Understanding Foreign Direct Investment in East Asia

We recount East Asia's experience with foreign direct investment (FDI). We document that, contrary to the Rybczynski theorem, capital flows in the region cause the host country's labor-intensive industry to expand and its capital-intensive industry to decline. We also present narrative evidence that sheds light on how FDI is affected by the host's country's locational advantages, whether Asian FDI is footloose, and how the PRC has become the center of Factory Asia. Finally, we show that the evolution of production networks in the region can be explained partly by changes in the service cost of linking geographically separated production blocks relative to the cost saving arising from slicing up the value chain

Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score

Aims: Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation. Methods and results: Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48-0.71 (recurrence) and 0.61-0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% -19% for bleeding. Conclusion: The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making

The duplication mutation of Quebec platelet disorder dysregulates <i>PLAU</i>, but not <i>C10orf55</i>, selectively increasing production of normal <i>PLAU</i> transcripts by megakaryocytes but not granulocytes

<div><p>Quebec Platelet disorder (QPD) is a unique bleeding disorder that markedly increases urokinase plasminogen activator (uPA) in megakaryocytes and platelets but not in plasma or urine. The cause is tandem duplication of a 78 kb region of chromosome 10 containing <i>PLAU</i> (the uPA gene) and <i>C10orf55</i>, a gene of unknown function. QPD increases uPA in platelets and megakaryocytes >100 fold, far more than expected for a gene duplication. To investigate the tissue-specific effect that <i>PLAU</i> duplication has on gene expression and transcript structure in QPD, we tested if QPD leads to: 1) overexpression of normal or unique <i>PLAU</i> transcripts; 2) increased uPA in leukocytes; 3) altered levels of <i>C10orf55</i> mRNA and/or protein in megakaryocytes and leukocytes; and 4) global changes in megakaryocyte gene expression. Primary cells and cultured megakaryocytes from donors were prepared for quantitative reverse polymerase chain reaction analyses, RNA-seq and protein expression analyses. Rapidly isolated blood leukocytes from QPD subjects showed only a 3.9 fold increase in <i>PLAU</i> transcript levels, in keeping with the normal to minimally increased uPA in affinity purified, QPD leukocytes. All subjects had more uPA in granulocytes than monocytes and minimal uPA in lymphocytes. QPD leukocytes expressed <i>PLAU</i> alleles in proportions consistent with an extra copy of <i>PLAU</i> on the disease chromosome, unlike QPD megakaryocytes. QPD <i>PLAU</i> transcripts were consistent with reference gene models, with a much higher proportion of reads originating from the disease chromosome in megakaryocytes than granulocytes. QPD and control megakaryocytes contained minimal reads for <i>C10orf55</i>, and C10orf55 protein was not increased in QPD megakaryocytes or platelets. Finally, our QPD megakaryocyte transcriptome analysis revealed a global down regulation of the interferon type 1 pathway. We suggest that the low endogenous levels of uPA in blood are actively regulated, and that the regulatory mechanisms are disrupted in QPD in a megakaryocyte-specific manner.</p></div