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Background The administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts. Methods This was a single-center, double-blind, randomized, placebo-controlled trial. Patients ≤ 48 months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48 h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study. Results A total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19–1.13; p  = 0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14–3.69, p  = 0.693), duration of mechanical ventilation (median, 47.5 h and 39.5 h, respectively; p  = 0.532), ICU stay (median, 114.5 h and 118 h, respectively; p  = 0.442), and hospital stay (median, 20 days and 20 days, respectively; p  = 0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS. Conclusions Prophylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo. Trial registration Name of the registry: Safety evaluation and therapeutic effect of levosimendan on the low cardiac output syndrome in patients after cardiopulmonary bypass. Trial registration number: ChiCTR1800016594. Date of registration: 11 June 2018. URL of trial registry record: http://www.chictr.org.cn/index.aspx

This paper argues that, in the presence of intersectoral input—output linkages, microeconomic idiosyncratic shocks may lead to aggregate fluctuations. We show that, as the economy becomes more disaggregated, the rate at which aggregate volatility decays is determined by the structure of the network capturing such linkages. Our main results provide a characterization of this relationship in terms of the importance of different sectors as suppliers to their immediate customers, as well as their role as indirect suppliers to chains of downstream sectors. Such higher-order interconnections capture the possibility of \"cascade effects\" whereby productivity shocks to a sector propagate not only to its immediate downstream customers, but also to the rest of the economy. Our results highlight that sizable aggregate volatility is obtained from sectoral idiosyncratic shocks only if there exists significant asymmetry in the roles that sectors play as suppliers to others, and that the \"sparseness\" of the input—output matrix is unrelated to the nature of aggregate fluctuations.

We develop a property-rights model of the firm in which production entails a continuum of uniquely sequenced stages. In each stage, a final-good producer contracts with a distinct supplier for the procurement of a customized stage-specific component. Our model yields a sharp characterization for the optimal allocation of ownership rights along the value chain. We show that the incentive to integrate suppliers varies system-atically with the relative position (upstream versus downstream) at which the supplier enters the production line. Furthermore, the nature of the relationship between integration and \"downstreamness\" depends crucially on the elasticity of demand faced by the final-good producer. Our model readily accommodates various sources of asymmetry across final-good producers and across suppliers within a production line, and we show how it can be taken to the data with international trade statistics. Combining data from the U.S. Census Bureau's Related Party Trade database and estimates of U.S. import demand elasticities from Broda and Weinstein (2006), we find empirical evidence broadly supportive of our key predictions. In the the process, we develop two novel measures of the average position of an industry in the value chain, which we construct using U.S. Input—Output Tables.

Chronic heart failure (CHF) is an important cause of hospital admission and death. Poor adherence to medication is common in some chronic illnesses and might reduce the population effectiveness of proven treatments. Because little is known about adherence in patients with CHF and about the consequences of non-adherence, we assessed the association between adherence and clinical outcome in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme. CHARM was a double-blind, randomised, controlled clinical trial, comparing the effects of the angiotensin receptor blocker candesartan with placebo in 7599 patients with CHF. Median follow-up was 38 months. The proportion of time patients took more than 80% of their study medication was defined as good adherence and 80% or less as poor adherence. We used a Cox proportional hazards regression model, with adherence as a time-dependent covariate in the model, to examine the association between adherence and mortality in the candesartan and placebo groups. We excluded 187 patients because of missing information on adherence. In the time-dependent Cox regression model, after adjustment for predictive factors (demographics, physiological and severity-of-illness variables, smoking history, and number of concomitant medications), good adherence was associated with lower all-cause mortality in all patients (hazard ratio [HR] 0·65, 95% CI 0·57–0·75, p<0·0001). The adjusted HR for good adherence was similar in the candesartan (0·66, 0·55–0·81, p<0·0001) and placebo (0·64, 0·53–0·78, p<0·0001) groups. Good adherence to medication is associated with a lower risk of death than poor adherence in patients with CHF, irrespective of assigned treatment. This finding suggests that adherence is a marker for adherence to effective treatments other than study medications, or to other adherence behaviours that affect outcome. Understanding these factors could provide an opportunity for new interventions, including those aimed at improving adherence.

This article seeks to verify the extent to which the formulation of two-dimensional location quotients (2D-LQ) entails a methodological advance in building or generating economic accounts related to sub-territories drawing from basic information. The input–output tables of the Euro Area 19 for 2010 and 2015 are references for analysis. We have used five statistics to measure similarity between true domestic coefficient matrices for ten countries (Austria, Belgium, Estonia, France, Germany, Italy, Latvia, Slovakia, Slovenia, and Spain) and the matrices they generate using nonsurvey techniques (CILQ, FLQ, AFLQ, and 2D-LQ). The focus substantially centers on ranking methodological efficiency by comparing the results of the four techniques mentioned above. The scope of the work employs standard parameters (associated with 2D-LQ) as guidance to ascertain the optimum parameters.

Using a multisector general equilibrium model, we show that the interplay of idiosyncratic microeconomic shocks and sectoral heterogeneity results in systematic departures in the likelihood of large economic downturns relative to what is implied by the normal distribution. Such departures can emerge even though GDP fluctuations are approximately normally distributed away from the tails, highlighting the different nature of large economic downturns from regular business-cycle fluctuations. We further demonstrate the special role of input-output linkages in generating tail comovements, whereby large recessions involve not only significant GDP contractions, but also large simultaneous declines across a wide range of industries.

Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements, neurohumoral activity, and left-ventricular remodelling when added to angiotensin-converting-enzyme (ACE) inhibitors in patients with chronic heart failure (CHF). We aimed to find out whether these drugs improve clinical outcome. Between March, 1999, and November, 1999, we enrolled 2548 patients with New York Heart Association functional class II–IV CHF and left-ventricular ejection fraction 40% or lower, and who were being treated with ACE inhibitors. We randomly assigned patients candesartan (n=1276, target dose 32 mg once daily) or placebo (n=1272). At baseline, 55% of patients were also treated with β blockers and 17% with spironolactone. The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF. Analysis was done by intention to treat. The median follow-up was 41 months. 483 (38%) patients in the candesartan group and 538 (42%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0·85 [95% CI 0·75–0·96], p=0·011; covariate adjusted p=0·010). Candesartan reduced each of the components of the primary outcome significantly, as well as the total number of hospital admissions for CHF. The benefits of candesartan were similar in all predefined subgroups, including patients receiving baseline β blocker treatment. The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction. Published online Sept 1, 2003 http://image.thelancet.com/extras/03art7417web.pdf

The B-type or brain natriuretic peptides (BNP) and the amino-terminal probrain natriuretic peptide (NT-proBNP) are good markers of prognosis and diagnosis in chronic heart failure (HF). It is unclear, however, whether differences in their biological characteristics modify their clinical correlates and prognostic performance in HF. This work aimed to provide a direct comparison of the prognostic value of BNP and NT-proBNP in patients with chronic and stable HF. We measured BNP and NT-proBNP at baseline in 3916 patients enrolled in the Valsartan Heart Failure Trial. To identify the variables associated with both peptides, we conducted simple and multivariable linear regression analyses. We used Cox multivariable regression models to evaluate the independent prognostic value for all-cause mortality, mortality and morbidity, and hospitalization for HF. Prognostic performance was assessed by pairwise comparisons of the area under the curve of receiver-operator characteristic curves. NT-proBNP and BNP had similar relationships with age, left ventrical ejection fraction, and internal diameter and creatinine clearance. Either peptide ranked as the first independent predictor of outcome after adjustment for major confounding clinical characteristics. ROC curves were almost superimposable for all-cause mortality (area under the curve (SE): BNP 0.665 (0.011) vs NT-proBNP 0.679 (0.011); P=0.0734), but NT-proBNP was superior to BNP for predicting mortality and morbidity (P=0.032) or hospitalization for HF (P=0.0143). Overall sensitivity and specificity ranged from 0.590 to 0.696. The natriuretic peptides BNP and NT-proBNP showed subtle differences in their relation to clinical characteristics and prognostic performance in a large population of patients with chronic and stable HF. They were the most powerful independent markers of outcome in HF.

The use of location quotients for the estimation of regional input-output tables has been found to be a useful and efficient tool to estimate intraregional production coefficients and multipliers. This paper considers some regionalisation methodologies based on location quotients for the estimation of input-output tables-some of which have hitherto not been analysed at the regional level-and studies which one provides the best estimation (best goodness of fit). We focus the analysis mainly on the accuracy of Flegg's location quotient (FLQ) and two-dimensional location quotient (2D-LQ). The analysis makes use of the multiregional input-output table for Korea for the year 2015 to evaluate the accuracy of the 2D-LQ method against FLQ. A novel proposal for the determination of the parameters corresponding to the 2D-LQ method is presented. This proposal is evaluated in Korean regions and is also applied to Spanish regions. The results obtained from the research conclude the general superiority of the 2D-LQ method, thus corroborating the results of other studies at the national level as well as the validity of our proposal.

Significance This original research paper addresses a key issue in sustainability science: How many and which natural resources are needed to sustain modern economies? Simple as it may seem, this question is far from trivial to answer and has indeed not been addressed satisfactorily in the scholarly literature. We use the most comprehensive and most highly resolved economic input–output framework of the world economy together with a detailed database of global material flows to calculate the full material requirements of all countries covering a period of two decades. Called the “material footprint,” this indicator provides a consumption perspective of resource use and new insights into the actual resource productivity of nations. Metrics on resource productivity currently used by governments suggest that some developed countries have increased the use of natural resources at a slower rate than economic growth (relative decoupling) or have even managed to use fewer resources over time (absolute decoupling). Using the material footprint (MF), a consumption-based indicator of resource use, we find the contrary: Achievements in decoupling in advanced economies are smaller than reported or even nonexistent. We present a time series analysis of the MF of 186 countries and identify material flows associated with global production and consumption networks in unprecedented specificity. By calculating raw material equivalents of international trade, we demonstrate that countries’ use of nondomestic resources is, on average, about threefold larger than the physical quantity of traded goods. As wealth grows, countries tend to reduce their domestic portion of materials extraction through international trade, whereas the overall mass of material consumption generally increases. With every 10% increase in gross domestic product, the average national MF increases by 6%. Our findings call into question the sole use of current resource productivity indicators in policy making and suggest the necessity of an additional focus on consumption-based accounting for natural resource use.