Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

Background: Vorapaxar is a new oral protease-activatedreceptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. Methods: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (KaplanMeier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. Conclusions: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)

Sex differences in hospital readmission among colorectal cancer patients.

Background: While several studies have analysed sex and socioeconomic differences in cancer incidence and mortality, sex differences in oncological health care have been seldom considered. Objective: To investigate sex based inequalities in hospital readmission among patients diagnosed with colorectal cancer. Design: Prospective cohort study. Setting: Hospital Universitary in L¿Hospitalet (Barcelona, Spain). Participants: Four hundred and three patients diagnosed with colorectal between January 1996 and December 1998 were actively followed up until 2002. Main outcome measurements and methods: Hospital readmission times related to colorectal cancer after surgical procedure. Cox proportional model with random effect (frailty) was used to estimate hazard rate ratios and 95% confidence intervals of readmission time for covariates analysed. Results: Crude hazard rate ratio of hospital readmission in men was 1.61 (95% CI 1.21 to 2.15). When other significant determinants of readmission were controlled for (including Dukes¿s stage, mortality, and Charlson¿s index) a significant risk of readmission was still present for men (hazard rate ratio: 1.52, 95% CI 1.17 to 1.96). Conclusions: In the case of colorectal cancer, women are less likely than men to be readmitted to the hospital, even after controlling for tumour characteristics, mortality, and comorbidity. New studies should investigate the role of other non-clinical variable such as differences in help seeking behaviours or structural or personal sex bias in the attention given to patients.

R&D poverty traps

In this paper we show that the R&D effort of a country and its economic growth are highly correlated. In order to analyze this relationship, we study the nature of the researching activity. In particular, we focus on the following characteristics of research: the inherent uncertainty of researching, the existence of a wage premium associated to innovative activities, and moral hazard. Assuming that a higher R&D effort translates into a higher R&D success probability, we show that when the R&D success probability is low, the economy is not willing to bear the risk associated to R&D activities. As a consequence, few researchers are hired and the economy stays in an R&D poverty trap, a situation where the economy is stacked in a low growth environment due to the uncertainty associated with the researching activity.

R&D poverty traps

In this paper we show that the R&D effort of a country and its economic growth are highly correlated. In order to analyze this relationship, we study the nature of the researching activity. In particular, we focus on the following characteristics of research: the inherent uncertainty of researching, the existence of a wage premium associated to innovative activities, and moral hazard. Assuming that a higher R&D effort translates into a higher R&D success probability, we show that when the R&D success probability is low, the economy is not willing to bear the risk associated to R&D activities. As a consequence, few researchers are hired and the economy stays in an R&D poverty trap, a situation where the economy is stacked in a low growth environment due to the uncertainty associated with the researching activity.

El Estudio de las inundaciones históricas desde un enfoque contextual. La ciudad de Girona, un ejemplo

Este artículo propone el enfoque contextual como nuevo marco de estudio de las inundaciones históricas. El enfoque contextual tiene su origen en la reflexión geográfica sobre los riesgos naturales iniciada en la escuela geográfica norteamericana hace ya más de medio siglo y pone especial énfasis en la dimensión humana de estos fenómenos definida geográfica e históricamente, sin olvidar los aspectos físicos de las inundaciones en el territorio objeto de estudio. En una primera parte del presente artículo se describen los niveles de análisis y componentes que componen el estudio de las inundaciones histórica5 desde el enfoque contextual. La segunda parte es una aplicación del enfoque contextual al caso de la ciudad de Girona

Empirical study of correlated survival times for recurrent events with proportional hazards margins and the effect of correlation and censoring.

Background: In longitudinal studies where subjects experience recurrent incidents over a period of time, such as respiratory infections, fever or diarrhea, statistical methods are required to take into account the within-subject correlation. Methods: For repeated events data with censored failure, the independent increment (AG), marginal (WLW) and conditional (PWP) models are three multiple failure models that generalize Cox"s proportional hazard model. In this paper, we revise the efficiency, accuracy and robustness of all three models under simulated scenarios with varying degrees of within-subject correlation, censoring levels, maximum number of possible recurrences and sample size. We also study the methods performance on a real dataset from a cohort study with bronchial obstruction. Results: We find substantial differences between methods and there is not an optimal method. AG and PWP seem to be preferable to WLW for low correlation levels but the situation reverts for high correlations. Conclusions: All methods are stable in front of censoring, worsen with increasing recurrence levels and share a bias problem which, among other consequences, makes asymptotic normal confidence intervals not fully reliable, although they are well developed theoretically.

The Quaternary Active Faults Database of Iberia (QAFI v.2.0)

The Quaternary Active Faults Database of Iberia (QAFI) is an initiative lead by the Institute of Geology and Mines of Spain (IGME) for building a public repository of scientific data regarding faults having documented activity during the last 2.59 Ma (Quaternary). QAFI also addresses a need to transfer geologic knowledge to practitioners of seismic hazard and risk in Iberia by identifying and characterizing seismogenic fault-sources. QAFI is populated by the information freely provided by more than 40 Earth science researchers, storing to date a total of 262 records. In this article we describe the development and evolution of the database, as well as its internal architecture. Aditionally, a first global analysis of the data is provided with a special focus on length and slip-rate fault parameters. Finally, the database completeness and the internal consistency of the data are discussed. Even though QAFI v.2.0 is the most current resource for calculating fault-related seismic hazard in Iberia, the database is still incomplete and requires further review.

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

Background: During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods: Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results: We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion: Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia.

Erosió hídrica en vinya per a producció de vi d'alta qualitat en zona mediterrània (Anoia-Penedès): quantificació de les pèrdues de nutrients per erosió del sòl i implicacions

La vinya, malgrat que no és una planta exigent pel que fa als sòls, es veu afectada per la pèrdua de sed per causa de l'erosió hídrica. En aquest treball es presenten uns primers resultats de mesures de pèrdues de sed en condicions reals de camp. Les parcel les control són de grans dimensions, conreades segons els costums de la zona. Com a referencia es prenen les pèrdues de sòl mitjanes, calculades a partir de l'USLE, per al conreu de vinya. Es determinen, a més de les pèrdues globals de sòlids, les de nutrients que això comporta. Tenint en compte que la metodologia emprada en el camp i en el laboratori condueix a resultats per defecte, les pèrdues mesurades del període de l'any de màximes pluges (tardor) són, de mitjana, de 13 Mg ha-1 en un sistema de cultiu tradicional i fins a 100 Mg ha-1 en un sistema de cultiu emparrat. La importància del problema a curt termini encareix els factors de producció i fa perillar la sostenibilitat de la vinya a llarg termini.

Protective effects of social networks on disability among older adults in Spain

The loss of autonomy at advanced ages is not only associated with ageing, but also with the characteristics of the physical and social environment. Recent investigations have shown that social networks, social engagement and participation act like predictors of disability among the elderly. The aim of this study is to determine whether social networks are related to the development and progression of disability in the early years of old age. The source of data is the first wave of the survey "Processes of Vulnerability among Spanish Elderly", carried out in 2005 to a sample of 1 244 individuals. The population object of study is the cohort aged 70 to 74 years in metropolitan areas (Madrid and Barcelona) and not institutionalized. Disability is measured by the development of basic activities of daily life (ADL), and instrumental activities of daily life (IADL). The structural aspects of the social relationships are measured through the diversity of social networks and participation. We used the social network index (SNI). For each point over the SNI, the risk of developing any type of disability decreased by 49% (HR = 0.51, 95%CI = 0.31-0.82). The SNI was a decisive factor in all forecasting models constructed with some hazard ratios (HR) that ranged from 0.29 (95%CI = 0.14-0.59) in the first model to 0.43 (95%CI 0.20-0.90) in the full model. The results of the present study showed a strong association between an active social life, emotional support provided by friends and confidents and disability. These findings suggest a protective effect of social networks on disability. Also, these results indicate that some family and emotional ties have a significant effect on both the prevalence and the incidence of disability.

Using vegetation to characterize the avalanche to Canal del Roc Roig, Vall de Núria (Eastern Pyrenees, Spain)

Avalanche hazard maps of high accuracy are difficult to produce. For land-use planning and management purposes, a good knowledge of extreme run-out zones and frequencies of avalanches is required. In the present work, vegetation recognition (especially focused on Pinus uncinata trees) and dendrochronological techniques are used to characterize avalanches that have occurred in historical times, helping to determine both the extent of large or extreme avalanches and their occurrence in time. Vegetation was studied at the Canal del Roc Roig (eastern Pyrenees, Spain) avalanche path. The avalanches descending this path affect the railway that reaches the Vall de Núria resort and the run-up to the opposite slope. During winter 1996, two important avalanches affecting this path were well documented. These are compared with the results of the vegetation study, consisting of an inventory of flora, the recording of vegetation damages along eight transverse profiles at different altitudes on the path and a dendrochronological sampling campaign. The data obtained contributed to a characterization of the predominant snow accumulation in the starting zone, the 1996 avalanches and the range of frequencies of large avalanches. Also, traces of avalanches that increase the path mapped in the avalanche paths map published by the Institut Cartogràfic de Catalunya in 2000 were identified, improving the initial existing information.

Using vegetation to characterize the avalanche to Canal del Roc Roig, Vall de Núria (Eastern Pyrenees, Spain)

Avalanche hazard maps of high accuracy are difficult to produce. For land-use planning and management purposes, a good knowledge of extreme run-out zones and frequencies of avalanches is required. In the present work, vegetation recognition (especially focused on Pinus uncinata trees) and dendrochronological techniques are used to characterize avalanches that have occurred in historical times, helping to determine both the extent of large or extreme avalanches and their occurrence in time. Vegetation was studied at the Canal del Roc Roig (eastern Pyrenees, Spain) avalanche path. The avalanches descending this path affect the railway that reaches the Vall de Núria resort and the run-up to the opposite slope. During winter 1996, two important avalanches affecting this path were well documented. These are compared with the results of the vegetation study, consisting of an inventory of flora, the recording of vegetation damages along eight transverse profiles at different altitudes on the path and a dendrochronological sampling campaign. The data obtained contributed to a characterization of the predominant snow accumulation in the starting zone, the 1996 avalanches and the range of frequencies of large avalanches. Also, traces of avalanches that increase the path mapped in the avalanche paths map published by the Institut Cartogràfic de Catalunya in 2000 were identified, improving the initial existing information.

Quaternary active tectonic structures in the offshore Bajo Segura basin (SE Iberian Peninsula Mediterranean Sea).

The Bajo Segura fault zone (BSFZ) is the northern terminal splay of the Eastern Betic shear zone (EBSZ), a large left-lateral strike-slip fault system of sigmoid geometry stretching more than 450 km from Alicante to Almería. The BSFZ extends from the onshore Bajo Segura basin further into the Mediterranean Sea and shows a moderate instrumental seismic activity characterized by small earthquakes. Nevertheless, the zone was affected by large historical earthquakes of which the largest was the 1829 Torrevieja earthquake (IEMS98 X). The onshore area of the BSFZ is marked by active transpressive structures (faults and folds), whereas the offshore area has been scarcely explored from the tectonic point of view. During the EVENT-SHELF cruise, a total of 10 high-resolution single-channel seismic sparker profiles were obtained along and across the offshore Bajo Segura basin. Analysis of these profiles resulted in (a) the identification of 6 Quaternary seismo-stratigraphic units bounded by five horizons corresponding to regional erosional surfaces related to global sea level lowstands; and (b) the mapping of the active sub-seafloor structures and their correlation with those described onshore. Moreover, the results suggest that the Bajo Segura blind thrust fault or the Torrevieja left-lateral strike-slip fault, with prolongation offshore, could be considered as the source of the 1829 Torrevieja earthquake. These data improve our understanding of present deformation along the BSFZ and provide new insights into the seismic hazard in the area.

Positive Outcomes Influence the Rate and Time to Publication, but Not the Impact Factor of Publications of Clinical Trial Results

Objectives: Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings: All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61-2·56) for studies with results classified as positive and 3·21 years (IC95 2·69-3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409) and negative result studies (median 8·266, interquartile range: 4·135-17·157). Conclusions: Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results. However, no differences have been found in terms of impact factor.

Preface: Extreme events induced by weather and climate change: evaluation, forecasting and proactive planning

This special issue of Natural Hazards and Earth System Sciences (NHESS) contains eight papers presented as oral or poster contributions in the Natural Hazards NH-1.2 session on"Extreme events induced by weather and climate change: evaluation, forecasting and proactive planning", held at the European Geosciences Union (EGU) General Assembly in Vienna, Austria, on 13-18 April 2008. The aim of the session was to provide an international forum for presenting new results and for discussing innovative ideas and concepts on extreme hydro-meteorological events, including: (i) the assessment of the risk posed by the extreme events, (ii) the expected changes in the frequency and intensity of the events driven by a changing climate and by multiple human- induced causes, (iii) new modelling approaches and original forecasting methods to predict extreme events and their consequences, and (iv) strategies for hazard mitigation and risk reduction, and for a improved adaptation to extreme hydro-meteorological events ...