History and Outlook for Glyphosate-Resistant Crops.

Glyphosate-resistant (GR) crops, commercially referred to as glyphosate-tolerant (GT), started the revolution in crop biotechnology in 1996. Growers rapidly accepted GR crops whenever they became available and made them the most rapidly adopted technology in agriculture history. Adoption usually meant sole reliance on glyphosate [N-(phosphonomethyl)glycine, CAS No. 1071-83-6] for weed control. Not surprisingly, weeds eventually evolved resistance and are forcing growers to change their weed management practices. Today, the widespread dissemination of GR weeds that are also resistant to other herbicide modes-of-action (MoA) has greatly reduced the value of the GR crop weed management systems. However, growers continue to use the technology widely in six major crops throughout North and South America. Integrated chemistry and seed providers seek to sustain glyphosate efficacy by promoting glyphosate combinations with other herbicides and stacking the traits necessary to enable the use of partner herbicides. These include glufosinate {4-[hydroxy(methyl)phosphinoyl]-DL-homoalanine, CAS No. 51276-47-2}, dicamba (3,6-dichloro-2-methoxybenzoic acid, CAS No. 1918-00-9), 2,4-D [2-(2,4-dichlorophenoxy)acetic acid, CAS No. 94-75-7], 4-hydroxyphenyl pyruvate dioxygenase inhibitors, acetyl coenzyme A carboxylase (ACCase) inhibitors, and other herbicides. Unfortunately, herbicide companies have not commercialized a new MoA for over 30 years and have nearly exhausted the useful herbicide trait possibilities. Today, glyphosate-based crop systems are still mainstays of weed management, but they cannot keep up with the capacity of weeds to evolve resistance. Growers desperately need new technologies, but no technology with the impact of glyphosate and GR crops is on the horizon. Although the expansion of GR crop traits is possible into new geographic areas and crops such as wheat and sugarcane and could have high value, the Roundup Ready® revolution is over. Its future is at a nexus and dependent on a variety of issues.

A Randomized Controlled Trial Comparing Learners' Decision-making, Anxiety, and Task Load During a Simulated Airway Crisis Using Two Difficult Airway Aids.

INTRODUCTION: The American Society of Anesthesiologists (ASA) difficult airway algorithm and the Vortex approach are difficult airway aids. Our objective was to demonstrate that a simpler cognitive model would facilitate improved decision-making during a process such as difficult airway management. We hypothesized the simpler Vortex approach would be associated with less anxiety and task load. METHODS: Medical students were randomized to the ASA algorithm (n = 33) or Vortex approach (n = 34). All learned basic airway techniques on day 1 of their rotation. Next, they watched a video of their respective aid then managed a simulated airway crisis. We assessed decision-making using a seven-point airway management score and a completeness score. Completeness was at least one attempt at each of four techniques (mask ventilation, supraglottic airway, intubation, and cricothyrotomy). Two validated tools, the State-Trait Anxiety Inventory Form Y and the National Aeronautics and Space Administration Task Load Index, were used to assess anxiety and task load. RESULTS: Students in the Vortex group had higher airway management scores [4.0 (interquartile range = 4.0 to 5.0) vs. 4.0 (3.0 to 4.0), P = 0.0003] and completeness (94.1% vs. 63.6%, P = 0.003). In the ASA group, the means (SD) of National Aeronautics and Space Administration Task Load Index scores of 55 or higher were observed in mental [61.4 (14.4)], temporal [62.3 (22.9)], and effort [57.1 (15.6)] domains. In the Vortex group, only the temporal load domain was 55 or higher [mean (SD) = 57.8 (25.4)]. There was no difference in anxiety. CONCLUSIONS: Medical students perform better in a simulated airway crisis after training in the simpler Vortex approach to guide decision-making. Students in the ASA group had task load scores indicative of high cognitive load.

The rise and future of glyphosate and glyphosate-resistant crops.

Glyphosate and glyphosate-resistant crops had a revolutionary impact on weed management practices, but the epidemic of glyphosate-resistant (GR) weeds is rapidly decreasing the value of these technologies. In areas that fully adopted glyphosate and GR crops, GR weeds evolved and glyphosate and glyphosate traits now must be combined with other technologies. The chemical company solution is to combine glyphosate with other chemicals, and the seed company solution is to combine glyphosate resistance with other traits. Unfortunately, companies have not discovered a new commercial herbicide mode-of-action for over 30 years and have already developed or are developing traits for all existing herbicide types with high utility. Glyphosate mixtures and glyphosate trait combinations will be the mainstays of weed management for many growers, but are not going to be enough to keep up with the capacity of weeds to evolve resistance. Glufosinate, auxin, HPPD-inhibiting and other herbicide traits, even when combined with glyphosate resistance, are incremental and temporary solutions. Herbicide and seed businesses are not going to be able to support what critics call the chemical and transgenic treadmills for much longer. The long time without the discovery of a new herbicide mode-of-action and the epidemic of resistant weeds is forcing many growers to spend much more to manage weeds and creating a worst of times, best of times predicament for the crop protection and seed industry. © 2016 Society of Chemical Industry.

Broad 4-hydroxyphenylpyruvate dioxygenase inhibitor herbicide tolerance in soybean with an optimized enzyme and expression cassette.

With an optimized expression cassette consisting of the soybean (Glycine max) native promoter modified for enhanced expression driving a chimeric gene coding for the soybean native amino-terminal 86 amino acids fused to an insensitive shuffled variant of maize (Zea mays) 4-hydroxyphenylpyruvate dioxygenase (HPPD), we achieved field tolerance in transgenic soybean plants to the HPPD-inhibiting herbicides mesotrione, isoxaflutole, and tembotrione. Directed evolution of maize HPPD was accomplished by progressively incorporating amino acids from naturally occurring diversity and novel substitutions identified by saturation mutagenesis, combined at random through shuffling. Localization of heterologously expressed HPPD mimicked that of the native enzyme, which was shown to be dually targeted to chloroplasts and the cytosol. Analysis of the native soybean HPPD gene revealed two transcription start sites, leading to transcripts encoding two HPPD polypeptides. The N-terminal region of the longer encoded peptide directs proteins to the chloroplast, while the short form remains in the cytosol. In contrast, maize HPPD was found almost exclusively in chloroplasts. Evolved HPPD enzymes showed insensitivity to five inhibitor herbicides. In 2013 field trials, transgenic soybean events made with optimized promoter and HPPD variant expression cassettes were tested with three herbicides and showed tolerance to four times the labeled rates of mesotrione and isoxaflutole and two times the labeled rates of tembotrione.

Current state of herbicides in herbicide-resistant crops.

Current herbicide and herbicide trait practices are changing in response to the rapid spread of glyphosate-resistant weeds. Growers urgently needed glyphosate when glyphosate-resistant crops became available because weeds were becoming widely resistant to most commonly used selective herbicides, making weed management too complex and time consuming for large farm operations. Glyphosate made weed management easy and efficient by controlling all emerged weeds at a wide range of application timings. However, the intensive use of glyphosate over wide areas and concomitant decline in the use of other herbicides led eventually to the widespread evolution of weeds resistant to glyphosate. Today, weeds that are resistant to glyphosate and other herbicide types are threatening current crop production practices. Unfortunately, all commercial herbicide modes of action are over 20 years old and have resistant weed problems. The severity of the problem has prompted the renewal of efforts to discover new weed management technologies. One technology will be a new generation of crops with resistance to glyphosate, glufosinate and other existing herbicide modes of action. Other technologies will include new chemical, biological, cultural and mechanical methods for weed management. From the onset of commercialization, growers must now preserve the utility of new technologies by integrating their use with other weed management technologies in diverse and sustainable systems.

The benefits of herbicide-resistant crops.

Since 1996, genetically modified herbicide-resistant crops, primarily glyphosate-resistant soybean, corn, cotton and canola, have helped to revolutionize weed management and have become an important tool in crop production practices. Glyphosate-resistant crops have enabled the implementation of weed management practices that have improved yield and profitability while better protecting the environment. Growers have recognized their benefits and have made glyphosate-resistant crops the most rapidly adopted technology in the history of agriculture. Weed management systems with glyphosate-resistant crops have often relied on glyphosate alone, have been easy to use and have been effective, economical and more environmentally friendly than the systems they have replaced. Glyphosate has worked extremely well in controlling weeds in glyphosate-resistant crops for more than a decade, but some key weeds have evolved resistance, and using glyphosate alone has proved unsustainable. Now, growers need to renew their weed management practices and use glyphosate with other cultural, mechanical and herbicide options in integrated systems. New multiple-herbicide-resistant crops with resistance to glyphosate and other herbicides will expand the utility of existing herbicide technologies and will be an important component of future weed management systems that help to sustain the current benefits of high-efficiency and high-production agriculture.

Herbicide-resistant crops: utilities and limitations for herbicide-resistant weed management.

Since 1996, genetically modified herbicide-resistant (HR) crops, particularly glyphosate-resistant (GR) crops, have transformed the tactics that corn, soybean, and cotton growers use to manage weeds. The use of GR crops continues to grow, but weeds are adapting to the common practice of using only glyphosate to control weeds. Growers using only a single mode of action to manage weeds need to change to a more diverse array of herbicidal, mechanical, and cultural practices to maintain the effectiveness of glyphosate. Unfortunately, the introduction of GR crops and the high initial efficacy of glyphosate often lead to a decline in the use of other herbicide options and less investment by industry to discover new herbicide active ingredients. With some exceptions, most growers can still manage their weed problems with currently available selective and HR crop-enabled herbicides. However, current crop management systems are in jeopardy given the pace at which weed populations are evolving glyphosate resistance. New HR crop technologies will expand the utility of currently available herbicides and enable new interim solutions for growers to manage HR weeds, but will not replace the long-term need to diversify weed management tactics and discover herbicides with new modes of action. This paper reviews the strengths and weaknesses of anticipated weed management options and the best management practices that growers need to implement in HR crops to maximize the long-term benefits of current technologies and reduce weed shifts to difficult-to-control and HR weeds.

Let the right one in: a microeconomic approach to partner choice in mutualisms.

One of the main problems impeding the evolution of cooperation is partner choice. When information is asymmetric (the quality of a potential partner is known only to himself), it may seem that partner choice is not possible without signaling. Many mutualisms, however, exist without signaling, and the mechanisms by which hosts might select the right partners are unclear. Here we propose a general mechanism of partner choice, "screening," that is similar to the economic theory of mechanism design. Imposing the appropriate costs and rewards may induce the informed individuals to screen themselves according to their types and therefore allow a noninformed individual to establish associations with the correct partners in the absence of signaling. Several types of biological symbioses are good candidates for screening, including bobtail squid, ant-plants, gut microbiomes, and many animal and plant species that produce reactive oxygen species. We describe a series of diagnostic tests for screening. Screening games can apply to the cases where by-products, partner fidelity feedback, or host sanctions do not apply, therefore explaining the evolution of mutualism in systems where it is impossible for potential symbionts to signal their cooperativeness beforehand and where the host does not punish symbiont misbehavior.

New multiple-herbicide crop resistance and formulation technology to augment the utility of glyphosate.

Glyphosate has performed long and well, but now some weed communities are shifting to populations that survive glyphosate, and growers need new weed management technologies to augment glyphosate performance in glyphosate-resistant crops. Unfortunately, most companies are not developing any new selective herbicides with new modes of action to fill this need. Fortunately, companies are developing new herbicide-resistant crop technologies to combine with glyphosate resistance and expand the utility of existing herbicides. One of the first multiple-herbicide-resistant crops will have a molecular stack of a new metabolically based glyphosate resistance mechanism with an active-site-based resistance to a broad spectrum of ALS-inhibiting herbicides. Additionally, new formulation technology called homogeneous blends will be used in conjunction with glyphosate and ALS-resistant crops. This formulation technology satisfies governmental regulations, so that new herbicide mixture offerings with diverse modes of action can be commercialized more rapidly and less expensively. Together, homogeneous blends and multiple-herbicide-resistant crops can offer growers a wider choice of herbicide mixtures at rates and ratios to augment glyphosate and satisfy changing weed management needs.

Efficacy and safety of rofecoxib 12.5 mg versus nabumetone 1,000 mg in patients with osteoarthritis of the knee: a randomized controlled trial.

OBJECTIVES: To evaluate the use of starting doses of rofecoxib and nabumetone in patients with osteoarthritis (OA) of the knee. DESIGN: A 6-week, randomized, parallel-group, double-blind, placebo-controlled study. SETTING: One hundred thirteen outpatient sites in the United States. PARTICIPANTS: A total of 1,042 male and female patients aged 40 and older with OA of the knee (>6 months). INTERVENTIONS: Rofecoxib 12.5 mg once a day (n=424), nabumetone 1,000 mg once a day (n=410), or placebo (n=208) for 6 weeks. MEASUREMENTS: The primary efficacy endpoint was patient global assessment of response to therapy (PGART) over 6 weeks, which was also specifically evaluated over the first 6 days. The main safety measure was adverse events during the 6 weeks of treatment. RESULTS: The percentage of patients with a good or excellent response to therapy as assessed using PGART at Week 6 was significantly higher with rofecoxib (55.4%) than nabumetone (47.5%; P=.018) or placebo (26.7%; P<.001 vs rofecoxib or nabumetone). Median time to first report of a good or excellent PGART response was significantly shorter in patients treated with rofecoxib (2 days) than with nabumetone (4 days, P=.002) and placebo (>5 days, P<.001) (nabumetone vs placebo; P=.007). The safety profiles of rofecoxib and nabumetone were generally similar, including gastrointestinal, hypertensive, and renal adverse events. CONCLUSION: Rofecoxib 12.5 mg daily demonstrated better efficacy over 6 weeks of treatment and quicker onset of OA efficacy over the first 6 days than nabumetone 1,000 mg daily. Both therapies were generally well tolerated.