Vaccination strategies for the prevention of cervical cancer

Infection with high-risk human papillomaviruses (HPVs) is an essential step in the multistep process leading to cervical cancer. There are approximately 120 different types of HPV identified: of these, 18 are high-risk types associated with cervical cancer, with HPV-16 being the dominant type in most parts of the world. The major capsid protein of papillomavirus, produced in a number of expression systems, self assembles to form virus-like particles. Virus-like particles are the basis of the first generation of HPV vaccines presently being tested in clinical trials. Virus-like particles are highly immunogenic and afford protection from infection both in animal models and in Phase IIb clinical trials. A number of Phase III trials are in progress to determine if the vaccine will protect against cervical disease and, in some cases, genital warts. However, it is predicted that these vaccines will be too expensive for the developing world, where they are desperately needed. Another problem is that they will be type specific. Novel approaches to the production of virus-like particles in plants, second-generation vaccine approaches including viral and bacterial vaccine vectors and DNA vaccines, as well as different routes of immunization, are also reviewed. © 2005 Future Drugs Ltd.

Third International Conference on plant-based vaccines and antibodies

This relatively new biennial meeting - the first was in Prague in 2005 - was chaired by Julian Ma (Guy's Hospital, London, UK), with Mario Pezzotti (University of Verona, Italy) as local organizer, and attracted approximately 180 delegates from 25 countries. The theme was 'Plant Expression Systems for Recombinant Pharmacologics': there were 46 talks gathered into two plenaries, 12 themed sessions and 72 posters. Topics covered included publicly funded and commercial developments, innovation, regulation and commercialization, competition with conventional technology, manufacture and new products. © 2009 Expert Reviews Ltd.

Identification of long intergenic region sequences involved in maize streak virus replication

The main cis-acting control regions for replication of the single-stranded DNA genome of maize streak virus (MSV) are believed to reside within an approximately 310 nt long intergenic region (LIR). However, neither the minimum LIR sequence required nor the sequence determinants of replication specificity have been determined experimentally. There are iterated sequences, or iterons, both within the conserved inverted-repeat sequences with the potential to form a stem-loop structure at the origin of virion-strand replication, and upstream of the rep gene TATA box (the rep-proximal iteron or RPI). Based on experimental analyses of similar iterons in viruses from other geminivirus genera and their proximity to known Rep-binding sites in the distantly related mastrevirus wheat dwarf virus, it has been hypothesized that the iterons may be Rep-binding and/or -recognition sequences. Here, a series of LIR deletion mutants was used to define the upper bounds of the LIR sequence required for replication. After identifying MSV strains and distinct mastreviruses with incompatible replication-specificity determinants (RSDs), LIR chimaeras were used to map the primary MSV RSD to a 67 nt sequence containing the RPI. Although the results generally support the prevailing hypothesis that MSV iterons are functional analogues of those found in other geminivirus genera, it is demonstrated that neither the inverted-repeat nor RPI sequences are absolute determinants of replication specificity. Moreover, widely divergent mastreviruses can trans-replicate one another. These results also suggest that sequences in the 67 nt region surrounding the RPI interact in a sequence-specific manner with those of the inverted repeat.

Maize streak virus: An old and complex 'emerging' pathogen

Maize streak virus (MSV; Genus Mastrevirus, Family Geminiviridae) occurs throughout Africa, where it causes what is probably the most serious viral crop disease on the continent. It is obligately transmitted by as many as six leafhopper species in the Genus Cicadulina, but mainly by C. mbila Naudé and C. storeyi. In addition to maize, it can infect over 80 other species in the Family Poaceae. Whereas 11 strains of MSV are currently known, only the MSV-A strain is known to cause economically significant streak disease in maize. Severe maize streak disease (MSD) manifests as pronounced, continuous parallel chlorotic streaks on leaves, with severe stunting of the affected plant and, usuallly, a failure to produce complete cobs or seed. Natural resistance to MSV in maize, and/or maize infections caused by non-maize-adapted MSV strains, can result in narrow, interrupted streaks and no obvious yield losses. MSV epidemiology is primarily governed by environmental influences on its vector species, resulting in erratic epidemics every 3-10 years. Even in epidemic years, disease incidences can vary from a few infected plants per field, with little associated yield loss, to 100% infection rates and complete yield loss. Taxonomy: The only virus species known to cause MSD is MSV, the type member of the Genus Mastrevirus in the Family Geminiviridae. In addition to the MSV-A strain, which causes the most severe form of streak disease in maize, 10 other MSV strains (MSV-B to MSV-K) are known to infect barley, wheat, oats, rye, sugarcane, millet and many wild, mostly annual, grass species. Seven other mastrevirus species, many with host and geographical ranges partially overlapping those of MSV, appear to infect primarily perennial grasses. Physical properties: MSV and all related grass mastreviruses have single-component, circular, single-stranded DNA genomes of approximately 2700 bases, encapsidated in 22 × 38-nm geminate particles comprising two incomplete T = 1 icosahedra, with 22 pentameric capsomers composed of a single 32-kDa capsid protein. Particles are generally stable in buffers of pH 4-8. Disease symptoms: In infected maize plants, streak disease initially manifests as minute, pale, circular spots on the lowest exposed portion of the youngest leaves. The only leaves that develop symptoms are those formed after infection, with older leaves remaining healthy. As the disease progresses, newer leaves emerge containing streaks up to several millimetres in length along the leaf veins, with primary veins being less affected than secondary or tertiary veins. The streaks are often fused laterally, appearing as narrow, broken, chlorotic stripes, which may extend over the entire length of severely affected leaves. Lesion colour generally varies from white to yellow, with some virus strains causing red pigmentation on maize leaves and abnormal shoot and flower bunching in grasses. Reduced photosynthesis and increased respiration usually lead to a reduction in leaf length and plant height; thus, maize plants infected at an early stage become severely stunted, producing undersized, misshapen cobs or giving no yield at all. Yield loss in susceptible maize is directly related to the time of infection: Infected seedlings produce no yield or are killed, whereas plants infected at later times are proportionately less affected. Disease control: Disease avoidance can be practised by only planting maize during the early season when viral inoculum loads are lowest. Leafhopper vectors can also be controlled with insecticides such as carbofuran. However, the development and use of streak-resistant cultivars is probably the most effective and economically viable means of preventing streak epidemics. Naturally occurring tolerance to MSV (meaning that, although plants become systemically infected, they do not suffer serious yield losses) has been found, which has primarily been attributed to a single gene, msv-1. However, other MSV resistance genes also exist and improved resistance has been achieved by concentrating these within individual maiz genotypes. Whereas true MSV immunity (meaning that plants cannot be symptomatically infected by the virus) has been achieved in lines that include multiple small-effect resistance genes together with msv-1, it has proven difficult to transfer this immunity into commercial maize genotypes. An alternative resistance strategy using genetic engineering is currently being investigated in South Africa. Useful websites: 〈http://www.mcb.uct.ac.za/MSV/mastrevirus.htm〉; 〈http://www. danforthcenter.org/iltab/geminiviridae/geminiaccess/mastrevirus/Mastrevirus. htm〉. © 2009 Blackwell Publishing Ltd.

Corneal changes following short-term rigid contact lens wear

Purpose: The aim of this cross-over study was to investigate the changes in corneal thickness, anterior and posterior corneal topography, corneal refractive power and ocular wavefront aberrations, following the short term use of rigid contact lenses. Method: Fourteen participants wore 4 different types of contact lenses (RGP lenses of 9.5 mm and 10.5 mm diameter, and for comparison a PMMA lens of 9.5 mm diameter and a soft silicone hydrogel lens) on 4 different days for a period of 8 h on each day. Measures were collected before and after contact lens wear and additionally on a baseline day. Results: Anterior corneal curvature generally showed a flattening with both of the RGP lenses and a steepening with the PMMA lens. A significant negative correlation was found between the change in corneal swelling and central and peripheral posterior corneal curvature (all p ≤ 0.001). RGP contact lenses caused a significant decrease in corneal refractive power (hyperopic shift) of approximately 0.5 D. The PMMA contact lenses caused the greatest corneal swelling in both the central (27.92 ± 15.49 μm, p < 0.001) and peripheral (17.78 ± 12.11 μm, p = 0.001) corneal regions, a significant flattening of the posterior cornea and an increase in ocular aberrations (all p ≤ 0.05). Conclusion: The corneal swelling associated with RGP lenses was relatively minor, but there was slight central corneal flattening and a clinically significant hyperopic change in corneal refractive power after the first day of lens wear. The PMMA contact lenses resulted in significant corneal swelling and reduced optical performance of the cornea.

Monocular myopic defocus and daily changes in axial length and choroidal thickness of human eyes

Recent research indicates that brief periods (60 minutes) of monocular defocus lead to small but significant changes in human axial length. However, the effects of longer periods of defocus on the axial length of human eyes are unknown. We examined the influence of a 12 hour period of monocular myopic defocus on the natural daily variations occurring in axial length and choroidal thickness of young adult emmetropes. A series of axial length and choroidal thickness measurements (collected at ~3 hourly intervals, with the first measurement at ~9 am and the final measurement at ~9 pm) were obtained for 13 emmetropic young adults over three consecutive days. The natural daily rhythms (Day 1, baseline day, no defocus), the daily rhythms with monocular myopic defocus (Day 2, defocus day, +1.50 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, recovery day, no defocus) were all examined. Significant variations over the course of the day were observed in both axial length and choroidal thickness on each of the three measurement days (p<0.0001). The magnitude and timing of the daily variations in axial length and choroidal thickness were significantly altered with the monocular myopic defocus on day 2 (p<0.0001). Following the introduction of monocular myopic defocus, the daily peak in axial length occurred approximately 6 hours later, and the peak in choroidal thickness approximately 8.5 hours earlier in the day compared to days 1 and 3 (with no defocus). The mean amplitude (peak to trough) of change in axial length (0.030 ± 0.012 on day 1, 0.020 ± 0.010 on day 2 and 0.033 ± 0.012 mm on day 3) and choroidal thickness (0.030 ± 0.007 on day 1, 0.022 ± 0.006 on day 2 and 0.027 ± 0.009 mm on day 3) were also significantly different between the three days (both p<0.05). The introduction of monocular myopic defocus disrupts the daily variations in axial length and choroidal thickness of human eyes (in terms of both amplitude and timing) that return to normal the following day after removal of the defocus.

Educational and occupational outcomes amongst African men from refugee backgrounds living in urban and regional Southeast Queensland

Over the last ten years, approximately one third of refugee and humanitarian entrants to Australia have been adult men. To date, little research has been done on their health and settlement issues. Many of these men have come from the African continent. This paper reports on the educational and employment outcomes of a group of 173 recently arrived adult African men from refugee backgrounds who have settled in Southeast Queensland. Given the current government policy focus on regional resettlement, the paper compares key outcomes between the adult African men who settled in metropolitan Brisbane with those living in the Toowoomba-Gatton region. The study uses a peer interviewer model and a mixed method approach. Overall, we have found that African men who have settled in regional areas face significantly greater educational and occupational challenges than those who settled in the urban area. They report more negative experiences at educational institutions, are more likely to take jobs that are below their level of skills and qualifications, are more dissatisfied with their jobs, and report greater discrimination and difficulties while trying to secure adequate employment in Australia. A number of policy implications are discussed.

Food insecurity among adults residing in disadvantaged urban areas : potential health and dietary consequences

Objective: Food insecurity is the limited or uncertain availability or access to nutritionally-adequate, culturally-appropriate and safe foods. Food insecurity may result in inadequate dietary intakes, overweight or obesity and the development of chronic disease. Internationally, few studies have focused on the range of potential health outcomes related to food insecurity among adults residing in disadvantaged locations and no such Australian studies exist. The objective of this study was to investigate associations between food insecurity, socio-demographic and health factors and dietary intakes among adults residing in disadvantaged urban areas. Design: Data were collected by mail survey (n= 505, 53% response rate), which ascertained information about food security status, demographic characteristics (such as age, gender, household income, education) fruit and vegetable intakes, take-away and meat consumption, general health, depression and chronic disease. Setting: Disadvantaged suburbs of Brisbane city, Australia, 2009. Subjects: Individuals aged ≥ 20 years. Results: Approximately one-in-four households (25%) were food insecure. Food insecurity was associated with lower household income, poorer general health, increased healthcare utilisation and depression. These associations remained after adjustment for age, gender and household income. Conclusion: Food insecurity is prevalent in urbanised disadvantaged areas in developed countries such as Australia. Low-income households are at high risk of experiencing food insecurity. Food insecurity may result in significant health burdens among the population, and this may be concentrated in socioeconomically-disadvantaged suburbs.

BabelFuse data fusion unit with precision wireless clock synchronisation

A significant issue encountered when fusing data received from multiple sensors is the accuracy of the timestamp associated with each piece of data. This is particularly important in applications such as Simultaneous Localisation and Mapping (SLAM) where vehicle velocity forms an important part of the mapping algorithms; on fastmoving vehicles, even millisecond inconsistencies in data timestamping can produce errors which need to be compensated for. The timestamping problem is compounded in a robot swarm environment due to the use of non-deterministic readily-available hardware (such as 802.11-based wireless) and inaccurate clock synchronisation protocols (such as Network Time Protocol (NTP)). As a result, the synchronisation of the clocks between robots can be out by tens-to-hundreds of milliseconds making correlation of data difficult and preventing the possibility of the units performing synchronised actions such as triggering cameras or intricate swarm manoeuvres. In this thesis, a complete data fusion unit is designed, implemented and tested. The unit, named BabelFuse, is able to accept sensor data from a number of low-speed communication buses (such as RS232, RS485 and CAN Bus) and also timestamp events that occur on General Purpose Input/Output (GPIO) pins referencing a submillisecondaccurate wirelessly-distributed "global" clock signal. In addition to its timestamping capabilities, it can also be used to trigger an attached camera at a predefined start time and frame rate. This functionality enables the creation of a wirelessly-synchronised distributed image acquisition system over a large geographic area; a real world application for this functionality is the creation of a platform to facilitate wirelessly-distributed 3D stereoscopic vision. A ‘best-practice’ design methodology is adopted within the project to ensure the final system operates according to its requirements. Initially, requirements are generated from which a high-level architecture is distilled. This architecture is then converted into a hardware specification and low-level design, which is then manufactured. The manufactured hardware is then verified to ensure it operates as designed and firmware and Linux Operating System (OS) drivers are written to provide the features and connectivity required of the system. Finally, integration testing is performed to ensure the unit functions as per its requirements. The BabelFuse System comprises of a single Grand Master unit which is responsible for maintaining the absolute value of the "global" clock. Slave nodes then determine their local clock o.set from that of the Grand Master via synchronisation events which occur multiple times per-second. The mechanism used for synchronising the clocks between the boards wirelessly makes use of specific hardware and a firmware protocol based on elements of the IEEE-1588 Precision Time Protocol (PTP). With the key requirement of the system being submillisecond-accurate clock synchronisation (as a basis for timestamping and camera triggering), automated testing is carried out to monitor the o.sets between each Slave and the Grand Master over time. A common strobe pulse is also sent to each unit for timestamping; the correlation between the timestamps of the di.erent units is used to validate the clock o.set results. Analysis of the automated test results show that the BabelFuse units are almost threemagnitudes more accurate than their requirement; clocks of the Slave and Grand Master units do not di.er by more than three microseconds over a running time of six hours and the mean clock o.set of Slaves to the Grand Master is less-than one microsecond. The common strobe pulse used to verify the clock o.set data yields a positive result with a maximum variation between units of less-than two microseconds and a mean value of less-than one microsecond. The camera triggering functionality is verified by connecting the trigger pulse output of each board to a four-channel digital oscilloscope and setting each unit to output a 100Hz periodic pulse with a common start time. The resulting waveform shows a maximum variation between the rising-edges of the pulses of approximately 39¥ìs, well below its target of 1ms.

What are the implications of peri-urban agriculture on food security in Australian cities?

Background: Periurban agriculture refers to agricultural practice occurring in areas with mixed rural and urban features. It is responsible 25% of the total gross value of economic production in Australia, despite only comprising 3% of the land used for agriculture. As populations grows and cities expand, they are constantly absorbing surrounding fringe areas, thus creating a new fringe, further from the city causing the periurban region to constantly shift outwards. Periurban regions are fundamental in the provision of fresh food to city populations and residential (and industrial) expansion taking over agricultural land has been noted as a major worldwide concern. Another major concern around the increase in urbanisation and resultant decrease in periurban agriculture is its potential effect on food security. Food security is the availability or access to nutritionally-adequate, culturally-relevant and safe foods in culturally-appropriate ways. Thus food insecurity occurs when access to or availability of these foods is compromised. There is an important level of connectedness between food security and food production and a decrease in periurban agriculture may have adverse effects on food security. A decrease in local, seasonal produce may result in a decrease in the availability of products and an increase in cost, as food must travel greater distances, incurring extra costs present at the consumer level. Currently, few Australian studies exist examining the change in periurban agriculture over time. Such information may prove useful for future health policy and interventions as well as infrastructure planning. The aim of this study is to investigate changes in periurban agriculture among capital cities of Australia. Methods: We compared data pertaining to selected commodities from the Australian Bureau of Statistics 2000-01 and 2005 -2006 Agricultural Census. This survey is distributed online or via mail on a five-yearly basis to approximately 175,000 Agricultural business to ascertain information on a range of factors, such as types of crops, livestock and land preparation practices. For the purpose of this study we compared the land being used for total crops, and cereal , oil seed, legume, fruit and vegetable crops separately. Data was analysed using repeated measures anova in spss. Results: Overall, total area available for crops in urbanised areas of Australia increased slightly by 1.8%. However, Sydney, Melbourne, Adelaide and Perth experienced decreases in the area available for fruit crops by 11%, 5%,and 4% respectively. Furthermore, Brisbane and Perth experienced decreases in land available for vegetable crops by 28% and 14% respectively. Finally, Sydney, Adelaide and Perth experienced decreases in land available for cereal crops by 10 – 79%. Conclusions: These findings suggest that population increases and consequent urban sprawl may be resulting in a decrease in peri-urban agriculture, specifically for several core food groups including fruit, breads and grain based foods. In doing so, access to or availability of these foods may be limited, and the cost of these foods is likely to increase, which may compromise food insecurity for certain sub-groups of the population.

A virtual environment to simulate the experience of psychosis

Psychosis is a mental disorder that affects 1-2% of the population at some point in their lives. One of the main causes of psychosis is the mental illness schizophrenia. Sufferers of this illness often have terrifying symptoms such as hallucinations, delusions, and thought disorder. This project aims to develop a virtual environment to simulate the experience of psychosis, focusing on re-creating auditory and visual hallucinations. A model of a psychiatric ward was created and the psychosis simulation software was written to re-create the auditory and visual hallucinations of one particular patient. The patient was very impressed with the simulation, and commented that it effectively re-created the same emotions that she experienced on a day-to-day basis during her psychotic episodes. It is hoped that this work will result in a useful educational tool about schizophrenia, leading to improved training of clinicians, and fostering improved understanding and empathy toward sufferers of schizophrenia in the community, ultimately improving the quality of life and chances of recovery of patients.

Bioreactor for blood product production

The feasibility of ex vivo blood production is limited by both biological and engineering challenges. From an engineering perspective, these challenges include the significant volumes required to generate even a single unit of a blood product, as well as the correspondingly high protein consumption required for such large volume cultures. Membrane bioreactors, such as hollow fiber bioreactors (HFBRs), enable cell densities approximately 100-fold greater than traditional culture systems and therefore may enable a significant reduction in culture working volumes. As cultured cells, and larger molecules, are retained within a fraction of the system volume, via a semipermeable membrane it may be possible to reduce protein consumption by limiting supplementation to only this fraction. Typically, HFBRs are complex perfusion systems having total volumes incompatible with bench scale screening and optimization of stem cell-based cultures. In this article we describe the use of a simplified HFBR system to assess the feasibility of this technology to produce blood products from umbilical cord blood-derived CD34+ hematopoietic stem progenitor cells (HSPCs). Unlike conventional HFBR systems used for protein manufacture, where cells are cultured in the extracapillary space, we have cultured cells in the intracapillary space, which is likely more compatible with the large-scale production of blood cell suspension cultures. Using this platform we direct HSPCs down the myeloid lineage, while targeting a 100-fold increase in cell density and the use of protein-free bulk medium. Our results demonstrate the potential of this system to deliver high cell densities, even in the absence of protein supplementation of the bulk medium.

How do allied health professionals evaluate new models of care? What are we measuring and why?

The aim of this study was to identify what outcome measures or quality indicators are being used to evaluate advanced and new roles in nine allied health professions and whether the measures are evaluating outcomes of interest to the patient, the clinician, or the healthcare provider. A systematic search strategy was used. Medical and allied health databases were searched and relevant articles extracted. Relevant studies with at least 1 outcome measure were evaluated. A total of 106 articles were identified that described advanced roles, however, only 23 of these described an outcome measure in sufficient detail to be included for review. The majority of the reported measures fit into the economic and process categories. The most reported outcome related to patients was satisfaction surveys. Measures of patient health outcomes were infrequently reported. It is unclear from the studies evaluated whether new models of allied healthcare can be shown to be as safe and effective as traditional care for a given procedure. Outcome measures chosen to evaluate these services often reflect organizational need and not patient outcomes. Organizations need to ensure that high-quality performance measures are chosen to evaluate the success of new health service innovations. There needs to be a move away from in-house type surveys that add little or no valid evidence as to the effect of a new innovation. More importance needs to be placed on patient outcomes as a measure of the quality of allied health interventions.

Review of refugee mental health interventions following resettlement : best practice and recommendations

There are increasing numbers of refugees worldwide, with approximately 16 million refugees in 2007 and over 2.5 million refugees resettled in the United States since the start of its humanitarian program. Psychologists and other health professionals who deliver mental health services for individuals from refugee backgrounds need to have confidence that the therapeutic interventions they employ are appropriate and effective for the clients with whom they work. The current review briefly surveys refugee research, examines empirical evaluations of therapeutic interventions in resettlement contexts, and provides recommendations for best practices and future directions in resettlement countries. The resettlement interventions found to be most effective typically target culturally homogeneous client samples and demonstrate moderate to large outcome effects on aspects of traumatic stress and anxiety reduction. Further evaluations of the array of psychotherapeutic, psychosocial, pharmacological, and other therapeutic approaches, including psychoeducational and community-based interventions that facilitate personal and community growth and change, are encouraged. There is a need for increased awareness, training and funding to implement longitudinal interventions that work collaboratively with clients from refugee backgrounds through the stages of resettlement.

Micromarrows—Three-dimensional coculture of hematopoietic stem cells and mesenchymal stromal cells

Hematopoietic stem cell (HSC) transplant is a well established curative therapy for some hematological malignancies. However, achieving adequate supply of HSC from some donor tissues can limit both its application and ultimate efficacy. The theory that this limitation could be overcome by expanding the HSC population before transplantation has motivated numerous laboratories to develop ex vivo expansion processes. Pioneering work in this field utilized stromal cells as support cells in cocultures with HSC to mimic the HSC niche. We hypothesized that through translation of this classic coculture system to a three-dimensional (3D) structure we could better replicate the niche environment and in turn enhance HSC expansion. Herein we describe a novel high-throughput 3D coculture system where murine-derived HSC can be cocultured with mesenchymal stem/stromal cells (MSC) in 3D microaggregates—which we term “micromarrows.” Micromarrows were formed using surface modified microwells and their ability to support HSC expansion was compared to classic two-dimensional (2D) cocultures. While both 2D and 3D systems provide only a modest total cell expansion in the minimally supplemented medium, the micromarrow system supported the expansion of approximately twice as many HSC candidates as the 2D controls. Histology revealed that at day 7, the majority of bound hematopoietic cells reside in the outer layers of the aggregate. Quantitative polymerase chain reaction demonstrates that MSC maintained in 3D aggregates express significantly higher levels of key hematopoietic niche factors relative to their 2D equivalents. Thus, we propose that the micromarrow platform represents a promising first step toward a high-throughput HSC 3D coculture system that may enable in vitro HSC niche recapitulation and subsequent extensive in vitro HSC self-renewal.