Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer

INTRODUCTION: Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. METHODS: Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m/10 min without routine steroid premedication) or paclitaxel (225 mg/m/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. RESULTS: A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade ≥3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). CONCLUSION: PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient. © 2008International Association for the Study of Lung Cancer.

SRL 172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer : phase III results

Background: This open-label, randomised phase III study was designed to further investigate the clinical activity and safety of SRL172 (killed Mycobacterium vaccae suspension) with chemotherapy in the treatment of non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomised to receive platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin, vinblastine and cisplatin or carboplatin) with (210 patients) or without (209 patients) monthly SRL172. Results: There was no statistical difference between the two groups in overall survival (primary efficacy end point) over the course of the study (median overall survival of 223 days versus 225 days; P = 0.65). However, a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group (90%), than in the chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase, the response rate was 37% in the combined group and 33% in the chemotherapy alone group. Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score (-14.3) than patients in the chemotherapy plus SRL172 group (-6.6) (P = 0.02). Conclusion: In this non-placebo controlled trial, SRL172 when added to standard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times. © 2004 European Society for Medical Oncology.

Front-line workers as intermediaries : the changing landscape of disability and employment services in Australia

Recent welfare reform in Australia has been constructed around the now-familiar principle of paid work and willingness to work as the fundamental marker of social citizenship. Beginning with the long-term unemployed in Australia in the mid 1990s, the scope of welfare reform has now extended to include people with a disability – which is a category of income support that has been growing in Australia. From the national government’s point of view this growth is a financial concern as it seeks to move as many people as possible into paid work to support the costs of an ageing population (DEWR, 2005). In doing so, the government has changed the meaning of disability in terms of eligibility for financial support from the state, and at the same time redefined the role of people with a disability with regard to work, and the role of the state with regard to the disabled. This has been a matter of some political contention in Australia.

Challenges of elementary science teaching: an Australian perspective

This chapter profiles research that has explored the role of affect in the teaching of science in Australia particularly on primary or elementary science education. Affect is a complex set of characteristics that relate to the interactions between an individual’s knowledge and emotional responses to a stimulus. Thus, there are many dimensions and theoretical frameworks that inform our understanding of how and why people behave in particular ways.

Developing an acculturation and resilience scale for use with culturally and linguistically diverse populations

Australian multicultural society consists of culturally and linguistically diverse (CALD) migrants, refugees and international students from different parts of the world. Despite hardships, these individuals show resilience and adapt successfully. However, there is a dearth of scales measuring these positive developments and personal strengths. The study describes the development and evaluation of a scale measuring resilience and acculturation of CALD people. Items were generated for the Acculturation and Resilience Scale (AARS).The AARS and other acculturation and psychological distress scales were administered to 225 CALD community members. Exploratory factor analyses resulted in a 27-item AARS with three subscales: Acculturation, Resilience, and Spirituality. The three-factor structure was subjected to a confirmatory factor analysis on a sample of 515 international students. The factor structure stability was upheld by the second sample. The psychometric properties were investigated using the two samples and demonstrated satisfactory internal consistency, test-retest reliability, and divergent validity. The scale addresses a major gap in the literature and can be used to measure the positive acculturation and resilience of the newly arrived and relocated individuals. Further research is warranted to examine the scale’s psychometric properties with migrants and refugees from a range of ethnic communities.

Australasian nutrition research for prevention and management of child obesity : innovation and progress in the last decade

The Food and Nutrition stream of Australasian Child and Adolescent Obesity Research Network (ACAORN) aims to improve the quality of dietary methodologies and the reporting of dietary intake within Australasian child obesity research (http://www.acaorn.org.au/streams/nutrition/). With 2012 marking ACAORN’s 10th anniversary, this commentary profiles a selection of child obesity nutrition research published over the last decade by Food and Nutrition Stream members. In addition, stream activities have included the development of an online selection guide to assist researchers in their selection of appropriate dietary intake methodologies (http://www.acaorn.org.au/streams/nutrition/dietary-intake/index.php). The quantity and quality of research to guide effective child obesity prevention and treatment has increased substantially over the last decade. ACAORN provides a successful case study of how research networks can provide a collegial atmosphere to foster and co-ordinate research efforts in an otherwise competitive environment.

High school students' perceptions of school science and science careers : a critical look at a critical issue

Disproportionate representation of males and females in science courses and careers continues to be of concern. This article explores gender differences in Australian high school students’ perceptions of school science and their intentions to study university science courses. Nearly 3800 15-year-old students responded to a range of 5-point Likert items relating to intentions to study science at university, perceptions of career-related instrumental issues such as remuneration and job security, self-rated science ability and enjoyment of school science. Australian boys and girls reported enjoying science to a similar extent, however boys reported enjoying it more in relation to other subjects than did girls, and rated their ability in science compared to others in their class more highly than did girls. There was no significant difference between the mean responses of girls and boys to the item “It is likely I will choose a science-related university course when I leave school” and the strongest predictors of responses to this item were items relating to students’ liking for school science and awareness from school science of new and exciting jobs, followed by their perceived self-ability. These results are discussed in relation to socio-scientific values that interact with identity and career choices, employment prospects in science, and implications for science education.

Reasons for non-urgent presentations to the emergency department in Saudi Arabia

Background The majority of patients who attend emergency departments (EDs) in Saudi Arabia have non-urgent problems, resulting in overcrowding, excessive waiting times and delayed care for more acutely ill patients. The purpose of this research was to examine the reasons for non-urgent visits to a Saudi ED and factors associated with patient perceptions of urgency. Methods We administered a survey to 350 consecutively presenting Canadian Triage and Acuity Scale (CTAS) IV or V adult patients at a large tertiary ED in Riyadh region, Saudi Arabia, during 25 days of data collection in March 2013. Results Over half of the sample usually visited the ED to access healthcare. The most common reasons for attending the ED were not having a regular healthcare provider (63%), being able to receive care on the same day (62%), and the convenience of and access to medical care 24/7 (62%). Approximately two-thirds of CTAS V patients and one-third of CTAS IV patients believed their condition was more urgent than their triage nurse rating. Conclusion Multiple factors influence non-urgent visits to the ED in the Saudi context including insufficient community awareness of the role of the ED and perceived lack of access to primary healthcare services.

Photodissociation of TEMPO-modified peptides: New approaches to radical-directed dissociation of biomolecules

Radical-directed dissociation of gas phase ions is emerging as a powerful and complementary alternative to traditional tandem mass spectrometric techniques for biomolecular structural analysis. Previous studies have identified that coupling of 2-[(2,2,6,6-tetramethylpiperidin-1-oxyl)methyl] benzoic acid (TEMPO-Bz) to the N-terminus of a peptide introduces a labile oxygen-carbon bond that can be selectively activated upon collisional activation to produce a radical ion. Here we demonstrate that structurally-defined peptide radical ions can also be generated upon UV laser photodissociation of the same TEMPO-Bz derivatives in a linear ion-trap mass spectrometer. When subjected to further mass spectrometric analyses, the radical ions formed by a single laser pulse undergo identical dissociations as those formed by collisional activation of the same precursor ion, and can thus be used to derive molecular structure. Mapping the initial radical formation process as a function of photon energy by photodissociation action spectroscopy reveals that photoproduct formation is selective but occurs only in modest yield across the wavelength range (300-220 nm), with the photoproduct yield maximised between 235 and 225 nm. Based on the analysis of a set of model compounds, structural modifications to the TEMPO-Bz derivative are suggested to optimise radical photoproduct yield. Future development of such probes offers the advantage of increased sensitivity and selectivity for radical-directed dissociation. © 2014 the Owner Societies.

Genetic polymorphisms in miRNAs targeting the estrogen receptor and their effect on breast cancer risk

Breast cancer is the cancer that most commonly affects women worldwide. This type of cancer is genetically complex, but is strongly linked to steroid hormone signalling systems. Because microRNAs act as translational regulators of multiple genes, including the steroid nuclear receptors, single nucleotide polymorphisms (SNPs) in microRNAs genes can have potentially wide-ranging influences on breast cancer development. Thus, this study was conducted to investigate the relationships between six SNPs (rs6977848, rs199981120, rs185641358, rs113054794, rs66461782, and rs12940701) located in four miRNA genes predicted to target the estrogen receptor (miR-148a, miR-221, miR-186, and miR-152) and breast cancer risk in Caucasian Australian women. By using high resolution melt analysis (HRM) and polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), 487 samples including 225 controls and 262 cases were genotyped. Analysis of their genotype and allele frequencies indicated that the differences between case and control populations was not significant for rs6977848, rs66461782, and rs12940701 because their p-values are 0.81, 0.93, 0.1 which are all above the threshold value (p=0.05). Our data thus suggests that these SNPs do not affect breast cancer risk in the tested population. In addition, rs199981120, rs185641358, and rs113054794 could not be found in this population, suggesting that these SNPs do not occur in Caucasian Australians.

Unconditionally secure disjointness tests for private datasets

We present two unconditional secure protocols for private set disjointness tests. In order to provide intuition of our protocols, we give a naive example that applies Sylvester matrices. Unfortunately, this simple construction is insecure as it reveals information about the intersection cardinality. More specifically, it discloses its lower bound. By using the Lagrange interpolation, we provide a protocol for the honest-but-curious case without revealing any additional information. Finally, we describe a protocol that is secure against malicious adversaries. In this protocol, a verification test is applied to detect misbehaving participants. Both protocols require O(1) rounds of communication. Our protocols are more efficient than the previous protocols in terms of communication and computation overhead. Unlike previous protocols whose security relies on computational assumptions, our protocols provide information theoretic security. To our knowledge, our protocols are the first ones that have been designed without a generic secure function evaluation. More important, they are the most efficient protocols for private disjointness tests in the malicious adversary case.

An ancient duplication of apple MYB transcription factors is responsible for novel red fruit-flesh phenotyp

Anthocyanin accumulation is coordinated in plants by a number of conserved transcription factors. In apple (Malus × domestica), an R2R3 MYB transcription factor has been shown to control fruit flesh and foliage anthocyanin pigmentation (MYB10) and fruit skin color (MYB1). However, the pattern of expression and allelic variation at these loci does not explain all anthocyanin-related apple phenotypes. One such example is an open-pollinated seedling of cv Sangrado that has green foliage and develops red flesh in the fruit cortex late in maturity. We used methods that combine plant breeding, molecular biology, and genomics to identify duplicated MYB transcription factors that could control this phenotype. We then demonstrated that the red-flesh cortex phenotype is associated with enhanced expression of MYB110a, a paralog of MYB10. Functional characterization of MYB110a showed that it was able to up-regulate anthocyanin biosynthesis in tobacco (Nicotiana tabacum). The chromosomal location of MYB110a is consistent with a whole-genome duplication event that occurred during the evolution of apple within the Maloideae family. Both MYB10 and MYB110a have conserved function in some cultivars, but they differ in their expression pattern and response to fruit maturity.

Developing agency in the creative career : a design-based framework for work integrated learning

Research shows that approximately half of creative practitioners operate as embedded creatives by securing gainful employment within organisations located in the field beyond their core discipline. This foregrounds the significance of having the skills necessary to successfully cross the disciplinary boundaries in order to negotiate a professional role. The multiple implications of such reframing for emerging creative practitioners who navigate uncertain professional boundaries include developing a skill of identifying and successfully targeting the shifting professional and industry coordinates while remaining responsive to changes. A further implication involves creative practitioners engaging in a continuous cycle of re-negotiation of their professional identity making the management of multiple professional selves - along with creating and recreating a meaningful frame of references such as the language around their emerging practice - a necessary skill. This chapter presents a case study of a set of Work Integrated Learning subjects designed to develop in creative industries practitioners the skills to manage their emerging professional identities in response to the shifts in the professional world.

Soluble laminin and arginine-glycine-aspartic acid containing peptides differentially regulate type IV collagenase messenger RNA, activation, and localization in testicular cell culture

Rat testicular cells in culture produce several metalloproteinases including type IV collagenases (Sang et al. Biol Reprod 1990; 43:946-955, 956-964). We have now investigated the regulation of testicular cell type IV collagenase and other metalloprotemases in vitro. Soluble laminin stimulated Sertoli cell type IV collagenase mRNA levels. However, three peptides corresponding to different domains of the laminin molecule (CSRAKQAASIKVASADR, FALRGDNP, CLQDGDVRV) did not influence type IV collagenase mENA levels. Zyniographic analysis of medium collected from these cultures revealed that neither soluble laminin nor any of the peptides influenced 72-Wa type IV collagenase protein levels. However, peptide FALRGDNP resulted in both, a selective increase in two higher molecular-weight metalloprotemnases (83 kDa and 110 Wa and in an activation of the 72-Wa rat type IV collagenase. Interleukin-1, phorbol ester, testosterone, and FSH did not affect collagenase activation, lmmunocytochemical studies demonstrated that the addition of soluble laminin resulted in a redistribution of type IV collagenase from intracellular vesicles to the cell-substrate region beneath the cells. Peptide FALRGDNP induced a change from a vesicular to peripheral plasma membrane type of staining pattern. Zymography of plasma membrane preparations demonstrated triton-soluble gelatinases of 76 Wa, 83 Wa, and 110 Wa and a triton-insoluble gelatinase of 225 Wa, These results indicate that testicular cell type IV collagenase mRNA levels, enzyme activation, and distribution are influenced by laminin and RGD-containing peptides.