Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease

Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a 'vicious cycle' of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The behaviour of the model compares well with published experimental data. The model serves as a first step to understand the development of MM-induced bone disease and could be applied further to evaluate the current therapies against MM-induced bone disease and even suggests new potential therapeutic targets

Cronin Effect at Different Rapidities at RHIC

Calculations of the nuclear modification factor, R_dAu, for pi^0 production in dAu collisions at s_NN^1/2 = 200 GeV are presented. The applied pQCD-improved parton model incorporates intrinsic k_T. Nuclear multiscattering and nuclear shadowing are considered in the Au nucleus. Theoretical results are displayed for midrapidity and high pseudorapidity (eta), and compared to preliminary PHENIX and BRAHMS data.Comment: Contributed to 17th International Conference on Ultra Relativistic Nucleus-Nucleus Collisions (Quark Matter 2004), Oakland, California, 11-17 Jan 200

Modelling microbiome recovery after antibiotics using a stability landscape framework

Treatment with antibiotics is one of the most extreme perturbations to the human microbiome. Even standard courses of antibiotics dramatically reduce the microbiome’s diversity and can cause transitions to dysbiotic states. Conceptually, this is often described as a ‘stability landscape’: the microbiome sits in a landscape with multiple stable equilibria, and sufficiently strong perturbations can shift the microbiome from its normal equilibrium to another state. However, this picture is only qualitative and has not been incorporated in previous mathematical models of the effects of antibiotics. Here, we outline a simple quantitative model based on the stability landscape concept and demonstrate its success on real data. Our analytical impulse-response model has minimal assumptions with three parameters. We fit this model in a Bayesian framework to data from a previous study of the year-long effects of short courses of four common antibiotics on the gut and oral microbiomes, allowing us to compare parameters between antibiotics and microbiomes, and further validate our model using data from another study looking at the impact of a combination of last-resort antibiotics on the gut microbiome. Using Bayesian model selection we find support for a long-term transition to an alternative microbiome state after courses of certain antibiotics in both the gut and oral microbiomes. Quantitative stability landscape frameworks are an exciting avenue for future microbiome modelling

Defining human-machine micro-task workflows for constitution making

This paper presents a novel task-oriented approach to crowdsource the drafting of a constitution. By considering micro-tasking as a particular form of crowdsourcing, it defines a workflow-based approach based on Onto2Flow, an ontology that models the basic concepts and roles to represent workflow-definitions. The approach is then applied to a prototype platform for constitution-making where human workers are requested to contribute to a set of tasks. The paper concludes by discussing previous approaches to participatory constitution-making and identifying areas for future work.This work is part-funded by FEDER Funds, by the ERDF (European Regional Development Fund) through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through the FCT (Portuguese Foundation for Science and Technology) within the project FCOMP-01-0124-FEDER-028980 (PTDC/EEI-SII/1386/2012). The work of Nuno Luz is supported by the doctoral grant SFRH/BD/70302/2010. The work of Marta Poblet draws from previous research within the framework of the project “Crowdsourcing: instrumentos semánticos para el desarrollo de la participación y la mediación online” (DER 2012-39492-C02-01) by the Spanish Ministry of Economy and Competitiveness.info:eu-repo/semantics/publishedVersio

Ethnic Variations in the Prevalence of Diabetic Retinopathy in People with Diabetes Attending Screening in the United Kingdom (DRIVE UK)

AIMS: To compare the prevalence of diabetic retinopathy (DR) in people of various ethnic groups with diabetes in the United Kingdom (UK). METHODS: The Diabetic Retinopathy In Various Ethnic groups in UK (DRIVE UK) Study is a cross-sectional study on the ethnic variations of the prevalence of DR and visual impairment in two multi-racial cohorts in the UK. People on the diabetes register in West Yorkshire and South East London who were screened, treated or monitored between April 2008 to July 2009 (London) or August 2009 (West Yorkshire) were included in the study. Data included age, sex, ethnic group, type of diabetes, presenting visual acuity and the results of grading of diabetic retinopathy. Prevalence estimates for the ethnic groups were age-standardised to the white European population for comparison purposes. RESULTS: Out of 57,144 people on the two diabetic registers, data were available on 50,285 individuals (88.0%), of these 3,323 had type 1 and 46,962 had type 2 diabetes. In type 2 diabetes, the prevalence of any DR was 38.0% (95% confidence interval (CI) 37.4% to 38.5%) in white Europeans compared to 52.4% (51.2% to 53.6%) in African/Afro-Caribbeans and 42.3% (40.3% to 44.2%) in South Asians. Similarly, sight threatening DR was also significantly more prevalent in Afro-Caribbeans (11.5%, 95% CI 10.7% to 12.3%) and South Asians (10.3%, 9.0% to 11.5%) compared to white Europeans (5.5%, 5.3% to 5.8%). Differences observed in Type 1 diabetes did not achieve conventional levels of statistical significance, but there were lower numbers for these analyses. CONCLUSIONS: Minority ethnic communities with type 2 diabetes in the UK are more prone to diabetic retinopathy, including sight-threatening retinopathy and maculopathy compared to white Europeans

Natural images from the birthplace of the human eye

Here we introduce a database of calibrated natural images publicly available through an easy-to-use web interface. Using a Nikon D70 digital SLR camera, we acquired about 5000 six-megapixel images of Okavango Delta of Botswana, a tropical savanna habitat similar to where the human eye is thought to have evolved. Some sequences of images were captured unsystematically while following a baboon troop, while others were designed to vary a single parameter such as aperture, object distance, time of day or position on the horizon. Images are available in the raw RGB format and in grayscale. Images are also available in units relevant to the physiology of human cone photoreceptors, where pixel values represent the expected number of photoisomerizations per second for cones sensitive to long (L), medium (M) and short (S) wavelengths. This database is distributed under a Creative Commons Attribution-Noncommercial Unported license to facilitate research in computer vision, psychophysics of perception, and visual neuroscience.Comment: Submitted to PLoS ON

Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome

There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson-plus and the UK National PSP Research Network (PROSPECT-MR). Resting-state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large-scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between-network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five-fold cross-validation. In PSP and CBS, between-network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between-network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics