Molecular profiling of cutaneous squamous cell carcinoma

PhDCutaneous squamous cell carcinoma (cSCC) is the second most common form of non-melanoma skin cancer and accounts for the majority of deaths from this disease. Its incidence is increasing rapidly, contributing significant morbidity to patients and a burden on healthcare resources. The molecular events underlying cSCC development remain largely uncharacterised, despite the well established role of ultraviolet radiation as a principal carcinogen. Genomewide analyses of the genetic changes underlying cSCC development have shown they are subject to large chromosomal aberrations, which often involve whole chromosome arms. Many of these events occur in a high proportion of tumours, yet the genes they target are unknown. In this study, genomewide expression microarray data has been obtained from a series of cSCC and integrated with single nucleotide polymorphism (SNP) microarray data, to provide a comprehensive analysis of the events associated with tumour development. In total, 222 genes were identified as differentially expressed in cSCC, of which, 21% were concordant with copy number changes. Previous genomewide SNP data of cSCC had identified microdeletions within the PTPRD gene in a subset of tumours (Purdie et al., 2009). This was investigated in further detail and revealed microdeletions in this gene were significantly associated with metastatic cSCC. Sequencing analysis showed 37% of cSCC had a mutation at this locus, which suggests PTPRD is aberrant in a significant proportion of tumours. Decreased expression levels of PTPRD were correspondingly found in moderately and poorly differentiated tumours. The role of PTPRD in skin biology is not known and further functional work is required to elucidate its role in skin cancer. Taken together, these data provide a valuable insight into the genetic background against which cSCC develop. Furthermore, the association of PTPRD disruption with aggressive tumours may potentially be of future benefit as a prognostic biomarker and therapeutic target

Promoting inclusion oral-health:social interventions to reduce oral health inequities

The aim of this collection of papers is to provide the reader with a cogent understanding of the role of evidence in the development of social or community-based interventions to promote inclusion oral-health and reduce oral health, health, and psychosocial inequities. In addition, this material will include various methods used for their implementation and evaluation. At the outset, the reader will be offered a working definition of inclusion oral-health, which will be modelled on the work of Luchenski et al. [1]. The interventions described are theoretically underpinned by a pluralistic definition of evidence-based practice [2] and the radical discourse of health promotion as postulated by Laverack and Labonte [3] and others [4,5]. This Special Issue will consist of eight papers, including an introduction. The first three papers will examine the various sources of evidence used to transform top-down into bottom-up community-based interventions for people experiencing homelessness; people in custody and for families residing in areas of high social deprivation. The final four papers will report on the implementation and evaluation of social or community-based interventions. This collection of research papers will highlight the importance of focusing on prevention and the adoption of a common risk factor agenda to tackle oral health, health and psychosocial inequities felt by those most excluded in our societies

mekoFUN für die Grundbildung: metakognitiv fundierte Bildungsarbeit mit Geringqualifizierten

Das neue Forschungsprojekt mekoFun beruht auf dem Konzept des metakognitiv fundierten Lernens. Dieser Ansatz wurde im Vorgängerprojekt KLASSIK bei älteren Lernern und dabei auch bei Lernenden mit eher niedrigen Intelligenzwerten erprobt und erfolgreich umgesetzt

The Relationship between Model Biases in East Asian Summer Monsoon Rainfall and Land Evaporation

This is the final version. Available on open access from Springer via the DOI in this recordThe East Asian Summer Monsoon (EASM) provides the majority of annual rainfall to countries in East Asia. Although state-of-the-art models broadly project increased EASM rainfall, the spread of projections is large and simulations of present-day rainfall show significant climatological biases. Systematic evapotranspiration biases occur locally over East Asia, and globally over land, in simulations both with and without a coupled ocean. This study explores the relationship between evapotranspiration and EASM precipitation biases. First, idealized model simulations are presented in which the parameterization of land evaporation is modified, while sea surface temperature is fixed. The results suggest a feedback whereby excessive evapotranspiration over East Asia results in cooling of land, a weakened monsoon low, and a shift of rainfall from the Philippine Sea to China, further fueling evapotranspiration. Cross-model regressions against evapotranspiration over China indicate a similar pattern of behavior in Atmospheric Model Intercomparison Project (AMIP) simulations. Possible causes of this pattern are investigated. The feedback is not explained by an overly intense global hydrological cycle or by differences in radiative processes. Analysis of land-only simulations indicates that evapotranspiration biases are present even when models are forced with prescribed rainfall. These are strengthened when coupled to the atmosphere, suggesting a role for land-model errors in driving atmospheric biases. Coupled atmosphere-ocean models are shown to have similar evapotranspiration biases to those in AMIP over China, but different precipitation biases, including a northward shift in the ITCZ over the Pacific and Atlantic Oceans.UK-China Research and Innovation Partnership Fun

Identification of single nucleotide polymorphisms from the transcriptome of an organism with a whole genome duplication

BACKGROUND: The common ancestor of salmonid fishes, including rainbow trout (Oncorhynchus mykiss), experienced a whole genome duplication between 20 and 100 million years ago, and many of the duplicated genes have been retained in the trout genome. This retention complicates efforts to detect allelic variation in salmonid fishes. Specifically, single nucleotide polymorphism (SNP) detection is problematic because nucleotide variation can be found between the duplicate copies (paralogs) of a gene as well as between alleles. RESULTS: We present a method of differentiating between allelic and paralogous (gene copy) sequence variants, allowing identification of SNPs in organisms with multiple copies of a gene or set of genes. The basic strategy is to: 1) identify windows of unique cDNA sequences with homology to each other, 2) compare these unique cDNAs if they are not shared between individuals (i.e. the cDNA is homozygous in one individual and homozygous for another cDNA in the other individual), and 3) give a “SNP score” value between zero and one to each candidate sequence variant based on six criteria. Using this strategy we were able to detect about seven thousand potential SNPs from the transcriptomes of several clonal lines of rainbow trout. When directly compared to a pre-validated set of SNPs in polyploid wheat, we were also able to estimate the false-positive rate of this strategy as 0 to 28% depending on parameters used. CONCLUSIONS: This strategy has an advantage over traditional techniques of SNP identification because another dimension of sequencing information is utilized. This method is especially well suited for identifying SNPs in polyploids, both outbred and inbred, but would tend to be conservative for diploid organisms

Mapping Alternative Impact: Alternative approaches to impact from co-produced research

No abstract available

Use of tramadol in a Labrador retriever presenting with self-mutilation of the tail

A 30-month-old Labrador retriever bitch with a history of atopy was presented for acuteonset tail biting that was leading to self-mutilation. The problem began 8 months before consultation and was resolved after 2 months, but it recurred 3 months later and continued for 3 months until the time of consultation. The current episode was difficult to interrupt and was being controlled through the use of an Elizabethan collar. There had been no history of injury to the tail. On examination of the tail, an irregularity was palpated approximately midway on the dorsal surface. Radiographs of the tail showed soft-tissue swelling cranially and presence of an ossicle between the mid-caudal vertebrae. Mutilation stopped with administration of tramadol and paracetamol and started again when the medication was discontinued. No behavior modification was implemented. Although there is a possibility that the tramadol was treating a psychogenically driven self-mutilation behavior, it is more likely that pain was the initiating cause for the behavior. This case report highlights the importance of careful medical evaluation of suspected behavioral problems and discusses the possible use of tramadol in self-mutilation.http://www.journals.elsevier.com/journal-of-veterinary-behavior-clinical-applications-and-research/mn201