A REGIONAL COMPARISON OF RISK-EFFICIENT SOYBEAN MARKETING STRATEGIES

Risk-efficient portfolios from a subset of marketing strategies were identified using Target-MOTAD. Portfolios were generated for Illinois, Arkansas, and South Carolina to determine whether regional price and yield characteristics affected the optimal marketing strategy selection during 1972-1985. The results support previous conclusions that the risk borne when following a combination of marketing strategies was less than the risk of any single marketing strategy examined. The results also show that the marketing strategies representing efficient risk-return combinations for a producer in one region were different from the efficient risk-return combinations for a producer in another region. Therefore, generic marketing advice would have produced results less preferred in one region than in another.Marketing,

Thermodynamically self-consistent liquid state theories for systems with bounded potentials

The mean spherical approximation (MSA) can be solved semi-analytically for the Gaussian core model (GCM) and yields - rather surprisingly - exactly the same expressions for the energy and the virial equations. Taking advantage of this semi-analytical framework, we apply the concept of the self-consistent Ornstein-Zernike approximation (SCOZA) to the GCM: a state-dependent function K is introduced in the MSA closure relation which is determined to enforce thermodynamic consistency between the compressibility route and either the virial or energy route. Utilizing standard thermodynamic relations this leads to two different differential equations for the function K that have to be solved numerically. Generalizing our concept we propose an integro-differential-equation based formulation of the SCOZA which, although requiring a fully numerical solution, has the advantage that it is no longer restricted to the availability of an analytic solution for a particular system. Rather it can be used for an arbitrary potential and even in combination with other closure relations, such as a modification of the hypernetted chain approximation.Comment: 11 pages, 11 figures, submitted to J. Chem. Phy

Telomere Length and Its Relation to Human Health

Telomeres are complex nucleotide sequences that cap the end of chromosomes from degradation, unwanted recombination‐fusion, inappropriate activation of DNA damage response and play a critical role in cell division and chromosome stability. There is growing evidence that telomere stability can be affected by occupational and environmental exposure, as some of these factors have been correlated with increase in inflammation, oxidative stress, DNA damage, chromosome aberration, and epigenetic alterations. Both extremely short and long telomeres have been associated with neurodegenerative, cardiovascular diseases (CVD) and cancer risk. Occupational and environmental exposure to several synthetic and natural chemicals has been found to be associated with changes in telomere length, although the molecular mechanism is not fully understood. Telomeric DNA is relatively less capable of repair, resulting in accelerated shortening during the cell cycle and replicative senescence. It is recognized that diet plays an important role in telomere maintenance. Prevention of exposure to environmental and occupational hazards as well as psychological stressors can reduce the risk of telomere instability. This review provides a broad evaluation of the associated mechanism between human health and environmental and occupational exposure with telomere length, including recent findings and future perspectives

Evaluating the impact of laboratory-based eligibility criteria by race/ethnicity in first-line clinical trials of DLBCL

Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, with demographics broadly similar to the US patients diagnosed with lymphoma, we evaluated the impact of laboratory eligibility criteria from recent first-line DLBCL trials across various racial and ethnic backgrounds. There were significant differences in the baseline laboratory values by race/ethnicity with Black/African American (AA) patients having the lowest mean hemoglobin and highest creatinine clearance. Based on recent clinical trial eligibility criteria, AA and Hispanic patients had higher rates of laboratory-based ineligibility than non-Hispanic White patients. The largest gap in the clinical outcomes between eligible and noneligible patients was noted within AA patients with an overall survival hazard ratio based on POLARIX clinical trial criteria of 4.09 (95% confidence interval, 1.83-9.14). A thoughtful approach to the utility of each criterion and cutoffs for eligibility needs to be evaluated in the context of its differential impact across various racial/ethnic groups

Tumor-immune signatures of treatment resistance to brentuximab vedotin with ipilimumab and/or nivolumab in Hodgkin lymphoma

UNLABELLED: To investigate the cellular and molecular mechanisms associated with targeting CD30-expressing Hodgkin lymphoma (HL) and immune checkpoint modulation induced by combination therapies of CTLA4 and PD1, we leveraged Phase 1/2 multicenter open-label trial NCT01896999 that enrolled patients with refractory or relapsed HL (R/R HL). Using peripheral blood, we assessed soluble proteins, cell composition, T-cell clonality, and tumor antigen-specific antibodies in 54 patients enrolled in the phase 1 component of the trial. NCT01896999 reported high (\u3e75%) overall objective response rates with brentuximab vedotin (BV) in combination with ipilimumab (I) and/or nivolumab (N) in patients with R/R HL. We observed a durable increase in soluble PD1 and plasmacytoid dendritic cells as well as decreases in plasma CCL17, ANGPT2, MMP12, IL13, and CXCL13 in N-containing regimens (BV + N and BV + I + N) compared with BV + I (P \u3c 0.05). Nonresponders and patients with short progression-free survival showed elevated CXCL9, CXCL13, CD5, CCL17, adenosine-deaminase, and MUC16 at baseline or after one treatment cycle and a higher prevalence of NY-ESO-1-specific autoantibodies (P \u3c 0.05). The results suggest a circulating tumor-immune-derived signature of BV ± I ± N treatment resistance that may be useful for patient stratification in combination checkpoint therapy. SIGNIFICANCE: Identification of multi-omic immune markers from peripheral blood may help elucidate resistance mechanisms to checkpoint inhibitor and antibody-drug conjugate combinations with potential implications for treatment decisions in relapsed HL

Matching-adjusted indirect comparison from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence (LEO CReWE) study to a clinical trial of mosunetuzumab in relapsed or refractory follicular lymphoma

Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate (ORR) of 80%, complete response (CR) rate of 60%, and a median progression-free survival (PFS) of 17.9 months in patients with relapsed/refractory (R/R) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy. Historical data from cohorts receiving therapy for R/R FL can provide some context for interpretation of single-arm trials. We compared the results from the mosunetuzumab trial to outcomes from a cohort of patients with R/R FL from the LEO Consortium for Real World Evidence (LEO CReWE). We applied clinical trial eligibility criteria to the LEO CReWE cohort and utilized matching- adjusted indirect comparison weighting to balance the clinical characteristics of the LEO CReWE cohort with those from the mosunetuzumab trial. ORR (73%, 95% CI: 65-80%) and CR rates (53%, 95% CI: 45-61%) observed in the weighted LEO CReWE cohort were lower than those reported on the mosunetuzumab trial (ORR=80%, 95% CI: 70-88%; CR=60%, 95% CI: 49-70%, respectively). PFS at 12 months was similar in the weighted LEO CReWE (60%, 95% CI: 51-69%) and the mosunetuzumab (58%, 95% CI: 47-68%) trial. Sensitivity analyses examining the impact of matching variables, selection of line of therapy, and application of eligibility criteria provide context for best practices in this setting

Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: Long-term efficacy and safety from the phase II LOTIS-2 study

Therapies that demonstrate durable, long-term responses with manageable safety and tolerability are needed for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), an anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer, demonstrated single-agent antitumor activity in the pivotal phase II LOTIS-2 study in heavily pretreated patients with R/R DLBCL. Here we present updated efficacy and safety analyses from LOTIS-2, performed for all patients and in subsets of patients with a complete response (CR), including patients with CR who were event-free (no progressive disease or death) for ≥1 year and ≥2 years from cycle 1, day 1 of treatment. Lonca was administered every 3 weeks (0.15 mg/kg for 2 cycles; 0.075 mg/kg for subsequent cycles). As of the final data cutoff (September 15, 2022; median follow-up: 7.8 months [range, 0.3-42.6]), 70 of 145 (48.3%) patients achieved an overall response. Thirty-six (24.8%) patients achieved CR, of which 16 (44%) and 11 (31%) were event-free for ≥1 year and ≥2 years, respectively. In the all-treated population, the median overall survival was 9.5 months; the median progression-free survival was 4.9 months. Among patients with CR, median overall survival and progression-free survival were not reached, with 24-month overall and progression-free survival rates of 68.2% (95% CI: 50.0-81.0) and 72.5% (95% CI: 48.2-86.8), respectively. No new safety concerns were detected. With additional follow-up, Lonca continued to demonstrate durable, long-term responses with manageable safety and tolerability in patients with CR (clinicaltrials gov. Identifier: NCT03589469)