Development towards a point-of-care system to monitor pregnancy and fertility biomarkers

The aim of this thesis was to develop a point of care (POC) device that could monitor progesterone and oestriol in saliva. These hormones have a key role to play in both female fertility and pregnancy. Understanding the concentration of progesterone in the body is key to understanding a patient’s fertility and pregnancy status. Combining progesterone and oestriol detection can give valuable insight into when labour may commence during pregnancy. This can be achieved by measuring the progesterone to oestriol ratio in saliva samples, throughout the pregnancy progesterone is the more dominant hormone but a few weeks before labour oestriol becomes the more dominant hormone. Saliva was chosen as the biological sample due to the ease of collection as well as it providing a better chemical understanding of the active hormonal concentrations compared to blood. Typical levels in saliva are 100 ng mL⁻¹ for progesterone and 0 - 5 ng mL⁻¹ for oestriol.The work presented began with the design of a chemiluminescence immunoassay which could be translated onto a microfluidic device, this approach would provide both good sensitivity and selectivity. Chemiluminescence was chosen as a detection system due to the high sensitivities that can be achieved with simple instrumentation where a CCD camera could be used to also obtain spatial information. The CL assay involved the chemical immobilisation of the antibodies onto glass slides. Silanisation with (3-aminopropyl)triethoxysilane (APTES) in combination with a N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide/N-hydroxysulfosuccinimide (EDC/sulfo-NHS) linker proved the most successful immobilisation method, with a LOD of 33 ±3 pg mL⁻¹ being achieved for progesterone in 10 mM phosphate buffered saline (PBS). This method however lacked reproducibility and did not transfer well on to polymer substrates or the microfluidic devices due to problems with the antibody immobilisation procedure. Immobilisation of anti-progesterone was then investigated on a range of electrode surfaces (Au, glassy carbon and ITO). This immobilisation procedure involved electrochemically depositing nitrobenzene onto the electrode surface followed by an electrochemical reduction of the nitro groups to the corresponding amine. To allow electrochemical detection ferrocene was tagged to the anti-progesterone antibodies to give a redox tag. The antibodies were then immobilised through an EDC/sulfo-NHS linkage. This method proved to be successful and very reproducible. By tagging ferrocene onto the antibody a rigid structure was achieved during the immobilisation procedure allowing the ideal antibody orientation, this process also allowed quantification of the concentration of antibodies on the surface (4.46 x10⁻⁷ mol m⁻²). Electrochemical based immunoassays were successfully carried with a 15 min incubation time for progesterone giving LODs of 1 pg mL⁻¹ for the gold and glassy carbon and 0.1 pg mL⁻¹ for the ITO. The ITO performed better than the other materials due to the electrode being uniformly flat enabling more efficient surface modifications. The methodology was also translated for use with artificial saliva with a LOD of 1.7 pg mL⁻¹ for progesterone.Once the electrochemical immobilisation platform had been shown to be successful this was taken forward as a potential route to carry out a CL immunoassay. This novel approach utilised the oxidised ferrocene tag on the antibody as the catalyst for the luminol CL reaction. A static system was devised in which the antibodies had been immobilised on to ITO using the electrochemical approach and the CL reagents added by pipette, LODs of 2.35 and 2.54 pg mL⁻¹ were obtained for progesterone and oestriol respectively in saliva after a 30 min incubation time. The static system could therefore be used as a POC device for these hormones meeting the aims of this thesis. The next step was then to start developing a more automated method within a flow cell. Initially the ITO electrode with the pre-prepared immobilised antibody and the oxidised ferrocene tag was incorporated into a macrofluidic device. The CL immunoassay was successfully carried out in the macrofluidic device although the LODs were an order of magnitude higher than those seen from the static system for both progesterone and oestriol in saliva due to the large volume of the flow cell. Finally the ITO electrode with pre-prepared immobilised antibody with the oxidised ferrocene tag was slotted into the microfluidic device that had been designed and measurement were made. There was however problems with the design and possible new designs are discussed

Developing measures for valuing changes in biodiversity : final report

This document reports the findings from the DEFRA funded research project 'Developing measures for valuing changes in biodiversity'. The aim of the research was to develop an appropriate framework that will enable cost-effective and robust valuations of the total economic value of changes to biodiversity in the UK countryside. The research involved a review of ecological and economic literature on the valuation of biodiversity changes. The information gathered from this review, along with the findings from a series of public focus groups and an expert review of valuation methodologies, were used to develop a suite of valuation instruments that were used to measure the economic value of different aspects of biodiversity. Contingent valuation and choice experiment studies were administered to households in Cambridgeshire and Northumberland, while valuation workshops were conducted in Northumberland only. The data from these studies were also used to test for benefits transfer

Classroom Assistants’ use of talk in the construction and negotiation of identities

Since 1998 there has been a dramatic increase in the numbers of paid, additional, support staff, employed in Scottish primary schools as successive Scottish governments have attempted to raise standards by freeing teachers from administrative and ‘housekeeping’ duties and allowing them to teach. Of these additional staff, currently just over 4000 are classroom assistants, with a remit to provide general class learning and teaching support, including social inclusion and pupil discipline, under the direction of a fully registered teacher. Classroom assistants in Scotland are almost exclusively White women, typically aged 31-50, but concentrated in the 41-50 age range, partnered and with children of school age. These women exist on the margins of school hierarchies as witnessed by short-term contracts, low pay, limited access to formal training and low status. Nevertheless, many classroom assistants seem willing to accept poor working conditions as a trade off for family friendly working hours. Given these working conditions the study sought to consider several key questions: • Why are classroom assistants willing to undertake work that has low status, low pay and insecurity? • How do classroom assistants create and maintain a sense of integrity and commitment to their work? • How do classroom assistants create and sustain positive social and professional identities in this context? • Why do classroom assistants appear to be complicit, to some extent, in their own oppression? To achieve this the study used a critical ethnographic methods to explore the lived experiences of 13 classroom assistants as they supported pupils in two Scottish primary schools. The key insights were firstly that a Bourdieuian account of class, combined with an understanding of patriarchy, provided an explanation of these women’s labour market decisions. In addition, ‘preference theory’, was rejected in favour of a range of constraints, particularly having children and the associated childcare costs, that were considered much more important factors. Secondly, classroom assistants performed versions of ‘emphasised femininity’ as part of their identity as ‘classroom assistants’. Thirdly, the notion of ‘respectability’ was a crucial analytical tool in explaining not only these women’s constant struggle for recognition, but also their continuing oppression. And finally, classroom assistants told a particular type of talk, the ‘atrocity story’, which contributed to the social production of occupational boundaries. The study concluded that from their position of insecure and poorly paid employment, classroom assistants justified and reconciled their position by drawing on talk of moral superiority associated with mothering and caring to construct and perform identities that created the spaces and boundaries from which they positioned themselves as superior to both parents and teachers. As a result they were able to negotiate their roles within the micro-political world of the school

Brexit is changing the scenario for private equity in the UK

There are both threats and opportunities for private equity firms and their portfolio companies, write Mike Wright, Kevin Amess, Nick Bacon, John Gilligan and Nick Wilso

The California Planet Survey II. A Saturn-Mass Planet Orbiting the M Dwarf Gl649

We report precise Doppler measurements of the nearby (d = 10.34 pc) M dwarf Gl649 that reveal the presence of a planet with a minimum mass Msini = 0.328 Mjup in an eccentric (e = 0.30), 598.3 day orbit. Our photometric monitoring reveals Gl649 to be a new variable star with brightness changes on both rotational and decadal timescales. However, neither of these timescales are consistent with the 600-day Doppler signal and so provide strong support for planetary reflex motion as the best interpretation of the observed radial velocity variations. Gl649b is only the seventh Doppler-detected giant planet around an M dwarf. The properties of the planet and host-star therefore contribute significant information to our knowledge of planet formation around low-mass stars. We revise and refine the occurrence rate of giant planets around M dwarfs based on the California Planet Survey sample of low-mass stars (M* < 0.6 Msun). We find that f = 3.4^{+2.2}_{-0.9}% of stars with M* < 0.6 Msun harbor planets with Msini > 0.3$ Mjup and a < 2.5 AU. When we restrict our analysis to metal-rich stars with [Fe/H] > +0.2 we find the occurrence rate is 10.7^{+5.9}_{-4.2}%.Comment: 8 pages, 4 figures, 3 tables, PASP accepte

Cutoff in the Bernoulli-Laplace Model With Unequal Colors and Urn Sizes

We consider a generalization of the Bernoulli-Laplace model in which there are two urns and $n$ total balls, of which $r$ are red and $n - r$ white, and where the left urn holds $m$ balls. At each time increment, $k$ balls are chosen uniformly at random from each urn and then swapped. This system can be used to model phenomena such as gas particle interchange between containers or card shuffling. Under a reasonable set of assumptions, we bound the mixing time of the resulting Markov chain asymptotically in $n$ with cutoff at $\log{n}$ and constant window. Among other techniques, we employ the spectral analysis of arXiv:0906.4242 on the Markov transition kernel and the chain coupling tools of arXiv:2203.08647 and arXiv:1606.01437

Search Engine Optimisation in UK news production

This is an Author's Accepted Manuscript of an article published in Journalism Practice, 5(4), 462 - 477, 2011, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/17512786.2010.551020.This paper represents an exploratory study into an emerging culture in UK online newsrooms—the practice of Search Engine Optimisation (SEO), which assesses its impact on news production. Comprising a short-term participant observational case study at a national online news publisher, and a series of semi-structured, in-depth interviews with SEO professionals at three further UK media organisations, the author sets out to establish how SEO is operationalised in the newsroom, and what consequences these practices have for online news production. SEO practice is found to be varied and application is not universal. Not all UK news organisations are making the most of SEO even though some publishers take a highly sophisticated approach. Efforts are constrained by time, resources and management support, as well as off-page technical issues. SEO policy is found, in some cases, to inform editorial policy, but there is resistance to the principal of SEO driving decision-making. Several themes are established which call for further research

A gene × gene interaction between DRD2 and DRD4 is associated with conduct disorder and antisocial behavior in males

<p>Abstract</p> <p>Background</p> <p>Antisocial behaviors are complex polygenic phenotypes that are due to a multifactorial arrangement of genetic polymorphisms. Little empirical research, however, has been undertaken that examines gene × gene interactions in the etiology of conduct disorder and antisocial behavior. This study examined whether adolescent conduct disorder and adult antisocial behavior were related to the dopamine D2 receptor polymorphism (DRD2) and the dopamine D4 receptor polymorphism (DRD4).</p> <p>Methods</p> <p>A sample of 872 male participants from the National Longitudinal Study of Adolescent Health (Add Health) completed self-report questionnaires that tapped adolescent conduct disorder and adult antisocial behavior. DNA was genotyped for DRD2 and DRD4.</p> <p>Results</p> <p>Multivariate regression analysis revealed that neither DRD2 nor DRD4 had significant independent effects on conduct disorder or antisocial behavior. However, DRD2 interacted with DRD4 to predict variation in adolescent conduct disorder and in adult antisocial behavior.</p> <p>Conclusion</p> <p>The results suggest that a gene × gene interaction between DRD2 and DRD4 is associated with the development of conduct disorder and adult antisocial behavior in males.</p

Prospectus, September 3, 1986

https://spark.parkland.edu/prospectus_1986/1019/thumbnail.jp

Increased hyperpolarized [1-13 C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13 C-labelled bicarbonate.

Arthritic conditions are a major source of chronic pain. Furthering our understanding of disease mechanisms creates the opportunity to develop more targeted therapeutics. In rheumatoid arthritis (RA), measurements of pH in human synovial fluid suggest that acidosis occurs, but that this is highly variable between individuals. Here we sought to determine if tissue acidosis occurs in a widely used rodent arthritis model: complete Freund's adjuvant (CFA)-induced inflammation. CFA robustly evoked paw and ankle swelling, concomitant with worsening clinical scores over time. We used magnetic resonance spectroscopic imaging of hyperpolarized [1-13 C]pyruvate metabolism to demonstrate that CFA induces an increase in the lactate-to-pyruvate ratio. This increase is indicative of enhanced glycolysis and an increased lactate concentration, as has been observed in the synovial fluid from RA patients, and which was correlated with acidosis. We also measured the 13 CO2 /H13 CO3- ratio, in animals injected with hyperpolarized H13 CO3- , to estimate extracellular tissue pH and showed that despite the apparent increase in glycolytic activity in CFA-induced inflammation there was no accompanying decrease in extracellular pH. The pH was 7.23 ± 0.06 in control paws and 7.32 ± 0.09 in inflamed paws. These results could explain why mice lacking acid-sensing ion channel subunits 1, 2 and 3 do not display any changes in mechanical or thermal hyperalgesia in CFA-induced inflammation