Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer

Background: The Lung Cancer Cetuximab Study is an open-label, randomized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone, in patients with advanced EGFR-expressing, non-small-cell lung cancer (NSCLC). End points of the study are activity, safety and pharmacokinetics. Patients and methods: Following randomization, for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m2, day 1) and vinorelbine (25 mg/m2 on days 1 and 8) alone or following cetuximab treatment (initial dose 400 mg/m, followed by 250 mg/m2 weekly thereafter). Results: Eighty-six patients were randomly allocated to the study (43 per arm). Confirmed response rates were 28% in the cisplatin/vinorelbine arm (A) and 35% in the cetuximab plus cisplatin/vinorelbine arm (B). Median progression-free survival (PFS) was 4.6 months in arm A and 5.0 months in arm B, with PFS rates at 12 months of 0% and 15%, respectively. Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0% and 16%, respectively. The cetuximab combination was well tolerated. Conclusion: In the first-line treatment of advanced NSCLC, the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone. © 2007 European Society for Medical Oncology.

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.

Chemotherapy for upper gastrointestinal tumours

The aim of this review is to identify current chemotherapy treatment for tumours of the oesophagus, stomach, pancreas, and liver. The role of both neoadjuvant, adjuvant, and palliative chemotherapy regimens will be discussed. This review will be of interest to oncologists in clarifying current issues regarding chemotherapy, and to physicians in other medical specialties, to increase their general understanding of benefits and drawbacks of chemotherapy in this patient group.

Examining the impact of climate change on dengue transmission in the Asia-Pacific region

Dengue fever (DF) is a serious public health concern in many parts of the world. An increase in DF incidence has been observed globally over the past decades. Multiple factors including urbanisation, increased international travels and global climate change are thought to be responsible for increased DF. However, little research has been conducted in the Asia-Pacific region about the impact of these changes on dengue transmission. The overarching aim of this thesis is to explore the spatiotemporal pattern of DF transmission in the Asia-Pacific region and project the future risk of DF attributable to climate change. Annual data of DF outbreaks for sixteen countries in the Asia-Pacific region over the last fifty years were used in this study. The results show that the geographic range of DF in this region increased significantly over the study period. Thailand, Vietnam and Laos were identified as the highest risk areas and there was a southward expansion observed in the transmission pattern of DF which might have originated from Philippines or Thailand. Additionally, the detailed DF data were obtained and the space-time clustering of DF transmission was examined in Bangladesh. Monthly DF data were used for the entire country at the district level during 2000-2009. Dhaka district was identified as the most likely DF cluster in Bangladesh and several districts of the southern part of Bangladesh were identified as secondary clusters in the years 2000-2002. In order to examine the association between meteorological factors and DF transmission and to project the future risk of DF using different climate change scenarios, the climate-DF relationship was examined in Dhaka, Bangladesh. The results show that climate variability (particularly maximum temperature and relative humidity) was positively associated with DF transmission in Dhaka. The effects of climate variability were observed at a lag of four months which might help to potentially control and prevent DF outbreaks through effective vector management and community education. Based on the quantitative assessment of the climate-DF relationship, projected climate change will likely increase mosquito abundance and activity and DF in this area. Assuming a temperature increase of 3.3oC without any adaptation measures and significant changes in socio-economic conditions, the consequence will be devastating, with a projected annual increase of 16,030 cases in Dhaka, Bangladesh by the end of this century. Therefore, public health authorities need to be prepared for likely increase of DF transmission in this region. This study adds to the literature on the recent trends of DF and impacts of climate change on DF transmission. These findings may have significant public health implications for the control and prevention of DF, particularly in the Asia- Pacific region.

Direct iodination of isoindolines and isoindoline nitroxides as precursors to functionalized nitroxides

A new method for the direct aryl iodination of isoindolines and isoindoline nitroxides which utilizes periodic acid and potassium iodide in sulfuric acid is presented. Di-iodo functionalized tetramethyl and tetraethyl isoindolines and a di-iodo tetramethyl isoindoline nitroxide were prepared in high yield (70-82%). The analogous mono-iodo species were afforded in modest yield (34-48%). Iodinated nitrones were also obtained from a tetraethyl isoindoline nitroxide.

Molecular dynamics investigation on shearing between osteopontin and hydroxyapatite in biological materials

Bone, a hard biological material, possesses a combination of high stiffness and toughness, even though the main basic building blocks of bone are simply mineral platelets and protein molecules. Bone has a very complex microstructure with at least seven hierachical levels. This unique material characteristic attracts great attention, but the deformation mechanisms in bone have not been well understood. Simulation at nano-length scale such as molecular dynamics (MD) is proven to be a powerful tool to investigate bone nanomechanics for developing new artificial biological materials. This study focuses on the ultra large and thin layer of extrafibrillar protein matrix (thickness = ~ 1 nm) located between mineralized collagen fibrils (MCF). Non-collagenous proteins such as osteopontin (OPN) can be found in this protein matrix, while MCF consists mainly of hydroxyapatite (HA) nanoplatelets (thickness = 1.5 – 4.5 nm). By using molecular dynamics method, an OPN peptide was pulled between two HA mineral platelets with water in presence. Periodic boundary condition (PBC) was applied. The results indicate that the mechanical response of OPN peptide greatly depends on the attractive electrostatics interaction between the acidic residues in OPN peptide and HA mineral surfaces. These bonds restrict the movement of OPN peptide, leading to a high energy dissipation under shear loading.

Methodologies for measuring research impact for a new interdisciplinary institute

Interdisciplinary research is often funded by national government initiatives or large corporate sponsorship, and as such, demands periodic reporting on the use of those funds. For reasons of accountability, governance and communication to the tax payer, knowledge of the outcomes of the research need to be measured and understood. The interdisciplinary approach to research raises many challenges for impact reporting. This presentation will consider what are the best practice workflow models and methodologies.Novel methodologies that can be added to the usual metrics of academic publications include analysis of percentage share of total publications in a subject or keyword field, calculating most cited publication in a key phrase category, analysis of who has cited or reviewed the work, and benchmarking of this data against others in that same category. At QUT, interest in how collaborative networking is trending in a research theme has led to the creation of some useful co-authorship graphs that demonstrate the network positions of authors and the strength of their scientific collaborations within a group. The scale of international collaborations is also worth including in the assessment. However, despite all of the tools and techniques available, the most useful way a researcher can help themselves and the process is to set up and maintain their researcher identifier and profile.

An efficient proactive route maintenance process for reliable data transmissions in sensor networks

For industrial wireless sensor networks, maintaining the routing path for a high packet delivery ratio is one of the key objectives in network operations. It is important to both provide the high data delivery rate at the sink node and guarantee a timely delivery of the data packet at the sink node. Most proactive routing protocols for sensor networks are based on simple periodic updates to distribute the routing information. A faulty link causes packet loss and retransmission at the source until periodic route update packets are issued and the link has been identified as broken. We propose a new proactive route maintenance process where periodic update is backed-up with a secondary layer of local updates repeating with shorter periods for timely discovery of broken links. Proposed route maintenance scheme improves reliability of the network by decreasing the packet loss due to delayed identification of broken links. We show by simulation that proposed mechanism behaves better than the existing popular routing protocols (AODV, AOMDV and DSDV) in terms of end-to-end delay, routing overhead, packet reception ratio.

A threshold analysis of dengue transmission in terms of weather variables and imported dengue cases in Australia

Dengue virus (DENV) transmission in Australia is driven by weather factors and imported dengue fever (DF) cases. However, uncertainty remains regarding the threshold effects of high-order interactions among weather factors and imported DF cases and the impact of these factors on autochthonous DF. A time-series regression tree model was used to assess the threshold effects of natural temporal variations of weekly weather factors and weekly imported DF cases in relation to incidence of weekly autochthonous DF from 1 January 2000 to 31 December 2009 in Townsville and Cairns, Australia. In Cairns, mean weekly autochthonous DF incidence increased 16.3-fold when the 3-week lagged moving average maximum temperature was <32 °C, the 4-week lagged moving average minimum temperature was ≥24 °C and the sum of imported DF cases in the previous 2 weeks was >0. When the 3-week lagged moving average maximum temperature was ≥32 °C and the other two conditions mentioned above remained the same, mean weekly autochthonous DF incidence only increased 4.6-fold. In Townsville, the mean weekly incidence of autochthonous DF increased 10-fold when 3-week lagged moving average rainfall was ≥27 mm, but it only increased 1.8-fold when rainfall was <27 mm during January to June. Thus, we found different responses of autochthonous DF incidence to weather factors and imported DF cases in Townsville and Cairns. Imported DF cases may also trigger and enhance local outbreaks under favorable climate conditions.

Imported Dengue cases, weather variation and autochthonous Dengue incidence in Cairns, Australia

BACKGROUND Dengue fever (DF) outbreaks often arise from imported DF cases in Cairns, Australia. Few studies have incorporated imported DF cases in the estimation of the relationship between weather variability and incidence of autochthonous DF. The study aimed to examine the impact of weather variability on autochthonous DF infection after accounting for imported DF cases and then to explore the possibility of developing an empirical forecast system. METHODOLOGY/PRINCIPAL FINDS Data on weather variables, notified DF cases (including those acquired locally and overseas), and population size in Cairns were supplied by the Australian Bureau of Meteorology, Queensland Health, and Australian Bureau of Statistics. A time-series negative-binomial hurdle model was used to assess the effects of imported DF cases and weather variability on autochthonous DF incidence. Our results showed that monthly autochthonous DF incidences were significantly associated with monthly imported DF cases (Relative Risk (RR):1.52; 95% confidence interval (CI): 1.01-2.28), monthly minimum temperature ((o)C) (RR: 2.28; 95% CI: 1.77-2.93), monthly relative humidity (%) (RR: 1.21; 95% CI: 1.06-1.37), monthly rainfall (mm) (RR: 0.50; 95% CI: 0.31-0.81) and monthly standard deviation of daily relative humidity (%) (RR: 1.27; 95% CI: 1.08-1.50). In the zero hurdle component, the occurrence of monthly autochthonous DF cases was significantly associated with monthly minimum temperature (Odds Ratio (OR): 1.64; 95% CI: 1.01-2.67). CONCLUSIONS/SIGNIFICANCE Our research suggested that incidences of monthly autochthonous DF were strongly positively associated with monthly imported DF cases, local minimum temperature and inter-month relative humidity variability in Cairns. Moreover, DF outbreak in Cairns was driven by imported DF cases only under favourable seasons and weather conditions in the study.

A pilot study exploring Australian general practice nurses roles, responsibilities and professional development needs in well and sick child care

Aim Explore practice nurses' (PNs) role in child health and development, and advising parents about child health issues. Background Introduction of the four-year-old child health check into general practice in 2008 placed additional responsibilities on PNs in child health and wellness. This study explores their readiness to expand their practice into this area. Design Integrated mixed method design, self-report survey. Method A purpose-developed questionnaire explored demographics, child health roles and responsibilities, difficulties encountered, professional development needs, barriers and facilitators, and professional development activities undertaken in the past year. Surveys were posted to 218 PNs in one rural Division of General Practice (DGP) in Queensland, Australia; 29 responded. Results PNs reported a significant role in well and sick child care (93.1%) though few had a paediatric/child health background (14.3%). Roles included immunisations (92.3%), child health checks (65.4%), general child health and development (26.9%), asthma (23.1%), feeding (15.4%), fever (11.5%), settling/sleeping (11.5%). PNs were interested in learning more about (81.5%) and incorporating more child health into their practice (81.5%). Professional development in childhood growth and development (80.0%), health and illness (60.0%) and advising new mothers (20.0%) was needed. Conclusions PNs play a substantial role in child health, are unprepared for the complexities of this role and have preferred methods for undertaking professional development to address knowledge deficits. Implications for practice PNs are unprepared for an advanced role in child health and wellness. Significant gaps in their knowledge to support this role were identified. This ever-expanding role requires close monitoring to ensure knowledge precedes expectations to practice.

Cross-layer design for traffic management in wireless networked control systems

Wireless networked control systems (WNCSs) have been increasingly deployed in industrial applications. As they require timely data packet transmissions, it is difficult to make efficient use of the limited channel resources, particularly in contention based wireless networks in the layered network architecture. Aiming to maintain the WNCSs under critical real-time traffic condition at which the WNCSs marginally meet the real-time requirements, a cross-layer design (CLD) approach is presented in this paper to adaptively adjust the control period to achieve improved channel utilization while still maintaining effective and timely packet transmissions. The effectiveness of the proposed approach is demonstrated through simulation studies.

Dynamic spatiotemporal trends of dengue transmission in the Asia-Pacific region, 1955–2004

BACKGROUND: Dengue fever (DF) is one of the most important emerging arboviral human diseases. Globally, DF incidence has increased by 30-fold over the last fifty years, and the geographic range of the virus and its vectors has expanded. The disease is now endemic in more than 120 countries in tropical and subtropical parts of the world. This study examines the spatiotemporal trends of DF transmission in the Asia-Pacific region over a 50-year period, and identified the disease's cluster areas. METHODOLOGY AND FINDINGS: The World Health Organization's DengueNet provided the annual number of DF cases in 16 countries in the Asia-Pacific region for the period 1955 to 2004. This fifty-year dataset was divided into five ten-year periods as the basis for the investigation of DF transmission trends. Space-time cluster analyses were conducted using scan statistics to detect the disease clusters. This study shows an increasing trend in the spatiotemporal distribution of DF in the Asia-Pacific region over the study period. Thailand, Vietnam, Laos, Singapore and Malaysia are identified as the most likely clusters (relative risk = 13.02) of DF transmission in this region in the period studied (1995 to 2004). The study also indicates that, for the most part, DF transmission has expanded southwards in the region. CONCLUSIONS: This information will lead to the improvement of DF prevention and control strategies in the Asia-Pacific region by prioritizing control efforts and directing them where they are most needed.

Learning detectors quickly with stationary statistics

Computer vision is increasingly becoming interested in the rapid estimation of object detectors. The canonical strategy of using Hard Negative Mining to train a Support Vector Machine is slow, since the large negative set must be traversed at least once per detector. Recent work has demonstrated that, with an assumption of signal stationarity, Linear Discriminant Analysis is able to learn comparable detectors without ever revisiting the negative set. Even with this insight, the time to learn a detector can still be on the order of minutes. Correlation filters, on the other hand, can produce a detector in under a second. However, this involves the unnatural assumption that the statistics are periodic, and requires the negative set to be re-sampled per detector size. These two methods differ chie y in the structure which they impose on the co- variance matrix of all examples. This paper is a comparative study which develops techniques (i) to assume periodic statistics without needing to revisit the negative set and (ii) to accelerate the estimation of detectors with aperiodic statistics. It is experimentally verified that periodicity is detrimental.

The impact of heat waves on children's health : a systematic review

Young children are thought to be particularly sensitive to heatwaves, but relatively less research attention has been paid to this field to date. A systematic review was conducted to elucidate the relationship between heat waves and children’s health. Literature published up to August 2012 were identified using the following MeSH terms and keywords: “heatwave”, “heat wave”, “child health”, “morbidity”, “hospital admission”, “emergency department visit”, “family practice”, “primary health care”, “death” and “mortality”. Of the 628 publications identified, 12 met the selection criteria. The existing literature does not consistently suggest that mortality among children increases significantly during heat waves, even though infants were associated with more heat-related deaths. Exposure to heat waves in the perinatal period may pose a threat to children’s health. Pediatric diseases or conditions associated with heat waves include renal disease, respiratory disease, electrolyte imbalance and fever. Future research should focus on how to develop a consistent definition of a heat wave from a children’s health perspective, identifying the best measure of children’s exposure to heat waves, exploring sensitive outcome measures to quantify the impact of heat waves on children, evaluating the possible impacts of heat waves on children’s birth outcomes, and understanding the differences in vulnerability to heat waves among children of different ages and from different income countries. Projection of the children’s disease burden caused by heat waves under climate change scenarios, and development of effective heat wave mitigation and adaptation strategies that incorporate other child protective health measures, are also strongly recommended.