Is there a subgroup of long-term evolution among patients with advanced lung cancer?: Hints from the analysis of survival curves from cancer registry data

Background: Recently, with the access of low toxicity biological and targeted therapies, evidence of the existence of a long-term survival subpopulation of cancer patients is appearing. We have studied an unselected population with advanced lung cancer to look for evidence of multimodality in survival distribution, and estimate the proportion of long-term survivors. Methods: We used survival data of 4944 patients with non-small-cell lung cancer (NSCLC) stages IIIb-IV at diagnostic, registered in the National Cancer Registry of Cuba (NCRC) between January 1998 and December 2006. We fitted one-component survival model and two-component mixture models to identify short-and long-term survivors. Bayesian information criterion was used for model selection. Results: For all of the selected parametric distributions the two components model presented the best fit. The population with short-term survival (almost 4 months median survival) represented 64% of patients. The population of long-term survival included 35% of patients, and showed a median survival around 12 months. None of the patients of short-term survival was still alive at month 24, while 10% of the patients of long-term survival died afterwards. Conclusions: There is a subgroup showing long-term evolution among patients with advanced lung cancer. As survival rates continue to improve with the new generation of therapies, prognostic models considering short-and long-term survival subpopulations should be considered in clinical research.

Understanding function and function-to-form evolution

This is a report on a workshop held at Cambridge University Engineering Design Centre, 17-10 June 1992. This workshop was held to discuss the issue of 'function' and 'function-to-form' evolution in mechanical design. The authors organised this workshop as they felt that their understanding of these topics was incomplete and that discussions between researchers might help to clarify some key issues.

The topic chosen for the workshop proved to be a stimulating one. The term 'function' is part of a designer's daily vocabulary, however there is poor agreement about its definition. In order to develop computer systems to support product evolution, a precise definition is required. Further the value of 'function' and 'function-to-form' evolution as a good choice of workshop topic is evident from the lack of firm conclusions that resulted from the sessions. This lack of consensus made for lively discussion and left participants questioning many of their preconceived ideas.

Attendance at the workshop was by invitation only. A list of the participants (not all those invited could attend due to time and financial constraints) is given in Appendix 1.

Epitope mapping of antibodies to alpha-synuclein in LRRK2 mutation carriers, idiopathic Parkinson disease patients, and healthy controls

Alpha-synuclein (Snca) plays a major role in Parkinson disease (PD). Circulating anti-Snca antibodies has been described in PD patients and healthy controls, but they have been poorly characterized. This study was designed to assess the prevalence of anti-Snca reactivity in human subjects carrying the LRRK2 mutation, idiopathic PD (iPD) patients, and healthy controls and to map the epitopes of the anti-Snca antibodies. Antibodies to Snca were detected by ELISA and immunoblotting using purified recombinant Snca in plasma from individuals carrying LRRK2 mutations (104), iPD patients (59), and healthy controls (83). Epitopes of antibodies were mapped using recombinant protein constructs comprising different regions of Snca. Clear positive anti-Snca reactivity showed no correlation with age, sex, years of evolution, or the disability scores for PD patients and anti-Snca reactivity was not prevalent in human patients with other neurological or autoimmune diseases. Thirteen of the positive individuals were carriers of LRRK2 mutations either non-manifesting (8 out 49 screened) or manifesting (5 positive out 55), three positive (out of 59) were iPD patients, and five positive (out of 83) were healthy controls. Epitope mapping showed that antibodies against the N-terminal (a.a. 1-60) or C-terminal (a.a. 109-140) regions of Snca predominate in LRRK2 mutation carriers and iPD patients, being N122 a critical amino acid for recognition by the anti-C-terminal directed antibodies. Anti-Snca circulating antibodies seem to cluster within families carrying the LRRK2 mutation indicating possible genetic or common environmental factors in the generation of anti-Snca antibodies. These results suggest that case-controls' studies are insufficient and further studies in family cohorts of patients and healthy controls should be undertaken, to progress in the understanding of the possible relationship of anti-Snca antibodies and PD patholog

Subtypes of Patients Experiencing Exacerbations of COPD and Associations with Outcomes

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition characterized by occasional exacerbations. Identifying clinical subtypes among patients experiencing COPD exacerbations (ECOPD) could help better understand the pathophysiologic mechanisms involved in exacerbations, establish different strategies of treatment, and improve the process of care and patient prognosis. The objective of this study was to identify subtypes of ECOPD patients attending emergency departments using clinical variables and to validate the results using several outcomes. We evaluated data collected as part of the IRYSS-COPD prospective cohort study conducted in 16 hospitals in Spain. Variables collected from ECOPD patients attending one of the emergency departments included arterial blood gases, presence of comorbidities, previous COPD treatment, baseline severity of COPD, and previous hospitalizations for ECOPD. Patient subtypes were identified by combining results from multiple correspondence analysis and cluster analysis. Results were validated using key outcomes of ECOPD evolution. Four ECOPD subtypes were identified based on the severity of the current exacerbation and general health status (largely a function of comorbidities): subtype A (n = 934), neither high comorbidity nor severe exacerbation; subtype B (n = 682), moderate comorbidities; subtype C (n = 562), severe comorbidities related to mortality; and subtype D (n = 309), very severe process of exacerbation, significantly related to mortality and admission to an intensive care unit. Subtype D experienced the highest rate of mortality, admission to an intensive care unit and need for noninvasive mechanical ventilation, followed by subtype C. Subtypes A and B were primarily related to other serious complications. Hospitalization rate was more than 50% for all the subtypes, although significantly higher for subtypes C and D than for subtypes A and B. These results could help identify characteristics to categorize ECOPD patients for more appropriate care, and help test interventions and treatments in subgroups with poor evolution and outcomes.

Las políticas tecnológicas y de innovación en la Comunidad Autónoma de Euskadi: El caso de los Clusters

[ES] En el presente trabajo se ha tratado de analizar la evolución de las políticas tecnológicas y de innovación en la Comunidad Autónoma de Euskadi (CAE), en las últimas tres décadas, prestando especial atención a la política de clusters. Es evidente el avance tecnológico e innovador experimentado por Euskadi en este período, basado en la estrecha cooperación desarrollada entre las universidades, las instituciones públicas y las empresas privadas. En este marco, la CAE fue pionera en el diseño y puesta en marcha de una política de clusters a principios de los años noventa. Tras más de dos décadas de funcionamiento de dicha política, ésta parece haberse consolidado existiendo en la actualidad 13 asociaciones cluster en Euskadi.

Island life in the Cretaceous - faunal composition, biogeography, evolution, and extinction of land-living vertebrates on the Late Cretaceous European archipelago

The Late Cretaceous was a time of tremendous global change, as the final stages of the Age of Dinosaurs were shaped by climate and sea level fluctuations and witness to marked paleogeographic and faunal changes, before the end-Cretaceous bolide impact. The terrestrial fossil record of Late Cretaceous Europe is becoming increasingly better understood, based largely on intensive fieldwork over the past two decades, promising new insights into latest Cretaceous faunal evolution. We review the terrestrial Late Cretaceous record from Europe and discuss its importance for understanding the paleogeography, ecology, evolution, and extinction of land-dwelling vertebrates. We review the major Late Cretaceous faunas from Austria, Hungary, France, Spain, Portugal, and Romania, as well as more fragmentary records from elsewhere in Europe. We discuss the paleogeographic background and history of assembly of these faunas, and argue that they are comprised of an endemic 'core' supplemented with various immigration waves. These faunas lived on an island archipelago, and we describe how this insular setting led to ecological peculiarities such as low diversity, a preponderance of primitive taxa, and marked changes in morphology (particularly body size dwarfing). We conclude by discussing the importance of the European record in understanding the end-Cretaceous extinction and show that there is no clear evidence that dinosaurs or other groups were undergoing long-term declines in Europe prior to the bolide impact.