Ureaplasma parvum : understanding the complexities of intra-amniotic infection in an ovine model

The human Ureaplasma species are the most frequently isolated bacteria from the upper genital tract of pregnant women and can cause clinically asymptomatic, intra-uterine infections, which are difficult to treat with antimicrobials. Ureaplasma infection of the upper genital tract during pregnancy has been associated with numerous adverse outcomes including preterm birth, chorioamnionitis and neonatal respiratory diseases. The mechanisms by which ureaplasmas are able to chronically colonise the amniotic fluid and avoid eradication by (i) the host immune response and (ii) maternally-administered antimicrobials, remain virtually unexplored. To address this gap within the literature, this study investigated potential mechanisms by which ureaplasmas are able to cause chronic, intra-amniotic infections in an established ovine model. In this PhD program of research the effectiveness of standard, maternal erythromycin for the treatment of chronic, intra-amniotic ureaplasma infections was evaluated. At 55 days of gestation pregnant ewes received an intra-amniotic injection of either: a clinical Ureaplasma parvum serovar 3 isolate that was sensitive to macrolide antibiotics (n = 16); or 10B medium (n = 16). At 100 days of gestation, ewes were then randomised to receive either maternal erythromycin treatment (30 mg/kg/day for four days) or no treatment. Ureaplasmas were isolated from amniotic fluid, chorioamnion, umbilical cord and fetal lung specimens, which were collected at the time of preterm delivery of the fetus (125 days of gestation). Surprisingly, the numbers of ureaplasmas colonising the amniotic fluid and fetal tissues were not different between experimentally-infected animals that received erythromycin treatment or infected animals that did not receive treatment (p > 0.05), nor were there any differences in fetal inflammation and histological chorioamnionitis between these groups (p > 0.05). These data demonstrate the inability of maternal erythromycin to eradicate intra-uterine ureaplasma infections. Erythromycin was detected in the amniotic fluid of animals that received antimicrobial treatment (but not in those that did not receive treatment) by liquid chromatography-mass spectrometry; however, the concentrations were below therapeutic levels (<10 – 76 ng/mL). These findings indicate that the ineffectiveness of standard, maternal erythromycin treatment of intra-amniotic ureaplasma infections may be due to the poor placental transfer of this drug. Subsequently, the phenotypic and genotypic characteristics of ureaplasmas isolated from the amniotic fluid and chorioamnion of pregnant sheep after chronic, intra-amniotic infection and low-level exposure to erythromycin were investigated. At 55 days of gestation twelve pregnant ewes received an intra-amniotic injection of a clinical U. parvum serovar 3 isolate, which was sensitive to macrolide antibiotics. At 100 days of gestation, ewes received standard maternal erythromycin treatment (30 mg/kg/day for four days, n = 6) or saline (n = 6). Preterm fetuses were surgically delivered at 125 days of gestation and ureaplasmas were cultured from the amniotic fluid and the chorioamnion. The minimum inhibitory concentrations (MICs) of erythromycin, azithromycin and roxithromycin were determined for cultured ureaplasma isolates, and antimicrobial susceptibilities were different between ureaplasmas isolated from the amniotic fluid (MIC range = 0.08 – 1.0 mg/L) and chorioamnion (MIC range = 0.06 – 5.33 mg/L). However, the increased resistance to macrolide antibiotics observed in chorioamnion ureaplasma isolates occurred independently of exposure to erythromycin in vivo. Remarkably, domain V of the 23S ribosomal RNA gene (which is the target site of macrolide antimicrobials) of chorioamnion ureaplasmas demonstrated significant variability (125 polymorphisms out of 422 sequenced nucleotides, 29.6%) when compared to the amniotic fluid ureaplasma isolates and the inoculum strain. This sequence variability did not occur as a consequence of exposure to erythromycin, as the nucleotide substitutions were identical between chorioamnion ureaplasmas isolated from different animals, including those that did not receive erythromycin treatment. We propose that these mosaic-like 23S ribosomal RNA gene sequences may represent gene fragments transferred via horizontal gene transfer. The significant differences observed in (i) susceptibility to macrolide antimicrobials and (ii) 23S ribosomal RNA sequences of ureaplasmas isolated from the amniotic fluid and chorioamnion suggests that the anatomical site from which they were isolated may exert selective pressures that alter the socio-microbiological structure of the bacterial population, by selecting for genetic changes and altered antimicrobial susceptibility profiles. The final experiment for this PhD examined antigenic size variation of the multiple banded antigen (MBA, a surface-exposed lipoprotein and predicted ureaplasmal virulence factor) in chronic, intra-amniotic ureaplasma infections. Previously defined ‘virulent-derived’ and ‘avirulent-derived’ clonal U. parvum serovar 6 isolates (each expressing a single MBA protein) were injected into the amniotic fluid of pregnant ewes (n = 20) at 55 days of gestation, and amniotic fluid was collected by amniocentesis every two weeks until the time of near-term delivery of the fetus (at 140 days of gestation). Both the avirulent and virulent clonal ureaplasma strains generated MBA size variants (ranging in size from 32 – 170 kDa) within the amniotic fluid of pregnant ewes. The mean number of MBA size variants produced within the amniotic fluid was not different between the virulent (mean = 4.2 MBA variants) and avirulent (mean = 4.6 MBA variants) ureaplasma strains (p = 0.87). Intra-amniotic infection with the virulent strain was significantly associated with the presence of meconium-stained amniotic fluid (p = 0.01), which is an indicator of fetal distress in utero. However, the severity of histological chorioamnionitis was not different between the avirulent and virulent groups. We demonstrated that ureaplasmas were able to persist within the amniotic fluid of pregnant sheep for 85 days, despite the host mounting an innate and adaptive immune response. Pro-inflammatory cytokines (interleukin (IL)-1â, IL-6 and IL-8) were elevated within the chorioamnion tissue of pregnant sheep from both the avirulent and virulent treatment groups, and this was significantly associated with the production of anti-ureaplasma IgG antibodies within maternal sera (p < 0.05). These findings suggested that the inability of the host immune response to eradicate ureaplasmas from the amniotic cavity may be due to continual size variation of MBA surface-exposed epitopes. Taken together, these data confirm that ureaplasmas are able to cause long-term in utero infections in a sheep model, despite standard antimicrobial treatment and the development of a host immune response. The overall findings of this PhD project suggest that ureaplasmas are able to cause chronic, intra-amniotic infections due to (i) the limited placental transfer of erythromycin, which prevents the accumulation of therapeutic concentrations within the amniotic fluid; (ii) the ability of ureaplasmas to undergo rapid selection and genetic variation in vivo, resulting in ureaplasma isolates with variable MICs to macrolide antimicrobials colonising the amniotic fluid and chorioamnion; and (iii) antigenic size variation of the MBA, which may prevent eradication of ureaplasmas by the host immune response and account for differences in neonatal outcomes. The outcomes of this program of study have improved our understanding of the biology and pathogenesis of this highly adapted microorganism.

A fundamental numerical and theoretical study for the vibrational properties of nanowires

Based on the molecular dynamics (MD) simulation and the classical Euler-Bernoulli beam theory, a fundamental study of the vibrational performance of the Ag nanowire (NW) is carried out. A comprehensive analysis of the quality (Q)-factor, natural frequency, beat vibration, as well as high vibration mode is presented. Two excitation approaches, i.e., velocity excitation and displacement excitation, have been successfully implemented to achieve the vibration of NWs. Upon these two kinds of excitations, consistent results are obtained, i.e., the increase of the initial excitation amplitude will lead to a decrease to the Q-factor, and moderate plastic deformation could increase the first natural frequency. Meanwhile, the beat vibration driven by a single relatively large excitation or two uniform excitations in both two lateral directions is observed. It is concluded that the nonlinear changing trend of external energy magnitude does not necessarily mean a nonconstant Q-factor. In particular, the first order natural frequency of the Ag NW is observed to decrease with the increase of temperature. Furthermore, comparing with the predictions by Euler- Bernoulli beam theory, the MD simulation provides a larger and smaller first vibration frequencies for the clamped-clamped and clamped-free thin Ag NWs, respectively. Additionally, for thin NWs, the first order natural frequency exhibits a parabolic relationship with the excitation magnitudes. The frequencies of the higher vibration modes tend to be low in comparison to Euler-Bernoulli beam theory predictions. A combined initial excitation is proposed which is capable to drive the NW under a multi-mode vibration and arrows the coexistence of all the following low vibration modes. This work sheds lights on the better understanding of the mechanical properties of NWs and benefits the increasing utilities of NWs in diverse nano-electronic devices.

Management strategies to harness cultural diversity on Australian constructions sites : a social identity perspective

Construction sites around the world employ large numbers of people from diverse cultural backgrounds. The effective management of this cultural diversity has important implications for the productivity, safety, health and welfare of construction workers and for the performance and reputation of firms which employ them. The findings of a three year, multi-staged study of cultural diversity management practices on construction sites are critiqued using social identity theory. This reveals that so called "best-practice" diversity management strategies may have an opposite effect to that intended. It is concluded that the management of diversity on construction projects would benefit from being informed by social identity research.

Simulating a latent susceptible pool to examine the impact on cardiovascular mortality

The health effects of cold and hot temperatures are strongest in the frail and elderly. A large number of deaths in this "susceptible pool" after heat waves and cold snaps can cause mortality displacement, where an immediate increase in mortality is somewhat offset by a subsequent decrease in the following weeks. There may also be longer-term implications, as reductions in the pool caused by hot summers can reduce cold-related mortality in the following winter. A state-space model was used to simulate the numbers in the susceptible pool over time. We simulated the effects of harsh winters and heat waves, and varied the size of the susceptible pool. The larger the susceptible pool the smaller the mortality displacement. When 1% of the population were susceptible a harsh winter lead to an average of just 3 months of life lost per cold-related death, whereas a pool size of 10% meant that 24 months of life were lost per death. The impact of a cold spell on months of life lost was greater when the increased risk of death also applied to healthy people. The number of deaths caused by an August heat wave were reduced when there was a prior heat wave in June which reduced the susceptible pool. We were able to mimic some observed seasonal patterns in mortality using a simple state-space model. A better understanding of the size and dynamics of the susceptible pool will improve our understanding of the health effects of temperature.

Vertical particle concentration profiles around urban office buildings

Despite its role in determining both indoor and outdoor human exposure to anthropogenic particles, there is limited information describing vertical profiles of particle concentrations in urban environments, especially for ultrafine particles. Furthermore, the results of the few studies performed have been inconsistent. As such, this study aimed to assess the influence of vehicle emissions and nucleation formation on particle characteristics (particle number size distribution-PNSD and PM 2.5 concentration) at different heights around three urban office buildings located next to busy roads in Brisbane, Australia, and place these results in the broader context of the existing literature. Two sets of instruments were used to simultaneously measure PNSD, particle number (PN) and PM 2.5 concentrations, respectively, for up to three weeks at each building. The results showed that both PNSD and PM 2.5 concentration around building envelopes were influenced by vehicle emissions and new particle formation, and that they exhibited variability across the three different office buildings. During nucleation events, PN concentration in size range of <30 nm and total PN concentration increased (7-65% and 5-46%, respectively), while PM 2.5 concentration decreased (36-52%) with height. This study has shown an under acknowledged role for nucleation in producing particles that can affect large numbers of people, due to the high density and occupancy of urban office buildings and the fact that the vast majority of people's time is spent indoors. These findings highlight important new information related to the previously overlooked role of particle formation in the urban atmosphere and its potential effects on selection of air intake locations and appropriate filter types when designing or upgrading mechanical ventilation systems in urban office buildings. The results also serve to better define particle behaviour and variability around building envelopes, which has implications for studies of both human exposure and particle dynamics. © 2012 Author(s).

Tooth fracture risk analysis based on a new finite element dental structure models using micro-CT data

The finite element (FE) analysis is an effective method to study the strength and predict the fracture risk of endodontically-treated teeth. This paper presents a rapid method developed to generate a comprehensive tooth FE model using data retrieved from micro-computed tomography (μCT). With this method, the inhomogeneity of material properties of teeth was included into the model without dividing the tooth model into different regions. The material properties of the tooth were assumed to be related to the mineral density. The fracture risk at different tooth portions was assessed for root canal treatments. The micro-CT images of a tooth were processed by a Matlab software programme and the CT numbers were retrieved. The tooth contours were obtained with thresholding segmentation using Amira. The inner and outer surfaces of the tooth were imported into Solidworks and a three-dimensional (3D) tooth model was constructed. An assembly of the tooth model with the periodontal ligament (PDL) layer and surrounding bone was imported into ABAQUS. The material properties of the tooth were calculated from the retrieved CT numbers via ABAQUS user's subroutines. Three root canal geometries (original and two enlargements) were investigated. The proposed method in this study can generate detailed 3D finite element models of a tooth with different root canal enlargements and filling materials, and would be very useful for the assessment of the fracture risk at different tooth portions after root canal treatments.

Unsteady natural convection within a differentially heated enclosure of sinusoidal corrugated side walls

Numerically investigation of natural convection within a differentially heated modified square enclosure with sinusoidally corrugated side walls has been performed for different values of Rayleigh number. The fluid inside the enclosure considered is air and is quiescent, initially. The top and bottom surfaces are flat and considered as adiabatic. Results reveal three main stages: an initial stage, a transitory or oscillatory stage and a steady stage for the development of natural convection flow inside the corrugated cavity. The numerical scheme is based on the finite element method adapted to triangular non-uniform mesh element by a non-linear parametric solution algorithm. Investigation has been performed for the Rayleigh number, Ra ranging from 105 to 108 with variation of corrugation amplitude and frequency. Constant physical properties for the fluid medium have been assumed. Results have been presented in terms of the isotherms, streamlines, temperature plots, average Nusselt numbers, traveling waves and thermal boundary layer thickness plots, temperature and velocity profiles. The effects of sudden differential heating and its consequent transient behavior on fluid flow and heat transfer characteristics have been observed for the range of governing parameters. The present results show that the transient phenomena are greatly influenced by the variation of the Rayleigh Number with corrugation amplitude and frequency.

Engaging undergraduate nursing students in face-to-face tutorials

Chronic nursing shortages have placed increasing pressure on many nursing schools to recruit greater numbers of students with the consequence of larger class sizes. Larger class sizes have the potential to lead to student disengagement. This paper describes a case study that examined the strategies used by a group of nursing lecturers to engage students and to overcome passivity in a Bachelor of Nursing programme. A non-participant observer attended 20 tutorials to observe five academics deliver four tutorials each. Academics were interviewed both individually and as a group following the completion of all tutorial observations. All observations, field notes, interviews and focus groups were coded separately and major themes identified. From this analysis two broad categories emerged: getting students involved; and engagement as a struggle. Academics used a wide variety of techniques to interest and involve students. Additionally, academics desired an equal relationship with students. They believed that both they and the students had some power to influence the dynamics of tutorials and that neither party had ultimate power. The findings of this study serve to re-emphasise past literature which suggests that to engage students, the academics must also engage.

A novel SNP in COMT is associated with alcohol dependence but not opiate or nicotine dependence: a case control study

Background It is well established that COMT is a strong candidate gene for substance use disorder and schizophrenia. Recently we identified two SNPs in COMT (rs4680 and rs165774) that are associated with schizophrenia in an Australian cohort. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. Association of both rs4680 and rs165774 with substance dependence, a common comorbidity of schizophrenia has not been investigated. Methods To determine whether COMT is important in substance dependence, rs165774 and rs4680 were genotyped and haplotyped in patients with nicotine, alcohol and opiate dependence. Results The rs165774 SNP was associated with alcohol dependence. However, it was not associated with nicotine or opiate dependence. Individuals with alcohol dependence were more than twice as likely to carry the GG or AG genotypes compared to the AA genotype, indicating a dominant mode of inheritance. The rs4680 SNP showed a weak association with alcohol dependence at the allele level that did not reach significance at the genotype level but it was not associated with nicotine or opiate dependence. Analysis of rs165774/rs4680 haplotypes also revealed association with alcohol dependence with the G/G haplotype being almost 1.5 times more common in alcohol-dependent cases. Conclusions Our study provides further support for the importance of the COMT in alcohol dependence in addition to schizophrenia. It is possible that the rs165774 SNP, in combination with rs4680, results in a common molecular variant of COMT that contributes to schizophrenia and alcohol dependence susceptibility. This is potentially important for future studies of comorbidity. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

Ageing of people with an intellectual disability: Effective training for frontline workers

While the attainment of late life represents a significant achievement for people with an intellectual disability, increased life expectancy has resulted in growing concerns about the extent to which disability service providers are ready to meet the changing needs of increasing numbers of older people and facilitate their ongoing social inclusion. Training of frontline disability staff is widely accepted as an effective strategy for increasing organisational capacity to contribute to improved quality of life for people with an intellectual disability. The study identifies training needs analyses and 'ready-to-deliver' training programs for frontline disability services staff working with adults with an intellectual disability who are ageing, assesses whether the training programs contribute to improved quality of life outcomes for service users, and makes recommendations for future research and development of training for disability services staff who work with older people with intellectual disability.

Concentration and oxidative potential of on-road particle emissions and their relationship with traffic composition : Relevance to exposure assessment

Particles emitted by vehicles are known to cause detrimental health effects, with their size and oxidative potential among the main factors responsible. Therefore, understanding the relationship between traffic composition and both the physical characteristics and oxidative potential of particles is critical. To contribute to the limited knowledge base in this area, we investigated this relationship in a 4.5 km road tunnel in Brisbane, Australia. On-road concentrations of ultrafine particles (<100 nm, UFPs), fine particles (PM2.5), CO, CO2 and particle associated reactive oxygen species (ROS) were measured using vehicle-based mobile sampling. UFPs were measured using a condensation particle counter and PM2.5 with a DustTrak aerosol photometer. A new profluorescent nitroxide probe, BPEAnit, was used to determine ROS levels. Comparative measurements were also performed on an above-ground road to assess the role of emission dilution on the parameters measured. The profile of UFP and PM2.5 concentration with distance through the tunnel was determined, and demonstrated relationships with both road gradient and tunnel ventilation. ROS levels in the tunnel were found to be high compared to an open road with similar traffic characteristics, which was attributed to the substantial difference in estimated emission dilution ratios on the two roadways. Principal component analysis (PCA) revealed that the levels of pollutants and ROS were generally better correlated with total traffic count, rather than the traffic composition (i.e. diesel and gasoline-powered vehicles). A possible reason for the lack of correlation with HDV, which has previously been shown to be strongly associated with UFPs especially, was the low absolute numbers encountered during the sampling. This may have made their contribution to in-tunnel pollution largely indistinguishable from the total vehicle volume. For ROS, the stronger association observed with HDV and gasoline vehicles when combined (total traffic count) compared to when considered individually may signal a role for the interaction of their emissions as a determinant of on-road ROS in this pilot study. If further validated, this should not be overlooked in studies of on- or near-road particle exposure and its potential health effects.

The increased popularity of mopeds and motor scooters : exploring usage patterns and safety outcomes

Increased use of powered two-wheelers (PTWs) often underlies increases in the number of reported crashes, promoting research into PTW safety. PTW riders are overrepresented in crash and injury statistics relative to exposure and, as such, are considered vulnerable road users. PTW use has increased substantially over the last decade in many developed countries. One such country is Australia, where moped and scooter use has increased at a faster rate than motorcycle use in recent years. Increased moped use is particularly evident in the State of Queensland which is one of four Australian jurisdictions where moped riding is permitted for car licence holders and a motorcycle licence is not required. A moped is commonly a small motor scooter and is limited to a maximum design speed of 50 km/h and a maximum engine cylinder capacity of 50 cubic centimetres. Scooters exceeding either of these specifications are classed as motorcycles in all Australian jurisdictions. While an extensive body of knowledge exists on motorcycle safety, some of which is relevant to moped and scooter safety, the latter PTW types have received comparatively little focused research attention. Much of the research on moped safety to date has been conducted in Europe where they have been popular since the mid 20th century, while some studies have also been conducted in the United States. This research is of limited relevance to Australia due to socio-cultural, economic, regulatory and environmental differences. Moreover, while some studies have compared motorcycles to mopeds in terms of safety, no research to date has specifically examined the differences and similarities between mopeds and larger scooters, or between larger scooters and motorcycles. To address the need for a better understanding of moped and scooter use and safety, the current program of research involved three complementary studies designed to achieve the following aims: (1) develop better knowledge and understanding of moped and scooter usage trends and patterns; and (2) determine the factors leading to differences in moped, scooter and motorcycle safety. Study 1 involved six-monthly observations of PTW types in inner city parking areas of Queensland’s capital city, Brisbane, to monitor and quantify the types of PTW in use over a two year period. Study 2 involved an analysis of Queensland PTW crash and registration data, primarily comparing the police-reported crash involvement of mopeds, scooters and motorcycles over a five year period (N = 7,347). Study 3 employed both qualitative and quantitative methods to examine moped and scooter usage in two components: (a) four focus group discussions with Brisbane-based Queensland moped and scooter riders (N = 23); and (b) a state-wide survey of Queensland moped and scooter riders (N = 192). Study 1 found that of the PTW types parked in inner city Brisbane over the study period (N = 2,642), more than one third (36.1%) were mopeds or larger scooters. The number of PTWs observed increased at each six-monthly phase, but there were no significant changes in the proportions of PTW types observed across study phases. There were no significant differences in the proportions or numbers of PTW type observed by season. Study 2 revealed some important differences between mopeds, scooters and motorcycles in terms of safety and usage through analysis of crash and registration data. All Queensland PTW registrations doubled between 2001 and 2009, but there was an almost fifteen-fold increase in moped registrations. Mopeds subsequently increased as a proportion of Queensland registered PTWs from 1.2 percent to 8.8 percent over this nine year period. Moped and scooter crashes increased at a faster rate than motorcycle crashes over the five year study period from July 2003 to June 2008, reflecting their relatively greater increased usage. Crash rates per 10,000 registrations for the study period were only slightly higher for mopeds (133.4) than for motorcycles and scooters combined (124.8), but estimated crash rates per million vehicle kilometres travelled were higher for mopeds (6.3) than motorcycles and scooters (1.7). While the number of crashes increased for each PTW type over the study period, the rate of crashes per 10,000 registrations declined by 40 percent for mopeds compared with 22 percent for motorcycles and scooters combined. Moped and scooter crashes were generally less severe than motorcycle crashes and this was related to the particular crash characteristics of the PTW types rather than to the PTW types themselves. Compared to motorcycle and moped crashes, scooter crashes were less likely to be single vehicle crashes, to involve a speeding or impaired rider, to involve poor road conditions, or to be attributed to rider error. Scooter and moped crashes were more likely than motorcycle crashes to occur on weekdays, in lower speed zones and at intersections. Scooter riders were older on average (39) than moped (32) and motorcycle (35) riders, while moped riders were more likely to be female (36%) than scooter (22%) or motorcycle riders (7%). The licence characteristics of scooter and motorcycle riders were similar, with moped riders more likely to be licensed outside of Queensland and less likely to hold a full or open licence. The PTW type could not be identified in 15 percent of all cases, indicating a need for more complete recording of vehicle details in the registration data. The focus groups in Study 3a and the survey in Study 3b suggested that moped and scooter riders are a heterogeneous population in terms of demographic characteristics, riding experience, and knowledge and attitudes regarding safety and risk. The self-reported crash involvement of Study 3b respondents suggests that most moped and scooter crashes result in no injury or minor injury and are not reported to police. Study 3 provided some explanation for differences observed in Study 2 between mopeds and scooters in terms of crash involvement. On the whole, scooter riders were older, more experienced, more likely to have undertaken rider training and to value rider training programs. Scooter riders were also more likely to use protective clothing and to seek out safety-related information. This research has some important practical implications regarding moped and scooter use and safety. While mopeds and scooters are generally similar in terms of usage, and their usage has increased, scooter riders appear to be safer than moped riders due to some combination of superior skills and safer riding behaviour. It is reasonable to expect that mopeds and scooters will remain popular in Queensland in future and that their usage may further increase, along with that of motorcycles. Future policy and planning should consider potential options for encouraging moped riders to acquire better riding skills and greater safety awareness. While rider training and licensing appears an obvious potential countermeasure, the effectiveness of rider training has not been established and other options should also be strongly considered. Such options might include rider education and safety promotion, while interventions could also target other road users and urban infrastructure. Future research is warranted in regard to moped and scooter safety, particularly where the use of those PTWs has increased substantially from low levels. Research could address areas such as rider training and licensing (including program evaluations), the need for more detailed and reliable data (particularly crash and exposure data), protective clothing use, risks associated with lane splitting and filtering, and tourist use of mopeds. Some of this research would likely be relevant to motorcycle use and safety, as well as that of mopeds and scooters.

Combined VEGF and PDGF treatment reduces secondary degeneration after spinal cord injury

Trauma to the spinal cord creates an initial physical injury damaging neurons, glia, and blood vessels, which then induces a prolonged inflammatory response, leading to secondary degeneration of spinal cord tissue, and further loss of neurons and glia surrounding the initial site of injury. Angiogenesis is a critical step in tissue repair, but in the injured spinal cord angiogenesis fails; blood vessels formed initially later regress. Stabilizing the angiogenic response is therefore a potential target to improve recovery after spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) can initiate angiogenesis, but cannot sustain blood vessel maturation. Platelet-derived growth factor (PDGF) can promote blood vessel stability and maturation. We therefore investigated a combined application of VEGF and PDGF as treatment for traumatic spinal cord injury, with the aim to reduce secondary degeneration by promotion of angiogenesis. Immediately after hemisection of the spinal cord in the rat we delivered VEGF and PDGF and to the injury site. One and 3 months later the size of the lesion was significantly smaller in the treated group compared to controls, and there was significantly reduced gliosis surrounding the lesion. There was no significant effect of the treatment on blood vessel density, although there was a significant reduction in the numbers of macrophages/microglia surrounding the lesion, and a shift in the distribution of morphological and immunological phenotypes of these inflammatory cells. VEGF and PDGF delivered singly exacerbated secondary degeneration, increasing the size of the lesion cavity. These results demonstrate a novel therapeutic intervention for SCI, and reveal an unanticipated synergy for these growth factors whereby they modulated inflammatory processes and created a microenvironment conducive to axon preservation/sprouting.

ACE research briefing paper 005: Global Entrepreneurship Monitor (GEM) - Australia 2011 National Report

This report maps the current state of entrepreneurship in Australia using data from the Global Entrepreneurship Monitor (GEM) for the year 2011. Entrepreneurship is regarded as a crucial driver for economic well-being. Entrepreneurial activity in new and established firms drives innovation and creates jobs. Entrepreneurs also fuel competition thereby contributing indirectly to market and productivity growth along with improving competitiveness of the national economy. Given the economic landscape that exists as a result of the global financial crisis (GFC), it is probably more important than ever for us to understand the effects and drivers of entrepreneurial activity and attitudes in Australia. The central finding of this report is that entrepreneurship is certainly alive and well in Australia. With 10.5 per cent of the adult population involved in setting up a new business or owning a newly founded business as measured by the total entrepreneurial activity rate (TEA) in 2011, Australia ranks second only to the United States among the innovation-driven (developed) economies. Compared with 2010 the TEA rate has increased by 2.7 percentage points. Furthermore, in regard to employee entrepreneurial activity (EEA) rate in established firms, Australia ranks above average. According to GEM data, 5 per cent of the adult population is engaged in developing or launching new products, a new business unit or subsidiary for their employer. Further analysis of the GEM data also clearly shows that Australia compares well with other major economies in terms of the ‘quality’ of entrepreneurial activities being pursued. Indeed, it is not only the quantity of entrepreneurs but also the level of their aspirations and business goals that are important drivers for economic growth. On average, for each business started in Australia driven by the lack of alternatives for the founder to generate income from any other source, there are five other businesses started where the founders specifically want to take advantage of a business opportunity that they believe will increase their personal income or independence. With respect to innovativeness, 31 per cent of Australian new businesses offer products or services which they consider to be new to customers or where very few, or in some cases no, other businesses offer the same product or service. Both these indicators are higher than the average for innovation-driven economies. Somewhat below average is the international orientation of Australian entrepreneurs whereby only 12 per cent aim at having a substantial share of customers from international markets. So what drives this high quantity and quality of entrepreneurship in Australia? The analysis of the data suggests it is a combination of both business opportunities and entrepreneurial skills. It seems that around 50 per cent of the Australian population identify opportunities for a start-up venture and believe that they have the necessary skills to start a business. Furthermore, a large majority of the Australian population report that high media attention for entrepreneurship provides successful role models for prospective entrepreneurs. As a result, 12 per cent of our respondents have expressed the intention to start a business within the next three years. These numbers are all well above average when compared to the other major economies. With regard to gender, the GEM survey shows a high proportion of female entrepreneurs. Approximately 8.4 per cent of adult females are actually involved in setting up a business or have recently done so. Although this female TEA rate is slightly down from 2010, Australia ranks second among the innovation-driven economies. This paints a healthy picture of access to entrepreneurial opportunities for Australian women.