968 resultados para Garnier, Louise Bary, 1836-


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In an Australian context, the term hooning refers to risky driving behaviours such as illegal street racing and speed trials, as well as behaviours that involve unnecessary noise and smoke, which include burn outs, donuts, fish tails, drifting and other skids. Hooning receives considerable negative media attention in Australia, and since the 1990s all Australian jurisdictions have implemented vehicle impoundment programs to deal with the problem. However, there is limited objective evidence of the road safety risk associated with hooning behaviours. Attempts to estimate the risk associated with hooning are limited by official data collection and storage practices, and the willingness of drivers to admit to their illegal behaviour in the event of a crash. International evidence suggests that illegal street racing is associated with only a small proportion of fatal crashes; however, hooning in an Australian context encompasses a broader group of driving behaviours than illegal street racing alone, and it is possible that the road safety risks will differ with these behaviours. There is evidence from North American jurisdictions that vehicle impoundment programs are effective for managing drink driving offenders, and drivers who continue to drive while disqualified or suspended both during and post-impoundment. However, these programs used impoundment periods of 30 – 180 days (depending on the number of previous offences). In Queensland the penalty for a first hooning offence is 48 hours, while the vehicle can be impounded for up to 3 months for a second offence, or permanently for a third or subsequent offence within three years. Thus, it remains unclear whether similar effects will be seen for hooning offenders in Australia, as no evaluations of vehicle impoundment programs for hooning have been published. To address these research needs, this program of research consisted of three complementary studies designed to: (1) investigate the road safety implications of hooning behaviours in terms of the risks associated with the specific behaviours, and the drivers who engage in these behaviours; and (2) assess the effectiveness of current approaches to dealing with the problem; in order to (3) inform policy and practice in the area of hooning behaviour. Study 1 involved qualitative (N = 22) and quantitative (N = 290) research with drivers who admitted engaging in hooning behaviours on Queensland roads. Study 2 involved a systematic profile of a large sample of drivers (N = 834) detected and punished for a hooning offence in Queensland, and a comparison of their driving and crash histories with a randomly sampled group of Queensland drivers with the same gender and age distribution. Study 3 examined the post-impoundment driving behaviour of hooning offenders (N = 610) to examine the effects of vehicle impoundment on driving behaviour. The theoretical framework used to guide the research incorporated expanded deterrence theory, social learning theory, and driver thrill-seeking perspectives. This framework was used to explore factors contributing to hooning behaviours, and interpret the results of the aspects of the research designed to explore the effectiveness of vehicle impoundment as a countermeasure for hooning. Variables from each of the perspectives were related to hooning measures, highlighting the complexity of the behaviour. This research found that the road safety risk of hooning behaviours appears low, as only a small proportion of the hooning offences in Study 2 resulted in a crash. However, Study 1 found that hooning-related crashes are less likely to be reported than general crashes, particularly when they do not involve an injury, and that higher frequencies of hooning behaviours are associated with hooning-related crash involvement. Further, approximately one fifth of drivers in Study 1 reported being involved in a hooning-related crash in the previous three years, which is comparable to general crash involvement among the general population of drivers in Queensland. Given that hooning-related crashes represented only a sub-set of crash involvement for this sample, this suggests that there are risks associated with hooning behaviour that are not apparent in official data sources. Further, the main evidence of risk associated with the behaviour appears to relate to the hooning driver, as Study 2 found that these drivers are likely to engage in other risky driving behaviours (particularly speeding and driving vehicles with defects or illegal modifications), and have significantly more traffic infringements, licence sanctions and crashes than drivers of a similar (i.e., young) age. Self-report data from the Study 1 samples indicated that Queensland’s vehicle impoundment and forfeiture laws are perceived as severe, and that many drivers have reduced their hooning behaviour to avoid detection. However, it appears that it is more common for drivers to have simply changed the location of their hooning behaviour to avoid detection. When the post-impoundment driving behaviour of the sample of hooning offenders was compared to their pre-impoundment behaviour to examine the effectiveness of vehicle impoundment in Study 3, it was found that there was a small but significant reduction in hooning offences, and also for other traffic infringements generally. As Study 3 was observational, it was not possible to control for extraneous variables, and is, therefore, possible that some of this reduction was due to other factors, such as a reduction in driving exposure, the effects of changes to Queensland’s Graduated Driver Licensing scheme that were implemented during the study period and affected many drivers in the offender sample due to their age, or the extension of vehicle impoundment to other types of offences in Queensland during the post-impoundment period. However, there was a protective effect observed, in that hooning offenders did not show the increase in traffic infringements in the post period that occurred within the comparison sample. This suggests that there may be some effect of vehicle impoundment on the driving behaviour of hooning offenders, and that this effect is not limited to their hooning driving behaviour. To be more confident in these results, it is necessary to measure driving exposure during the post periods to control for issues such as offenders being denied access to vehicles. While it was not the primary aim of this program of research to compare the utility of different theoretical perspectives, the findings of the research have a number of theoretical implications. For example, it was found that only some of the deterrence variables were related to hooning behaviours, and sometimes in the opposite direction to predictions. Further, social learning theory variables had stronger associations with hooning. These results suggest that a purely legal approach to understanding hooning behaviours, and designing and implementing countermeasures designed to reduce these behaviours, are unlikely to be successful. This research also had implications for policy and practice, and a number of recommendations were made throughout the thesis to improve the quality of relevant data collection practices. Some of these changes have already occurred since the expansion of the application of vehicle impoundment programs to other offences in Queensland. It was also recommended that the operational and resource costs of these laws should be compared to the road safety benefits in ongoing evaluations of effectiveness to ensure that finite traffic policing resources are allocated in a way that produces maximum road safety benefits. However, as the evidence of risk associated with the hooning driver is more compelling than that associated with hooning behaviour, it was argued that the hooning driver may represent the better target for intervention. Suggestions for future research include ongoing evaluations of the effectiveness of vehicle impoundment programs for hooning and other high-risk driving behaviours, and the exploration of additional potential targets for intervention to reduce hooning behaviour. As the body of knowledge regarding the factors contributing to hooning increases, along with the identification of potential barriers to the effectiveness of current countermeasures, recommendations for changes in policy and practice for hooning behaviours can be made.

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A bioassay technique, based on surface-enhanced Raman scattering (SERS) tagged gold nanoparticles encapsulated with a biotin functionalised polymer, has been demonstrated through the spectroscopic detection of a streptavidin binding event. A methodical series of steps preceded these results: synthesis of nanoparticles which were found to give a reproducible SERS signal; design and synthesis of polymers with RAFT-functional end groups able to encapsulate the gold nanoparticle. The polymer also enabled the attachment of a biotin molecule functionalised so that it could be attached to the hybrid nanoparticle through a modular process. Finally, the demonstrations of a positive bioassay for this model construct using streptavidin/biotin binding. The synthesis of silver and gold nanoparticles was performed by using tri-sodium citrate as the reducing agent. The shape of the silver nanoparticles was quite difficult to control. Gold nanoparticles were able to be prepared in more regular shapes (spherical) and therefore gave a more consistent and reproducible SERS signal. The synthesis of gold nanoparticles with a diameter of 30 nm was the most reproducible and these were also stable over the longest periods of time. From the SERS results the optimal size of gold nanoparticles was found to be approximately 30 nm. Obtaining a consistent SERS signal with nanoparticles smaller than this was particularly difficult. Nanoparticles more than 50 nm in diameter were too large to remain suspended for longer than a day or two and formed a precipitate, rendering the solutions useless for our desired application. Gold nanoparticles dispersed in water were able to be stabilised by the addition of as-synthesised polymers dissolved in a water miscible solvent. Polymer stabilised AuNPs could not be formed from polymers synthesised by conventional free radical polymerization, i.e. polymers that did not possess a sulphur containing end-group. This indicated that the sulphur-containing functionality present within the polymers was essential for the self assembly process to occur. Polymer stabilization of the gold colloid was evidenced by a range of techniques including, visible spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and Raman spectroscopy. After treatment of the hybrid nanoparticles with a series of SERS tags, focussing on 2-quinolinethiol the SERS signals were found to have comparable signal intensity to the citrate stabilised gold nanoparticles. This finding illustrates that the stabilization process does not interfere with the ability of gold nanoparticles to act as substrates for the SERS effect. Incorporation of a biotin moiety into the hybrid nanoparticles was achieved through a =click‘ reaction between an alkyne-functionalised polymer and an azido-functionalised biotin analogue. This functionalized biotin was prepared through a 4-step synthesis from biotin. Upon exposure of the surface-bound streptavidin to biotin-functionalised polymer hybrid gold nanoparticles, then washing, a SERS signal was obtained from the 2-quinolinethiol which was attached to the gold nanoparticles (positive assay). After exposure to functionalised polymer hybrid gold nanoparticles without biotin present then washing a SERS signal was not obtained as the nanoparticles did not bind to the streptavidin (negative assay). These results illustrate the applicability of the use of SERS active functional-polymer encapsulated gold nanoparticles for bioassay application.

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The interoperable and loosely-coupled web services architecture, while beneficial, can be resource-intensive, and is thus susceptible to denial of service (DoS) attacks in which an attacker can use a relatively insignificant amount of resources to exhaust the computational resources of a web service. We investigate the effectiveness of defending web services from DoS attacks using client puzzles, a cryptographic countermeasure which provides a form of gradual authentication by requiring the client to solve some computationally difficult problems before access is granted. In particular, we describe a mechanism for integrating a hash-based puzzle into existing web services frameworks and analyze the effectiveness of the countermeasure using a variety of scenarios on a network testbed. Client puzzles are an effective defence against flooding attacks. They can also mitigate certain types of semantic-based attacks, although they may not be the optimal solution.

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Chlamydia trachomatis is a major cause of sexually transmitted diseases worldwide. There currently is no vaccine to protect against chlamydial infection of the female reproductive tract. Vaccine development has predominantly involved using the murine model, however infection of female guinea pigs with Chlamydia caviae more closely resembles chlamydial infection of the human female reproductive tract, and presents a better model to assess potential human chlamydial vaccines. We immunised female guinea pigs intranasally with recombinant major outer membrane protein (r-MOMP) combined with CpG-10109 and cholera toxin adjuvants. Both systemic and mucosal immune responses were elicited in immunised animals. MOMP-specific IgG and IgA were present in the vaginal mucosae, and high levels of MOMP-specific IgG were detected in the serum of immunised animals. Antibodies from the vaginal mucosae were also shown to be capable of neutralising C. caviae in vitro. Following immunisation, animals were challenged intravaginally with a live C. caviae infection of 102 inclusion forming units. We observed a decrease in duration of infection and a significant (p<0.025) reduction in infection load in r-MOMP immunised animals, compared to animals immunised with adjuvant only. Importantly, we also observed a marked reduction in upper reproductive tract (URT) pathology in r-MOMP immunised animals. Intranasal immunisation of female guinea pigs with r-MOMP was able to provide partial protection against C. caviae infection, not only by reducing chlamydial burden but also URT pathology. This data demonstrates the value of using the guinea pig model to evaluate potential chlamydial vaccines for protection against infection and disease pathology caused by C. trachomatis in the female reproductive tract.

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There are approximately 92 million new chlamydial infections of the genital tract in humans diagnosed each year, costing health care systems billions of dollars in treatment not only of acute infections, but also of associated inflammatory sequelae, such as pelvic inflammatory disease (PID) and ectopic pregnancy. These numbers are increasing at a steady rate and, due to the asymptomatic nature of infections, the incidence may be underestimated and the costs of treatment therefore higher. Over the previous few decades there has been a large amount of research into the development of an efficacious vaccine against genital tract chlamydial infections. The majority of this research has focused on females, due to the high rate of development of associated diseases, including PID, which can lead to ectopic pregnancy and infertility. In light of the increasing infection rates that have occurred despite the availability of antibiotics, and the asymptomatic nature of chlamydial infections, it is imperative that an efficacious vaccine that protects against infection and associated pathology be developed.

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Infertility is a worldwide health problem with one in six couples suffering from this condition and with a major economic burden on the global healthcare industry. Estimates of the current global infertility rate suggest that 15% of couples are infertile (Zegers-Hochschild et al 2009) defined as: (1) failure to conceive after 12 months of unprotected sexual intercourse (i.e. infertility); (2) repeated implantation failure following ART cycles; or (3) recurrent miscarriage without difficulty conceiving (natural conceptions). Tubal factor infertility is among the leading causes of female factor infertility accounting for 7-9.8% of all female factor infertilities. Tubal disease directly causes from 36% to 85% of all cases of female factor infertility in developed and developing nations respectively and is associated with polymicrobial aetiologies. One of the leading global causes of tubal factor infertility is thought to be symptomatic (and asymptomatic in up to 70% cases) infection of the female reproductive tract with the sexually transmitted pathogen, Chlamydia trachomatis. Infection-related damage to the Fallopian tubes caused by Chlamydia accounts for more than 70% of cases of infertility in women from developing nations such as sub-Saharan Africa (Sharma et al 2009). Bacterial vaginosis, a condition associated with increased transmission of sexually transmitted infections including those caused by Neisseria gonorrhoeae and Mycoplasma genitalium is present in two thirds of women with pelvic inflammatory disease (PID). This review will focus on (1) the polymicrobial aetiologies of tubal factor infertility and (2) studies involved in screening for, and treatment and control of, Chlamydial infection to prevent PID and the associated sequelae of Fallopian tube inflammation that may lead to infertility and ectopic pregnancy.

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Female sex hormones are known to regulate the adaptive and innate immune functions of the female reproductive tract. This review aims to update our current knowledge of the effects of the sex hormones estradiol and progesterone in the female reproductive tract on innate immunity, antigen presentation, specific immune responses, antibody secretion, genital tract infections caused by Chlamydia trachomatis, and vaccine-induced immunity.

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Intrinsically photosensitive retinal ganglion cells (ipRGCs) in the eye transmit the environmental light level, projecting to the suprachiasmatic nucleus (SCN) (Berson, Dunn & Takao, 2002; Hattar, Liao, Takao, Berson & Yau, 2002), the location of the circadian biological clock, and the olivary pretectal nucleus (OPN) of the pretectum, the start of the pupil reflex pathway (Hattar, Liao, Takao, Berson & Yau, 2002; Dacey, Liao, Peterson, Robinson, Smith, Pokorny, Yau & Gamlin, 2005). The SCN synchronizes the circadian rhythm, a cycle of biological processes coordinated to the solar day, and drives the sleep/wake cycle by controlling the release of melatonin from the pineal gland (Claustrat, Brun & Chazot, 2005). Encoded photic input from ipRGCs to the OPN also contributes to the pupil light reflex (PLR), the constriction and recovery of the pupil in response to light. IpRGCs control the post-illumination component of the PLR, the partial pupil constriction maintained for > 30 sec after a stimulus offset (Gamlin, McDougal, Pokorny, Smith, Yau & Dacey, 2007; Kankipati, Girkin & Gamlin, 2010; Markwell, Feigl & Zele, 2010). It is unknown if intrinsic ipRGC and cone-mediated inputs to ipRGCs show circadian variation in their photon-counting activity under constant illumination. If ipRGCs demonstrate circadian variation of the pupil response under constant illumination in vivo, when in vitro ipRGC activity does not (Weng, Wong & Berson, 2009), this would support central control of the ipRGC circadian activity. A preliminary experiment was conducted to determine the spectral sensitivity of the ipRGC post-illumination pupil response under the experimental conditions, confirming the successful isolation of the ipRGC response (Gamlin, et al., 2007) for the circadian experiment. In this main experiment, we demonstrate that ipRGC photon-counting activity has a circadian rhythm under constant experimental conditions, while direct rod and cone contributions to the PLR do not. Intrinsic ipRGC contributions to the post-illumination pupil response decreased 2:46 h prior to melatonin onset for our group model, with the peak ipRGC attenuation occurring 1:25 h after melatonin onset. Our results suggest a centrally controlled evening decrease in ipRGC activity, independent of environmental light, which is temporally synchronized (demonstrates a temporal phase-advanced relationship) to the SCN mediated release of melatonin. In the future the ipRGC post-illumination pupil response could be developed as a fast, non-invasive measure of circadian rhythm. This study establishes a basis for future investigation of cortical feedback mechanisms that modulate ipRGC activity.

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Sing & Grow is an early intervention music therapy programme for families with children from birth to 3 years of age, who are socially, economically, or physically disadvantaged. It aims to improve parenting skills and confidence, promote positive parent–child interactions, stimulate child development, and provide social networking opportunities. Music and song activities are used in a therapeutic context to enhance parenting skills, improve parent–child interactions, provide essential developmental stimulation for children, promote social support for parenting, and strengthen links between parents and community services.

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Sing & Grow is a short term early intervention music therapy program for at risk families. Sing & Grow uses music to strengthen parent-child relationships by increasing positive parent-child interactions, assisting parents to bond with their children, and extending the repertoire of parents’ skills in relating to their child through interactive . Both the Australian and New Zealand governments are looking for evidence based research to highlight the effectiveness of funded programs in early childhood. As a government funded program, independent evaluation is a requirement of the delivery of the service. This paper explains the process involved in setting up and managing this large scale evaluation from engaging the evaluators and designing the project, to the data gathering stage. It describes the various challenges encountered and concludes that a highly collaborative and communicative partnership bet en researchers and clinicians is essential to ensure data can be gathered with minimal disturbance to clinical music therapy practice.

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The CDKN2A gene maps to chromosome 9p21-22 and is responsible for melanoma susceptibility in some families. Its product, p16, binds specifically to CDK4 and CDK6 in vitro and in vivo, inhibiting their kinase activity. CDKN2A is homozygously deleted or mutated in a large proportion of tumor cell lines and some primary tumors, including melanomas. The aim of this study was to investigate the involvement of CDKN2A and elucidate the mechanisms of p16 inactivation in a panel of 60 cell lines derived from sporadic melanomas. Twenty-six (43%) of the melanoma lines were homozygously deleted for CDKN2A, and an additional 15 (25%) lines carried missense, nonsense, or frameshift mutations. All but one of the latter group were shown by microsatellite analysis to be hemizygous for the region of 9p surrounding CDKN2A. p16 was detected by Western blotting in only five of the cell lines carrying mutations. Immunoprecipitation of p16 in these lines, followed by Western blotting to detect the coprecipitation of CDK4 and CDK6, revealed that p16 was functionally compromised in all cell lines but the one that carried a heterozygous CDKN2A mutation. In the remaining 19 lines that carried wild-type CDKN2A alleles, Western blot analysis and immunoprecipitation indicated that 11 cell lines expressed a wild-type protein. Northern blotting was performed on the remaining eight cell lines and revealed that one cell line carried an aberrantly sized RNA transcript, and two other cell lines failed to express RNA. The promoter was found to be methylated in five cell lines that expressed CDKN2A transcript but not p16. Presumably, the message seen by Northern blotting in these cell lines is the result of cross-hybridization of the total cDNA probe with the exon 1beta transcript. Microsatellite analysis revealed that the majority of these cell lines were hemi/homozygous for the region surrounding CDKN2A, indicating that the wild-type allele had been lost. In the 11 cell lines that expressed functional p16, microsatellite analysis revealed loss of heterozygosity at the markers immediately surrounding CDKN2A in five cases, and the previously characterized R24C mutation of CDK4 was identified in one of the remaining 6 lines. These data indicate that 55 of 60 (92%) melanoma cell lines demonstrated some aberration of CDKN2A or CDK4, thus suggesting that this pathway is a primary genetic target in melanoma development.