Modelling mutational landscapes of human cancers in vitro

Experimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens recapitulate key features of mutational signatures observed in human cancers. In experiments with several cancer-causing agents we obtained high genome-wide concordance between human tumour mutation data and in vitro data with respect to predominant substitution types, strand bias and sequence context. Moreover, we found signature mutations in well-studied human cancer driver genes. To explore endogenous mutagenesis, we used MEFs ectopically expressing activation-induced cytidine deaminase (AID) and observed an excess of AID signature mutations in immortalised cell lines compared to their non-transgenic counterparts. MEF immortalisation is thus a simple and powerful strategy for modelling cancer mutation landscapes that facilitates the interpretation of human tumour genome-wide sequencing data

Why does cultural policy change? Policy discourse and policy subsystem : a case study of the evolution of cultural policy in Catalonia

This is an Author's Accepted Manuscript of an article published in International journal of cultural policy, Vol. 18, N. 1 (2012), p. 13-30 [copyright Taylor & Francis]Culture has come to play a fundamental strategic role in the territorial development that seeks to integrate knowledge economy with social cohesion, governance and sustainability. However, cultural policies have been unable to respond to the dilemmas and expectations that this new order presents. In order to appreciate the consequences of this process, it is essential to gain a better understanding of cultural policy change dynamics. This paper develops a framework for analysing cultural policy stability and change and applies it to the evolution of cultural policy in Catalonia. Both policy continuity and change are conditioned by the evolution of policy discourse on culture and the characteristics of the cultural policy subsystem. Within this framework, we also take into account the role of factors that are exogenous to the cultural domain. Lastly this paper addresses particular characteristics of cultural policy change in regions or stateless nations

Agglomeration, Inequality and Economic Growth (WP)

The impact of income inequality on economic growth is dependent on several factors, including the time horizon considered, the initial level of income and its initial distribution. Yet, as growth and inequality are also uneven across space, it is also pertinent to consider the effects of the geographical agglomeration of economic activity. Moreover, it would also seem pertinent to consider not just the levels of inequality and agglomeration, but also the changes they undergo -i.e., their within-country evolution- and how these two processes interact with each other. By applying different econometric specifications and by introducing different measures of agglomeration at country level -specifically, urbanization and urban concentration rates-, this study analyzes how inequality and agglomeration -both their levels and their evolution- influence economic growth in function of the country’s level of development and its initial income distribution. Our results suggest, in line with previous studies, that while high inequality levels are a limiting factor for long-run growth, increasing inequality and increasing agglomeration have the potential to enhance growth in low-income countries where income distribution remains relatively equal, but can result in congestion diseconomies in high-income countries, especially if income distribution becomes particularly unequal

Time-trend and variations in the proportion of second-eye cataract surgery

<p>Abstract</p> <p>Background</p> <p>Despite recommendations for greater use of second-eye cataract surgery and the bilateral progression of the disease, there is a substantial proportion of unmet need for this treatment. Few studies have explored the factors associated with second-eye cataract surgery utilisation. The objective of our study was to estimate the proportion of second-eye cataract surgery, evaluate its time-trend, and explore differences in utilisation by patients' gender, age, and region of residence.</p> <p>Methods</p> <p>All senile cataract surgeries performed between 1999 and 2002 in the public health system of Catalonia (Spain) were obtained from the Minimum Data Set. The proportion of second-eye surgery from November 2000 to December 2002 was calculated. The time-trend of this proportion was characterised through linear regression models with the logarithmic transformation of time.</p> <p>Results</p> <p>The proportion of second-eye surgery was 30.0% and showed an increasing trend from 24.8% (95% Confidence Interval [CI] 21.6; 26.1) in November 2000 to 31.8% (95% CI 31.4; 33.6) in December 2002. This proportion was 1.9% (95% CI 0.9; 2.9) higher in women (p < 0.001) and held constant across time. Male patients aged less than 60 had the lowest proportion (22.6%; 95% CI 22.4; 22.9) and females between 70 and 79 had the highest proportion (27.4%; 95% CI 26.9; 27.9). The time-trend for the proportion of second-eye surgery in those aged over 80 years was greater than for younger ages, showing an increase of 9% at the end of the period for both males and females. Variations between regions decreased over time because regions with the lowest initial proportions of second-eye surgery (approximately 17%) showed a greater increase over the study period.</p> <p>Conclusion</p> <p>We predict greater utilization of second-eye surgery in patients aged 70 to 79 years and in women. A greater increase in the utilisation rates of second-eye surgery is expected in the regions with lower proportions and in older patients. The observed trend suggests that there will be a substantial proportion of unmet need for bilateral surgery.</p

A Novel Semi-Supervised Methodology for Extracting Tumor Type-Specific MRS Sources in Human Brain Data

BackgroundThe clinical investigation of human brain tumors often starts with a non-invasive imaging study, providing information about the tumor extent and location, but little insight into the biochemistry of the analyzed tissue. Magnetic Resonance Spectroscopy can complement imaging by supplying a metabolic fingerprint of the tissue. This study analyzes single-voxel magnetic resonance spectra, which represent signal information in the frequency domain. Given that a single voxel may contain a heterogeneous mix of tissues, signal source identification is a relevant challenge for the problem of tumor type classification from the spectroscopic signal.Methodology/Principal FindingsNon-negative matrix factorization techniques have recently shown their potential for the identification of meaningful sources from brain tissue spectroscopy data. In this study, we use a convex variant of these methods that is capable of handling negatively-valued data and generating sources that can be interpreted as tumor class prototypes. A novel approach to convex non-negative matrix factorization is proposed, in which prior knowledge about class information is utilized in model optimization. Class-specific information is integrated into this semi-supervised process by setting the metric of a latent variable space where the matrix factorization is carried out. The reported experimental study comprises 196 cases from different tumor types drawn from two international, multi-center databases. The results indicate that the proposed approach outperforms a purely unsupervised process by achieving near perfect correlation of the extracted sources with the mean spectra of the tumor types. It also improves tissue type classification.Conclusions/SignificanceWe show that source extraction by unsupervised matrix factorization benefits from the integration of the available class information, so operating in a semi-supervised learning manner, for discriminative source identification and brain tumor labeling from single-voxel spectroscopy data. We are confident that the proposed methodology has wider applicability for biomedical signal processing

Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use

Cunill R, Castells X, González-Pinto A, Arrojo M, Bernardo M, Sáiz PA, Flórez G, Torrens M, Tirado-Muñoz J, Fonseca F, Arranz B, Garriga M, Goikolea JM, Zorrilla I, Becoña E, López A, San

Domestic knowledge, inequalities and differences

Research suggests that domestic knowledge is an expression of gender differences, which is constructed and deployed through unequal social relations, and is able to empower women if it gains collective spaces of expression. The article presents an analysis of parental involvement at school in Spain so as to underpin the former thesis and highlight its connection with the political theory about the "sexual contract"

Breast radiation dose with contrast-enhanced mammography-guided biopsy: a retrospective comparison with stereotactic and tomosynthesis guidance

Objectives: This retrospective study aimed to compare the average glandular dose (AGD) per acquisition in breast biopsies guided by contrast-enhanced mammography (CEM), conventional stereotactic breast biopsy (SBB), and digital breast tomosynthesis (DBT). The study also investigated the influence of compressed breast thickness (CBT) and density on AGD. Furthermore, the study aimed to estimate the AGD per procedure for each guidance modality. Methods: The study included 163 female patients (mean age 57 ± 10 years) who underwent mammography-guided biopsies using SBB (9%), DBT (65%), or CEM (26%) guidance. AGD and CBT data were extracted from DICOM headers, and breast density was visually assessed. Statistical analyses included two-sample t-tests and descriptive statistics. Results: Mean AGD per acquisition varied slightly among CEM (1.48 ± 0.22 mGy), SBB (1.49 ± 0.40 mGy), and DBT (1.55 ± 0.47 mGy), with CEM presenting higher AGD at lower CBTs and less dose escalation at higher CBTs. For CBT &gt; 55 mm, CEM showed reduced AGD compared to SBB and DBT (p &lt; 0.001). Breast density had minimal impact on AGD, except for category A. The estimated AGD per procedure was approximately 11.84 mGy for CEM, 11.92 mGy for SBB, and 6.2 mGy for DBT. Conclusion: The study found mean AGD per acquisition to be similar for CEM and SBB, with DBT slightly higher. CEM demonstrated higher AGD at lower CBT but lower AGD at higher CBT, indicating reduced dose escalation with increasing thickness. While breast density had minimal overall impact, variations were noted in category A. DBT was more dose-efficient per procedure due to fewer acquisitions required. Clinical relevance statement: CEM guidance provides effective lesion visualization within safe radiation limits, improving the precision of percutaneous image-guided breast interventions and supporting its potential consideration in a wider range of breast diagnostic procedures. Key Points: Limited data exist on the AGD using CEM guidance for breast biopsies. CEM and SBB exhibit similar AGD per acquisition; DBT demonstrated the lowest AGD&nbsp;per procedure. Radiation from CEM guidance fits within safe limits for percutaneous image-guided breast interventions. Graphical Abstract: (Figure presented.