally exists and separated from other cellular components also found there. The genes found in the human body are made of nucleic acid. The particular gene with which the patent in suit is concerned (BRCA1) is a human breast and ovarian cancer disposing gene. Various mutations that may be present in this gene have been linked to various forms of cancer including breast cancer and ovarian cancer.' The judge held in this particular case that Myriad Genetics’ patent claims were a "manner of manufacture" under s 6 of the Statute of Monopolies and s 18(1)(a) of the Patents Act 1990 (Cth). The matter is currently under appeal in the Full Court of the Federal Court of Australia. This article interprets the dispute over Myriad Genetics in light of the scholarly work of Nobel Laureate Professor Joseph Stiglitz on inequality. Such work has significant explanatory power in the context of intellectual property and biotechnology. First, Stiglitz has contended that "societal inequality was a result not just of the laws of economics, but also of how we shape the economy — through politics, including through almost every aspect of our legal system". Stiglitz is concerned that "our intellectual property regime … contributes needlessly to the gravest form of inequality." He maintains: "The right to life should not be contingent on the ability to pay." Second, Stiglitz worries that "some of the most iniquitous aspects of inequality creation within our economic system are a result of 'rent-seeking': profits, and inequality, generated by manipulating social or political conditions to get a larger share of the economic pie, rather than increasing the size of that pie". He observes that "the most iniquitous aspect of this wealth appropriation arises when the wealth that goes to the top comes at the expense of the bottom." Third, Stiglitz comments: "When the legal regime governing intellectual property rights is designed poorly, it facilitates rent-seeking" and "the result is that there is actually less innovation and more inequality." He is concerned that intellectual property regimes "create monopoly rents that impede access to health both create inequality and hamper growth more generally." Finally, Stiglitz has recommended: "Government-financed research, foundations, and the prize system … are alternatives, with major advantages, and without the inequality-increasing disadvantages of the current intellectual property rights system.’" This article provides a critical analysis of the Australian litigation and debate surrounding Myriad Genetics’ patents in respect of genetic testing for BRCA1. First, it considers the ruling of Nicholas J in the Federal Court of Australia that Myriad Genetics’ patent was a manner of manufacture as it related to an artificially created state of affairs, and not mere products of nature. Second, it examines the policy debate over gene patents in Australia, and its relevance to the litigation involving Myriad Genetics. Third, it examines comparative law, and contrasts the ruling by Nicholas J in the Federal Court of Australia with developments in the United States, Canada, and the European Union. Fourth, this piece considers the reaction to the decision of Nicholas at first instance in Australia. Fifth, the article assesses the prospects of an appeal to the Full Federal Court of Australia over the Myriad Genetics’ patents. Finally, this article observes that, whatever happens in respect of litigation against Myriad Genetics, there remains controversy over Genetic Technologies Limited. The Melbourne firm has been aggressively licensing and enforcing its related patents on non-coding DNA and genomic mapping.

EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma

Background We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5–10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12–undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.

Environmental efficiency of energy, materials, and emissions

This study estimates the environmental efficiency of international listed firms in 10 worldwide sectors from 2007 to 2013 by applying an order-m method, a non-parametric approach based on free disposal hull with subsampling bootstrapping. Using a conventional output of gross profit and two conventional inputs of labor and capital, this study examines the order-m environmental efficiency accounting for the presence of each of 10 undesirable inputs/outputs and measures the shadow prices of each undesirable input and output. The results show that there is greater potential for the reduction of undesirable inputs rather than bad outputs. On average, total energy, electricity, or water usage has the potential to be reduced by 50%. The median shadow prices of undesirable inputs, however, are much higher than the surveyed representative market prices. Approximately 10% of the firms in the sample appear to be potential sellers or production reducers in terms of undesirable inputs/outputs, which implies that the price of each item at the current level has little impact on most of the firms. Moreover, this study shows that the environmental, social, and governance activities of a firm do not considerably affect environmental efficiency.