Graph-based Mumford-Shah segmentation of dynamic PET with application to input function estimation

Author name used in this publication: (David) Dagan Feng2004-2005 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Tetranucleotide and Low Microsatellite Instability Are Inversely Associated with the CpG Island Methylator Phenotype in Colorectal Cancer

MSH3 gene or protein deficiency or loss-of-function in colorectal cancer can cause a DNA mismatch repair defect known as “elevated microsatellite alterations at selected tetranucleotide repeats” (EMAST). A high percentage of MSI-H tumors exhibit EMAST, while MSI-L is also linked with EMAST. However, the distribution of CpG island methylator phenotype (CIMP) within the EMAST spectrum is not known. Five tetranucleotide repeat and five MSI markers were used to classify 100 sporadic colorectal tumours for EMAST, MSI-H and MSI-L according to the number of unstable markers detected. Promoter methylation was determined using methylation-specific PCR for MSH3, MCC, CDKN2A (p16) and five CIMP marker genes. EMAST was found in 55% of sporadic colorectal carcinomas. Carcinomas with only one positive marker (EMAST-1/5, 26%) were associated with advanced tumour stage, increased lymph node metastasis, MSI-L and lack of CIMP-H. EMAST-2/5 (16%) carcinomas displayed some methylation but MSI was rare. Carcinomas with ≥3 positive EMAST markers (13%) were more likely to have a proximal colon location and be MSI-H and CIMP-H. Our study suggests that EMAST/MSI-L is a valuable prognostic and predictive marker for colorectal carcinomas that do not display the high methylation phenotype CIMP-H

Social sciences research in neglected tropical diseases 3: Investment in social science research in neglected diseases of poverty: a case study of Bill and Melinda Gates Foundation

This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: The level of funding provides a good proxy for the level of commitment or prioritisation given to a particular issue. While the need for research relevant to social, economic, cultural and behavioural aspects of neglected tropical diseases (NTD) control has been acknowledged, there is limited data on the level of funding that supports NTD social science research. METHOD: A case study was carried out in which the spending of a major independent funder, the Bill and Melinda Gates Foundation (BMGF) - was analysed. A total of 67 projects funded between October 1998 and November 2008 were identified from the BMGF database. With the help of keywords within the titles of 67 grantees, they were categorised as social science or non-social science research based on available definition of social science. A descriptive analysis was conducted. RESULTS: Of 67 projects analysed, 26 projects (39%) were social science related while 41 projects (61%) were basic science or other translational research including drug development. A total of US$697 million was spent to fund the projects, of which 35$ 241 million) went to social science research. Although the level of funding for social science research has generally been lower than that for non-social science research over 10 year period, social science research attracted more funding in 2004 and 2008. CONCLUSION: The evidence presented in this case study indicates that funding on NTD social science research compared to basic and translational research is not as low as it is perceived to be. However, as there is the acute need for improved delivery and utilisation of current NTD drugs/technologies, informed by research from social science approaches, funding priorities need to reflect the need to invest significantly more in NTD social science research

Border Terriers under primary veterinary care in England: demography and disorders

The Border Terrier is a working terrier type that is generally considered to be a relatively healthy and hardy breed. This study aimed to characterise the demography and common disorders of Border Terriers receiving veterinary care in England using de-identified electronic patient record data within the VetCompass™ Programme

Acquiring Tetanus After Hemorrhoid Banding and Other Gastrointestinal Procedures

Tetanus after hemorrhoidal banding is an extremely rare but serious complication of the procedure. We describe the second reported case of this complication and review the literature concerning tetanus after different gastrointestinal procedures. Although a rare complication, practicing physicians need to be aware of the clinical presentation of this deadly disease when encountered in at-risk patient populations. Such cases also reemphasize the importance of primary tetanus immunization and follow-up boosters for all vulnerable patients

Social sciences research in neglected tropical diseases 2: A bibliographic analysis

The official published version of the article can be found at the link below.Background There are strong arguments for social science and interdisciplinary research in the neglected tropical diseases. These diseases represent a rich and dynamic interplay between vector, host, and pathogen which occurs within social, physical and biological contexts. The overwhelming sense, however, is that neglected tropical diseases research is a biomedical endeavour largely excluding the social sciences. The purpose of this review is to provide a baseline for discussing the quantum and nature of the science that is being conducted, and the extent to which the social sciences are a part of that. Methods A bibliographic analysis was conducted of neglected tropical diseases related research papers published over the past 10 years in biomedical and social sciences. The analysis had textual and bibliometric facets, and focussed on chikungunya, dengue, visceral leishmaniasis, and onchocerciasis. Results There is substantial variation in the number of publications associated with each disease. The proportion of the research that is social science based appears remarkably consistent (<4%). A textual analysis, however, reveals a degree of misclassification by the abstracting service where a surprising proportion of the "social sciences" research was pure clinical research. Much of the social sciences research also tends to be "hand maiden" research focused on the implementation of biomedical solutions. Conclusion There is little evidence that scientists pay any attention to the complex social, cultural, biological, and environmental dynamic involved in human pathogenesis. There is little investigator driven social science and a poor presence of interdisciplinary science. The research needs more sophisticated funders and priority setters who are not beguiled by uncritical biomedical promises

Consensus Analysis of Whole Transcriptome Profiles from Two Breast Cancer Patient Cohorts Reveals Long Non-Coding RNAs Associated with Intrinsic Subtype and the Tumour Microenvironment.

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cellular processes and diseases such as cancer; however, their functions remain poorly characterised. Several studies have demonstrated that lncRNAs are typically disease and tumour subtype specific, particularly in breast cancer where lncRNA expression alone is sufficient to discriminate samples based on hormone status and molecular intrinsic subtype. However, little attempt has been made to assess the reproducibility of lncRNA signatures across more than one dataset. In this work, we derive consensus lncRNA signatures indicative of breast cancer subtype based on two clinical RNA-Seq datasets: the Utah Breast Cancer Study and The Cancer Genome Atlas, through integration of differential expression and hypothesis-free clustering analyses. The most consistent signature is associated with breast cancers of the basal-like subtype, leading us to generate a putative set of six lncRNA basal-like breast cancer markers, at least two of which may have a role in cis-regulation of known poor prognosis markers. Through in silico functional characterization of individual signatures and integration of expression data from pre-clinical cancer models, we discover that discordance between signatures derived from different clinical cohorts can arise from the strong influence of non-cancerous cells in tumour samples. As a consequence, we identify nine lncRNAs putatively associated with breast cancer associated fibroblasts, or the immune response. Overall, our study establishes the confounding effects of tumour purity on lncRNA signature derivation, and generates several novel hypotheses on the role of lncRNAs in basal-like breast cancers and the tumour microenvironment

Age is no barrier: predictors of academic success in older learners

Although predictors of academic success have been identified in young adults, such predictors are unlikely to translate directly to an older student population, where such information is scarce. The current study aimed to examine cognitive, psychosocial, lifetime, and genetic predictors of university-level academic performance in older adults (50–79 years old). Participants were mostly female (71%) and had a greater than high school education level (M = 14.06 years, SD = 2.76), on average. Two multiple linear regression analyses were conducted. The first examined all potential predictors of grade point average (GPA) in the subset of participants who had volunteered samples for genetic analysis (N = 181). Significant predictors of GPA were then re-examined in a second multiple linear regression using the full sample (N = 329). Our data show that the cognitive domains of episodic memory and language processing, in conjunction with midlife engagement in cognitively stimulating activities, have a role in predicting academic performance as measured by GPA in the first year of study. In contrast, it was determined that age, IQ, gender, working memory, psychosocial factors, and common brain gene polymorphisms linked to brain function, plasticity and degeneration (APOE, BDNF, COMT, KIBRA, SERT) did not influence academic performance. These findings demonstrate that ageing does not impede academic achievement, and that discrete cognitive skills as well as lifetime engagement in cognitively stimulating activities can promote academic success in older adults

The course of pain drawings during a 10-week treatment period in patients with acute and sub-acute low back pain

BACKGROUND: Pain drawings are widely used as an assessment of patients' subjective pain in low back pain patients being considered for surgery. Less work has been done on primary health care patients. Moreover, the possible correlation between pain drawing modalities and other pain assessment methods, such as pain score and functional variables needs to be described. Thus, the objectives were to describe the course of pain drawings during treatment in primary health care for low back pain patients. METHODS: 160 primary health care outpatients with acute or sub-acute low back pain were studied during 10 weeks of a stay active concept versus manual therapy in addition to the stay active concept. The patients filled out 3 pain drawings each, at baseline and after 5 and 10 weeks of treatment. In addition the patients also reported pain and functional variables during the 3 measurement periods. RESULTS: The proportion of areas marked, the mean number of areas marked (pain drawing score), mean number of modalities used (area score), and the proportion of patients with pain radiation all decreased during the 10-week treatment period. Most of the improvement occurred during the first half of the period. The seven different pain modalities in the pain drawing were correlated to pain and functional variables. In case of no radiation some modalities were associated with more pain and disability than others, a finding that grew stronger over time. For patients with pain radiation, the modality differences were smaller and inconsistent. CONCLUSION: Pain modalities are significantly correlated with pain and functional variables. There is a shift from painful modalities to less painful ones over time