Races 0 (Foc-0) and 5 (Foc-5) of Fusarium oxysporum f. sp. ciceris differ in virulence and induce yellowing or wilting syndrome, respectively, in chickpea. We modeled the combined effects of soil ...temperature and inoculum density of Foc-0 and Foc-5 on disease developed in chickpea cvs. P-2245 and PV-61 differing in susceptibility to those races, using quantitative nonlinear models. Disease development over time in the temperature range of 10 to 30°C and inoculum densities between 6 and 8,000 chlamydospores g(^-1) of soil was described by the Weibull function. Four response variables (the reciprocal incubation period, the final disease intensity, the standardized area under the disease progress curve, and the intrinsic rate of disease development) characterized the disease development. Response surface models that expressed the combined effect of inoculum density and temperature were developed by substituting the intrinsic rate of disease development in the Weibull or exponential functions with a beta function describing the relationship of response variables to temperature. The models estimated 22 to 26°C as the most favorable soil temperature for infection of cvs. P-2245 and PV-61 by Foc-5, and 24 to 28°C for infection of cv. P-2245 by Foc-0. At 10°C, no disease developed except in cv. P-2245 inoculated with Foc-5. At optimum soil temperature, maximum disease intensity developed with Foc-5 and Foc-0 at 6 and 50 chlamydospores g(^-1) of soil respectively, in cv. P-2245, and with Foc-5 at 1,000 chlamydospores g(^-1) of soil in cv. PV-61. The models were used to construct risk threshold charts that can be used to estimate the potential risk of Fusarium wilt epidemics in a geographical area based on soil temperature, the race and inoculum density in soil, and the level of susceptibility of the chickpea cultivar.
ABSTRACT Specific primers and polymerase chain reaction (PCR) assays that identify Fusarium oxysporum f. sp. ciceris and each of the F. oxysporum f. sp. ciceris pathogenic races 0, 1A, 5, and 6 were ...developed. F. oxysporum f. sp. ciceris- and race-specific random amplified polymorphic DNA (RAPD) markers identified in a previous study were cloned and sequenced, and sequence characterized amplified region (SCAR) primers for specific PCR were developed. Each cloned RAPD marker was characterized by Southern hybridization analysis of Eco RI-digested genomic DNA of a subset of F. oxysporum f. sp. ciceris and nonpathogenic F. oxysporum isolates. All except two cloned RAPD markers consisted of DNA sequences that were found highly repetitive in the genome of all F. oxysporum f. sp. ciceris races. F. oxysporum f. sp. ciceris isolates representing eight reported races from a wide geographic range, nonpathogenic F. oxysporum isolates, isolates of F. oxysporum f. spp. lycopersici, melonis, niveum, phaseoli, and pisi, and isolates of 47 different Fusarium spp. were tested using the SCAR markers developed. The specific primer pairs amplified a single 1,503-bp product from all F. oxysporum f. sp. ciceris isolates; and single 900- and 1,000-bp products were selectively amplified from race 0 and race 6 isolates, respectively. The specificity of these amplifications was confirmed by hybridization analysis of the PCR products. A race 5-specific identification assay was developed using a touchdown-PCR procedure. A joint use of race 0- and race 6-specific SCAR primers in a single-PCR reaction together with a PCR assay using the race 6-specific primer pair correctly identified race 1A isolates for which no RAPD marker had been found previously. All the PCR assays described herein detected up to 0.1 ng of fungal genomic DNA. The specific SCAR primers and PCR assays developed in this study clearly identify and differentiate isolates of F. oxysporum f. sp. ciceris and of each of its pathogenic races 0, 1A, 5, and 6.
COVID-19 disease is accompanied by a dysregulated immune response and hypercoagulability. The Anti-Coronavirus Therapies (ACT) inpatient trial aimed to evaluate anti-inflammatory therapy with ...colchicine and antithrombotic therapy with the combination of rivaroxaban and aspirin for prevention of disease progression in patients hospitalised with COVID-19.
The ACT inpatient, open-label, 2 × 2 factorial, randomised, controlled trial was done at 62 clinical centres in 11 countries. Patients aged at least 18 years with symptomatic, laboratory confirmed COVID-19 who were within 72 h of hospitalisation or worsening clinically if already hospitalised were randomly assigned (1:1) to receive colchicine 1·2 mg followed by 0·6 mg 2 h later and then 0·6 mg twice daily for 28 days versus usual care; and in a second (1:1) randomisation, to the combination of rivaroxaban 2·5 mg twice daily plus aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome, assessed at 45 days in the intention-to-treat population, for the colchicine randomisation was the composite of the need for high-flow oxygen, mechanical ventilation, or death; and for the rivaroxaban plus aspirin randomisation was the composite of major thrombosis (myocardial infarction, stroke, acute limb ischaemia, or pulmonary embolism), the need for high-flow oxygen, mechanical ventilation, or death. The trial is registered at www.
gov, NCT04324463 and is ongoing.
Between Oct 2, 2020, and Feb 10, 2022, at 62 sites in 11 countries, 2749 patients were randomly assigned to colchicine or control and the combination of rivaroxaban and aspirin or to the control. 2611 patients were included in the analysis of colchicine (n=1304) versus control (n=1307); 2119 patients were included in the analysis of rivaroxaban and aspirin (n=1063) versus control (n=1056). Follow-up was more than 98% complete. Overall, 368 (28·2%) of 1304 patients allocated to colchicine and 356 (27·2%) of 1307 allocated to control had a primary outcome (hazard ratio HR 1·04, 95% CI 0·90-1·21, p=0·58); and 281 (26·4%) of 1063 patients allocated to the combination of rivaroxaban and aspirin and 300 (28·4%) of 1056 allocated to control had a primary outcome (HR 0·92, 95% CI 0·78-1·09, p=0·32). Results were consistent in subgroups defined by vaccination status, disease severity at baseline, and timing of randomisation in relation to onset of symptoms. There was no increase in the number of patients who had at least one serious adverse event for colchicine versus control groups (87 6·7% of 1304 vs 90 6·9% of 1307) or with rivaroxaban and aspirin versus control groups (85 8·0% vs 91 8·6%). Among patients assigned to colchicine, 8 (0·61%) had adverse events that led to discontinuation of study drug, mostly gastrointestinal in nature. 17 (1·6%) patients assigned to the combination of rivaroxaban and aspirin had bleeding compared with seven (0·66%) of those allocated to control (p=0·042); the number of serious bleeding events was two (0·19%) versus six (0·57%), respectively (p=0·18). No patients assigned to rivaroxaban and aspirin had serious adverse events that led to discontinuation of study drug.
Among patients hospitalised with COVID-19, neither colchicine nor the combination of rivaroxaban and aspirin prevent disease progression or death.
Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, Thistledown Foundation.
For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.
It is unknown whether clinical benefit of proprotein convertase subtilisin/kexin type 9 inhibitors is associated with baseline or on-treatment triglyceride concentrations.
This study sought to ...examine relations between triglyceride levels and the effect of alirocumab vs placebo on cardiovascular outcomes using prespecified and post hoc analyses of the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial.
Patients with recent acute coronary syndrome (ACS) (n = 18,924) and elevated atherogenic lipoproteins despite optimized statin therapy were randomized to alirocumab 75 to 150 mg or matching placebo every 2 weeks subcutaneously. Major adverse cardiovascular events (MACE) were examined in relation to continuous or dichotomous triglyceride concentrations.
Median baseline triglyceride concentration was 129 mg/dL. In both treatment groups, a 10-mg/dL higher baseline concentration was associated with an adjusted MACE HR of 1.008 (95% CI: 1.003-1.013; P < 0.005). Baseline triglycerides ≥150 vs <150 mg/dL were associated with a HR of 1.184 (95% CI: 1.080-1.297; P < 0.005). Versus placebo, alirocumab reduced low-density lipoprotein cholesterol from baseline (average, 54.7%) and reduced MACE (HR: 0.85; 95% CI: 0.78-0.93). At month 4, triglyceride levels were reduced from baseline by median 17.7 mg/dL (P < 0.001) and 0.9 mg/dL (P = NS) with alirocumab and placebo, respectively. A 10-mg/dL decline from baseline in triglycerides was associated with lower subsequent risk of MACE with placebo (HR: 0.988; 95% CI: 0.982-0.995; P < 0.005) but not with alirocumab (HR: 0.999; 95% CI: 0.987-1.010; P = 0.82).
Among patients with recent ACS on optimized statin therapy, baseline triglycerides was associated with cardiovascular risk. However, the reduction in triglycerides with alirocumab did not contribute to its clinical benefit. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)
In patients with coronary or peripheral artery disease, the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse ...cardiovascular events and mortality and increased bleeding.
This study sought to explore the effects of the combination of rivaroxaban and aspirin compared with aspirin on sites, timing, severity, and management of bleeding in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) study.
This study reports, by treatment group, the number and proportion of patients; hazard rate ratios for bleeding according to site and severity; the timing of bleeding using landmark analyses; and the number and proportion of patients who received blood products and other hemostatic treatments.
Of 27,395 patients enrolled (mean age 68 years, 22% women), 18,278 were randomized to the combination of rivaroxaban and aspirin or to aspirin alone and followed for a mean of 23 months. Compared with aspirin alone, the combination increased modified International Society on Thrombosis and Hemostasis major bleeding (288 of 9,152 3.1% vs. 170 of 9,126 1.9%), (HR: 1.70; 95% CI: 1.40 to 2.05; p < 0.001), International Society on Thrombosis and Hemostasis major bleeding (206 of 9,152 2.3% vs. 116 of 9,126 1.3%), (HR: 1.78; 95% CI: 1.41 to 2.23; p < 0.0001), and minor bleeding (838 of 9,152 9.2% vs. 503 of 9,126 5.5%), (HR: 1.70; 95% CI 1.52 to 1.90; p < 0.0001); the combination also increased the need for any red cell transfusion (87 of 9,152 1.0% vs. 44 of 9,126 0.5%), (HR: 1.97; 95% CI 1.37 to 2.83, p = 0.0002). The gastrointestinal (GI) tract was the most common site of increased major bleeding (140 of 9,152 1.5% vs. 65 of 9,126 0.7%), (HR: 2.15; 95% CI: 1.60 to 2.89; p < 0.001), and the increase in bleeding was predominantly in the first year after randomization. Approximately one-third of major GI bleeding was gastric or duodenal, one-third was colonic or rectal, and one-third was from an unknown GI site. The study investigators reported that approximately three-quarters of major bleeding episodes were of mild or moderate intensity. A similar proportion of patients in each treatment group who experienced major bleeding received platelets, clotting factors, or other hemostatic agents.
The combination of rivaroxaban and aspirin compared with aspirin alone increased major bleeding, mainly from the GI tract. Most excess bleeding occurred during the first year after randomization, was of mild or moderate intensity, and was managed with conventional supportive therapy. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease COMPASS; NCT01776424)
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Purpose
Chemotherapy-induced diarrhea (CID) is a common symptom that occurs in 50 to 80% of patients. Given that the majority of the data on the occurrence and severity of CID is based on ...physician-rated toxicity criteria, this study’s purposes were to identify subgroups of patients with distinct CID profiles and determine how these subgroups differ in terms of demographic and clinical characteristics; severity, frequency, and distress of CID; the co-occurrence of common GI symptoms; and QOL.
Methods
Patients (
n
= 1133) completed the Memorial Symptom Assessment Scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct diarrhea profiles. Differences among these subgroups were evaluated using parametric and nonparametric statistics.
Results
Four distinct diarrhea profiles were identified: none (58.3%), decreasing (22.0%), increasing (5.2%), and high (14.5%). Compared with the none class, patients in the high class had a lower functional status, a worse comorbidity profile, were more likely to have gastrointestinal cancer, and were more likely to receive chemotherapy on a 14-day cycle. No differences were found among the classes in the percentages of patients who received chemotherapy with a targeted therapy.
Conclusion
Given that CID occurred in over 40% of the patients, clinicians should assess for this symptom and other common GI symptoms and initiate appropriate pharmacologic and dietary interventions.
•Optimization by simulated annealing, pattern search (PS) & ranking and selection (RS).•Lower/upper bounds for near-optimal solutions by PS enhanced by RS indifferent zone.•Analysis of periodic ...stochastic inventory model with auto-correlated demands (ACD).•Study Markov-modulated interrelated demands with empirical probability distribution.•Inventory performance significantly declines as ACD increases and disregarded.
A consumer demand that presents auto-correlated components is a class of demand commonly found in competitive markets in which consumers may develop preferences for certain products which influence their willingness to purchase them again. This behavior may be observed in inventory systems whose products are subject to promotion plans in which mechanisms that incentivize the demand are implemented. Inventory systems that ignore these dependency components may severely impair their performance. This paper analyzes a stochastic inventory model where the control review system is periodic, is categorized as a lost-sale case, and is exposed to this class of auto-correlated demand pattern. The demand for products is characterized as a discrete Markov-modulated demand in which product quantities of the same item may relate to one another according to an empirical probability distribution. A simulation-based optimization that combines simulated annealing, pattern search, and ranking and selection (SAPS&RS) methods to approximate near-optimal solutions to this problem is employed. Lower and upper bounds for a range of near-optimal solutions are determined by the pattern search step enhanced by ranking and selection—indifferent zone. Results indicate that inventory performance significantly declines as the autocorrelation increases and is disregarded.
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