The synthesis of novel nitroxides and their application as small-molecule antioxidants and profluorescent probes for oxidative stress

The detection and potential treatment of oxidative stress in biological systems has been explored using isoindoline-based nitroxide radicals. A novel tetraethyl-fluorescein nitroxide was synthesised for its use as a profluorescent probe for redox processes in biological systems. This tetraethyl system, as well as a tetramethyl-fluorescein nitroxide, were shown to be sensitive and selective probes for superoxide in vitro. The redox environment of cellular systems was also explored using the tetramethylfluorescein species based on its reduction to the hydroxylamine. Flow cytometry was employed to assess the extent of nitroxide reduction, reflecting the overall cellular redox environment. Treatment of normal fibroblasts with rotenone and 2-deoxyglucose resulted in an oxidising cellular environment as shown by the lack of reduction of the fluorescein-nitroxide system. Assessment of the tetraethyl-fluorescein nitroxide system in the same way demonstrated its enhanced resistance to reduction and offers the potential to detect and image biologically relevant reactive oxygen species directly. Importantly, these profluorescent nitroxide compounds were shown to be more effective than the more widely used and commercially available probes for reactive oxygen species such as 2’,7’-dichlorodihydrofluorescein diacetate. Fluorescence imaging of the tetramethyl-fluorescein nitroxide and a number of other rhodamine-nitroxide derivatives was undertaken, revealing the differential cellular localisation of these systems and thus their potential for the detection of redox changes in specific cellular compartments. As well as developing novel methods for the detection of oxidative stress, a number of novel isoindoline nitroxides were synthesised for their potential application as small-molecule antioxidants. These compounds incorporated known pharmacophores into the isoindoline-nitroxide structure in an attempt to increase their efficacy in biological systems. A primary and a secondary amine nitroxide were synthesised which incorporated the phenethylamine backbone of the sympathomimetic amine class of drugs. Initial assessment of the novel primary amine derivative indicated a protective effect comparable to that of 5-carboxy-1,1,3,3- tetramethylisoindolin-2-yloxyl. Methoxy-substituted nitroxides were also synthesised as potential antioxidants for their structural similarity to some amphetamine type stimulants. A copper-catalysed methodology provided access to both the mono- and di-substituted methoxy-nitroxides. Deprotection of the ethers in these compounds using boron tribromide successfully produced a phenolnitroxide, however the catechol moiety in the disubstituted derivative appeared to undergo reaction with the nitroxide to produce quinone-like degradation products. A novel fluoran-nitroxide was also synthesised from the methoxy-substituted nitroxide, providing a pH-sensitive spin probe. An amino-acid precursor containing a nitroxide moiety was also synthesised for its application as a dual-action antioxidant. N-Acetyl protection of the nitroxide radical was necessary prior to the Erlenmeyer reaction with N-acetyl glycine. Hydrolysis and reduction of the azlactone intermediate produced a novel amino acid precursor with significant potential as an effective antioxidant.

Cystine-mediated oxidative defence in Lactobacillus reuteri BR11

Lactobacillus reuteri BR11 possesses an abundant cystine uptake (Cyu) ABC-transporter that was previously found to be involved in a novel mechanism of oxidative defence mediated by cystine. The current study aimed to elucidate this mechanism with a focus on the role of the co-transcribed cystathionine ã-lyase (Cgl). Growth studies of wild-type L. reuteri BR11 and mutants inactivated in cgl and the cystine-binding protein encoding gene cyuC showed that in contrast to the Cyu transporter, whose inactivation led to growth arrest in aerated cultures, Cgl is not crucial for oxidative defence. However, the role of Cgl in oxidative defence became apparent in the presence of severe oxidative damage and cysteine deprivation. Cysteine was found to be protective against oxidative stress, and the action of Cgl in both cysteine biosynthesis and degradation poses a seemingly futile pathway that deprives the intracellular cysteine pool. To further characterise the relationship between Cgl activity and cysteine and their roles in oxidative defence, enzymatic assays were performed on purified Cgl, and intracellular concentrations of cysteine, cystathionine and methionine were determined. Cgl was highly active towards cystine and cystathionine and less active towards cysteine in vitro, suggesting the main function of Cgl to be cysteine biosynthesis. Cysteine was found at high concentrations in the cell, but the levels were not significantly affected by inactivation of cgl or growth under aerobic conditions. It was concluded that both anabolic and catabolic activities of Cgl towards cysteine contribute to oxidative defence, the former by maintaining an intracellular reservoir of thiol analogous to glutathione, and the latter by producing H2S which is readily secreted, thus creating a reducing extracellular environment. The significance of the Cyu transporter to the physiology of L. reuteri BR11 prompted a phylogenetic study to determine its presence in bacteria. Orthologs of the Cyu transporter that are closest matches to the Cyu transporter are only limited to several species of Lactobacillus and Leuconostoc. Outside the Lactobacillales order, the closest matching orthologs belong to Proteobacteria, and there are more orthologs in Proteobacteria than non-Lactobacillales Firmicutes, suggesting that the Cyu transporter locus was present in the ancestor of the Proteobacteria and Firmicutes, and over evolutionary time has been lost or diverged in many Firmicutes. The clustering of the Cyu transporter locus with a gene encoding a Cgl family protein is even rarer. It was only found in L. reuteri, Lactobacillus vaginalis, Weissella paramesenteroides, the Lactobacillus casei group, and several Campylobacter sp. An accompanying phylogenetic study of L. reuteri BR11 using multi-locus sequence analysis showed that L. reuteri BR11 had diverged from more than 100 strains of L. reuteri isolated from various hosts and geographical locations. However, comparison with other Lactobacillus species supported the current classification of BR11 as L. reuteri. The most closely related species to L. reuteri is L. vaginalis or Lactobacillus antri, depending on the housekeeping gene used for analysis. The close evolutionary relationship of L. vaginalis to L. reuteri and the high degree of sequence identity between the cgl-cyuABC loci in both species suggest that the Cyu system is highly likely to perform similar functions in L. vaginalis. In search of other genes that function in oxidative defence, a number of mutants which were inactivated in genes that confer increased resistance to oxidative stress in other bacteria were constructed. The genes targeted were ahpC (peroxidase component of the alkyl hydroperoxide reductase system), tpx (thiol peroxidase), osmC (osmotically induced protein C), mntH (Mn2+/Fe2+ transporter), gshA (ã-glutamylcysteine synthetase) and msrA (methionine sulfoxide reductase). The ahpC and mntH mutants had slightly lower minimum inhibitory concentrations of organic peroxides, suggesting these genes might be involved in resistance to organic peroxides in L. reuteri. However, none of the mutants exhibited growth defects in aerated cultures, in stark contrast to the cyuC mutant. This may be due to compensatory functions of other genes, a hypothesis which cannot be tested until a robust protocol for constructing markerless multiple gene deletion mutants in L. reuteri is developed. These results highlight the importance of the Cyu transporter in oxidative defence and provide a foundation for extending the research of this system in other bacteria.

Double jeopardy : comorbid anxiety and depression in later life

Comorbid depression and anxiety in late life present challenges for geriatric mental health care providers. These challenges include identifying the often complex diagnostic presentations both clinically and in a research context. This potent comorbidity can be conceived as double jeopardy in older adults, further diminishing their quality of life. Geriatric health care providers need to understand psychiatric comorbidity of this type for accurate diagnosis and early referral to specialists, and to coordinate interdisciplinary care. Researchers in the field also need to recognize potential multiple impacts of comorbidities with respect to assessment and treatment domains. This article describes the prevalence of late-life depression and anxiety disorders and reviews studies on this comorbidity in older adults. Risk factors and protective factors for anxiety and depression in later life are reviewed, and information is provided about comparative symptoms, the selection of assessment tools, and challenges to the provision of interdisciplinary, evidence-based care.

Modest visual impairments and headlamp glare reduce pedestrian visability at night

Background: This study investigated the effects of experimentally induced visual impairment, headlamp glare and clothing on pedestrian visibility. Methods: 28 young adults (M=27.6±4.7 yrs) drove around a closed road circuit at night while pedestrians walked in place at the roadside. Pedestrians wore either black clothing, black clothing with a rectangular vest consisting of 1325 cm2 of retroreflective tape, or the same amount of tape positioned on the extremities in a configuration that conveyed biological motion (“biomotion”). Visual impairment was induced by goggles containing either blurring lenses, simulated cataracts, or clear lenses; visual acuity for the cataract and blurred lens conditions was matched. Drivers pressed a response pad when they first recognized that a pedestrian was present. Sixteen participants drove around the circuit in the presence of headlamp glare while twelve drove without glare. Results: Visual impairment, headlamp glare and pedestrian clothing all significantly affected drivers’ ability to recognize pedestrians (p<0.05). The simulated cataracts were more disruptive than blur, even though acuity was matched across the two manipulations. Pedestrians were recognized more often and at longer distances when they wore “biomotion” clothing than either the vest or black clothing, even in the presence of visual impairment and glare. Conclusions: Drivers’ ability to see and respond to pedestrians at night is degraded by modest visual impairments even when vision meets driver licensing requirements; glare further exacerbates these effects. Clothing that includes retroreflective tape in a biological motion configuration is relatively robust to visual impairment and glare.

Perceptions of visability and conspicuity of biomotion clothing configuration for road workers at road work sites

Aims: This study determined whether the visibility benefits of positioning retroreflective strips in biological motion configurations were evident at real world road worker sites. ---------- Methods: 20 visually normal drivers (M=40.3 years) participated in this study that was conducted at two road work sites (one suburban and one freeway) on two separate nights. At each site, four road workers walked in place wearing one of four different clothing options: a) standard road worker night vest, b) standard night vest plus retroreflective strips on thighs, c) standard night vest plus retroreflective strips on ankles and knees, d) standard night vest plus retroreflective strips on eight moveable joints (full biomotion). Participants seated in stationary vehicles at three different distances (80m, 160m, 240m) rated the relative conspicuity of the four road workers using a series of a standardized visibility and ranking scales. ---------- Results: Adding retroreflective strips in the full biomotion configuration to the standard night vest significantly (p<0.001) enhanced perceptions of road worker visibility compared to the standard vest alone, or in combination with thigh retroreflective markings. These visibility benefits were evident at all distances and at both sites. Retroreflective markings at the ankles and knees also provided visibility benefits compared to the standard vest, however, the full biomotion configuration was significantly better than all of the other configurations. ---------- Conclusions: These data provide the first evidence that the benefits of biomotion retroreflective markings that have been previously demonstrated under laboratory and closed- and open-road conditions are also evident at real work sites.

Use of IEEE 1588-2008 for a sampled value process bus in transmission substations

IEC Technical Committee 57 (TC57) published a series of standards and technical reports for “Communication networks and systems for power utility automation” as the IEC 61850 series. Sampled value (SV) process buses allow for the removal of potentially lethal voltages and damaging currents inside substation control rooms and marshalling kiosks, reduce the amount of cabling required in substations, and facilitate the adoption of non-conventional instrument transformers. IEC 61850-9-2 provides an inter-operable solution to support multi-vendor process bus solutions. A time synchronisation system is required for a SV process bus, however the details are not defined in IEC 61850-9-2. IEEE Std 1588-2008, Precision Time Protocol version 2 (PTPv2), provides the greatest accuracy of network based time transfer systems, with timing errors of less than 100 ns achievable. PTPv2 is proposed by the IEC Smart Grid Strategy Group to synchronise IEC 61850 based substation automation systems. IEC 61850-9-2, PTPv2 and Ethernet are three complementary protocols that together define the future of sampled value digital process connections in substations. The suitability of PTPv2 for use with SV is evaluated, with preliminary results indicating that steady state performance is acceptable (jitter < 300 ns), and that extremely stable grandmaster oscillators are required to ensure SV timing requirements are met when recovering from loss of external synchronisation (such as GPS).

Anticipated behaviours of emergency prehospital medical care providers during an influenza pandemic

Introduction: Emergency prehospital medical care providers are frontline health workers during emergencies. However, little is known about their attitudes, perceptions, and likely behaviors during emergency conditions. Understanding these attitudes and behaviors is crucial to mitigating the psychological and operational effects of biohazard events such as pandemic influenza, and will support the business continuity of essential prehospital services. ----- ----- Problem: This study was designed to investigate the association between knowledge and attitudes regarding avian influenza on likely behavioral responses of Australian emergency prehospital medical care providers in pandemic conditions. ----- ----- Methods: Using a reply-paid postal questionnaire, the knowledge and attitudes of a national, stratified, random sample of the Australian emergency prehospital medical care workforce in relation to pandemic influenza were investigated. In addition to knowledge and attitudes, there were five measures of anticipated behavior during pandemic conditions: (1) preparedness to wear personal protective equipment (PPE); (2) preparedness to change role; (3) willingness to work; and likely refusal to work with colleagues who were exposed to (4) known and (5) suspected influenza. Multiple logistic regression models were constructed to determine the independent predictors of each of the anticipated behaviors, while controlling for other relevant variables. ----- ----- Results: Almost half (43%) of the 725 emergency prehospital medical care personnel who responded to the survey indicated that they would be unwilling to work during pandemic conditions; one-quarter indicated that they would not be prepared to work in PPE; and one-third would refuse to work with a colleague exposed to a known case of pandemic human influenza. Willingness to work during a pandemic (OR = 1.41; 95% CI = 1.0–1.9), and willingness to change roles (OR = 1.44; 95% CI = 1.04–2.0) significantly increased with adequate knowledge about infectious agents generally. Generally, refusal to work with exposed (OR = 0.48; 95% CI = 0.3–0.7) or potentially exposed (OR = 0.43; 95% CI = 0.3–0.6) colleagues significantly decreased with adequate knowledge about infectious agents. Confidence in the employer’s capacity to respond appropriately to a pandemic significantly increased employee willingness to work (OR = 2.83; 95% CI = 1.9–4.1); willingness to change roles during a pandemic (OR = 1.52; 95% CI = 1.1–2.1); preparedness to wear PPE (OR = 1.68; 95% CI = 1.1–2.5); and significantly decreased the likelihood of refusing to work with colleagues exposed to (suspected) influenza (OR = 0.59; 95% CI = 0.4–0.9). ----- ----- Conclusions:These findings indicate that education and training alone will not adequately prepare the emergency prehospital medical workforce for a pandemic. It is crucial to address the concerns of ambulance personnel and the perceived concerns of their relationship with partners in order to maintain an effective prehospital emergency medical care service during pandemic conditions.

Test and evaluation system for multi-protocol sampled value protection schemes

Proposed transmission smart grids will use a digital platform for the automation of substations operating at voltage levels of 110 kV and above. The IEC 61850 series of standards, released in parts over the last ten years, provide a specification for substation communications networks and systems. These standards, along with IEEE Std 1588-2008 Precision Time Protocol version 2 (PTPv2) for precision timing, are recommended by the both IEC Smart Grid Strategy Group and the NIST Framework and Roadmap for Smart Grid Interoperability Standards for substation automation. IEC 61850-8-1 and IEC 61850-9-2 provide an inter-operable solution to support multi-vendor digital process bus solutions, allowing for the removal of potentially lethal voltages and damaging currents from substation control rooms, a reduction in the amount of cabling required in substations, and facilitates the adoption of non-conventional instrument transformers (NCITs). IEC 61850, PTPv2 and Ethernet are three complementary protocol families that together define the future of sampled value digital process connections for smart substation automation. This paper describes a specific test and evaluation system that uses real time simulation, protection relays, PTPv2 time clocks and artificial network impairment that is being used to investigate technical impediments to the adoption of SV process bus systems by transmission utilities. Knowing the limits of a digital process bus, especially when sampled values and NCITs are included, will enable utilities to make informed decisions regarding the adoption of this technology.

The social context of motorcycle riding and the key determinants influencing rider behaviour : a qualitative investigation

Objective: Given the increasing popularity of motorcycle riding and heightened risk of injury or death associated with being a rider, this study explored rider behaviour as a determinant of rider safety and, in particular, key beliefs and motivations which influence such behaviour. To enhance the effectiveness of future education and training interventions, it is important to understand riders’ own views about what influences how they ride. Specifically, this study sought to identify key determinants of riders’ behaviour in relation to the social context of riding including social and identity-related influences relating to the group (group norms and group identity) as well as the self (moral/personal norm and self-identity). ----- ----- Method: Qualitative research was undertaken via group discussions with motorcycle riders (n = 41). Results: The findings revealed that those in the group with which one rides represent an important source of social influence. Also, the motorcyclist (group) identity was associated with a range of beliefs, expectations, and behaviours considered to be normative. Exploration of the construct of personal norm revealed that riders were most cognizant of the “wrong things to do” when riding; among those issues raised was the importance of protective clothing (albeit for the protection of others and, in particular, pillion passengers). Finally, self-identity as a motorcyclist appeared to be important to a rider’s self-concept and was likely to influence their on-road behaviour. ----- ----- Conclusion: Overall, the insight provided by the current study may facilitate the development of interventions including rider training as well as public education and mass media messages. The findings suggest that these interventions should incorporate factors associated with the social nature of riding in order to best align it with some of the key beliefs and motivations underpinning riders’ on-road behaviours.

Transcutaneous immunization with novel lipid-based adjuvants induces protection against gastric Helicobacter pylori infection

The development of vaccines to combat pathogens that infect across mucosal surfaces has been a major goal of vaccine research. Successful mucosal vaccination requires the co-administration of adjuvants that can overcome the state of immune tolerance normally associated with mucosal application of proteins. In the case of oral immunization, delivery systems are also required to protect vaccine antigens against destruction by gastric pH and digestive enzymes. Furthermore, adjuvants used for mucosal delivery must be free of neurotoxic effects like those induced by the commonly used experimental mucosal adjuvant cholera toxin. Maintenance of the "cold chain" is also essential for the effectiveness of any vaccine and adjuvants/delivery systems that enhance the stability of a vaccine would offer a significant advantage. Needle-free methods of vaccination that induce protective immunity at multiple mucosal surfaces are also desirable for rapid vaccination of large populations. In the present study we show that transcutaneous immunization (TCI) using Lipid C, a novel lipid-based matrix originally developed for oral immunization, containing soluble Helicobacter sonicate significantly reduces the gastric bacterial burden in mice following gastric challenge with live Helicobacter pylori. Protection is associated with the production of splenic gamma interferon and gastric IgA and was achieved without the co-administration of potent and potentially toxic adjuvants, although protection was further enhanced by inclusion of CpG-ODN and cholera toxin in the lipid delivery system.

The link between belongingness and depressive symptoms: An exploration in the workplace interpersonal context

Interpersonal factors are crucial to a deepened understanding of depression. Belongingness, also referred to as connectedness, has been established as a strong risk/protective factor for depressive symptoms. To elucidate this link it may be beneficial to investigate the relative importance of specific psychosocial contexts as belongingness foci. Here we investigate the construct of workplace belongingness. Employees at a disability services organisation (N = 125) completed measures of depressive symptoms, anxiety symptoms, workplace belongingness and organisational commitment. Psychometric analyses, including Horn's parallel analyses, indicate that workplace belongingness is a unitary, robust and measurable construct. Correlational data indicate a substantial relationship with depressive symptoms (r = −.54) and anxiety symptoms (r = −.39). The difference between these correlations was statistically significant, supporting the particular importance of belongingness cognitions to the etiology of depression. Multiple regression analyses support the hypothesis that workplace belongingness mediates the relationship between affective organisational commitment and depressive symptoms. It is likely that workplaces have the potential to foster environments that are intrinsically less depressogenic by facilitating workplace belongingness. From a clinical perspective, cognitions regarding the workplace psychosocial context appear to be highly salient to individual psychological health, and hence warrant substantial attention.

Illegal street racing and associated (hooning) behaviours

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.

Fitness and fatness in childhood obesity : implications of physical activity

Overweight and obesity are a significant cause of poor health worldwide, particularly in conjunction with low levels of physical activity (PA). PA is health-protective and essential for the physical growth and development of children, promoting physical and psychological health while simultaneously increasing the probability of remaining active as an adult. However, many obese children and adolescents have a unique set of physiological, biomechanical, and neuromuscular barriers to PA that they must overcome. It is essential to understand the influence of these barriers on an obese child's motivation in order to exercise and tailor exercise programs to the special needs of this population. Chapter Outline • Introduction • Defining Physical Activity, Exercise, and Physical Fitness • Physical Activity, Physical Fitness, And Motor Competence In Obese Children • Physical Activity and Obesity in Children • Physical Fitness in Obese Children • Balance and Gait in Obese Children • Motor Competence in Obese Children • Physical Activity Guidelines for Obese Children • Clinical Assessment of the Obese Child • Physical Activity Characteristics: Mode • Physical Activity Characteristics: Intensity • Physical Activity Characteristics: Frequency • Physical Activity Characteristics: Duration • Conclusion

Protection of distributed generation interfaced networks

With the rapid increase in electrical energy demand, power generation in the form of distributed generation is becoming more important. However, the connections of distributed generators (DGs) to a distribution network or a microgrid can create several protection issues. The protection of these networks using protective devices based only on current is a challenging task due to the change in fault current levels and fault current direction. The isolation of a faulted segment from such networks will be difficult if converter interfaced DGs are connected as these DGs limit their output currents during the fault. Furthermore, if DG sources are intermittent, the current sensing protective relays are difficult to set since fault current changes with time depending on the availability of DG sources. The system restoration after a fault occurs is also a challenging protection issue in a converter interfaced DG connected distribution network or a microgrid. Usually, all the DGs will be disconnected immediately after a fault in the network. The safety of personnel and equipment of the distribution network, reclosing with DGs and arc extinction are the major reasons for these DG disconnections. In this thesis, an inverse time admittance (ITA) relay is proposed to protect a distribution network or a microgrid which has several converter interfaced DG connections. The ITA relay is capable of detecting faults and isolating a faulted segment from the network, allowing unfaulted segments to operate either in grid connected or islanded mode operations. The relay does not make the tripping decision based on only the fault current. It also uses the voltage at the relay location. Therefore, the ITA relay can be used effectively in a DG connected network in which fault current level is low or fault current level changes with time. Different case studies are considered to evaluate the performance of the ITA relays in comparison to some of the existing protection schemes. The relay performance is evaluated in different types of distribution networks: radial, the IEEE 34 node test feeder and a mesh network. The results are validated through PSCAD simulations and MATLAB calculations. Several experimental tests are carried out to validate the numerical results in a laboratory test feeder by implementing the ITA relay in LabVIEW. Furthermore, a novel control strategy based on fold back current control is proposed for a converter interfaced DG to overcome the problems associated with the system restoration. The control strategy enables the self extinction of arc if the fault is a temporary arc fault. This also helps in self system restoration if DG capacity is sufficient to supply the load. The coordination with reclosers without disconnecting the DGs from the network is discussed. This results in increased reliability in the network by reduction of customer outages.

Edaravone containing isoindoline nitroxides for the potential treatment of cardiovascular ischaemia

A novel antioxidant for the potential treatment of ischaemia was designed by incorporating an isoindoline nitroxide into the framework of the free radical scavenger edaravone. 5-(3-Methyl-pyrazol-5-ol-1-yl)-1,1,3,3-tetramethylisoindolin-2-yloxyl 7 was prepared by N-arylation of 3-methyl-5-pyrazolone with 5-iodo-1,1,3,3-tetramethylisoindoline-2-yloxyl 8 in the presence of catalytic copper(I)iodide. Evaluation of 7, its methoxyamine derivative 10 and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) against edaravone 1 in ischaemic rat atrial cardiomyocytes revealed significant decreases in cell death after prolonged ischaemia for each agent; however the protective effect of the novel antioxidant 7 (showing greater than 85% reduction in cell death at 100 μM) was significantly enhanced over that of edaravone 1 alone. Furthermore, the activity for 7 was found to be equal to or greater than the potent cardioprotective agent N6-cyclopentyladenosine (CPA). The methoxyamine adduct 10 and edaravone 1 showed no difference between the extent of reduction in cell death whilst CTMIO had only a modest protective effect.