Prognostic models for predicting the risk of foot ulcer or amputation in people with type 2 diabetes: a systematic review and external validation study

Aims/hypothesis Approximately 25% of people with type 2 diabetes experience a foot ulcer and their risk of amputation is 10-20 times higher than that of people without type 2 diabetes. Prognostic models can aid in targeted monitoring but an overview of their performance is lacking. This study aimed to systematically review prognostic models for the risk of foot ulcer or amputation and quantify their predictive performance in an independent cohort.Methods A systematic review identified studies developing prognostic models for foot ulcer or amputation over minimal 1 year follow-up applicable to people with type 2 diabetes. After data extraction and risk of bias assessment (both in duplicate), selected models were externally validated in a prospective cohort with a 5 year follow-up in terms of discrimination (C statistics) and calibration (calibration plots).Results We identified 21 studies with 34 models predicting polyneuropathy, foot ulcer or amputation. Eleven models were validated in 7624 participants, of whom 485 developed an ulcer and 70 underwent amputation. The models for foot ulcer showed C statistics (95% CI) ranging from 0.54 (0.54, 0.54) to 0.81 (0.75, 0.86) and models for amputation showed C statistics (95% CI) ranging from 0.63 (0.55, 0.71) to 0.86 (0.78, 0.94). Most models underestimated the ulcer or amputation risk in the highest risk quintiles. Three models performed well to predict a combined endpoint of amputation and foot ulcer (C statistics >0.75).Conclusions/interpretation Thirty-four prognostic models for the risk of foot ulcer or amputation were identified. Although the performance of the models varied considerably, three models performed well to predict foot ulcer or amputation and may be applicable to clinical practice.Therapeutic cell differentiatio

Comparison of s- and d-wave gap symmetry in nonequilibrium superconductivity

Recent application of ultrafast pump/probe optical techniques to superconductors has renewed interest in nonequilibrium superconductivity and the predictions that would be available for novel superconductors, such as the high-Tc cuprates. We have reexamined two of the classical models which have been used in the past to interpret nonequilibrium experiments with some success: the mu* model of Owen and Scalapino and the T* model of Parker. Predictions depend on pairing symmetry. For instance, the gap suppression due to excess quasiparticle density n in the mu* model, varies as n^{3/2} in d-wave as opposed to n for s-wave. Finally, we consider these models in the context of S-I-N tunneling and optical excitation experiments. While we confirm that recent pump/probe experiments in YBCO, as presently interpreted, are in conflict with d-wave pairing, we refute the further claim that they agree with s-wave.Comment: 14 pages, 11 figure

Cross-border electronic commerce: distance effects and express delivery in European Union markets

This empirical study examines distance effects on cross-border electronic commerce and in particular the importance of express delivery in reducing the time dimension of distance. E-commerce provides suppliers with a range of opportunities to reduce distance as perceived by online buyers. They can reduce psychological barriers to cross-border demand by designing websites that simplify the search for and comparison of products and suppliers across countries. They can reduce cost barriers by applying pricing strategies that redistribute transportation costs, and they can overcome time barriers offering express delivery services. This study of 721 regions in five countries of the European Union shows that distance is not “dead” in e-commerce, that express delivery reduces distance for cross-border demand, and that e-demand delivered by express services is more time sensitive and less price sensitive than e-demand satisfied by standard delivery. The willingness of e-customers to pay for express services is shown to be affected by income and by the relative lead-time benefits and express charges. Furthermore, the adoption of express delivery is positively associated with e-loyalty in terms of repurchase rates. The results confirm the importance for e-suppliers of cleverly designed delivery services to reduce distance in order to attract online customers across borders

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Data and Code for: Product Variety, the Cost of Living and Welfare Across Countries

Cavallo, A., Feenstra, R.C., & Inklaar, R.C., (2022). Product Variety, the Cost of Living and Welfare Across Countries. American Economic Journal: Macroeconomics, forthcoming</i