How to improve public sector finances in Honduras

The objectives of a public sector management program should be to use resources more efficiently rationalize public sector operations and reduce financial disequilibrium. This report presents a comprehensive policy program to improve public finances in Honduras. It recommends that Honduran authorities prepare an action plan for improving public sector management. The plan should include the following measures: (a) increase savings; (b) introduce efficiency-saving measures; (c) improve budgeting, debt management and tax collection; (d) standardize accounting practices and properly account for debt service obligations; (e) start external management audits of enterprises; and (f) establish financial targets for, and reduce government transfers to, public enterprises. It also recommends measures to: (g) improve service delivery; (h) implement a well-defined privatization program; (i) prepare and implement a growth oriented and financially feasible public investment program; (j) improve decisionmaking and increase accountability and autonomy in public enterprises; (k) improve coordination of the sector; (l) target subsidies; and (m) improve better financial information on the public sector.Environmental Economics&Policies,Public Sector Economics&Finance,National Governance,Banks&Banking Reform,Economic Stabilization

Harmonizing tax policies in Central America

This report proposes an action plan for the rationalization of tax structures for Central America. To harmonize tax policies among Central American nations, the report recommends the following: (a) continuing trade liberalization, by reducing thelevel and dispersion of effective trade protection; (b) shifting the tax system from reliance on trade to reliance on domestic transactions and income; (c) making the value added tax the backbone of the tax system; and (d) improving tax administration. It also recommends; (e) harmonizing taxes on inputs and exempting nontraditional exporters from paying import duties; (f) moving toward coordinating factor incomes to avoid double taxation; (g) eliminating all quantitative import restrictions, prior imports deposits, non-common import tariffs and other restrictions on imports from other Central American Common Market (CACM) members; (h) applying similar principles in designing export taxes on coffee and bananas; and (i) not using differential exchange rates to discriminate against regional trade. If implemented, it is hoped that these reforms, along with other structural reforms, would help spark the latent growth potential in Central American economies.Environmental Economics&Policies,Economic Theory&Research,TF054105-DONOR FUNDED OPERATION ADMINISTRATION FEE INCOME AND EXPENSE ACCOUNT,Trade and Regional Integration,Public Sector Economics&Finance

Identification of microRNAs associated with allergic airway disease using a genetically diverse mouse population

Abstract Background Allergic airway diseases (AADs) such as asthma are characterized in part by granulocytic airway inflammation. The gene regulatory networks that govern granulocyte recruitment are poorly understood, but evidence is accruing that microRNAs (miRNAs) play an important role. To identify miRNAs that may underlie AADs, we used two complementary approaches that leveraged the genotypic and phenotypic diversity of the Collaborative Cross (CC) mouse population. In the first approach, we sought to identify miRNA expression quantitative trait loci (eQTL) that overlap QTL for AAD-related phenotypes. Specifically, CC founder strains and incipient lines of the CC were sensitized and challenged with house dust mite allergen followed by measurement of granulocyte recruitment to the lung. Total lung RNA was isolated and miRNA was measured using arrays for CC founders and qRT-PCR for incipient CC lines. Results Among CC founders, 92 miRNAs were differentially expressed. We measured the expression of 40 of the most highly expressed of these 92 miRNAs in the incipient lines of the CC and identified 18 eQTL corresponding to 14 different miRNAs. Surprisingly, half of these eQTL were distal to the corresponding miRNAs, and even on different chromosomes. One of the largest-effect local miRNA eQTL was for miR-342-3p, for which we identified putative causal variants by bioinformatic analysis of the effects of single nucleotide polymorphisms on RNA structure. None of the miRNA eQTL co-localized with QTL for eosinophil or neutrophil recruitment. In the second approach, we constructed putative miRNA/mRNA regulatory networks and identified three miRNAs (miR-497, miR-351 and miR-31) as candidate master regulators of genes associated with neutrophil recruitment. Analysis of a dataset from human keratinocytes transfected with a miR-31 inhibitor revealed two target genes in common with miR-31 targets correlated with neutrophils, namely Oxsr1 and Nsf. Conclusions miRNA expression in the allergically inflamed murine lung is regulated by genetic loci that are smaller in effect size compared to mRNA eQTL and often act in trans. Thus our results indicate that the genetic architecture of miRNA expression is different from mRNA expression. We identified three miRNAs, miR-497, miR-351 and miR-31, that are candidate master regulators of genes associated with neutrophil recruitment. Because miR-31 is expressed in airway epithelia and is predicted to target genes with known links to neutrophilic inflammation, we suggest that miR-31 is a potentially novel regulator of airway inflammation

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old