Learning Koopman eigenfunctions of stochastic diffusions with optimal importance sampling and ISOKANN

The dominant eigenfunctions of the Koopman operator characterize the metastabilities and slow-timescale dynamics of stochastic diffusion processes. In the context of molecular dynamics and Markov state modeling, they allow for a description of the location and frequencies of rare transitions, which are hard to obtain by direct simulation alone. In this article, we reformulate the eigenproblem in terms of the ISOKANN framework, an iterative algorithm that learns the eigenfunctions by alternating between short burst simulations and a mixture of machine learning and classical numerics, which naturally leads to a proof of convergence. We furthermore show how the intermediate iterates can be used to reduce the sampling variance by importance sampling and optimal control (enhanced sampling), as well as to select locations for further training (adaptive sampling). We demonstrate the usage of our proposed method in experiments, increasing the approximation accuracy by several orders of magnitude

The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats

The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well

Socioeconomic inequalities in the incidence and prevalence of type 2 diabetes mellitus in Europe

The aim of this study was to analyze socioeconomic position (SEP) inequalities in the prevalence and incidence of type 2 diabetes mellitus (T2DM) in people aged 50 years and over in Europe and to describe the contribution of body mass index (BMI) and other possible mediators. This was a cross-sectional and longitudinal study including men and women ≥ 50 years old in 11 European countries in 2004 and 2006 (n = 21,323). The prevalence and cumulative incidence of T2DM were calculated with self-reported T2DM or when the individual took drugs for diabetes. Prevalence ratio (PR) and relative risk (RR) of prevalent and incident T2DM were calculated according to educational level and adjusted by BMI and other possible mediators. The age-adjusted and country-adjusted prevalence of T2DM in 2004 was 10.2% in men and 8.5% in women. Compared to those with higher education, men and women with lower education had a PR [95% CI] of T2DM of 1.29 [1.12-1.50] and 1.61 [1.39-1.86], respectively. SEP-related inequalities in incidence (RR [95%CI]) were 1.88 [1.35-2.62] in women and 1.04 [0.78-1.40] in men. Adjusting for potential mediators reduced inequalities in the prevalence and incidence of T2DM among women by 26.2% and 21.6%, respectively, and inequalities in prevalence among men by 44.8%. We observed significant inequalities in the prevalence and incidence (women only) of T2DM as a function of socioeconomic position. These inequalities were mediated by BM

Socioeconomic inequalities in the incidence and prevalence of type 2 diabetes mellitus in Europe

This paper uses data from SHARE release 2.3.0, November 13th 2009. SHARE data collection in 2004-2007 was primarily funded by the European Commission through its 5th and 6th framework programs (project numbers QLK6-CT-2001-00360; RII-CT-2006-062193; CIT5-CT-2005-028857). Additional funding by the US National Institute on Aging (grant numbers U01 AG09740-13S2; P01 AG005842; P01 AG08291; P30 AG12815; Y1-AG-4553-01; OGHA 04-064; R21 AG025169) as well as by various national sources is gratefully acknowledged (see http://www.share-project.org for a full list of funding institutions). This article forms part of the doctoral dissertation of Albert Espelt at the Universitat Pompeu Fabra of Barcelona.Objective: The aim of this study was to analyze socioeconomic position (SEP) inequalities in the prevalence and incidence of type 2 diabetes mellitus (T2DM) in people aged 50 years and over in Europe and to describe the contribution of body mass index (BMI) and other possible mediators. Methods: This was a cross-sectional and longitudinal study including men and women ≥50 years old in 11 European countries in 2004 and 2006 (. n=. 21,323). The prevalence and cumulative incidence of T2DM were calculated with self-reported T2DM or when the individual took drugs for diabetes. Prevalence ratio (PR) and relative risk (RR) of prevalent and incident T2DM were calculated according to educational level and adjusted by BMI and other possible mediators. Results: The age-adjusted and country-adjusted prevalence of T2DM in 2004 was 10.2% in men and 8.5% in women. Compared to those with higher education, men and women with lower education had a PR [95% CI] of T2DM of 1.29 [1.12-1.50] and 1.61 [1.39-1.86], respectively. SEP-related inequalities in incidence (RR [95%CI]) were 1.88 [1.35-2.62] in women and 1.04 [0.78-1.40] in men. Adjusting for potential mediators reduced inequalities in the prevalence and incidence of T2DM among women by 26.2% and 21.6%, respectively, and inequalities in prevalence among men by 44.8%. Conclusions: We observed significant inequalities in the prevalence and incidence (women only) of T2DM as a function of socioeconomic position. These inequalities were mediated by BMI.Objetivo: Analizar las desigualdades por posición socioeconómica en la prevalencia y la incidencia de diabetes mellitus de tipo 2 (DM2) en las personas de 50 o más años de edad en Europa, y describir la contribución del índice de masa corporal (IMC) y la de otros posibles mediadores. Métodos: Estudio de diseño transversal y longitudinal que incluye personas de 50 o más años de edad de 11 países de Europa, entre 2004 y 2006 (n = 21.323). Se calculó la prevalencia y la incidencia acumulada de DM2 a partir del autorreporte de DM2 o de si la persona consumía fármacos para la diabetes. Se estimaron riesgos relativos (RR) de incidencia y razones de prevalencia (RP) de DM2 según el nivel educativo, y se ajustaron por el IMC y otros posibles mediadores. Resultados: La prevalencia de DM2 ajustada por edad y país en 2004 era del 10,2% en los hombres y del 8,5% en las mujeres. Comparado con las personas con un nivel de estudios más alto, los hombres y las mujeres con menor nivel de estudios tenían una RP (IC95%) de DM2 de 1,29 (1,12-1,50) y 1,61 (1,39-1,86), respectivamente. Las desigualdades por posición socioeconómica en la incidencia (RR [IC95%]) eran de 1,88 (1,35-2,62) en las mujeres y de 1,04 (0,78-1,40) en los hombres. Ajustando por los potenciales mediadores, las desigualdades en la prevalencia y la incidencia de DM2 se redujeron en las mujeres un 26,2% y un 21,6%, respectivamente, y las desigualdades en la prevalencia en los hombres un 44,8%. Conclusiones: Se observan desigualdades en la prevalencia y la incidencia (sólo en las mujeres) de DM2 en función de la posición socioeconómica. Estas desigualdades estaban mediadas por el IMC

The prothrombin time/international normalized ratio (PT/INR) Line: derivation of local INR with commercial thromboplastins and coagulometers--two independent studies.

BACKGROUND: The WHO scheme for prothrombin time (PT) standardization has been limited in application, because of its difficulties in implementation, particularly the need for mandatory manual PT testing and for local provision of thromboplastin international reference preparations (IRP). METHODS: The value of a new simpler procedure to derive international normalized ratio (INR), the PT/INR Line, based on only five European Concerted Action on Anticoagulation (ECAA) calibrant plasmas certified by experienced centres has been assessed in two independent exercises using a range of commercial thromboplastins and coagulometers. INRs were compared with manual certified values with thromboplastin IRP from expert centres and in the second study also with INRs from local ISI calibrations. RESULTS: In the first study with the PT/INR Line, 8.7% deviation from certified INRs was reduced to 1.1% with human reagents, and from 7.0% to 2.6% with rabbit reagents. In the second study, deviation was reduced from 11.2% to 0.4% with human reagents by both local ISI calibration and the PT/INR Line. With rabbit reagents, 10.4% deviation was reduced to 1.1% with both procedures; 4.9% deviation was reduced to 0.5% with bovine/combined reagents with local ISI calibrations and to 2.9% with the PT/INR Line. Mean INR dispersion was reduced with all thromboplastins and automated systems using the PT/INR Line. CONCLUSIONS: The procedure using the PT/INR Line provides reliable INR derivation without the need for WHO ISI calibration across the range of locally used commercial thromboplastins and automated PT systems included in two independent international studies