Exploration of the spatial epidemiology of tick borne pathogens of livestock in Southern Cumbria

Changes to farm production subsidies are provoking the maintenance of far less stock. Given thatwildlife is more abundant in sustainable uplands, pathogens able to exploit both wild-living anddomesticated hosts are of particular concern. Tick-borne pathogens are not only a case in point; butalso their threat is now augmented by increasing tick abundance, changing climate, and theextraordinary nationwide increase in the abundance of deer (that serve as a key host species). The major objective of this thesis was to further understand the spatial distribution of questingIxodes ricinus ticks across farms in Southern Cumbria; as well as to attempt to understand theepidemiological and ecological factors that have a significant influence on the patterns of infectionsin livestock. This project integrated field work, GIS, molecular methods and citizen science in aneffort to understand these complex epidemiologies. Results demonstrated that: I. ricinus exhibit a patchy distribution across all study sites, withproximity to woodland indicated as the main driver behind this. The causal agent of tick borne fever,Anaplasma phagocytophilum was observed across the sites, with sheep being implicated as the maindrivers behind this, rather than deer. Conflicting to anecdotal evidence, Babesia divergens (the agent of red water fever in cattle) was notfound at any of the sites. However, the discovery of B. venatorum in a new area of the UK is ofpotential medical importance. In addition to the confirmation of B. OO-2012, and a B. odocoilei- likespecies; this, to the best of my knowledge, is the first recording of these pathogens in the UK. Contrary to scientific studies, Borrelia afzelli was observed in adult I ricinus females feeding oncattle; suggesting that the results from in vitro assays do not seamlessly translate into the field, andthat further work is needed to quantify the role cattle may play in the circulation of Borrelia, which isof public health importance. Louping Ill Virus was sampled for, but was not confirmed. The truly multidisciplinary nature of this project, has demonstrated the need for a holistic approachwhen considering the ecology and epidemiology of tick borne diseas

Mobile phone and tablet apps to support young people’s management of their physical long-term conditions: a systematic review protocol

Background: The prevalence of long-term or chronic conditions that limit activity and reduce quality of life in young people aged 10-24 years is rising. This group has distinct health care needs and requires tailored support strategies to facilitate increasing personal responsibility for the management of their condition wherever possible, as they mature. Mobile phone and tablet mobile technologies featuring software program apps are already well used by young people for social networking or gaming. They have also been utilized in health care to support personal condition management, using condition-specific and patient-tailored software. Such apps have much potential, and there is an emerging body of literature on their use in a health context making this review timely. Objective: The objective of this paper is to develop a systematic review protocol focused on identifying and assessing the effectiveness of mobile phone and tablet apps that support young people’s management of their chronic conditions. Methods: The search strategy will include a combination of standardized indexed search terms and free-text terms related to the key concepts of young people; long-term conditions and mobile technology. Peer-reviewed journal articles published from 2003 that meet the inclusion and exclusion criteria will be identified through searching the generated hits from 5 bibliographical databases. Two independent reviewers will screen the titles and abstracts to determine which articles focus on testing interventions identified as a mobile phone or tablet apps, and that have been designed and delivered to support the management of long-term conditions in young people aged 10-24 years. Data extraction and quality assessment tools will be used to facilitate consistent analysis and synthesis. It is anticipated that several studies will meet the selection criteria but that these are likely to be heterogeneous in terms of study design, reported outcomes, follow-up times, participants’ age, and health condition. Sub-group analyses will be undertaken and where possible meta-analyses will take place.Results: This review will synthesize available knowledge surrounding tablet and mobile phone apps that support management of long term physical health conditions in young people. The findings will be synthesized to determine which elements of the technologies were most effective for this population. Conclusions: This systematic review aims to synthesize existing literature in order to generate findings that will facilitate the development of an app intervention. The review will form the first phase of development and evaluation of a complex intervention as recommended by the United Kingdom Medical Research Council. The knowledge gained from the review will be verified in subsequent phases, which will include primary qualitative work with health professionals and young people with long term conditions as research participants. Young people living with long-term conditions will be involved as co-researchers and consumer advisors in all subsequent phases to develop and evaluate an app to support the management of long-term physical health conditions

Optimisation of NMR dynamic models I. Minimisation algorithms and their performance within the model-free and Brownian rotational diffusion spaces

The key to obtaining the model-free description of the dynamics of a macromolecule is the optimisation of the model-free and Brownian rotational diffusion parameters using the collected R1, R2 and steady-state NOE relaxation data. The problem of optimising the chi-squared value is often assumed to be trivial, however, the long chain of dependencies required for its calculation complicates the model-free chi-squared space. Convolutions are induced by the Lorentzian form of the spectral density functions, the linear recombinations of certain spectral density values to obtain the relaxation rates, the calculation of the NOE using the ratio of two of these rates, and finally the quadratic form of the chi-squared equation itself. Two major topological features of the model-free space complicate optimisation. The first is a long, shallow valley which commences at infinite correlation times and gradually approaches the minimum. The most severe convolution occurs for motions on two timescales in which the minimum is often located at the end of a long, deep, curved tunnel or multidimensional valley through the space. A large number of optimisation algorithms will be investigated and their performance compared to determine which techniques are suitable for use in model-free analysis. Local optimisation algorithms will be shown to be sufficient for minimisation not only within the model-free space but also for the minimisation of the Brownian rotational diffusion tensor. In addition the performance of the programs Modelfree and Dasha are investigated. A number of model-free optimisation failures were identified: the inability to slide along the limits, the singular matrix failure of the Levenberg–Marquardt minimisation algorithm, the low precision of both programs, and a bug in Modelfree. Significantly, the singular matrix failure of the Levenberg–Marquardt algorithm occurs when internal correlation times are undefined and is greatly amplified in model-free analysis by both the grid search and constraint algorithms. The program relax (http://www.nmr-relax.com) is also presented as a new software package designed for the analysis of macromolecular dynamics through the use of NMR relaxation data and which alleviates all of the problems inherent within model-free analysis

Linking disease epidemiology and livestock productivity: the case of bovine respiratory disease in France

Concerns are growing over the impact of livestock farming on environment and public health. The livestock industry is faced with the double constraint of limiting its use of natural resources and antimicrobials while ensuring its economic sustainability. In this context, reliable methods are needed to evaluate the effect of the prevention of endemic animal diseases on the productivity of livestock production systems. In this study, an epidemiological and productivity model was used to link changes in Bovine Respiratory Disease (BRD) incidence with the productivity of the beef and dairy cattle sectors in France. Cattle production parameters significantly affected by BRD were selected through literature review. Previous field study results and national cattle performance estimates were used to infer growth performances, mortality rates and carcass quality in the cattle affected and not affected by BRD. A steady-state deterministic herd production model was used to predict the productivity of the dairy and beef sector and their defined compartments (breeding-fattening, feedlot young bulls, and feedlot veal) in case of BRD incidence reduction by 20%, 50% or 100%. Results suggested that BRD should be controlled at a priority in beef breeding farms as eradication of BRD in beef calves would increase the whole beef sector’s productivity by 4.7–5.5% while eradication in other production stages would result in lower productivity gain in their respective sectors. However, the analysis performed at compartment level showed that, in both the beef and dairy sector, young bull and veal feedlot enterprises derive more economic benefits from BRD eradication for their own compartment (increase in productivity of 8.7–12.8% for beef young bulls) than the breeding farms (increase in productivity of 5.1–6% for beef calves), which may limit the investments in BRD control

The economic pressures for biosimilar drug use in cancer medicine

The main rationale for using biosimilar drugs is for cost saving. The market development for biosimilar drugs will therefore depend on the degree to which cost saving measures are required by nations, medical insurers and individuals and the absolute savings that could be gained by switching from original drugs. This paper is designed to discover the degree to which financial constraints will drive future health spending and to discover if legal or safety issues could impact on any trend. A structured literature search was performed for papers and documents to 27 August 2011. Where multiple sources of data were available on a topic, data from papers and reports by multinational or national bodies were used in preference to data from regions or individual hospitals. Almost all health systems face current significant cost pressures. The twin driver of increasing cancer prevalence as populations age and cancer medicine costs rising faster than inflation places oncology as the most significant single cost problem. For some countries, this is predicted to make medicine unaffordable within a decade. Most developed countries have planned to embrace biosimilar use as a cost-control measure. Biosimilar introduction into the EU has already forced prices down, both the price of biosimilar drugs and competitive price reductions in originator drugs. Compound annual growth rates of use have been predicted at 65.8% per year. Most developed countries have planned to embrace biosimilar use as a major cost-control measure. Only legal blocks and safety concerns are likely to act against this trend. For centralised healthcare systems, and those with a strong tradition of generic medicine use, biosimilar use will clearly rise with predictions of more than 80% of prescriptions of some biologic drugs within 1 year of market entry in the USA. Delaying the implementation of such programmes however risks a real crisis in healthcare delivery for many countries and hospitals that few can now afford

Haldane's rule in the 21st century

Haldane's Rule (HR), which states that 'when in the offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous (heterogametic) sex', is one of the most general patterns in speciation biology. We review the literature of the past 15 years and find that among the similar to 85 new studies, many consider taxa that traditionally have not been the focus for HR investigations. The new studies increased to nine, the number of 'phylogenetically independent' groups that comply with HR. They continue to support the dominance and faster-male theories as explanations for HR, although due to increased reliance on indirect data (from, for example, differential introgression of cytoplasmic versus chromosomal loci in natural hybrid zones) unambiguous novel results are rare. We further highlight how research on organisms with sex determination systems different from those traditionally considered may lead to more insight in the underlying causes of HR. In particular, haplodiploid organisms provide opportunities for testing specific predictions of the dominance and faster X chromosome theory, and we present new data that show that the faster-male component of HR is supported in hermaphrodites, suggesting that genes involved in male function may evolve faster than those expressed in the female function. Heredity (2011) 107, 95-102; doi:10.1038/hdy.2010.170; published online 12 January 201

Fitness Consequences of Advanced Ancestral Age over Three Generations in Humans

A rapid rise in age at parenthood in contemporary societies has increased interest in reports of higher prevalence of de novo mutations and health problems in individuals with older fathers, but the fitness consequences of such age effects over several generations remain untested. Here, we use extensive pedigree data on seven pre-industrial Finnish populations to show how the ages of ancestors for up to three generations are associated with fitness traits. Individuals whose fathers, grandfathers and great-grandfathers fathered their lineage on average under age 30 were ~13% more likely to survive to adulthood than those whose ancestors fathered their lineage at over 40 years. In addition, females had a lower probability of marriage if their male ancestors were older. These findings are consistent with an increase of the number of accumulated de novo mutations with male age, suggesting that deleterious mutations acquired from recent ancestors may be a substantial burden to fitness in humans. However, possible non-mutational explanations for the observed associations are also discussed

How to make a sex chromosome

Sex chromosomes can evolve once recombination is halted between a homologous pair of chromosomes. Owing to detailed studies using key model systems, we have a nuanced understanding and a rich review literature of what happens to sex chromosomes once recombination is arrested. However, three broad questions remain unanswered. First, why do sex chromosomes stop recombining in the first place? Second, how is recombination halted? Finally, why does the spread of recombination suppression, and therefore the rate of sex chromosome divergence, vary so substantially across clades? In this review, we consider each of these three questions in turn to address fundamental questions in the field, summarize our current understanding, and highlight important areas for future work

Designing Bioactive Delivery Systems for Tissue Regeneration

The direct infusion of macromolecules into defect sites generally does not impart adequate physiological responses. Without the protection of delivery systems, inductive molecules may likely redistribute away from their desired locale and are vulnerable to degradation. In order to achieve efficacy, large doses supplied at interval time periods are necessary, often at great expense and ensuing detrimental side effects. The selection of a delivery system plays an important role in the rate of re-growth and functionality of regenerating tissue: not only do the release kinetics of inductive molecules and their consequent bioactivities need to be considered, but also how the delivery system interacts and integrates with its surrounding host environment. In the current review, we describe the means of release of macromolecules from hydrogels, polymeric microspheres, and porous scaffolds along with the selection and utilization of bioactive delivery systems in a variety of tissue-engineering strategies