Publications by authors named "Francisco J Rubio"

Background: Cancer survival is a key component to assess the overall effectiveness of healthcare systems in their cancer management efforts. A key supporting tool for planning and decision making was introduced with the development of an index of cancer survival that summarises survival for all adults and cancer types into one single estimate, but the implementation details have not been previously described.

Methods: We detail the construction of the index, including the structure, the calculation of 'sex-age-cancer' specific weights and our proposed modelling strategy to estimate net survival.

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Article Synopsis
  • More deprived cancer patients are more likely to present to the emergency department for colon cancer, which is linked to lower symptom awareness and higher comorbidities.
  • A study analyzed hospital admission data to understand patterns of emergency admissions before cancer diagnosis, focusing on differences between the most and least deprived patients.
  • Results showed that deprived patients had more emergency admissions for non-specific symptoms in the months leading up to their diagnosis, suggesting healthcare access issues could contribute to socio-economic disparities in cancer presentations.
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Relative survival represents the preferred framework for the analysis of population cancer survival data. The aim is to model the survival probability associated with cancer in the absence of information about the cause of death. Recent data linkage developments have allowed for incorporating the place of residence into the population cancer databases; however, modeling this spatial information has received little attention in the relative survival setting.

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We study parametric inference on a rich class of hazard regression models in the presence of right-censoring. Previous literature has reported some inferential challenges, such as multimodal or flat likelihood surfaces, in this class of models for some particular data sets. We formalize the study of these inferential problems by linking them to the concepts of near-redundancy and practical nonidentifiability of parameters.

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To reduce the breast cancer burden, the French National Organised Breast Cancer Screening Programme (FNOBCSP) was implemented in 2004. The recommended participation rate has never been achieved and socio-territorial inequities in participation have been reported on several occasions. We investigated the functional forms and consistency of the relationships between neighbourhood deprivation, travel time to the nearest accredited radiology centre and screening uptake.

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Unobserved individual heterogeneity is a common challenge in population cancer survival studies. This heterogeneity is usually associated with the combination of model misspecification and the failure to record truly relevant variables. We investigate the effects of unobserved individual heterogeneity in the context of excess hazard models, one of the main tools in cancer epidemiology.

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In many applications of survival data analysis, the individuals are treated in different medical centres or belong to different clusters defined by geographical or administrative regions. The analysis of such data requires accounting for between-cluster variability. Ignoring such variability would impose unrealistic assumptions in the analysis and could affect the inference on the statistical models.

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Cancer survival represents one of the main indicators of interest in cancer epidemiology. However, the survival of cancer patients can be affected by several factors, such as comorbidities, that may interact with the cancer biology. Moreover, it is interesting to understand how different cancer sites and tumour stages are affected by different comorbidities.

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We introduce a numerically tractable formulation of Bayesian joint models for longitudinal and survival data. The longitudinal process is modeled using generalized linear mixed models, while the survival process is modeled using a parametric general hazard structure. The two processes are linked by sharing fixed and random effects, separating the effects that play a role at the time scale from those that affect the hazard scale.

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Background: Large and complex population-based cancer data are becoming broadly available, thanks to purposeful linkage between cancer registry data and health electronic records. Aiming at understanding the explanatory power of factors on cancer survival, the modelling and selection of variables need to be understood and exploited properly for improving model-based estimates of cancer survival.

Method: We assess the performances of well-known model selection strategies developed by Royston and Sauerbrei and Wynant and Abrahamowicz that we adapt to the relative survival data setting and to test for interaction terms.

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Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat mood and anxiety disorders. Chronic treatment with this antidepressant drug is thought to favor functional recovery by promoting structural and molecular changes in several forebrain areas. At the synaptic level, chronic fluoxetine induces an increased size and density of dendritic spines and an increased ratio of GluN2A over GluN2B N-methyl-D-aspartate (NMDA) receptor subunits.

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Article Synopsis
  • Cancer epidemiology uses regression models to assess excess mortality and cancer survival based on population data.
  • Background mortality rates for cancer patients are typically derived from life tables considering age and sex, but lack other important factors like deprivation and ethnicity.
  • The study proposes two methods to correct biases in excess hazard regression models from mismatched life tables, demonstrating their effectiveness through simulations and applying them to lung cancer patient data.
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Survival data analysis results are usually communicated through the overall survival probability. Alternative measures provide additional insights and may help in communicating the results to a wider audience. We describe these alternative measures in two data settings, the overall survival setting and the relative survival setting, the latter corresponding to the particular competing risk setting in which the cause of death is unavailable or unreliable.

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Many preclinical studies examined cue-induced relapse to heroin and cocaine seeking in animal models, but most of these studies examined only one drug at a time. In human addicts, however, polydrug use of cocaine and heroin is common. We used a polydrug self-administration relapse model in rats to determine similarities and differences in brain areas activated during cue-induced reinstatement of heroin and cocaine seeking.

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Background: Reducing hospital emergency admissions is a key target for all modern health systems.

Methods: We analysed colon cancer patients diagnosed in 2011-13 in England. We screened their individual Hospital Episode Statistics records in the 90 days pre-diagnosis, the 90 days post-diagnosis, and the 90 days pre-death (in the year following diagnosis), for the occurrence of hospital emergency admissions (HEAs).

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The proportional hazards model represents the most commonly assumed hazard structure when analysing time to event data using regression models. We study a general hazard structure which contains, as particular cases, proportional hazards, accelerated hazards, and accelerated failure time structures, as well as combinations of these. We propose an approach to apply these different hazard structures, based on a flexible parametric distribution (exponentiated Weibull) for the baseline hazard.

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Background: Emergency presentations (EP) represent over a third of all lung cancer admissions in England. Such presentations usually reflect late stage disease and are associated with poor survival. General practitioners (GPs) act as gate-keepers to secondary care and so we sought to understand the association between GP practice characteristics and lung cancer EP.

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Bayesian variable selection often assumes normality, but the effects of model misspecification are not sufficiently understood. There are sound reasons behind this assumption, particularly for large : ease of interpretation, analytical and computational convenience. More flexible frameworks exist, including semi- or non-parametric models, often at the cost of some tractability.

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We study Bayesian linear regression models with skew-symmetric scale mixtures of normal error distributions. These kinds of models can be used to capture departures from the usual assumption of normality of the errors in terms of heavy tails and asymmetry. We propose a general noninformative prior structure for these regression models and show that the corresponding posterior distribution is proper under mild conditions.

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Background: Eosinophilic oesophagitis (EoE) is characterized by the presence of eosinophils in oesophageal mucosa. Other inflammatory cells, mainly lymphocytes, dendritic cells, and mast cells may also play an important role in this disease. The aim of this study is to compare the inflammatory pattern of the mucosa between EoE and gastro-oesophageal reflux disease (GERD), using automatic image analysis in digital slides, and to assess treatment response after elimination diet and food challenge test.

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Methamphetamine and other drugs activate a small proportion of all neurons in the brain. We previously developed a fluorescence-activated cell sorting (FACS)-based method to characterize molecular alterations induced selectively in activated neurons that express the neural activity marker Fos. However, this method requires pooling samples from many rats.

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The antidepressant drug fluoxetine is widely used for the treatment of a broad range of psychiatric disorders. Its mechanism of action is thought to involve cellular adaptations that are induced with a slow time course after initiation of treatment. To gain insight into the signaling pathways underlying such changes, the expression levels of proteins in a microsomal sub-fraction enriched in intracellular membranes from the rat forebrain was analyzed after two weeks of treatment with fluoxetine.

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Article Synopsis
  • Antidepressant drugs, like SSRIs (specifically fluoxetine), are used to treat major depressive disorder and other psychiatric conditions, leading to changes in the brain's synapses.
  • In a study with adult male rats, fluoxetine increased the density of mushroom-type dendritic spines in certain forebrain areas, linked to heightened glutamate receptor presence.
  • However, prolonged fluoxetine treatment impaired long-term potentiation (LTP) and long-term depression (LTD) specifically at certain synapses in the hippocampus, demonstrating how these drugs can cause structural and functional changes in a selective manner.
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Fluoxetine is currently being administered for long-term maintenance and for prophylactic reasons following the remission of depressive symptoms and several other psychiatric and neurological conditions. We have previously found that in naïve adult male rats, repetitive administration of fluoxetine induced maturation of telencephalic dendritic spines. This finding was associated with the presence of a higher proportion of GluA2- and GluN2A-containing glutamate receptors.

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A lot of effort has been developed to bypass the use of embryonic stem cells (ES) in human therapies, because of several concerns and ethical issues. Some unsolved problems of using stem cells for human therapies, excluding the human embryonic origin, are: how to regulate cell plasticity and proliferation, immunological compatibility, potential adverse side-effects when stem cells are systemically administrated, and the in vivo signals to rule out a specific cell fate after transplantation. Currently, it is known that almost all tissues of an adult organism have somatic stem cells (SSC).

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