The search for biomarkers of facial eczema, following a sporidesmin challenge in dairy cows, using mass spectrometry and nuclear magnetic resonance of serum, urine, and milk : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Sciences at Massey University, Palmerston North, Manawatu, New Zealand

Facial eczema (FE) is a secondary photosensitisation disease of ruminants that is significant in terms of both its economic importance to New Zealand and its impact on animal welfare. The clinical photosensitivity signs, caused by the retention of phytoporphyrin, occur secondarily to hepatobiliary damage caused by the mycotoxin sporidesmin. Currently it is difficult to diagnose subclinical animals and those in the early stages of the disease. The project was aimed at applying new analytical and statistical techniques, to attempt the early diagnosis of FE in dairy cows following the administration of a single oral dose (0.24 mg/kg) of sporidesmin. Well-established traditional techniques including production parameters, liver enzyme (GGT, GDH) activity measurements, as well as measurements of phytoporphyrin by fluorescence spectroscopy were made for comparison. Serum, urine, and milk were analysed using 1H Nuclear Magnetic Resonance (NMR), multivariate analysis (MVA), and time series statistics. Urine and milk did not prove useful for identification of sporidesmin intoxication. Serum metabolites differed between treated cows before and after administration of the toxin, and could distinguish samples belonging to the clinical group. The metabolites that were identified as being relevant to this classification were a mixture of glycoproteins, carboxylic acids, ketone bodies, amino-acids, glutamate, and glycerol, which were elevated for treated cattle, and acetate, choline, isoleucine, trimethylamine N-oxide, lipids, lipoproteins, cholesterol, and -glucose, which showed decreased concentrations. Citrate was found to be at higher concentration in non-responders and subclinicals only. When serum was analysed using ultra performance liquid chromatography electrospray ionisation mass spectrometry (UPLC/ESI-MS) and UPLC tandem MS (MS/MS), only samples from clinical cows could be discriminated. The molecular ions involved could be tentatively identified as a combination of taurine- and glycine-conjugated bile acids. These bile acids all became elevated. This study confirmed that liver enzyme activities (GGT, GDH) and phytoporphyrin concentrations are not effective as markers of early stage sporidesmin damage. Additionally, the new techniques were unable to detect early stage FE. However, some markers of treated cows were identified. The research does provide a strong foundation for future applications of metabolomics analysis, with MVA and time series statistics, for early stage FE diagnosis

Proton-proton collisions at the Large Hadron Collider's ALICE Experiment: diffraction and high multiplicity

Diffraction in pp collisions contributes approximately 30 % of the inelastic cross section. Its influence on the pseudorapidity density is not well constrained at high energy. A method to estimate the contributing fractions of diffractive events to the inelastic cross section has been developed, and the fractions are measured in the ALICE detector at 900 GeV (7 TeV) to be f$_D$=0.278$\pm$0.055 (f$_D$=0.28$\pm$0.054) respectively. These results are compatible with recent ATLAS and ALICE measurements. Bjorken’s energy density relation suggests that, in high multiplicity pp collisions at the LHC, an environment comparable to A-A collisions at RHIC could be produced. Such events are of great interest to the ALICE Collaboration. Constraints on the running conditions have been established for obtaining a high multiplicity pp data sample using the ALICE detector’s multiplicity trigger. A model independent method to separate a multiplicity distribution from ‘pile-up’ contributions has been developed, and used in connection with other findings to establish a suitable threshold for a multiplicity trigger. It has been demonstrated data obtained under these conditions for 3 months can be used to conduct early strangeness analyses with multiplicities of over 5 times the mean. These findings have resulted in over 16 million high multiplicity events being obtained to date

Inequalities in Human Well-Being in the Urban Ganges Brahmaputra Meghna Delta

The recently endorsed Sustainable Development Goals (SDGs) agenda unanimously agrees on the need to focus on inclusive development, the importance of eradicating extreme poverty and managing often complex human well-being impacts of rapid urban growth. Sustainable and inclusive urbanisation will accelerate progress towards the SDGs and contribute to eradicating extreme poverty. In tropical delta regions, such as the Ganges Brahmaputra Meghna delta region, urban growth and resulting intra-urban inequalities are accelerated by the impact of environmental and climate change. In this context, the present study uses the 2010 Household Income and Expenditure Survey to analyse the extent of wealth-based inequalities in human well-being in the urban delta region and the determinants of selected welfare measures. The results suggest that the extent of intra-urban inequalities is greatest in educational attainment and access to postnatal healthcare and relatively low in the occurrence of gastric disease. The paper concludes by providing policy recommendations to reduce increasing wealth inequalities in urban areas, thus contributing to sustainable development of the region

Examining the Urban advantage in maternal health care in developing countries

Although recent survey data make it possible to examine inequalities in maternal and newborn health care in developing countries, analyses have not tended to take into consideration the special nature of urban poverty. Using improved methods to measure urban poverty in 30 countries, we found substantial inequalities in maternal and newborn health, and in access to health care. The ‘‘urban advantage’’ is, for some, non-existent. The urban poor do not necessarily have better access to services than the rural poor, despite their proximity to services. There are two main patterns of urban inequality in developing countries: (1) massive exclusion, in which most of the population do not have access to services, and (2) urban marginalisation, in which only the poor are excluded. At a country level, these two types of inequality can be further subdivided on the basis of rural access levels. Inequity is not mandatory. Patterns of health inequality differ with context, and there are examples of countries with relatively small degrees of urban inequity. Women and their babies need to have access to care, especially around the time of birth. Different strategies to achieve universal coverage in urban areas are needed according to urban inequality typology, but the evidence for what works is restricted to a few case studies

The causes of maternal mortality in adolescents in low and middle income countries: a systematic review of the literature

Background: While the main causes of maternal mortality in low and middle income countries are well understood, less is known about whether patterns for maternal deaths among adolescents are the same as for older women. This study systematically reviews the literature on cause of maternal death in adolescence. Where possible we compare the main causes for adolescents with those for older women to ascertain differences and similarity in patterns of mortality. Methods: An initial search for papers and grey literature in English, Spanish and Portuguese was carried out using a number of electronic databases based on a pre-determined search strategy. The outcome of interest was the proportion of maternal deaths amongst adolescents by cause of death. A total of 15 papers met the inclusion criteria established in the study protocol. Results: The main causes of maternal mortality in adolescents are similar to those of older women: hypertensive disorders, haemorrhage, abortion and sepsis. However there was marked heterogeneity between papers which could indicate country or regional differences in the importance of specific causes of adolescent maternal mortality. When compared with causes of death for older women, hypertensive disorders were found to be a more important cause of mortality for adolescents in a number of studies in a range of settings. In terms of indirect causes of death, there are indications that malaria is a particularly important cause of adolescent maternal mortality in some countries. Conclusion: The main causes of maternal mortality in adolescents are broadly similar to those for older women, although the findings suggest some heterogeneity between countries and regions. However there is evidence that the relative importance of specific causes may differ for this younger age group compared to women over the age of 20 years. In particular hypertensive conditions make up a larger share of maternal deaths in adolescents than older women. Further, large scale studies are needed to investigate this question further

Mapping adolescent first births within three east African countries using data from Demographic and Health Surveys: exploring geospatial methods to inform policy

Background: Early adolescent pregnancy presents a major barrier to the health and wellbeing of young women and their children. Previous studies suggest geographic heterogeneity in adolescent births, with clear “hot spots” experiencing very high prevalence of teenage pregnancy. As the reduction of adolescent pregnancy is a priority in many countries, further detailed information of the geographical areas where they most commonly occur is of value to national and district level policy makers. The aim of this study is to develop a comprehensive assessment of the geographical distribution of adolescent first births in Uganda, Kenya and Tanzania using Demographic and Household (DHS) data using descriptive, spatial analysis and spatial modelling methods.Methods: The most recent Demographic and Health Surveys (DHS) among women aged 20 to 29 in Tanzania, Kenya, and Uganda were utilised. Analyses were carried out on first births occurring before the age of 20 years, but were disaggregated in to three age groups: &lt;16, 16/17 and 18/19 years. In addition to basic descriptive choropleths, prevalence maps were created from the GPS-located cluster data utilising adaptive bandwidth kernel density estimates. To map adolescent first birth at district level with estimates of uncertainty, a Bayesian hierarchical regression modelling approach was used, employing the Integrated Nested Laplace Approximation (INLA) technique.Results: The findings show marked geographic heterogeneity among adolescent first births, particularly among those under 16 years. Disparities are greater in Kenya and Uganda than Tanzania. The INLA analysis which produces estimates from smaller areas suggest “pockets” of high prevalence of first births, with marked differences between neighbouring districts. Many of these high prevalence areas can be linked with underlying poverty.Conclusions: There is marked geographic heterogeneity in the prevalence of adolescent first births in East Africa, particularly in the youngest age groups. Geospatial techniques can identify these inequalities and provide policy-makers with the information needed to target areas of high prevalence and focus scarce resources where they are most needed.<br/

Immuno-fluorescent Labeling of Microtubules and Centrosomal Proteins in Ex Vivo Intestinal Tissue and 3D In Vitro Intestinal Organoids.

The advent of 3D in vitro organoids that mimic the in vivo tissue architecture and morphogenesis has greatly advanced the ability to study key biological questions in cell and developmental biology. In addition, organoids together with recent technical advances in gene editing and viral gene delivery promises to advance medical research and development of new drugs for treatment of diseases. Organoids grown in vitro in basement matrix provide powerful model systems for studying the behavior and function of various proteins and are well suited for live-imaging of fluorescent-tagged proteins. However, establishing the expression and localization of the endogenous proteins in ex vivo tissue and in in vitro organoids is important to verify the behavior of the tagged proteins. To this end we have developed and modified tissue isolation, fixation, and immuno-labeling protocols for localization of microtubules, centrosomal, and associated proteins in ex vivo intestinal tissue and in in vitro intestinal organoids. The aim was for the fixative to preserve the 3D architecture of the organoids/tissue while also preserving antibody antigenicity and enabling good penetration and clearance of fixative and antibodies. Exposure to cold depolymerizes all but stable microtubules and this was a key factor when modifying the various protocols. We found that increasing the ethylenediaminetetraacetic acid (EDTA) concentration from 3 mM to 30 mM gave efficient detachment of villi and crypts in the small intestine while 3 mM EDTA was sufficient for colonic crypts. The developed formaldehyde/methanol fixation protocol gave very good structural preservation while also preserving antigenicity for effective labeling of microtubules, actin, and the end-binding (EB) proteins. It also worked for the centrosomal protein ninein although the methanol protocol worked more consistently. We further established that fixation and immuno-labeling of microtubules and associated proteins could be achieved with organoids isolated from or remaining within the basement matrix

Population dynamics, delta vulnerability and environmental change: comparison of the Mekong, Ganges–Brahmaputra and Amazon delta regions

Tropical delta regions are at risk of multiple threats including relative sea level rise and human alterations, making them more and more vulnerable to extreme floods, storms, surges, salinity intrusion, and other hazards which could also increase in magnitude and frequency with a changing climate. Given the environmental vulnerability of tropical deltas, understanding the interlinkages between population dynamics and environmental change in these regions is crucial for ensuring efficient policy planning and progress toward social and ecological sustainability. Here, we provide an overview of population trends and dynamics in the Ganges–Brahmaputra, Mekong and Amazon deltas. Using multiple data sources, including census data and Demographic and Health Surveys, a discussion regarding the components of population change is undertaken in the context of environmental factors affecting the demographic landscape of the three delta regions. We find that the demographic trends in all cases are broadly reflective of national trends, although important differences exist within and across the study areas. Moreover, all three delta regions have been experiencing shifts in population structures resulting in aging populations, the latter being most rapid in the Mekong delta. The environmental impacts on the different components of population change are important, and more extensive research is required to effectively quantify the underlying relationships. The paper concludes by discussing selected policy implications in the context of sustainable development of delta regions and beyond

The Effectiveness of the KiVa Bullying Prevention Program in Wales, UK: Results from a Pragmatic Cluster Randomized Controlled Trial

AbstractThe study evaluated the implementation fidelity and effectiveness of KiVa, an evidence-based program that aims to prevent and address bullying in schools, with a particular emphasis on changing the role of bystanders. The study was a two-arm waitlist control cluster randomized controlled trial in which 22 primary schools (clusters) (N = 3214 students aged 7–11) were allocated using a 1:1 ratio to intervention (KiVa; 11 clusters, n = 1588 students) and a waitlist control (usual school provision; 11 clusters, n = 1892 children)). The trial statistician (but not schools or researchers) remained blind to allocation status. The outcomes were as follows: student-reported victimization (primary outcome) and bullying perpetration; teacher-reported child behavior and emotional well-being; and school absenteeism (administrative records). Implementation fidelity was measured using teacher-completed online records (for class lessons) and independent researcher observations (for school-wide elements). Outcome analyses involved 11 intervention schools (n = 1578 children) and 10 control schools (n = 1636 children). There was no statistically significant effect on the primary outcome of child-reported victimization (adjusted intervention/control OR 0.76; 95% CI 0.55 to 1.06; p = 0.11) or on the secondary outcomes. The impact on victimization was not moderated by child gender, age, or victimization status at baseline. Lesson adherence was good but exposure (lesson length) was lower than the recommended amount, and there was considerable variability in the implementation of whole school elements. The trial found insufficient evidence to conclude that KiVa had an effect on the primary outcome. A larger trial of KiVa in the UK is warranted, however, with attention to issues regarding implementation fidelity. Trial registration: Current Controlled Trials ISRCTN23999021 Date 10-6-13</jats:p