Therapeutic LMP1 polyepitope vaccine for EBV-assolciated Hodgkin disease and nasopharyngeal carcinoma

Development of an epitope-based vaccination strategy designed to enhance Epstein-Barr virus (EBV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) is increasingly being considered as a preferred approach for the treatment of EBV-associated relapsed Hodgkin disease (HD) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane proteins, LMP1 and LMP2, are the only target antigens available for therapeutic augmentation of CTL responses in patients with HD and NPC. Here, we describe preclinical studies using a recombinant poxvirus vaccine that encodes a polyepitope protein comprising 6 HLA A2-restricted epitopes derived from LMP1. Human cells infected with this recombinant polyepitope construct were efficiently recognized by LM1-specific CTL lines from HLAA2 healthy individuals. Furthermore, immunization of HLrA A2/K-b mice with this polyepitope vaccine consistently generated strong LMP1 -specific CTL responses to 5 of the. 6 epitopes, which were readily detected by both ex vivo and in vitro assays. More important, this polyepitope vaccine successfully reversed the outgrowth of LMP1-expressing tumors in HLA A2/Kb mice. These studies provide an important platform for the development of an LMP-based polyepitope vaccine as an immunotherapeutic tool for the treatment of EBV-associated HD and NPC. (C) 2003 by The American Society of Hematology.

Making developmental biology relevant to undergraduates in an era of economic rationalism in Australia

This report describes the road map we followed at our university to accommodate three main factors: financial pressure within the university system; desire to enhance the learning experience of undergraduates; and motivation to increase the prominence of the discipline of developmental biology in our university. We engineered a novel, multi-year undergraduate developmental biology program which was student-oriented, ensuring that students were continually exposed to the underlying principles and philosophy of this discipline throughout their undergraduate career. Among its key features are introductory lectures in core courses in the first year, which emphasize the relevance of developmental biology to tissue engineering, reproductive medicine, therapeutic approaches in medicine, agriculture and aquaculture. State-of-the-art animated computer graphics and images of high visual impact are also used. In addition, students are streamed into the developmental biology track in the second year, using courses like human embryology and courses shared with cell biology, which include practicals based on modern experimental approaches. Finally, fully dedicated third-year courses in developmental biology are undertaken in conjunction with stand-alone practical courses where students experience first-hand work in a research laboratory. Our philosophy is a cradle-to-grave approach to the education of undergraduates so as to prepare highly motivated, enthusiastic and well-educated developmental biologists for entry into graduate programs and ultimately post-doctoral research.

How does residue management impact soil organic matter composition and quality under Eucalyptus globulus plantations in southwestern Australia?

This study investigated the influence of harvest residue management practices on soil organic matter (SOM) composition and quality from two second-rotation Eucalyptus globulus plantations in southwestern Australia, using solid-state 13C nuclear magnetic resonance (NMR) spectroscopy with cross-polarisation and magic-angle-spinning (CPMAS). Soil samples (0–5 cm) were collected every 12 months for 5 years from two sites that had contrasting soil types and fertility. Harvest residue management treatments established at both sites were (a) no harvest residues; and (b) double harvest residues. The use of 13C CPMAS and DD NMR spectroscopy enabled the successful non-destructive detection of SOM quality changes in the two E. globulus plantations. Relative intensities of 13C CPMAS NMR spectral regions were similar at both sites, and for both harvest residue treatments, indicating that SOM composition was also similar. Dipolar dephasing (DD) NMR spectra revealed resonances in SOM assigned to lignin and tannin structures, with larger resonances in the carbonyl and alkyl C regions that were indicative of cuticular material, enabling detection of changes in SOM quality. Retention of double harvest residues on the soil surface increased the soil quality compared with removal of all harvest residues at both sites as indicated by the NMR aromaticities, but this was most noticeable at Manjimup, which had greater initial soil fertility.

Clinical and economic impact of exercise electrocardiography and exercise echocardiography in clinical practice

Background Patients with known or suspected coronary disease are often investigated to facilitate risk assessment. We sought to examine the cost-effectiveness of strategies based on exercise echocardiography and exercise electrocardiography. Methods and results We studied 7656 patients undergoing exercise testing; of whom half underwent exercise echocardiography. Risk was defined with the Duke treadmill score for those undergoing exercise electrocardiography alone, and by the extent of ischaemia by exercise echocardiography. Cox proportional hazards models, risk adjusted for pretest likelihood of coronary artery disease, were used to estimate time to cardiac death or myocardial infarction. Costs (including diagnostic and revascularisation procedures, hospitalisations, and events) were calculated, inflation-corrected to year 2000 using Medicare trust fund rates and discounted at a rate of 5%. A decision model was employed to assess the marginal cost effectiveness (cost/life year saved) of exercise echo compared with exercise electrocardiography. Exercise echocardiography identified more patients as low-risk (51% vs 24%, p<0.001), and fewer as intermediate- (27% vs 51%, p<0.001) and high-risk (22% vs 4%); survival was greater in low- and intermediate- risk and less in high-risk patients. Although initial procedural costs and revascularisation costs (in intermediate- high risk patients) were greater, exercise echocardiography was associated with a greater incremental life expectancy (0.2 years) and a lower use of additional diagnostic procedures when compared with exercise electrocardiography (especially in lower risk patients). Using decision analysis, exercise echocardiography (Euro 2615/life year saved) was more cost effective than exercise electrocardiography. Conclusion Exercise echocardiography may enhance cost-effectiveness for the detection and management of at risk patients with known or suspected coronary disease. (C) 2003 Published by Elsevier Science Ltd on behalf of The European Society of Cardiology.

Chapter 16: Prophylactic Human Papillomavirus Vaccines

Candidate prophylactic vaccines based on papillomavirus L1 virus-like particles (VLPs) are currently in human clinical trials. The main long-term goal of the vaccine is to reduce the incidence of cervical cancer and its precursors. In animal papillomavirus models, systemic immunization with L1 VLPs can induce high titers of neutralizing antibodies that confer protection against high-dose experimental papillomavirus challenge. In humans, systemic vaccination with L1 VLPs has been well tolerated and induced high serum antibody titers (at least 40 times higher than titers seen following natural infection). A recent proof of principle HPV16 L1 VLP efficacy trial has shown excellent protection against persistent HPV16 infection and associated cytological abnormalities. Large scale efficacy trials of L1 VLPs from HPV16 and 18 (the HPV types found most frequently in cervical cancer), with or without HPV6 and 11 (the HPV types responsible for most genital warts), are planned. If the results of these large trials support the encouraging results of the early trials, they should lead to a commercial prophylactic HPV vaccine. Implementation issues may include how to make the vaccine available in the developing world, where the majority of cervical cancer cases occur, the appropriate age of vaccination, and the role of male vaccination. Because a VLP vaccine is likely to provide type-specific protection, increasing the number of cancer-associated HPV types in the vaccine is a likely approach to broadening the protection to additional types. There will probably also be efforts to develop alternative vaccine formulations better suited to implementation in developing countries as well as attempts to develop vaccines with a therapeutic activity against established HPV infection because a combined prophylactic/therapeutic vaccine may be expected to have an even greater impact than a purely prophylactic vaccine on HPV induced disease.

A comprehensive insight into floc characteristics and their impact on compressibility and settleability of activated sludge

This paper presents a comprehensive study of sludge floc characteristics and their impact on compressibility and settleability of activated sludge in full scale wastewater treatment processes. The sludge flocs were characterised by morphological (floc size distribution, fractal dimension, filament index), physical (flocculating ability, viscosity, hydrophobicity and surface charge) and chemical (polymeric constituents and metal content) parameters. Compressibility and settleability were defined in terms of the sludge volume index (SVI) and zone settling velocity (ZSV). The floc morphological and physical properties had important influence on the sludge compressibility and settleability. Sludges containing large flocs and high quantities of filaments, corresponding to lower values of fractal dimension (D-f), demonstrated poor compressibility and settleability. Sludge flocs with high flocculating ability had lower SVI and higher ZSV, whereas high values of hydrophobicity, negative surface charge and viscosity of the sludge flocs correlated to high SVI and low ZSV. The quantity of the polymeric compounds protein. humic substances and carbohydrate in the sludge and the extracted extracellular polymeric substances (EPS) had significant positive correlations with SVI. The ZSV was quantitatively independent of the polymeric constituents. High concentrations of the extracted EPS were related to poor compressibility and settleability. The cationic ions Ca, Mg, Al and Fe in the sludge improved significantly the sludge compressibility and settleability. (C) 2003 Elsevier Science B.V. All rights reserved.

Therapeutic potential of venom peptides

Venomous animals have evolved a vast array of peptide toxins for prey capture and defence. These peptides are directed against a wide variety of pharmacological targets, making them an invaluable source of ligands for studying the properties of these targets in different experimental paradigms. A number of these peptides have been used in vivo for proof-of-concept studies, with several having undergone preclinical or clinical development for the treatment of pain, diabetes, multiple sclerosis and cardiovascular diseases. Here we survey the pharmacology of venom peptides and assess their therapeutic prospects.

Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months

CONTEXT: Despite more than 2 decades of outcomes research after very preterm birth, clinicians remain uncertain about the extent to which neonatal morbidities predict poor long-term outcomes of extremely low-birth-weight (ELBW) infants. OBJECTIVE: To determine the individual and combined prognostic effects of bronchopulmonary dysplasia (BPD), ultrasonographic signs of brain injury, and severe retinopathy of prematurity (ROP) on 18-month outcomes of ELBW infants. DESIGN: Inception cohort assembled for the Trial of Indomethacin Prophylaxis in Preterms (TIPP). SETTING AND PARTICIPANTS: A total of 910 infants with birth weights of 500 to 999 g who were admitted to 1 of 32 neonatal intensive care units in Canada, the United States, Australia, New Zealand, and Hong Kong between 1996 and 1998 and who survived to a postmenstrual age of 36 weeks. MAIN OUTCOME MEASURES: Combined end point of death or survival to 18 months with 1 or more of cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness. RESULTS: Each of the neonatal morbidities was similarly and independently correlated with a poor 18-month outcome. Odds ratios were 2.4 (95% confidence interval [CI], 1.8-3.2) for BPD, 3.7 (95% CI, 2.6-5.3) for brain injury, and 3.1 (95% CI, 1.9-5.0) for severe ROP. In children who were free of BPD, brain injury, and severe ROP the rate of poor long-term outcomes was 18% (95% CI, 14%-22%). Corresponding rates with any 1, any 2, and all 3 neonatal morbidities were 42% (95% CI, 37%-47%), 62% (95% CI, 53%-70%), and 88% (64%-99%), respectively. CONCLUSION: In ELBW infants who survive to a postmenstrual age of 36 weeks, a simple count of 3 common neonatal morbidities strongly predicts the risk of later death or neurosensory impairment.

Trends in physical activity participation and the impact of integrated campaigns among Australian adults, 1997-99

Objectives: To determine whether awareness of the moderate physical activity message and prevalence of participation changed among Australian adults between 1997 and 1999, and if changes differed across Australia. Methods: Data were compared on awareness of the moderate physical activity message and on physical activity participation from identical national physical activity surveys in 1997 and 1999. Results: In 1999, following integrated public health efforts, recognition of the Active Australia campaign was substantially higher in NSW/ACT (61.7%) than elsewhere (29.3%). Knowledge about benefits of moderate activity increased between 1997 and 1999, more so in States with public health campaigns. National participation in 'sufficient physical activity' declined between 1997 and 1999, from 63% to 57%, but the decline was smaller in NSW/ACT (4.4%) than in the other States (6.0%). Conclusions and implications: Declining trends in physical activity in Australia require increased public health investments, including strategic planning and public education, such as occurred in NSW (1997/98).

Impact of commercial fishing on Trindade Island and Martin Vaz Archipelago, Brazil : characteristics, conservation status of the species involved and prospects for preservation

Reportamos atividades de pesca comerciais no complexo insular mais afastado da costa brasileira: Ilha da Trindade e Arquipélago Martin Vaz. As atividades foram estudadas através de embarques e entrevistas com os mestres e pescadores das embarcações durante uma expedição cientifica realizada entre fevereiro e abril de 2007. Quatro modalidades de atividades de pesca são realizadas na região, capturando ao menos sete espécies que possuem algum risco de extinção. O estabelecimento de normas específicas de restrição para atividades que pescam sobre os recifes das ilhas é uma alternativa para a conservação das espécies ameaçadas. O monitoramento das embarcações pode ocorrer via satélite através do programa nacional de rastreamento de embarcações pesqueiras (PREPS).

Turkey's Accession to the European Union in terms of impact on the EU's security and defense policies: potential and drawbacks

This study explores the impact of Turkey's likely entry in the European Union (EU) in terms of the EU's foreign, security and defense policies. It reviews Turkish capabilities, namely its military capabilities, which could provide the EU with valuable defense assets. There are differences related to Turkey's relations with the EU, which have increasingly spilled over into the NATO, hindering the development of cooperation over crisis management operations. The article then delves in the implications of Turkey's strategic geographical location to EU policies. It reviews how far the EU and Turkey may have convergent interests in some of the neighboring regions, especially in the Middle East.