This thesis examines the dynamic of infectious diseases after natural disasters. Methods from epidemiology and geography intersect in the nexus of this research to form new insights into the risk of infectious disease in the aftermath of natural disaster and catastrophe. In the past decades, natural disasters have increased in frequency and magnitude, and with climate change progressing as it is, this trend is expected to continue. It is thus important to gain a fuller understanding of the dynamic between natural disaster and disease, and challenge the persisting problems in disaster and disease response efforts. Two approaches were taken to determine the risk of disease after disaster. Firstly, by pooling data from previously published literature, a form of meta-analysis was conducted to gain insight into risk patterns as well as to define relevant confounding factors that held significance in determining vulnerabilities of affected populations. For this analysis, a new tool was applied to identify relevant research, and this tool is expected to be useful in future study of the subject. Secondly, a set of empirical studies were conducted to determine the association between types of natural disasters, geographic region, and four distinct disease profiles. Cholera, malaria, tuberculosis, and the co-infection with HIV and tuberculosis served as examples for the types of diseases commonly observed after disasters (diarrhoeal diseases, vector-borne diseases, and acute respiratory infections). Logistic regression models were used to find the odds ratios for above average diseases at different tiers of disaster magnitude. It was shown in this research that the relative risk of infectious disease after natural disasters was 3.45, indicating a higher probability of disease after disasters. Specific results show that disasters affecting higher numbers of the population typically lead to increases in new infections. Most interestingly, tuberculosis relapses showed significant increases after natural disasters, especially meteorological and hydrological disasters.

A number of large scale Salmonella outbreaks have been associated with low aw food products where the significant causal factor was most likely cross-contamination. These studies sought to both: assess Salmonella survival and survival mechanisms when dried onto stainless steel under simulated food factory conditions, and to develop enhanced factory control approaches for this pathogen. Fifteen isolates of Salmonella survived 30 days under desiccation and one strain survived for one year and potentially could survive longer. Differences in the survival between different Salmonella serotypes, and isolates of the same serotype (S. Typhimurium), were noted. A 2-population Weibull model was used to model survival, since following an initial reduction in viability (72 h), no further reduction was seen. There was enhanced survival of Salmonella at lower temperatures and relative humidity, with the presence of food debris and when water was added. At a physiological level, attributes associated with osmoresistance (RDAR phenotype, motility, filamentation, EPS production) were not observed in all desiccation resistant strains, additionally survival was greater on surfaces rather than in hyperosmotic solutions. Desiccated cells did not show increased sodium hypochlorite and propanol resistance. To assess molecular survival mechanisms, three RNA extraction methods were compared and real-time RT-PCR was performed for 13 genes. All selected housekeeping genes showed change in expression therefore were not used. Genes in desiccation sensitive strain had higher fold change during desiccation than in resistant strain (aceA, nifU and otsB). The principles of HACCP were reviewed and a prerequisite management programme, based on a risk assessment of sources and vectors, was designed and applied in a low aw food factory, to help control Salmonella cross-contamination. These results suggest the potential for extended survival of Salmonella in food factories, describe the most suitable model to predict survival kinetics, give some insight into Salmonella survival mechanisms and stress responses under desiccation conditions and identify strains and methods for further research studies. The results also confirm the need to keep low aw factories free of food debris and to eliminate water to reduce Salmonella survival. Given the potential for Salmonella survival, the results also highlight the need for the control of cross contamination to the food product via an improved prerequisite management plan.

The recent identification of two novel influenza-like viruses in bats, H17N10 and H18N11 virus, and the discovery of serologically positive Eidolon helvum bats in Ghana for avian H9 virus prompted my hypothesis that, in addition to the large repertoire of zoonotic viruses hosted, bats may serve as asymptomatic reservoir species to conventional influenza A viruses found in birds and mammals. To begin to test this hypothesis, the susceptibility of three bat cell lines, derived from lung epithelial cells of Eidolon helvum, Carollia perspicillata and Tadarida brasiliensis (TB1-Lu), to low pathogenicity avian viruses (H2N3 [A/mallard duck/England/7277/06] virus and H6N1 virus [A/turkey/England/198/09] virus), and human viruses (USSR H1N1 virus [A/USSR/77] and pandemic H1N1 2009 virus [A/California/07/2009]) was determined. All three species of bat epithelial cells were found to be more robust and resistant to influenza virus infections than permissive MDCK cells. Infected bat cells produced lower levels of viral RNA and viral progeny, and were more viable than correspondingly treated MDCK cells. Interestingly, bat cells were more susceptible and replication permissive to avian than human influenza viruses. Among the bat cells, TB1-Lu cells were the least susceptible to influenza virus infection and that appears to be related to a lack of sialic acid α2,6-Gal receptors, mammalian virus-preferred host receptors, which were present in the other two bat species. The innate mechanisms underlying resistance to influenza virus infection in bats remains to be determined, however, inhibition of the JAK/STAT pathway was found not to affect virus production from infected bat cells suggesting that JAK/STAT signalling may not have a major role in influenza virus resistance in bat cells. Modulation of NF-κB signalling was found to affect virus production suggesting that tight regulation of NF-κB may be key in controlling the pro-inflammatory response to influenza infection in bat cells and warrants further investigation.

China is currently facing unprecedented health challenges; non-communicable diseases (NCD) now account for 80 percent of its 10.3 million deaths annually. China’s growing health challenges arise, at least in part, due to its rapidly aging population and are compounded by its inadequate social security provision and rapid urbanization. This dissertation examines the extent to the health and well-being of the elderly in China are affected in the presence of these demographic and social changes. It uses data from a rich but relatively underutilized data source, the China Health and Retirement Longitudinal Study (CHARLS). CHARLS is the first Health and Retirement Study (HRS) of its kind in China, and as such represents a rich source of data on health and well-being for the country. A two-province sample was piloted in 2008 and followed up in 2012, while a national wave was surveyed in 2011. This dissertation is a collection of three self-contained empirical studies on the health and well-being of the elderly in China. The first study examines the effect that chronic diseases have on different dimensions of health in a structural equation framework. The second study examines the extent to which elderly households are able to continue to finance their consumption in the presence of ill-health and the extent to which health insurance and family support from children play a role. In the last study, we further investigate the effect that adult children’s migration decisions have on the physical and subjective well-being of their elderly parents.

Eingereichte, nicht verteidigte Dissertation von 1914 - Mit einer biographischen Notiz, verfasst von Sheila Luck

Community pharmacies in England provide a variety of services including essential services such as the dispensing of medicines, advanced services such as Medicine Use Reviews, and enhanced and locally commissioned services, for example the minor ailments scheme. In October 2011 a new advanced service called the New Medicine Service (NMS) was introduced. It aimed to improve adherence to newly prescribed medicines for patients with certain long term conditions and reduce medicines wastage. This thesis aims to evaluate the implementation of the NMS by exploring how the service was developed and implemented, identifying both potential and actual barriers and facilitators to NMS implementation, investigating the proportion of prescription items that are eligible for the service, and examining the uptake and provision of the service. In order to achieve this several studies were carried out. Interviews were conducted with stakeholders involved in the service’s development and implementation. Focus groups were conducted with community pharmacists complimented by interviews with superintendent pharmacists both before and after the introduction of the NMS. Data regarding the number of prescription items eligible for the service were collected in community pharmacies, and an analysis of service records for a large national chain of pharmacies was carried out. The studies determined that there were four stages to the development and implementation of the NMS; pre-negotiation, negotiations, the launch phase, and post-implementation. Both community pharmacists and superintendent pharmacists were enthusiastic about the potential of the service prior to the introduction of the service and anticipated good uptake of the service which was confirmed by post-implementation results. Several barriers were identified prior to implementation, the most important of which was the payment structure. Post-implementation results confirmed that the payment structure had affected NMS implementation, and direct observations in pharmacies, that the opportunity rate to provide the service was nearly half of the payment structure’s theoretical rate. Analysis of service data showed the uptake of the NMS was greater than the uptake of MURs in 2005. The findings of this thesis provide policy makers, pharmacy stakeholders, community pharmacists, and researchers with knowledge of how pharmacy services are developed. It also provides insights about factors that can facilitate or hinder service provision, including pharmacist attitudes towards a service, certain service and pharmacy characteristics (such as the ability to carry out telephone consultations), company encouragement to provide the service, the experience of conducting other pharmacy services, pharmacist workload, the accreditation procedure, and the services payment structure. These insights can be used to improve future pharmacy services’ implementation.

Epidemiological studies indicate that the prevalence of obesity and overweight is increasing rapidly in both developed and developing countries. Against this background it is important to determine the effects of obesity upon health and well-being. Defining the impact of obesity upon behaviour lies within the scope of such studies. It is known that variation in the maternal diet during early sensitive periods of development can programme risk of obesity and metabolic dysfunction in offspring. Although the effect of maternal obesity and/ or obesogenic diet throughout pregnancy and lactation on a wide range of physiological systems in rats is well documented, the effect of such manipulations on behaviour is yet to be elucidated in detail. The initial aim of the present thesis was to use a rat model to investigate the relative contribution of maternal obesity induced by a hyperenergetic cafeteria diet (CD) prior to pregnancy and/or maternal exposure to the CD during pregnancy and lactation, on anxiety and exploratory behaviour in adult offspring. Despite all of the maternal feeding periods having some contribution to offspring behaviour, the lactation period appeared to be the most important, with maternal CD having an anxiolytic effect in offspring exposed to the elevated plus maze and open field paradigm. It was hypothesized that maternal exposure to CD during lactation would also impact upon appetite related behaviour and performance on behavioural measures of learning and memory in adult offspring. Maternal CD during the lactation period altered feeding behaviour as measured by the behavioural satiety sequence in adult offspring of both sexes. The structural integrity of feeding behaviour was grossly perturbed in female offspring, with a significant delay in the onset of satiety. Maternal CD during lactation enhanced memory performance on a novel object discrimination paradigm in male offspring, but reduced performance of females. CD feeding during lactation increased both 5-hydroxytryptamine (5-HT) and dopamine (DA) concentration and reduced 5-HT turnover in the hypothalamus, but not the hippocampus or the frontal cortex, in both male and female offspring. The findings outlined in the present thesis demonstrate for the first time that maternal exposure to an obesogenic diet during early sensitive periods of development can programme a range of behaviours in adult offspring of both sexes.

Osteoarthritis (OA) is a degenerative disease of synovial joints with an inflammatory component, which affects humans and companion animals, including horses. Current pharmacotherapy for OA is associated with deleterious side effects. Therefore, plant-derived products with anti-inflammatory properties may provide safer natural alternatives. The project aimed to use in vitro models of equine cartilage to test the hypothesis that plant-derived extracts would reduce inflammation and degradation in an explant model of early OA. The anti-inflammatory polyphenol, curcumin, significantly reduced interleukin-1 beta (lL-1β)-stimulated glycosaminoglycan, matrix metalloproteinase-3 and prostaglandin E[subscript]2 release in the explant model. Using a cocktail of plant extracts illustrated how different effects were observed depending on the solvent used to dissolve the raw material. Chondrocyte monolayers were used to determine that counteraction of IL-1β- stimulated effects in the explant model occurred at non-cytotoxic concentrations. The explant model was adapted for proteomic studies of the cartilage secretome. Several proteins involved in matrix function and degradation were identified. This adaptation may further our understanding of the processes in the early OA explant model and may facilitate studying the effects of anti-inflammatory compounds on the secretome. A concurrent field trial showed that the plant extract cocktail did not significantly improve mobility in horses with chronic hindlimb stiffness. However, it illustrated the need for practical, more objective markers to help select animals of similar disease status and determine effects in the joints. Therefore, the proteomic study highlighted the potential for in vitro models to support field trials by identifying in vivo biomarkers for diagnosing early OA and assessing therapeutic responses. In conclusion, in vitro models of equine cartilage have considerable potential for assessing the ability of plant extracts to target inflammatory pathways and catabolic mediators in OA. The data presented suggests that nutritional intervention using plant-derived extracts with putative anti-inflammatory properties may support equine joint health.

The modern Western diet is typically high in salt and fructose. Variations in maternal diet can have delayed developmental effects on the adult offspring’s cardiovascular function leading to acute or chronic hypertension. The aim of the work in this thesis was to determine the effect of moderate dietary salt and/or fructose intake on maternal and fetal growth, metabolic status and cardiovascular health of the adult offspring. Sprague Dawley rats were fed either 1) control diet (chow) with tap water, 2) salt diet, 4% NaCl, 3) fructose diet, purified chow plus 10% fructose in tap water or 4) fructose and salt diet for 28 days prior to conception, through gestation and lactation. Data were collected on the non-pregnant and pregnant dam, the fetus and neonate and the adult offspring. Cardiovascular data in adult offspring were recorded between the ages of 10-15 weeks by implanted radiotelemetry probes. Dams fed fructose prior to and during gestation increased caloric intake (P<0.001) from fructose water with a consequential decrease in total energy intake (P<0.001) from food. Increases in plasma glucose (P=0.04) (without an effect on insulin), triglyceride (P<0.014), non-esterified fatty acids (P<=0.05), cholesterol (P<0.001) and uric acid (P<0.004) were all increased by the consumption of fructose in pre-gestational females. Dams consuming salt prior to and during gestation elicited an increase in cardiac (P<0.001) and kidney tissue mass (P<0.001). Fructose-fed dams also displayed a significant redistribution of regional fat depots i.e. visceral fat increased (P<0.001) whilst gonadal fat decreased (P<0.008). Fructose also increased liver weight (P<0.001) and intra-hepatic triglyceride concentration was also observed to be increased (P<0.007). However, few effects on the fetus but subtle effects on fetal and neonatal growth were observed at this stage. Fructose and salt combined reduced litter size (7 vs. 14 pups) (P<0.001) without an effect on birth weight. Maternal fructose diet skewed the sex ratio in favour of males (60:40) (P<0.001) and maternal salt influenced placental architecture (decreased labyrinthine (P<0.007), increased trophoblast layer (P=0.03)) and had marked effects on maternal osmolality (P<0.001). Male (P=0.07) and female (P<0.02) offspring from fructose-fed mothers had relatively heavier livers. In the adult offspring male and female offspring plasma osmolality was significantly increased in offspring fed prenatal salt (P<0.001). In the offspring, maternal salt diet significantly increased (~15mmHg) basal mean arterial pressure (MAP) in the adult male offspring (P<0.001), but significantly decreased basal MAP (~8mmHg) in the adult female offspring. Both fructose and salt diet had effects on the circadian variation in blood pressure and heart rate. Subsequent cardiovascular challenges revealed little beyond an altered cardiovascular set-point in these offspring. The study emphasizes the importance of quality rather than quantity when assessing maternal diet, particularly in terms of its mineral and simple sugar content. In conclusion, data within this thesis demonstrates for the first time a moderate maternal dietary intake of salt and fructose can affect offspring osmolality profile and blood pressure in a sex-specific manner and produce a pattern of symptoms resembling NAFLD which, in part, are passed vertically to the offspring.

Commercial weight loss programmes (CWLPs) are structured weight loss programmes, which are provided to the public by commercial organisations for profit. These programmes offer a weight management service for overweight or obese adults who are willing and able to pay for their participation. There are few studies that have shown CWLPs are more effective than either usual or standard care in various healthcare settings. The extent to which elements of CWLPs contribute to weight reduction is not clear from these studies. The studies presented in this thesis aimed to i) systematically review the effectiveness of CWLPs in randomised controlled trials and ii) to evaluate the effectiveness of a pharmacist-led weight management clinic, Boots Pharmacy Weight Loss Programme (BPWLP), in achieving meaningful weight loss of the initial body weight at three months in overweight and obese clients who received a combination of orlistat, and diet and exercise advice. The systematic review evaluated percentage weight loss or change and used a narrative synthesis. Nine electronic databases (1980-2011) were searched. The review studies published in English were included and their quality was assessed, including assessment of risk of bias. The number of total titles, abstracts and full articles reviewed were 8484, 772 and 153, respectively. The final number of papers included in the review was 20 randomised studies of CWLPs, which were selected based on the application of inclusion and exclusion criteria. The evaluation of the BPWLP involved analysis of data from randomly collected customer record forms (CRFs) for clients who participated in the programme from January 2006 to January 2009. Five hundred and fifty-seven records were collected from 10 Boots pharmacies. Demographics data, history information, biometric data and information about the supply of orlistat were collected. Change in body weight (kg) was compared at baseline and three months using Wilcoxon Signed Rank Test. Seventy percent of the studies included in the systematic review were conducted in the US. There were three potential elements of effective CWLPs, which were calorie restriction, exercise and support. At 12 weeks, mean weight loss ranged from 3.3 to 12.7 kg. The mean weight loss in the BPWLP was 5.8 kg (p < 0.001). Similarly, sensitivity analysis using last-observation-carried-forward (LOCF) showed a statistically significant weight loss (p < 0.001) associated with the BPWLP. Sixty-two percent of clients, who completed the BPWLP, lost at least 5% of their initial body weight at three months. Although the BPWLP had a high dropout rate (70%), clients mainly left the programme because they achieved their desired weight loss. The studies presented in this thesis have shown that CWLPs are effective in helping clients to lose weight. The systematic review shows that the combination of calorie restriction, structured exercise and support is an effective first-line strategy in obesity treatment. The BPWLP, which uses orlistat 120 mg in combination with advice and support on diet and exercise, was shown to be effective in achieving weight loss for clients and is considered a second-line treatment. Health care professionals and policy makers should acknowledge and adopt such strategies in order to tackle the problem of obesity. In particular, pharmacists have an important role to play in facilitating effective weight reduction through the provision of dietary and exercise advice and the prescribing of orlistat. Further study should focus on the factors which contribute to long-term weight maintenance and the cost-effectiveness of CWLPs.