The role of chemotherapy in the treatment of adult soft tissue sarcomas

Adult soft tissue sarcomas are relatively rare tumours which are curable with radical surgery. Approximately 50% of patients will develop inoperable disease or metastases for which chemotherapy may be inappropriate. Only two cytotoxic agents - doxorubicin and ifosfamide - have activity in > 20% of patients. For both these agents there is evidence of a dose-response relationship. There is currently no good evidence that combination chemotherapy confers a clinical benefit compared with single agents. Outside a clinical trial, standard first-line therapy should be with single agent doxorubicin at a dose intensity ≥ 70 mg2 every 3 weeks. Approximately 25% of patients may be expected to respond to this regimen. There is the suggestion that responses may occur to ifosfamide in patients who progress on doxorubicin. The role of chemotherapy in the adjuvant setting remains uncertain. Several trials have suggested a modest relapse-free and overall survival benefit for the use of post-operative chemotherapy and a recent overview of 14 randomised trials confirms a small though significant benefit. These benefits have to be weighed against the toxicity of chemotherapy. The importance of treating all patients with soft tissue sarcomas in clinical trials is stressed. There is an urgent need to define new active agents to treat this disease.

Cisplatin and gemcitabine in the management of metastatic penile cancer

Penile cancer is rare and receives little public attention. There are few treatment options for advanced disease. The most active regimen to date is a combination of bleomycin, methotrexate, and cisplatin. However the treatment-related mortality is 11% and hence this combination has not been adapted as a standard of care. We report two cases of advanced penile cancer where a sustained palliative response was observed with combination chemotherapy using cisplatin and gemcitabine. Our experience demonstrates that this is a well tolerated regimen active in this setting. © 2009 Elsevier Inc. All rights reserved.

Lessons from the 4-hour standard in England for Australia

Australia is in the process of making the most important change to its health care system since the implementation of Medicare.1 We agree with Cameron and Cooke that there are important lessons for Australia from the implementation of the 4-hour rule in the United Kingdom. As in Robert Zemeckis’s 1985 movie classic, Back to the future, the old question of “If I had the opportunity to do something again, what would I have done differently?” applies. We challenge the assumption that Australia is embarking on something that the UK has recently abandoned. The UK has not actually abandoned the 4-hour rule but expanded it into a suite of eight indicators that include three time-based measures, including total time in the emergency department (ED).

Treatment rationale study design for the MetLung trial : a randomized, double-blind phase III study of onartuzumab (MetMAb) in combination with erlotinib versus erlotinib alone in patients who have received standard chemotherapy for stage IIIB or IV met-positive non-small-cell lung cancer

We present the treatment rationale and study design of the MetLung phase III study. This study will investigate onartuzumab (MetMAb) in combination with erlotinib compared with erlotinib alone, as second- or third-line treatment, in patients with advanced non-small-cell lung cancer (NSCLC) who are Met-positive by immunohistochemistry. Approximately 490 patients (245 per treatment arm) will receive erlotinib (150 mg oral daily) plus onartuzumab or placebo (15 mg/kg intravenous every 3 weeks) until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. The efficacy objectives of this study are to compare overall survival (OS) (primary endpoint), progression-free survival, and response rates between the 2 treatment arms. In addition, safety, quality of life, pharmacokinetics, and translational research will be investigated across treatment arms. If the primary objective (OS) is achieved, this study will provide robust results toward an alternative treatment option for patients with Met-positive second- or third-line NSCLC. © 2012 Elsevier Inc. All Rights Reserved.

Management of endocrine resistant breast cancer

Metastatic breast cancer (MBC) may present de novo but more commonly develops in women initially presenting with early breast cancer despite the widespread use of adjuvant hormonal and cytotoxic chemotherapy. MBC is incurable. Hormone sensitive MBC eventually becomes resistant to endocrine therapy in most women. Anthracyclines are the agents of choice in the treatment of endocrine resistant MBC. With the widespread use of anthracyclines in the adjuvant setting, taxanes have become the agents of choice for many patients. Recently capecitabine has become established as a standard of care for patients pretreated with anthracyclines and taxanes. However, a range of agents have activity as third line treatment. These include gemcitabine, vinorelbine and platinum analogues. The sequential use of non-cross resistant single agents rather than combination therapy is preferable in most women with MBC. Even though combination therapy can improve response rates and increase progression free interval, there is no robust evidence to indicate an advantage in terms of overall survival. Moreover, combination therapy is associated with a higher toxicity rate and poor quality of life. There is no role for dose-intense therapy, high dose therapy or maintenance chemotherapy outside the context of a clinical trial. The introduction of trastuzumab, monoclonal antibody targeting growth factor receptors, has improved the therapeutic options for women with tumours overexpressing HER2/neu. DNA micro-array profiles of tumours can potentially help to individualise therapy in future. Molecular targeted therapy has the potential to revolutionise the management of MBC.

Sequence and organization of barley yellow dwarf virus genomic RNA

The nucleotide sequence of the genomic RNA of barley yellow dwarf virus, PAV serotype was determined except for the 5′-terminal base, and its genome organization deduced. The 5,677 nucleotide genome contains five large open reading frames (ORFs). The genes for the coat protein (1) and the putative viral RNA-dependent RNA polymerase were identified. The latter shows a striking degree of similarity to that of carnation mottle virus (CarMV). By comparison with corona- and retrovirus RNAs, it is proposed that a translational frameshift is involved in expression of the polymerase. An ORF encoding an Mr 49,797 protein (50K ORF) may be translated by in-frame readthrough of the coat protein stop codon. The coat protein, an overlapping 17K ORF, and a 3′ 6.7K ORF are likely to be expressed via subgenomic mRNAs. © 1988 IRL Press Limited.

Marker gene elimination from transgenic barley, using co-transformation with adjacent 'twin T-DNAs' on a standard Agrobacterium transformation vector

We have tested a methodology for the elimination of the selectable marker gene after Agrobacterium-mediated transformation of barley. This involves segregation of the selectable marker gene away from the gene of interest following co-transformation using a plasmid carrying two T-DNAs, which were located adjacent to each other with no intervening region. A standard binary transformation vector was modified by insertion of a small section composed of an additional left and right T-DNA border, so that the selectable marker gene and the site for insertion of the gene of interest (GOI) were each flanked by a left and right border. Using this vector three different GOIs were transformed into barley. Analysis of transgene inheritance was facilitated by a novel and rapid assay utilizing PCR amplification from macerated leaf tissue. Co-insertion was observed in two thirds of transformants, and among these approximately one quarter had transgene inserts which segregated in the next generation to yield selectable marker-free transgenic plants. Insertion of non-T-DNA plasmid sequences was observed in only one of fourteen SMF lines tested. This technique thus provides a workable system for generating transgenic barley free from selectable marker genes, thereby obviating public concerns regarding proliferation of these genes.

The genome organization and affinities of an Australian isolate of carrot mottle umbravirus

The genomic sequence of an Australian isolate of carrot mottle umbravirus (CMoV-A) was determined from cDNA generated from dsRNA. This provides the first data on the genome organization and phylogeny of an umbravirus. The 4201-nucleotide genome contains four major open reading frames (ORFs). Analysis suggests that ORF2 encodes an RNA-dependent RNA polymerase, that ORF4 encodes a movement protein, and that the virus has no coat protein gene. The functions of ORFs 1 and 3 remain unknown. ORF2 is probably translated following ribosomal frameshifting. ORFs 3 and 4 are probably translated from a subgenomic mRNA. Sequence comparisons showed CMoV-A to be closely related to pea enation mosaic RNA2 NA2), but also to have affinities with the Bromoviridae. These findings shed light on the relationships between the luteoviruses, PEMV, and the umbraviruses and on the relationships between the carmo-like viruses and the Bromoviridae.

The Sessional Academic Success (SAS) project

The Sessional Academic Success (SAS) project is a sustainable, distributed model for supporting sessional staff at QUT. Developed by the Learning and Teaching Unit. SAS complements our Sessional Academic Program (SAP): a sequence of formal academic development workshops explained in complementary nomination. SAS recognises that while these programs are very well received and a crucial aspect of preparing and advancing sessional teachers, they are necessarily encapsulated in the moment of their delivery and are generic, as they address all faculties (with their varied cultures, processes and pedagogies). The SAS project extends this formal, centrally offered activity into local, ‘just in time’, ongoing support within schools. It takes a distributed leadership approach. Experienced sessional academics are recruited and employed as Sessional Academic Success Advisors (SASAs). They provide sessional staff in their schools with contextually specific, needs based, peer-to-peer development opportunities; one-on-one advice on classroom management and strategies for success; and help to trouble-shoot challenges. The SASAs are trained by the Learning and Teaching Unit co-ordinator, and ongoing support is provided centrally and by school-based co-ordinators. This team approach situates the SASAs at the centre of an organisation map (see diagram of support relationships below). The SAS project aims to support sessional staff in their professional development by: • Offering contextual, needs-based support at school level by harnessing local expertise; • Providing further development opportunities that are local and focal; SAS aims to retain Sessional Staff by: • Responding to self-nominated requests for support and ‘just in time’, safe and reliable advice in times of need; • Building sessional staff confidence through help with dealing with challenges from a trusted peer; • Building a supportive academic community for sessional staff, which helps them feel a part of faculty life, and a community of teaching practice. SAS aims to support sessional staff in the development of academic teaching careers by: • Recognising the capacity of experienced sessional staff to support their peers in ways that are unique, valuable and valued and providing the agency to do so; • Providing career advancement and leadership opportunities for sessional staff. SAS takes unique approaches within each school using strategies such as: • Welcomes and schools orientation by SASAs; • Regular check ins; face-to-face advice and online support; • Compiling local resources to complement university wide resources. • Sessional-to-sessional ‘just in time’ training (eg. assessment and marking when marking commences); • Peer feedback and mentoring (the opportunities to sit in more experiences sessionals’ classes; • Sessional staff awards (nominated by students); • Communities of practice to discuss topics and issues with a view to (and support for) publishing on learning and teaching. In these ways, SASAs complement support offered by unit coordinators, administrators, and the Learning and Teaching Unit. Pairing senior and ‘understudy’ advisors ensures a line of succession, sustainability and continuity. A pilot program commenced in 2012 involving three schools (Psychology and Social Work; Electrical Engineering and Computer Science; Media, Entertainment and Creative Arts). It will be expanded across schools in 2013.

Academic Development Program : QUT University Wide

The QUT Sessional Academic Program (SAP) has scaffolded levels, each with experience-appropriate objectives: • SAP 1: Introduction to Learning and Teaching aims to develop confidence and build awareness of pedagogy and managing class-room scenarios. • SAP 2: Learning and Teaching in Large Units focuses on aligning curriculum and assessment through learning activities and builds a community of teaching practice with sessionals and subject coordinators. • SAP 3: Developing your Teaching Practice focuses on whole of university and classroom strategies to ensure student success through effective feedback; reflective practice and learning communities. • SAP 4: Enhancing your Teaching Practice applies these factors to teaching success. In conjunction with: • Sessional Career Advancement Development: for Higher Degree Research students/ sessional staff who aspire to become academics provides guidance on developing an academic portfolio in teaching, research and service. And • Sessional Academic Success program providing ongoing, local support (see separate nomination). A critical factor in its success is its praxis approach. Theoretical principles are modelled. Eg, ‘active learning’ is explained and modelled through learning activities, which participants evaluate ‘on the fly’ against the criteria of learning, engagement and connection with peers. The topics ‘learning communities’ and ‘reflective practice’ are explored as a learning community–then applied in participants’ classes, with reflections shared in the next session. This produces a ‘meta-awareness’ of theory and principles, as they are explained, applied in practice, and critically analysed for their effectiveness in workshops.

Development of empirical equations for irradiance profile of a standard parabolic trough collector using Monte Carlo ray tracing technique

Irradiance profile around the receiver tube (RT) of a parabolic trough collector (PTC) is a key effect of optical performance that affects the overall energy performance of the collector. Thermal performance evaluation of the RT relies on the appropriate determination of the irradiance profile. This article explains a technique in which empirical equations were developed to calculate the local irradiance as a function of angular location of the RT of a standard PTC using a vigorously verified Monte Carlo ray tracing model. A large range of test conditions including daily normal insolation, spectral selective coatings and glass envelop conditions were selected from the published data by Dudley et al. [1] for the job. The R2 values of the equations are excellent that vary in between 0.9857 and 0.9999. Therefore, these equations can be used confidently to produce realistic non-uniform boundary heat flux profile around the RT at normal incidence for conjugate heat transfer analyses of the collector. Required values in the equations are daily normal insolation, and the spectral selective properties of the collector components. Since the equations are polynomial functions, data processing software can be employed to calculate the flux profile very easily and quickly. The ultimate goal of this research is to make the concentrating solar power technology cost competitive with conventional energy technology facilitating its ongoing research.

Compliance with standard precautions and occupational exposure reporting among operating room nurses in Australia

Occupational exposures of healthcare workers tend to occur because of inconsistent compliance with standard precautions. Also, incidence of occupational exposure is underreported among operating room personnel. The purpose of this project was to develop national estimates for compliance with standard precautions and occupational exposure reporting practices among operating room nurses in Australia. Data was obtained utilizing a 96-item self-report survey. The Standard Precautions and Occupational Exposure Reporting survey was distributed anonymously to 500 members of the Australian College of Operating Room Nurses. The Health Belief Model was the theoretical framework used to guide the analysis of data. Data was analysed to examine relationships between specific constructs of the Health Belief Model to identify factors that might influence the operating room nurse to undertake particular health behaviours to comply with standard precautions and occupational exposure reporting. Results of the study revealed compliance rates of 55.6% with double gloving, 59.1% with announcing sharps transfers, 71.9% with using a hands-free sharps pass technique, 81.9% with no needle recapping and 92.0% with adequate eye protection. Although 31.6% of respondents indicated receiving an occupational exposure in the past 12 months, only 82.6% of them reported their exposures. The results of this study provide national estimates of compliance with standard precautions and occupational exposure reporting among operating room nurses in Australia. These estimates can now be used as support for the development and implementation of measures to improve practices in order to reduce occupational exposures and, ultimately, disease transmission rates among this high-risk group.

Influences on compliance with standard precautions among operating room nurses

Background Occupational exposures of health care workers occur because of inconsistent compliance with standard precautions. The purpose of this study was to develop national estimates of compliance with standard precautions and occupational exposure reporting among operating room nurses (specifically, scrub nurses) in Australia and to assess variables that influence compliance. Methods A descriptive correlation design was used to investigate relationships between variables and compliance, using a theoretical framework, the Health Belief Model, to give meaning to the variables. Data collection was done through mail-out surveys to members of the Australian College of Operating Room Nurses. Results This article reports the results of compliance with the following 2 specific self-protective behaviors: double-gloving and wearing adequate eye protection. Mean compliance rates were 55.6% with always double-gloving during surgical procedures and 92% with always wearing adequate eye protection. In addition, the variable that had the most influence on compliance was the perception of barriers to compliance, specifically, that adhering to standard precautions interfered with duties. Conclusion These results have implications for the development of multifaceted perioperative infection control programs, including strategies for prevention, education, and policy development, to improve practices aimed at reducing occupational exposures among this high-risk group.

Adapting Lyubashevsky's signature schemes to the ring signature setting

Basing signature schemes on strong lattice problems has been a long standing open issue. Today, two families of lattice-based signature schemes are known: the ones based on the hash-and-sign construction of Gentry et al.; and Lyubashevsky’s schemes, which are based on the Fiat-Shamir framework. In this paper we show for the first time how to adapt the schemes of Lyubashevsky to the ring signature setting. In particular we transform the scheme of ASIACRYPT 2009 into a ring signature scheme that provides strong properties of security under the random oracle model. Anonymity is ensured in the sense that signatures of different users are within negligible statistical distance even under full key exposure. In fact, the scheme satisfies a notion which is stronger than the classical full key exposure setting as even if the keypair of the signing user is adversarially chosen, the statistical distance between signatures of different users remains negligible. Considering unforgeability, the best lattice-based ring signature schemes provide either unforgeability against arbitrary chosen subring attacks or insider corruption in log-sized rings. In this paper we present two variants of our scheme. In the basic one, unforgeability is ensured in those two settings. Increasing signature and key sizes by a factor k (typically 80 − 100), we provide a variant in which unforgeability is ensured against insider corruption attacks for arbitrary rings. The technique used is pretty general and can be adapted to other existing schemes.