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Karen Davies

Publications and source records attributed to Karen Davies.

10 recordsLinked to original sources

Experimentally-derived functional form for a population-averaged high-temporal-resolution arterial input function for dynamic contrast-enhanced MRI.

Rapid T(1)-weighted 3D spoiled gradient-echo (GRE) data sets were acquired in the abdomen of 23 cancer patients during a total of 113 separate visits to allow dynamic contrast-enhanced MRI (DCE-MRI) analysis of tumor microvasculature. The arterial input function (AIF) was measured in each patient at each visit using an automated AIF extraction method following a standardized bolus administration of gadodiamide. The AIFs for each patient were combined to obtain a mean AIF that is representative for any individual. The functional form of this general AIF may be useful for studies in which AIF measurements are not possible. Improvements in the reproducibility of DCE-MRI model parameters (K(trans), v(e), and v(p)) were observed when this new, high-temporal-resolution population AIF was used, indicating the potential for increased sensitivity to therapy-induced change.

Abdominal Neoplasms↗

Comparison of the performance of tracer kinetic model-driven registration for dynamic contrast enhanced MRI using different models of contrast enhancement.

RATIONALE AND OBJECTIVES: The quantitative analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) data is subject to model fitting errors caused by motion during the time-series data acquisition. However, the time-varying features that occur as a result of contrast enhancement can confound motion correction techniques based on conventional registration similarity measures. We have therefore developed a heuristic, locally controlled tracer kinetic model-driven registration procedure, in which the model accounts for contrast enhancement, and applied it to the registration of abdominal DCE-MRI data at high temporal resolution. MATERIALS AND METHODS: Using severely motion-corrupted data sets that had been excluded from analysis in a clinical trial of an antiangiogenic agent, we compared the results obtained when using different models to drive the tracer kinetic model-driven registration with those obtained when using a conventional registration against the time series mean image volume. RESULTS: Using tracer kinetic model-driven registration, it was possible to improve model fitting by reducing the sum of squared errors but the improvement was only realized when using a model that adequately described the features of the time series data. The registration against the time series mean significantly distorted the time series data, as did tracer kinetic model-driven registration using a simpler model of contrast enhancement. CONCLUSION: When an appropriate model is used, tracer kinetic model-driven registration influences motion-corrupted model fit parameter estimates and provides significant improvements in localization in three-dimensional parameter maps. This has positive implications for the use of quantitative DCE-MRI for example in clinical trials of antiangiogenic or antivascular agents.

Abdominal Neoplasms↗

The spectrum of paediatric and adolescent rheumatology.

A wide range of conditions comes under the umbrella of paediatric rheumatology. These problems are common in childhood and cover a wide variety of presentations and outcomes. Many conditions are benign and self-limiting, others run a chronic relapsing and remitting course; some are fatal. Broadly, rheumatological problems can be subdivided into inflammatory, mechanical, and behaviourally or psychologically driven aetiologies, although these are not mutually exclusive. The majority of patients with rheumatological conditions will present with symptoms that are easily localized to the musculoskeletal system. Sometimes, however, a child with a rheumatological condition may present less specifically: for example with fatigue, deterioration in school performance or growth retardation. In this case a rheumatological aetiology may be overlooked unless it is specifically suspected and a careful assessment for musculoskeletal symptoms and signs is undertaken. In order to arrive at the correct diagnosis and plan appropriate further management, it is therefore important for the clinician both to have an effective system to ensure that musculoskeletal symptoms are appropriately determined and assessed, and to be aware of the wide range of conditions, which can cause such symptoms in childhood and adolescence. The keys to this lie in acquiring the clinical skills necessary to accurately assess such patients and awareness of the changing differential diagnosis with the age of the child. In this chapter, we aim to address these issues, initially by discussing the prevalence of musculoskeletal symptoms in children and adolescents and the various conditions which cause them, and subsequently by looking at common presentations of rheumatic disease in childhood and suggesting an approach to diagnosis in each case.

Adolescent↗

Tracer kinetic model-driven registration for dynamic contrast enhanced MRI time series.

Motion during time-series data acquisition causes model-fitting errors in quantitative dynamic contrast-enhanced (DCE) MRI studies. Motion correction techniques using conventional registration cost functions may produce biased results because they were not designed to deal with the time-varying information content due to contrast enhancement. We present a locally-controlled, 3D translational registration process driven by tracer kinetic modeling that successfully registers abdominal DCE-MRI data at high temporal resolution and compare this method to a similar approach based on registration to the time series mean image in data from 8 patients. When the registration is driven by an appropriate model, we find significant improvements in model-fitting. Also, model-driven registration influences parameter estimates and reduces repeat study variability in measurements of blood volume.

Abdomen↗

Paternal imprints can be established on the maternal Igf2-H19 locus without altering replication timing of DNA.

Genomic imprinting in mammals marks the parental alleles in gametes, resulting in differential gene expression in offspring. A number of epigenetic features are associated with imprinted genes. These include differential DNA methylation, histone acetylation and methylation, subnuclear localization and DNA replication timing. While DNA methylation has been shown to be necessary both for establishment and maintenance of imprinting, the connections with the other types of epigenetic marking systems are not clear. Specifically, it is not known whether the other marking systems, either on their own or in conjunction with DNA methylation, are required for imprinting. Here we show that in the mouse mutant Minute (Mnt) the Igf2-H19 locus acquires a paternal methylation imprint in the maternal germline. DNA methylation of the H19 DMR is established in oogenesis, maintained during postzygotic development on the maternal allele, and erased in primordial germ cells. The fact that a paternal type methylation imprint can also be established in the maternal germline indicates that trans-acting factors that target methylation to this imprinted region are likely to be the same in both germlines. Surprisingly, however, asynchrony of DNA replication of the locus is maintained despite the altered expression and methylation imprint of Igf2 and H19. These results show clearly that replication asynchrony of this region is neither the determinant factor for, nor a consequence of, epigenetic modifications that are critical for genomic imprinting. Replication asynchrony may thus be regulated differently from methylation imprints and have a separate function.

Alleles↗

[Medical education seemingly "immune" to discussions on sex and gender. A study indicates that the gender perspective in teaching is limited].

This article builds upon qualitative interviews with teachers and students in the medical education at Lund university. The results found that a gender perspective is understood primarily in terms of the biological body. Awareness about the different conditions for male and female doctors in the labour market is also apparent. But knowledge about the gender system and its structures of power is not sufficiently problematized when concerning the patient-doctor relation or in teaching about health and sickness. Difficulties with integrating a gender perspective are importantly connected to what is designated as the core curriculum of the medical education. The doctors' attitudes towards a gender perspective and what is seen as "proper medical knowledge" become reproduced in the students.

Education, Medical↗

Disruption of mesodermal enhancers for Igf2 in the minute mutant.

The radiation-induced mutation minute (Mnt) in the mouse leads to intrauterine growth retardation with paternal transmission and has been linked to the distal chromosome 7 cluster of imprinted genes. We show that the mutation is an inversion, whose breakpoint distal to H19 disrupts and thus identifies an enhancer for Igf2 expression in skeletal muscle and tongue, and separates the gene from other mesodermal and extra-embryonic enhancers. Paternal transmission of Mnt leads to drastic downregulation of Igf2 transcripts in all mesodermal tissues and the placenta. Maternal transmission leads to methylation of the H19 differentially methylated region (DMR) and silencing of H19, showing that elements 3' of H19 can modify the maternal imprint. Methylation of the maternal DMR leads to biallelic expression of Igf2 in endodermal tissues and foetal overgrowth, demonstrating that methylation in vivo can open the chromatin boundary upstream of H19. Our work shows that most known enhancers for Igf2 are located 3' of H19 and establishes an important genetic paradigm for the inheritance of complex regulatory mutations in imprinted gene clusters.

Animals↗

Addressing the needs of an ethnic minority diabetic population.

Even if ethnic minority populations in our health community are small in numbers, it is important to identify factors that may affect the quality of the healthcare encounter, such as linguistic needs and health beliefs. Despite increased prevalence and morbidity of diabetes in certain ethnic minority groups, inequalities in health may exist and can be multifactorial in nature. This article looks at the importance of cultural sensitivity, so health professionals can articulate difference, show respect and understand health-related beliefs and values. Individual assessment means that health information can be given that values diversity and is specific to an individual. This article uses social and psychological theory to offer explanations as to how prejudice occurs, and looks at the start of a journey for a diabetes team that cares for a small ethnic minority population.

Attitude of Health Personnel↗

What is effective intervention?--using theories of health promotion.

The increased prevalence of chronic disease offers nurses the challenge of providing educational interventions for people living and managing a condition such as diabetes mellitus. This article uses theoretical models and approaches from health promotion to offer perspectives to explain behaviour and determinants of health. The competing needs and perspectives are applied to see their relevance within diabetes nursing care, and in particular when looking at patient outcomes for a group intervention, raising the question: what is an effective intervention? Evaluating interventions needs clear identifiable values and aims, although this article highlights that success of any intervention will mean different things for the participant or health professional. There is a need for research into the subjective experiences of people with diabetes managing an intensive insulin regimen, and to value and include a wider definition of evidence-based outcomes.

Attitude to Health↗