The primary objective of this study was to test the hypothesis that 1 or more dose levels of LY2140023 monohydrate, an oral prodrug of the potent metabotropic glutamate (mGlu) 2/3 receptor agonist LY404039, given to patients with schizophrenia for 4 weeks would demonstrate significantly greater efficacy than placebo. The HBBI study was a multicenter, randomized, double-blind, parallel, placebo- and active-controlled trial. Male and female patients aged 18 to 65 years who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia were randomized in a 2:2:2:2:2:1 ratio to receive 5-, 20-, 40-, or 80-mg LY2140023 monohydrate twice daily, placebo twice daily, or placebo (am) and 15 mg of olanzapine (pm) daily. Efficacy was defined as the change from baseline on the Positive and Negative Syndrome Scale (PANSS) total score assessed at 4 weeks. The primary analysis did not show that any of the 4 LY2140023 monohydrate doses were more efficacious than placebo as measured by the PANSS total score. Similarly, olanzapine did not significantly separate from placebo. A higher-than-anticipated treatment effect (14.6-point improvement) in the placebo group was observed on PANSS total score. LY2140023 monohydrate was generally well tolerated, although 4 patients reported the serious adverse event of convulsion. LY2140023 monohydrate-treated patients showed little change in dopamine-related adverse events and weight. The results of the HBBI study are considered to be inconclusive because LY2140023 monohydrate and the active control olanzapine did not separate from placebo in the treatment of patients with acutely exacerbated schizophrenia. Additional efficacy, safety, and tolerability testing are needed.
Placement of fertilizer in the seed furrow to increase nutrient availability is a common practice in row-crop production. While in-furrow application of fertilizer is widely utilized in the production of winter wheat (Triticum aestivum L.), there is a lack of work evaluating new formulations and nutrient combinations that are available. The objective of this study was to quantify the effects of in-furrow fertilizer products and combinations of products on winter wheat grain yield, nitrogen and mineral concentrations. Trials were conducted across five site-years in central Oklahoma using 11 fertilizer formulations placed in-furrow at the time of planting. In locations that soil test phosphorus (STP) levels or potassium were above sufficiency, the use of in-furrow fertilizers did not improve yield over the control. Inconsistency of response was noted at locations where STP levels were below the critical threshold. While one location showed no response to the addition of P regardless of source, two other locations had significant yield responses from three or more P-containing fertilizers. The addition of both sulphur and zinc resulted in increased yield over the base product at one low STP location. Nutrient concentrations were also influenced in nutrient-limited soils; however, no trends in response were present. Based upon the results of this study, the application of in-furrow fertilizer has the potential to increase winter wheat grain yield and nutrient concentration, when soil nutrients are limiting. As expected the addition of fertilizer when soil test levels are at or above a sufficiency did not increase grain yield.
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