Portable spectroscopy system for ultra-sensitive, real-time measurement of breath ethane

This thesis describes the development, characterisation and application of a portable spectroscopy system for ultra-sensitive, real-time detection of breath ethane. In healthcare, breath ethane is a widely accepted marker of free radical-induced cell damage and may be used to indicate changes in oxidative stress. The aim was to deliver a compact instrument capable of long-term, on-site use in a clinical environment, while also retaining the high performance previously achieved by lab-based systems at the University of Glasgow. The newly developed instrument has a sensitivity of 70 parts per trillion with a 1 Hz sampling rate. The system incorporates a cryogenicallycooled lead-salt laser and uses a second derivative wavelength modulation detection scheme. A thermally-managed closed-loop refrigeration system has eliminated the need for liquid coolants. The instrument has been field-tested to ensure target performance is sustained in a range of environments, both indoor and outdoor. It has since been used in a number of pilot clinical studies, both off-site and on-site, in which breath ethane was monitored as a marker of oxidative stress. The three main clinical areas investigated were dialysis, radiotherapy and intensive care. In the intensive care study, the instrument was modified to enable automatic breath sampling of inspired and expired gases of ventilated patients. This technique proved highly successful and the instrument then remained at the Southern General hospital, where it continued to be used as part of a wider study into breath ethane in intensive care patients. The use of the new spectroscopy system has enabled ultra-sensitive, rapid analysis of a large number of breath samples. The use of the new instrument, in particular for continual breath monitoring, has enabled the detection of short-lived fluctuations in breath ethane, yielding some interesting findings in a number of pilot clinical studies. Our results suggest that breath ethane may be used as an indicator of dynamic changes in oxidative stress. Further studies will be required to determine if such monitoring is of clinical benefit. Chapter 1 gives a general introduction to spectroscopy and some background to our project. A number of spectroscopic techniques and laser sources are discussed, along with a review of previous work in ethane detection. In chapter 2 some background theory of molecular spectroscopy is given, with a more detailed discussion of the wavelength modulation technique. Chapter 3 describes in detail the development of the portable spectroscopy system. The achieved performance and factors contributing to this performance are discussed in chapter 4. The field test of the instrument is reported on in chapter 5. In chapter 6 the application of the technology to breath analysis and the current challenges in this field are discussed. Example breath ethane measurements for healthy controls are provided. The clinical pilot studies conducted using the new system in areas of dialysis, intensive care and radiotherapy are discussed in chapters 7, 8, and 9 respectively. Chapter 10 contains the thesis summary and conclusions, with suggestions for future work

The Use of an Integrated Geographical Information System at South African Airports

The use of Geographic Information Systems (GIS) has, over the past few years, become an integral component of the operations at all airports owned and/or operated by the Airports Company South Africa (ACSA). What has however been lacking, is the application of this technology to practically manage and reduce risks out on the airfield. ACSA Bird and Wildlife Management has recently initiated a programme to utilize GIS and global positioning systems (GPS) on their airfields and all ACSA Wildlife Control Officers (WCOs) are now using handheld mobile computers with integrated GPS to record information and track their patrols out on the airfield. This integrated system allows for the recording of biological data such as bird or wildlife presence, as well as the recording of hazards such as standing water, termite nests, fence breaks, grass which needs cutting, and the presence of foreign object debris. A built-in e-mail system allows for rapid and precise information sharing as the presence of hazards are marked on a grid cell map. The reporting system allows for real time feedback to management meetings and adaptive problem management. The system also allows for the manual capturing of information regarding routes and observations without using the handheld GPS unit. This will be especially useful for smaller airports with a lower risk profile and where Fire and Rescue personnel record the information in the absence of dedicated WCOs. An additional advantage of the system is that it has been designed in a manner that allows for the development and integration of other management and reporting systems such as grass-cutting management tools, runway inspection reports, fence security patrols and weather data which will greatly enhance the proactive management steps taken at the airports

Driver knowledge and attitudes on animal vehicle collisions in Northern Tanzania

Roads are a major cause of wildlife mortality by animal-vehicle-collisions (AVCs). We monitored the patterns and frequency of AVCs on two sections of a major highway in Northern Tanzania and compared these patterns to the knowledge and perceptions of drivers who frequently use the roads. While actual field survey showed that more birds were killed by AVCs, mammals were perceived by the drivers to be the most common AVC. Drivers were indifferent to whether AVCs were a major problem on the road, and 67% strongly felt that AVCs were mainly accidental, either due to high vehicle speed or poor visibility at night. There was a negative correlation between the likelihood of a species being hit by vehicles and its average body mass. Only 35% of drivers said they had attended an educational program related to the impact of roads on wildlife. This study highlights a need for collaborative efforts between the wildlife conservation and road departments to educate road users on the importance of driving responsibly and exercising due care for wildlife and human safety. This should be coupled with effective mitigation measures to reduce the extent of AVCs

Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously-injected polymeric microsphere suspension formulations

Purpose: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such systems is still in its infancy. Methods: Suspension formulation physicochemical attributes may impact particulate deposition in subcutaneous (s.c.) tissue. Hence, the utility of synchrotron X-ray microcomputed tomography (μCT) for assessment of spatial distribution of suspension formulation components (PLG microspheres and vehicle) was evaluated in a porcine s.c. tissue model. Optical imaging of dyed vehicle and subsequent microscopic assessment of microsphere deposition was performed in parallel to compare the two approaches. Results: Our findings demonstrate that synchrotron μCT can be applied to the assessment of microsphere and vehicle distribution in s.c. tissue, and that microspheres can also be visualised in the absence of contrast agent using this approach. The technique was deemed superior to optical imaging of macrotomy for the characterisation of microsphere deposition owing to its non-invasive nature and relatively rapid data acquisition time. Conclusions: The μCT method outlined in this study provides a novel insight into the relative distribution of vehicle and suspended PLG microspheres following s.c. injection. A potential application for our findings is understanding the impact of injection, device and formulation variables on initial and temporal depot geometry in pre-clinical or ex-vivo models that can inform product design

The Impact of Visual Field Loss on Driving Skills: A Systematic Narrative Review

Purpose: To review the evidence on the impact of visual field loss on skills required for driving. Methods: A literature search was undertaken using a systematic approach. Papers within scope were identified by two independent reviewers, and papers were grouped into similar themes for discussion. Key findings: Evidence suggests that both binocular and monocular visual field defects have a negative impact on driving skills. Both central and peripheral cause difficulties, but the degree of impact is dependent on the defect severity and compensation ability. Many factors that affect compensation to visual field loss and the effects of visual field loss on driving skills are discussed, including cognitive status, age and duration of visual field loss. In summary, in central visual field loss compensation, strategies include reduction of overall driving speed; whereas, in peripheral field loss, increased scanning is reported to aid adaptation. Conclusions: For driving, there is evidence that complete and/or binocular visual field loss poses more of a difficulty than partial and/or monocular loss, and central defects cause more problems than peripheral defects. A lack of evidence exists concerning the impact of superior versus inferior defects. The level of peripheral vision loss that is incompatible with safe driving remains unknown, as compensation abilities vary widely between individuals. This review highlights a lack of evidence in relation to the impact of visual field loss on driving skills. Further research is required to strengthen the evidence to allow clinicians to better support people with visual field loss with driving advice

CONSTRAINING THE ANGULAR MOMENTUM EVOLUTION OF V455 ANDROMEDAE

Time-series photometry on the cataclysmic variable V455 Andromedae (hereafter V455 And, HS 2331+3905) reveals a rotation period shorter than the orbital period, implying the presence of a magnetic field. We expect that this magnetic field channels the accreted matter from the disk toward the white dwarf poles, classifying it as an Intermediate Polar. The two polar spinning emission areas are visible in the lightcurves at the rotation period of 67.61970396 ± 0.00000072 s, and its harmonic. Using photometric observations of V455 And obtained from 2007 October to 2015, we derive 3σ upper limits to the rate of change of the spin harmonic (SH) with time to be dPSH/dt ≤ −7.5 × 10−15 s s−1 employing the O–C method, and −5.4 × 10−15 s s−1 with a direct nonlinear least squares fit. There is no significant detection of a changing spin period for the duration of 2007 October–2015. The 3σ upper limit for the rate of change of spin period with time is dPspin/dt ≤ −10.8 × 10−15 s s−1 or −0.34 μs yr−1. V455 And underwent a large-amplitude dwarf nova outburst in 2007 September. The pre-outburst data reflect a period 4.8 ± 2.2 μs longer than the best-fit post-outburst spin period. The angular momentum gained by the white dwarf from matter accreted during outburst and its slight subsequent shrinking should both cause the star to spin slightly faster after the outburst. We estimate that the change in spin period due to the outburst should be 5 μs, consistent with the empirical determination of 4.8 ± 2.2 μs (3σ upper limit of 11.4 μs)

Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects

Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes

Improving effective contraception uptake through provision of bridging contraception within community pharmacies:findings from The Bridge-it Study process evaluation

OBJECTIVE: To present process evaluation results from the Bridge-it Study, a pragmatic cluster randomised cross-over trial to improve effective contraception uptake through provision of the progestogen only pill (POP) plus sexual and reproductive health (SRH) clinic rapid-access to women presenting to community pharmacies for emergency contraception (EC). RESEARCH DESIGN AND METHODS: A multimethod process evaluation was conducted to assess intervention implementation, mechanisms of change and contextual factors. Data were gathered from screening logs (n=599), observations of pharmacist training, analysis of data from 4-month follow-up questionnaires (n=406), monitoring of contemporaneous events and qualitative interviews with 22 pharmacists, 5 SRH clinical staff and 36 study participants in three participating UK sites in Lothian, Tayside and London. RESULTS: The intervention was largely delivered as intended and was acceptable. Pharmacists’, SRH clinical staff and participants’ accounts highlighted that providing a supply of POP with EC from the pharmacy as routine practice may have positive impacts on contraceptive practices in the short term, and potentially longer term. Key mechanisms of change included ease of access, increased awareness of contraception and services, and greater motivation and perceptions of self-efficacy. Few participants took up the offer to attend an SRH service (rapid-access component), and existing barriers within the SRH context were apparent (eg, lack of staff). Participant accounts highlight persistent barriers to accessing and using routine effective contraception remain. CONCLUSIONS: Implementation appeared to be acceptable and feasible, highlighting the potential for provision of POP within EC consultations as routine practice in community pharmacies. However, lack of engagement with the rapid access component of the intervention and existing barriers within the SRH context suggest that signposting to SRH services may be sufficient. Wider implementation should consider ways to address key implementation challenges to increase effectiveness and sustainability, and to overcome persistent barriers to accessing and using effective contraception. TRIAL REGISTRATION NUMBER: ISRCTN70616901

Population-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence Settings

Background:HIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and Findings:A transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8-15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.Conclusion:Providing safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated. © 2013 Dimitrov et al