Economic Issues and Analyses in Biotechnology

Although the evolution of the food and agricultural system in developed countries seems to be progressing at an ever-increasing rate, in reality this trend has largely been realized as small bursts of progress followed by relatively dormant periods until another break-through is achieved. These break-throughs occur in a variety of ways, including the scientific, such as the development of new hybrids and genetic lines, useful chemicals etc., the political, such as the opening of trade with China and other communist countries, and the behavioral changes such as the shift toward leaner meats, more natural food products, and more highly processed heat and serve preferences among consumers

Evaluation of Policy Scenarios for the 1990 Farm Bill

Three alternatives for 1990 farm legislation are examined: (1) a continuation of current legislation; (2) small reductions in producer support levels that are phased in after a two-year delay; and (3) more significant policy reforms that include immediate support reductions for grains and cotton, marketing quotas for dairy products and sugar, and an expanded conservation reserve. Analysis indicates that the alternatives to current policies reduce both government outlays on farm programs and net farm income. The effects on the supply, demand, and prices of most crop and livestock commodities are small. Marketing quotas protect sugar and dairy producer income and allow increased imports without significant budgetary effects, but at considerable cost to consumers

FAPRI U.S. Agricultural Sector Elasticities, Volume I: Crops

This report presents estimates of supply, demand, and price transmission elasticities for the U.S. crops sector. The estimates are derived from the U.S. crops model maintained by the Food and Agricultural Policy Research Institute (FAPRI) and are prepared in accordance with procedures stipulated by the Organization for Economic Cooperation and Development (OECD). The first section of this report provides a general overview and describes the procedures used to perform the elasticity calculations. Each succeeding section provides general information about the elasticity estimates for a particular activity. Specific attention is given to those results that may not be intuitively clear and, in particular, to the elasticities that depend on the interaction of two or more equations in the FAPRI modeling system

FAPRI U.S. Agricultural Sector Elasticities, Volume II: Livestock, Poultry, and Dairy

This report presents estimates of supply, demand, and price transmission elasticities for the U.S. livestock, poultry, and dairy sectors. The estimates are derived from models maintained by the Food and Agricultural Policy Research Institute (FAPRI) and are prepared in accordance with procedures stipulated by the Organization for Economic Cooperation and Development (OECD)

Implications of a GATT Agreement for World Commodity Markets, 1991-2000

A dynamic multicountry, multicommodity model is used to evaluate the impact of a moderate General Agreement on Tariffs and Trade (GATT) agreement. The terms of this agreement are as follows. 1) Export subsidy quantities (using annual and price wedges) are reduced by 50 percent from the 1986-88 average by 1996. 2) Import restrictions are tariffed and reduced by 33 percent form the 1986-88 average by 1996 (tariffs are measured by using an annual price wedge approach). 3) Internal supports, as measured by the aggregate measure of support (AMS) are reduced by 33 percent from the 1986-88 average by 1996 (fixed reference prices are used). The results indicate that the U.S. producers would benefit substantially from the agreement because the United States has made or will have made many of the cuts required by this moderate agreement. The results also indicate that the choice of the base year is a very important variable influencing the relative benefits and losses under any likely GATT agreement

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Economic Issues and Analyses in Biotechnology

Although the evolution of the food and agricultural system in developed countries seems to be progressing at an ever-increasing rate, in reality this trend has largely been realized as small bursts of progress followed by relatively dormant periods until another break-through is achieved. These break-throughs occur in a variety of ways, including the scientific, such as the development of new hybrids and genetic lines, useful chemicals etc., the political, such as the opening of trade with China and other communist countries, and the behavioral changes such as the shift toward leaner meats, more natural food products, and more highly processed "heat and serve" preferences among consumers.</p

Evaluation of Policy Scenarios for the 1990 Farm Bill

Three alternatives for 1990 farm legislation are examined: (1) a continuation of current legislation; (2) small reductions in producer support levels that are phased in after a two-year delay; and (3) more significant policy reforms that include immediate support reductions for grains and cotton, marketing quotas for dairy products and sugar, and an expanded conservation reserve. Analysis indicates that the alternatives to current policies reduce both government outlays on farm programs and net farm income. The effects on the supply, demand, and prices of most crop and livestock commodities are small. Marketing quotas protect sugar and dairy producer income and allow increased imports without significant budgetary effects, but at considerable cost to consumers.</p