Background: Peripartum cardiomyopathy (PPCM) is an incompletely understood disease that causes significant morbidity and mortality in many parts of the world, including Northern Nigeria. The aims of this Thesis were: [1] to determine if selenium deficiency, serum ceruloplasmin and traditional birth practices are risk factors for PPCM, in Kano, Nigeria; [2] to describe the one year survival and left ventricular reverse remodeling (LVRR) in a group of patients with PPCM from three referral hospitals in Kano, Nigeria; [3] to identify potential electrocardiographic (ECG) predictors of PPCM; and [4] to assess right ventricular systolic dysfunction (RVSD) and remodelling in a cohort of PPCM patients in Kano, Nigeria. Materials and Methods: The studies were carried out in 3 referral hospitals in Kano, Nigeria. Study 1: This was a case-control study. Critically low serum selenium concentration was defined as <70μg/L. Study 2: This was a longitudinal study. LVRR was defined as absolute increase in LV ejection fraction (LVEF) by ≥10.0% and decrease in LV end-diastolic dimension indexed to body surface area (LVEDDi) ≤33.0 mm/m2, while recovered LV systolic function as LVEF ≥55%, at 12 months follow-up. Study 3: This was a case-control study. Logistic regression models and a risk score were developed to determine ECG predictors of PPCM. Study 4: This was a longitudinal study and patients were followed up for 12 months. RVSD was defined as the presence of either tricuspid annular plane systolic excursion (TAPSE) <16mm or peak systolic wave (S’) tissue Doppler velocity of RV free wall <10cm/s. Recovery of RV systolic function was defined as an improvement of reduced TAPSE to ≥16mm or S’ to ≥10cm/s, without falling to reduced levels again, during follow-up. Results: Study 1: Total of 39 PPCM patients and 50 controls were consecutively recruited after satisfying the inclusion criteria. Mean serum selenium in patients (61.7±14.9μg/L) was significantly lower than in controls (118.4±45.6μg/L) (p<0.001). The prevalence of serum selenium <70μg/L was significantly higher among patients (76.9%) than controls (22.0%) (p<0.001). The mean ceruloplasmin and prevalence of socio-economic indices, multiparity, pregnancy-induced hypertension, obesity and twin pregnancy were not different between the groups (p>0.05). Logistic regression showed that rural residency significantly increased the odds for serum selenium <70μg/L by 2.773 fold (p=0.037). Study 2: A total of 33 patients were followed-up. Of the 17 survivors at 12 months, 8 patients (47.1%) satisfied the criteria for LVRR, of whom 5 (29.4%) had recovered LV systolic function, but LVRR was not predicted by any variable in the regression models. The prevalence of normal LV diastolic function increased from 11.1% at baseline to 35.3% at twelve months (p=0.02). At one year follow-up, 41.4% of patients had died (two thirds of them within the first 6 months), but mortality wasn’t predicted by any variable including LVRR. Study 3: A total of 54 PPCM and 77 controls were studied. A rise in heart rate by 1 beat/minute increased the odds of PPCM by 6.4% (p=0.001), while presence of ST-T-wave changes increased the odds of PPCM by 12.06 fold (p<0.001). In patients, QRS duration modestly correlated (r=0.4; p<0.003) with LV dimensions and end-systolic volume index (LVESVI), and was responsible for 19.9% of the variability of the latter (R2 = 0.199; p=0.003). A risk score of ≥2 had a sensitivity of 85.2%, specificity of 64.9%, negative predictive value of 86.2% and area under the curve of 83.8% (p<0.0001) for potentially predicting PPCM. Study 4: A total of 45 patients were studied. RV systolic function recovery occurred in a total of 8 patients (8/45; 17.8%), of whom 6 (75.0%) recovered in 6 months after diagnosis. The prevalence of RVSD fell from 71.1% at baseline to 36.4% at 6 months (p=0.007) and 18.8% at one year (p=0.0008 vs baseline; p=0.41 vs 6 month). Although 83.3% of the deceased had RVSD, it didn’t predict mortality in the regression models (p>0.05). Conclusion: These studies have shown that selenium deficiency seems to be a risk factor for PPCM in Kano, Nigeria, related to rural residency. However, serum ceruloplasmin, customary birth practices and some other characteristics were not associated with PPCM in the study area. They have also shown that PPCM patients had modest LVRR but high mortality at one year. In addition, using the ECG risk score could help to streamline the diagnosis of PPCM with significant accuracy, prior to confirmatory investigations in postpartum women. Finally, RVSD and reverse remodelling were common in Nigerians with PPCM, in whom the first 6 months after diagnosis seem to be critical for RV recovery and survival. / Summary

In the past decade Arabidopsis thaliana has become an important system for studying meiosis in flowering plants. The identification of meiotic mutants has provided an important approach to studying plant meiosis. The availability of the Arabidopsis genome sequence together with developments in proteomics and bioinformatics provides an additional route for the identification of meiotic proteins and analysis of their functional interrelationships. This study has used a proteomics approach to identify a member of the SWI2/SNF2 chromatin remodelling gene family (Atchr24). Although a variety defects was observed in Atchr24 male meiocytes cytogenetic, at least two T-DNA insertion lines on this gene appear normal. Secondly, this research has also used a bioinformatics approach to identify a potential orthologue of Pch2/TRIP13 in Arabidopsis. PCH2 (Pachytene checkpoint 2) is a member of the AAA+ ATPase family of proteins. This study reveals that AtPCH2 plays an essential role in the controlled formation of meiotic crossovers (COs). Cytogenetic analysis of two Atpch2 T-DNA insertion lines revealed a high frequency of univalents at MI. The number of chiasmata (COs) is reduced to ~ 70% of wild-type (WT). Genetic analysis revealed that Atpch2 has significantly weaker CO interference than WT leading to a redistribution of COs along the chromosomes. The recombination defect is accompanied by incomplete chromosome synapsis. Immunolocalisation of the chromosome axis protein AtASY3 and cohesin, AtSYN1 appears normal. However in contrast to WT, AtASY1 co-localises with the synaptonemal protein AtZYP1 in ii Atpch2 rather than becoming depleted in regions of synapsis and the meiotic progression of Atpch2 is delayed during pachytene by ~5 hours. These observations suggest a defect in remodeling of the chromosome axes and highlight how this process is essential for normal CO control.

Cancer and malaria are among the most life-threatening diseases globally. Cancer is responsible for about 125,000 annual deaths globally. In 2015, the World Health Organization report estimated that 236000-635000 people died of malaria. These diseases are complicated by the development of resistance to available chemotherapeutic agents. Natural products have been recognized for their major applications in the identification of drug leads in drug discovery. Viola philippica Car, Viola yedoensis Makino (Violaceae), Triclisia subcordata Oliv (Menispermeaceae) and Cyclicodiscus gabunensis Harms (Fabaceae) are medicinal plants traditionally used for the treatment of various diseases including malaria or cancer in China and West Africa. However, the bioactive compounds are unknown. Therefore, this study evaluated the in vitro anticancer and antimalarial activities of the four medicinal plants and searched their bioactive compounds. The in vitro anti-ovarian cancer and antimalarial assays were demonstrated respectively using sulforhodamine B dye and Syber green 1 fluorescence assay methods. Bioassay-guided fractionation and purification were performed. Structural elucidation was performed by nuclear magnetic resonance spectroscopy and mass spectrometry analysis. Results revealed the anticancer and antimalarial activities of T. subcordata; V. philippica, and V. yedoensis to be bisbenzylisoquinoline alkaloids (cycleanine, isochondodendrine and 2′-norcocsuline) and/or cyclotides. The cycleanine analogues were synthesized and found to be more potent than cycleanine. Induction of apoptosis by these alkaloids has also been determined. This study could serve as basis for the support of use of these plants in cancer and/or malaria treatment. The BBIQ alkaloids and analogues could serve as lead compounds in drug discovery. Future in vivo studies need to be carried out on these alkaloids to get drug approval.

Melaleuca alternifolia (Tea tree oil) is commonly used by the general public in the treatment of superficial dermatological conditions. There is a growing body of evidence to support its use as an anti-fungal and anti-bacterial agent. However, there is little evidence of the in vivo penetration of components of the oil through the skin, imperative to ensure its use is directed appropriately and safely. Furthermore the extent of TTO’s ability as an anti-inflammatory agent and its potential mode of action are not know. This thesis describes the adaption and validation of the method in vivo dermal microdialysis in order to identify and quantify components of tea tree oil present at the dermal epidermal junction following the topical application of 100% TTO. In vitro investigations identified that the addition of hydroxypoply –β-cyclodextrin to the perfusate, the adjustment of flow rate and the use of cuprophan membranes ensured optimal recovery of components. Furthermore tape stripping was utilized to identify components present within the stratum corneum (SC). These methods were coupled with gas chromatography-mass spectrometry and were successful in the identification and quantification of terpinen-4-ol, 115.64±28.1 (ng±SEM) and 1,8 cineole, 15.05±2.6 at the dermal epidermal junction (n=10). Also the presence of 9 hydrophilic and lipid components (overall subjects) were observed within this top layer of epidermis (n=7). In addition the potential anti-inflammatory action of TTO and its component T-4-ol is investigated in vitro using the HaCaT cell line (model keratinocytes) including exploration of a potential mode of action. An inflammatory action was induced using lipopolysaccharide (LPS) and the cell supernatant analysed using the MSD™ electronchemiluminesence assay. A statistically significant increase in the release of IL1β was observed when non-stimulated HaCaT cells were incubated with TTO (not T-4-ol alone), compared to control (medium alone). Furthermore a statistically significant increase in IL6 was observed when non-stimulated HaCaT cells were incubated with TTO and T-4-ol compared with the incubation of stimulated HaCaT cells with the oil and its component. Investigation into the effect of TTO and T-4-ol on the transcription factor NFқB demonstrated that the oil and its component did not exert its effect by initiation of this pathway. The findings of this research have implications for clinical practice, particularly in the use of TTO on areas of dermatological inflammation and its use on ‘healthy’ skin.

The rapid development of seriously drug-resistant pathogen strains has created a dangerous problem to public health. The discovery of new effective antimicrobials remains an urgent task to control microbial resistance. Natural products can offer special stereochemistry and unlimited diversity of natural leads which are biologically active or ready for development and structure optimization strategies. Four medicinal plants Cylicodiscus gabunensis (CG), Pogostemon cablin (PC), Perilla frutescens (PF) and Magnolia biondii (MB) were selected for investigation of their phytochemical composition and antiplasmodial and/or antibacterial properties. A bioassay guided fractionation method has been followed to characterize the antiplasmodial and antibacterial constituents of CG. Flash column chromatography and preparative HPLC were used to obtain the bioactive compounds. GC-MS, LC-MS, and NMR have been used for chemical analysis purposes. For evaluation of the antibacterial activity, disk diffusion assay, alamar blue microplate assay, time kill kinetic and scanning electron microscopy (SEM) methods have been used. The work led to the isolation of the most potent antiplasmodial fraction of CG with IC50 of 4.7.

This study investigate the effects of four Chinese herbs for their potential therapeutic use as analgesics. It involved screening for inhibitors of enkephalin-hydrolysing enzymes, especially selective NEP inhibitors, mixed NEP/APN inhibitors and mixed NEP/ACE inhibitors. NEP was the key enzyme in the screening systems. Four Chinese herbs Yan (Corydalis yanhusuo T. Wang); Gou (Nauclea sinensis Oliv. ); Qiang (Notopterygium incisum Ting ex H.T. Chang); and Chuan (Ligusticum chuanxiong Hort.) were tested for their inhibitory effects on NEP activity measured in a rat kidney extract. Aqueous extracts of Gou and Qiang showed the significant inhibitory activity on NEP but results with organic extracts were not significant. Gou showed the strongest inhibitory activity on NEP. It was found that Gou also showed an inhibitory activity on the other two enkephalin-hydrolysing enzymes, APN and ACE in the microsomal mixture. A rat-brain opiate-receptor preparation (section 5.2.1) was used in ligand binding experiments with competition for the receptor sites between the aqueous Gou extract and tritium-labelled naloxone. For very small quantities of Gou there was a lowering of naloxone binding showing the antagonistical action of Gou. At higher concentrations (> 4 mg/ml of Gou) there was a tendency for naloxone binding to increase demonstrating potential agonistic activity. To test whether one compound in Gou had inhibitory activity on the three enzymes, or several compounds acting together, the aqueous extract of Gou was separated by HPLC. The HPLC-eluted fractions were pooled into seven parts and collected. The seven eluates were assayed for their effects on NEP proteolysis of 3H(leu)- enkephalin. Only six eluates showed inhibitory activity on NEP. The three single compounds already fractionated by others (rhynchophylline, mitraphylline and poteropodine) were shown to correspond in the Pool 7. An unexpectedly large number of active fractions suggest that many active compounds are present in Gou. It can be concluded that of the four herbs tested Gou (Nauclea sinensis Oliv) offers considerable potential as a novel analgesic agent. The work described in this dissertation was carried out in the School of Biomolecular Science, Liverpool John Moores University from October 1994 to May 1999. Unless otherwise stated it is the original work of the author. This dissertation has not been submitted, in whole or in part, for any other degree at this or any other university.

Underground Residential Distribution (URD) power cables are aged due to electrical, thermal, mechanical, and environmental stresses during their service. The recent dielectric conditions of the cables are of much interest for utilities. The existing offline diagnostic method requires forceful disconnection of the URD cable for maintenance. Online recording and Fast Fourier Transform analysis of intentionally created transients in URD is one of the promising method to assess the current condition of the cable. For the bigger goal of developing an online power cable condition assessment, the measurement techniques which are required to be implemented has to be evaluated. In order for implementing the online measurement system, the requirements of the measurement system have to be identified at first. URD system model was simulated using Electro Magnetic Transient Program to identify the characteristics of induced transients. A list of requirements of the measurement system was created based on the simulation results

This practicum investigates the use of recreational vehicles and park model trailers within the east central Vancouver Island area with the objective of developing an understanding of their use as an alternative affordable housing option. As part of this research, and in order to provide a base reference point for a later analysis within the study, a review of literature on the topics of homelessness, evolution of the travel trailer, mobile home policy, living in an RV on the street, living in an RV park, and the emergency use of travel trailers was conducted. In addition, this research includes a review of Provincial regulations such as the BC Building Code, Residential Tenancy Policy Guideline how they relate to the use of RV and park model trailers. As well, this study includes a review and analysis of the zoning bylaw of various local governments on Vancouver Island with respect to the use and classification of RV and park model trailers. This practicum forms a case study of local government officials, campground operators and recreational vehicle dwellers on the use of RVs and park model trailers within the study area. [truncated] / February 2007

<p>This thesis presents a method for predicting radon (222Rn) levels in groundwater on a general scale, within an area of approximately 185 x 145 km2. The method applies to Swedish conditions, where 222Rn is the main contributor to natural radioactivity. Prediction of radon potential in groundwater is complex because there are many different factors affecting radon content, including geochemical and flow processes. The proposed method is based on univariate and multivariate statistical analyses and investigated the influence of different factors such as bedrock, soils, uranium distribution, altitude, distance to fractures and land use. A statistical variable based method (the RV method) was used to estimate risk values related to different radon concentrations. The method was calibrated and tested on more than 4400 drilled wells in Stockholm County. The weighted index (risk value) estimated by the RV method provided a fair prediction of radon potential in groundwater on a general scale. The RV method was successful in estimating the median radon concentration within 12 subregions (at a local scale, each of area 25 x 25 km2), based on weighted index values obtained from half of all wells tested. A high correlation between risk values and median radon concentrations was demonstrated. The factors bedrock, altitude, distance to fracture zone and distribution of uranium in bedrock were found to be significant in the prediction approach on a general scale. Visual data mining, which comprised analysis of 3D images, was a useful tool for data exploration but could not be used as an independent method for drawing conclusions regarding radon in groundwater. Results of a field study based on 38 drilled wells on the island of Ljusterö in the Stockholm archipelago showed that 222Rn concentrations in groundwater were weakly correlated to the parent elements (226Ra and 238U) in solution.</p>

Herbal medicine has experienced tangible revivals in both Vietnam and the United Kingdom since the mid-20th century, as reflected in sales of herbal medicinal products, numbers of users and the availability of training opportunities for aspiring herbalists. In both countries, this revival came on the back of more or less concerted official efforts to discourage and even ban the practice and use of herbal medicine, by colonial authorities (in Vietnam) or professional medical associations and regulatory bodies (in the UK). Utilising archaeological and genealogical methods as developed by Canguilhem, Foucault and others, this study seeks to account for these revivals by pursuing three particular lines of analysis. Firstly, by describing the formations of power-knowledge relations which have allowed Vietnamese and British herbal medicine to challenge biomedical monopolies in the latter half of the 20th century, it is argued that the ways in which ‘quackery’ is conceptualised and regulated against in both countries today, has undergone substantial transformations. Secondly, by identifying the techniques of truth making which either suggest or contest a superior efficacy (over placebo) for two particular herbal medicines in the treatment of depression (in the UK) and addiction (in Vietnam), the study demonstrates how the concept of ‘efficacy’ not only pertains to bio-physiological effects but also to the symbolic effects of the treatments in question. Finally, by asking what kind of ‘life’ herbal medicine is seen to be affecting, it is suggested that longevity has been joined by quality of life as a separate, yet inherently interlinked, therapeutic site. One of the key conclusions of the dissertation is, that the sub-disciplines of medical anthropology and sociology have played a crucial role in the 20th century births of ‘traditional medicine’ and ‘complementary and alternative medicine’ (as opposed to ‘primitive’ and ‘fringe’ medicine). Firstly, in diagnosing a ‘crisis of modern medicine’ by highlighting its dehumanising and toxifying effects, and secondly, in providing a theory of symbolic efficacy which could help explain the continued importance of what had in the past been written off as ‘esoteric’ or ‘backward’ healing practices. As a consequence, the study describes how an ongoing governmentalisation of human subjectivities has been a requisite side effect of modernisation in the recent revival and renaissance of herbal medicine in Vietnam and the United Kingdom.