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Rigid ryegrass (Lolium rigidum Gaudin) is the most problematic weed in Australia, with evolved resistance to multiple herbicide sites of action. Selection pressure by cinmethylin (Group 30, a fatty-acid thioesterase inhibitor) has been limited, because few populations have been exposed to the herbicide since its introduction in 2019. In this study, we examined the sensitivity of L. rigidum populations to this new herbicide. From a screening of almost 500 field populations in 2020, 28 potentially resistant populations were further investigated in a dose–response experiment. Seedlings from five populations surviving treatments of 250 or 375 g ai ha−1 cinmethylin were grown to maturity and seeds were harvested. The level of resistance found among the five putative-resistant parental populations of L. rigidum was negligible. In one population, one round of selection with cinmethylin resulted in a 2-fold increase in the lethal dose causing 50% mortality in the progeny population, although this dose was still only one-sixth of the recommended field rate of cinmethylin. Having a unique site of action, cinmethylin is a viable preemergence herbicide option to control existing multiple-resistance populations of L. rigidum. Comprehensive field monitoring and recurrent selection studies under controlled environmental conditions are needed to better ascertain the risk of L. rigidum evolving a high level of resistance to cinmethylin, although current data suggest that this risk is relatively low.

The control of multiple-resistant wild radish (Raphanus raphanistrum L.) populations in no-till Australian wheat (Triticum aestivum L.) crops has relied upon 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicides over the last decade. Two R. raphanistrum populations identified as putatively resistant to pyrasulfotole + bromoxynil in an initial large-scale screening trial were characterized and confirmed to be 5- to 8-fold (comparison of LD50 values) less sensitive than the susceptible control population to the HPPD inhibitor pyrasulfotole when plants were treated at the 4-leaf stage. The two pyrasulfotole-resistant populations exhibited up to 4-fold resistance to the coformulated herbicide mixture pyrasulfotole + bromoxynil and up to 9- and 11-fold cross-resistance to mesotrione and topramezone postemergence, respectively. A small-plot trial was conducted in the field from which of one of the populations suspected of resistance was originally collected. Pyrasulfotole + bromoxynil or topramezone + bromoxynil applied postemergence delivered reduced R. raphanistrum control (79% to 87%), whereas mesotrione applied preemergence was >99% effective. We report here the first case of field resistance to HPPD-inhibiting herbicides in R. raphanistrum, caused by 12 yr of continuous reliance on that mode of action. The mitigation of herbicide resistance in continuous no-till cropping requires a constant optimization of the herbicide technology via alternation and mixtures of multiple sites of action, use of preemergence herbicides, and ensuring postemergence herbicides are applied at the most sensitive plant growth stages.

Herbicide resistance, documented in many economically damaging weed species, is a major threat to global crop production. The injudicious use of herbicides, often in the absence of diverse weed control strategies, poses an immense selection pressure on weed communities for resistance evolution and weed adaptive traits such as high seed dormancy. This study evaluates the interaction among developing herbicide resistance, seed size, and seed dormancy of ripgut brome (Bromus diandrus Roth), wild oat (Avena fatua L.), and hare barley [Hordeum leporinum Link; syn. Hordeum murinum L. ssp. leporinum (Link) Arcang.] collected from within intensively managed fields (in-crop) in comparison with populations in surrounding ruderal (non-crop disturbed) areas with no history of exposure to herbicides within the Western Australian grainbelt. Seed size of the three species varied by farming system (continuous cereal-intensive annual crops, diverse annual crops, pasture based) and habitat (in-crop, ruderal). Field populations of H. leporinum and B. diandrus tended to have greater seed size compared with ruderal populations. Larger seeds had significantly more dormancy in all three weed species. Field-collected populations that were exposed to herbicide applications for at least the past 5 yr exhibited significantly greater seed dormancy compared with their counterparts present in ruderal areas within the same geographic area. The association between increased seed dormancy and developing multiple herbicide resistance further complicates effective weed management.

Herbicide-resistant (HR) crops are widely grown throughout the United States and Canada. These crop-trait technologies can enhance weed management and therefore can be an important component of integrated weed management (IWM) programs. Concomitantly, evolution of HR weed populations has become ubiquitous in agricultural areas where HR crops are grown. Nevertheless, crop cultivars with new or combined (stacked) HR traits continue to be developed and commercialized. This review, based on a symposium held at the Western Society of Weed Science annual meeting in 2021, examines the impact of HR crops on HR weed management in the U.S. Great Plains, U.S. Pacific Northwest, and the Canadian Prairies over the past 25 yr and their past and future contributions to IWM. We also provide an industry perspective on the future of HR crop development and the role of HR crops in resistance management. Expanded options for HR traits in both major and minor crops are expected. With proper stewardship, HR crops can reduce herbicide-use intensity and help reduce selection pressure on weed populations. However, their proper deployment in cropping systems must be carefully planned by considering a diverse crop rotation sequence with multiple HR and non-HR crops and maximizing crop competition to effectively manage HR weed populations. Based on past experiences in the cultivation of HR crops and associated herbicide use in the western United States and Canada, HR crops have been important determinants of both the selection and management of HR weeds.

Harvest weed seed control (HWSC) is a weed management technique that intercepts and destroys weed seeds before they replenish the soil weed seedbank and can be used to control herbicide-resistant weeds in global cropping systems. Wild radish (Raphanus raphanistrum L.) is a problematic, globally distributed weed species that is considered highly susceptible to HWSC, as it retains much of its seed on the plant during grain harvest. However, previous studies have demonstrated that R. raphanistrum is capable of adapting its life cycle, in particular its flowering time, to allow individuals more time to mature and potentially shed seeds before harvest, thereby evading HWSC interception. This study compared the vegetative growth plus physiological and ecological fitness of an early-flowering R. raphanistrum biotype with an unselected genetically related biotype to determine whether physiological costs of early flowering exist when in competition with wheat (Triticum aestivum L.). Early flowering time adaptation in R. raphanistrum did not change the relative growth rate or competitive ability of R. raphanistrum. However, the height of first flower was reduced in the early flowering time–selected population, indicating that this population would retain more pods below the typical harvest cutting height (15 cm) used in HWSC. The presence of wheat competition (160 to 200 plants m−2) increased flowering height in the early flowering time–selected population, which would likely increase the susceptibility of early-flowering R. raphanistrum plants to HWSC. Overall, early-flowering adaption in R. raphanistrum is a possible strategy to escape being captured by the HWSC; however, increasing crop competition is likely to be an effective strategy to maintain the effectiveness of HWSC.

Since the commercialization of herbicide-resistant (HR) crops, primarily glyphosate-resistant crops, their adoption has increased rapidly. Multiple herbicide resistance traits in crops such as canola (Brassica napus L.), corn (Zea mays L.), cotton (Gossypium hirsutum L.), and soybean [Glycine max (L.) Merr.] have become available in recent years, and management of their volunteers needs attention to prevent interference and yield loss in rotational crops. The objectives of this review were to summarize HR crop traits in barley (Hordeum vulgare L.), canola, corn, cotton, rice (Oryza sativa L.), soybean, sugarbeet (Beta vulgaris L.), and wheat (Triticum aestivum L.); assess their potential for volunteerism; and review existing literature on the interference of HR crop volunteers, yield loss, and their management in rotational crops. HR crop volunteers are problem weeds in agronomic cropping systems, and the impact of volunteerism depends on several factors, such as crop grown in rotation, the density of volunteers, management practices, and microclimate. Interference of imidazolinone-resistant (IR) barley or wheat volunteers can be a problem in rotational crops, particularly when IR crops such as canola or wheat are grown. HR canola volunteers are abundant in the Northern Great Plains due to high fecundity, seed loss before or during harvest, and secondary seed dormancy, and they can interfere in crops grown in rotation such as flax (Linum usitatissimum L.), field peas (Pisum sativum L.), and soybean. HR corn volunteers are competitive in crops grown in rotation such as corn, cotton, soybean, and sugarbeet, with yield loss depending on the density of HR corn volunteers. Volunteers of HR cotton, rice, soybean, and sugarbeet are not major concerns and can be controlled with existing herbicides. Herbicide options would be limited if the crop volunteers are multiple HR; therefore, recording the cultivar planted the previous year and selecting the appropriate herbicide are important. The increasing use of 2,4-D, dicamba, glufosinate, and glyphosate in North American cropping systems requires research on herbicide interactions and alternative herbicides or methods for controlling multiple HR crop volunteers.

Wild radish (Raphanus raphanistrum L.) is a problematic and economically damaging dicotyledonous weed infesting crops in many regions of the world. Resistance to the auxinic herbicides 2,4-D and dicamba is widespread in Western Australian R. raphanistrum populations, with the resistance mechanism appearing to involve alterations in the physiological response to synthetic auxins and in plant defense. This study aimed to determine whether these alterations cause inhibition in plant growth or reproduction that could potentially be exploited to manage 2,4-D–resistant populations in cropping areas. Therefore, the morphology and seed production of resistant and susceptible populations were compared in an outdoor pot study, with plants grown in the presence and absence of competition by wheat (Triticum aestivum L.). The susceptible and resistant R. raphanistrum populations were equally suppressed by wheat competition, with plant growth and seed production being decreased by approximately 50%. Although resistant populations produced less vegetative biomass than susceptible populations, there was no negative association between resistance and seed production. Therefore, it is unlikely that any nonherbicidal management practices will be more efficacious on 2,4-D–resistant than 2,4-D–susceptible R. raphanistrum populations.

As chemical management options for weeds become increasingly limited due to selection for herbicide resistance, investigation of additional nonchemical tools becomes necessary. Harvest weed seed control (HWSC) is a methodology of weed management that targets and destroys weed seeds that are otherwise dispersed by harvesters following threshing. It is not known whether problem weeds in western Canada retain their seeds in sufficient quantities until harvest at a height suitable for collection. A study was conducted at three sites over 2 yr to determine whether retention and height criteria were met by wild oat, false cleavers, and volunteer canola. Wild oat consistently shed seeds early, but seed retention was variable, averaging 56% at the time of wheat swathing, with continued losses until direct harvest of wheat and fababean. The majority of retained seeds were >45 cm above ground level, suitable for collection. Cleavers seed retention was highly variable by site-year, but generally greater than wild oat. The majority of seed was retained >15 cm above ground level and would be considered collectable. Canola seed typically had >95% retention, with the majority of seed retained >15 cm above ground level. The suitability ranking of the species for management with HWSC was canola > cleavers > wild oat. Efficacy of HWSC systems in western Canada will depend on the target species and site- and year-specific environmental conditions.Nomenclature: False cleavers, Galium spurium L. GALSP; volunteer canola, Brassica napus L. BRSNN; wild oat, Avena fatua L. AVEFA; fababean, Vicia faba L.; wheat, Triticum aestivum L.

The Harrington Seed Destructor (HSD), a novel weed control technology, has been highly effective in Australian cropping systems. To investigate its applicability to conditions in western Canada, stationary threshing was conducted to determine the impact of weed species, seed size, seed number, chaff load, and chaff type on efficacy of seed destruction. Control varied depending on species, with a range of 97.7% to 99.8%. Sieve-sized volunteer canola seed had a linear relationship of increasing control with increasing 1,000-seed weight. However, with greater than 98% control across all tested seed weights, it is unlikely that seed size alone will significantly influence control. Consistently high levels of control were observed at all tested seed densities (10 seeds to 1 million seeds). The response of weed seed control to chaff load was quadratic, but a narrow range of consistently high control (>97%) was again observed. Chaff type had a significant effect on weed seed control (98% to 98.6%); however, seed control values in canola chaff were likely confounded by a background presence of volunteer canola. Overall, the five parameters studied statistically influence control of weed seeds with the HSD. However, small differences between treatments are unlikely to affect the biological impact of the machine, which provides high levels of control for those weed seeds that can be introduced into the harvester.

Wild oat control options are limited in western Canada due to resistance to most common herbicides. Control of wild oat with pyroxasulfone, a soil-applied, very-long-chain fatty-acid inhibitor, was investigated. A series of greenhouse and field experiments were conducted to isolate the effects of vertical seed position, site of herbicide interception, and tillage on wild oat control with pyroxasulfone in comparison with triallate. In greenhouse experiments, wild oat shoot length (soil surface to leaf tip) was reduced (P10 cm. Shallow-seeded wild oat had delayed emergence, possibly due to reduced soil moisture, and herbicides reduced shoot growth to

Efficient natural dispersal of herbicide-resistance alleles via seed and pollen can markedly accelerate the incidence of herbicide-resistant weed populations across an agroecoregion. Studies were conducted in western Canada in 2014 and 2015 to investigate pollen- and seed-mediated gene flow in kochia. Pollen-mediated gene flow (PMGF) from glyphosate-resistant (GR) to non-GR kochia was quantified in a field trial (hub and spoke design) at Saskatoon, Saskatchewan. Seed-mediated gene flow of acetolactate synthase (ALS) inhibitor-resistant kochia as a function of tumbleweed speed and distance was estimated in cereal stubble fields at Lethbridge, Alberta and Scott, Saskatchewan. Regression analysis indicated that outcrossing from GR to adjacent non-GR kochia ranged from 5.3 to 7.5%, declining exponentially to 0.1 to 0.4% at 96 m distance. However, PMGF was significantly influenced by prevailing wind direction during pollination (maximum of 11 to 17% outcrossing down-wind). Seed dropped by tumbleweeds varied with distance and plant speed, approaching 90% or more (ca. 100,000 seeds or more) at distances of up to 1,000 m and plant speeds of up to 300 cm s–1. This study highlights the efficient proximal (pollen) and distal (seed) gene movement of this important GR weed.

Glyphosate-resistant (GR) giant ragweed, horseweed, and common ragweed were confirmed in southwestern Ontario, Canada in 2008, 2010, and 2011, respectively. In the western prairie provinces of Alberta and Saskatchewan, GR (plus acetolactate synthase inhibitor-resistant) kochia was discovered in 2011. This symposium paper estimates the environmental impact (EI) of the top herbicide treatments or programs used to manage these GR weed species in the major field crops grown in each region. For each herbicide treatment, EI (per ha basis) was calculated as the environmental impact quotient (EIQ), which quantifies the relative potential risk of pesticide active ingredients on human and ecological health based on risk components to farm workers, consumers, and the environment, multiplied by the application rate (kg ai ha−1). Total EI is defined as EI (per ha basis) multiplied by the application area (i.e., land area affected by a GR weed). It was assumed that all herbicide treatments would supplement the continued usage of glyphosate because of its broad spectrum weed control. For the control of these GR weeds, most treatments contain auxinic or protoporphyrinogen oxidase (PPO)-inhibiting herbicides. The majority of auxinic herbicide treatments result in low (EI ≤ 10) to moderate (11 to 20) EI, whereas all treatments of PPO inhibitors have low EI. Total EI of GR horseweed and kochia will generally be greater than that of giant or common ragweed because of rapid seed dispersal. For recommended herbicide treatments to control GR weeds (and herbicide-resistant weeds in general), EI data should be routinely included with cost and site of action in weed control extension publications and software, so that growers have the information needed to assess the EI of their actions.

Over 90% of Canadian kochia populations are resistant to acetolactate synthase (ALS)– inhibiting herbicides. We questioned whether the target site–based resistance could affect plant growth and competitiveness. Homozygous F2herbicide-resistant (HR) kochia plants with an amino acid substitution at Trp574(sources: Alberta [AB], Saskatchewan [SK], and Manitoba [MB]), or Pro197(MB, AB with two populations) were grown in replacement series with homozygous F2herbicide-susceptible (HS) plants from the corresponding heterogeneous population (total: six populations). In pure stands, growth of HR plants from AB and SK was similar to that of HS plants, regardless of mutation; conversely, MB2-HR plants (Trp574Leu) developed more slowly and were taller than MB2-HS plants. Final dry weight of HR plants in pure stands was similar across all six populations, whereas that for HS plants in pure stands and HR–HS plants in mixed stands (50–50%) varied with population. Results for AB and SK populations suggest little impact of either ALS mutation on kochia growth, whereas those for MB lines would suggest an unidentified factor (or factors) affecting the HS, HR, or both biotypes. The variable response within and between lines, and across HS biotypes highlights the importance of including populations of various origins and multiple susceptible controls in HR biotype studies.

Wild oat is the second-most abundant, but most economically important, weed across the Canadian Prairies of western Canada. Despite the serious economic effects of resistance to acetyl-CoA carboxylase (ACC) or acetolactate synthase (ALS) inhibitors or both in this weed throughout the Northern Great Plains of North America, little research has examined the basis for herbicide resistance. We investigated target-site and nontarget-site mechanisms conferring ACC- and ALS-inhibitor resistance in 16 wild oat populations from across western Canada (four ACC-inhibitor resistant, four ALS-inhibitor resistant, and eight ACC- and ALS-inhibitor resistant). TheACC1mutations were found in 8 of the 12 ACC inhibitor-resistant populations. The Ile1781Leu mutation was detected in three populations, the Trp2027Cys and Asp2078Gly mutations were in two populations each, and the Trp1999Cys, Ile2041Asn, Cys2088Arg, and Gly2096Ser substitutions were in one population each. Three populations had twoACC1mutations. Only 2 of the 12 ALS inhibitor-resistant populations had anALStarget-site mutation—Ser653Thr and Ser653Asn substitutions. This is the first global report ofALStarget-site mutations inAvenaspp. and four previously undocumentedACC1mutations in wild oat. Based on these molecular analyses, seedlings of five ACC + ALS inhibitor-resistant populations (one with anACC1mutation; four with noACCorALSmutations) were treated with malathion, a known cytochrome P450 monooxygenase inhibitor, followed by application of one of four ACC- or ALS-inhibiting herbicides. Malathion treatment often resulted in control or suppression of these populations, suggesting involvement of this enzyme system in contributing to resistance to both ACC and ALS inhibitors.

ALS inhibitor-resistant biotypes are the fastest growing class of herbicide-resistant (HR) weeds. A Canadian ALS inhibitor-resistant biotype of Russian thistle was first reported in 1989. The molecular basis for ALS-inhibitor resistance is unknown for Canadian populations of this polyploid weed species, and was determined in this study for one Alberta and two Saskatchewan HR Russian thistle populations. HR plants survived spray application of the ALS-inhibitor mixture thifensulfuron : tribenuron in the greenhouse. All three HR Russian thistle populations were heterogeneous and contained both HR and herbicide-susceptible (HS) individuals. The molecular basis for resistance was determined by sequencing theALSgene and/or conducting a TaqMan genotyping assay for single nucleotide polymorphism (SNP) for the Trp574Leu mutation. Two target-site mutations were observed: Trp574Leu in all three biotypes (554 individuals) and Pro197Gln in one biotype (one individual), suggesting multiple-founding events for Russian thistle HR populations in western Canada. Segregation patterns among F1 and F2 progeny arrays of HR lines sprayed under greenhouse conditions varied; some segregated (i.e., had HR and HS progeny), whereas other lines were exclusively HR. In contrast, no segregation of molecular types, i.e., Trp574, Trp/Leu574and Leu574, as would be expected with heterozygosity at a single locus Trp/Leu574, was observed. Such lack of segregation is consistent with the polyploid genome structure of Russian thistle and the presence of two copies of theALSgene. The presence of more than oneALSgene confounded the ability of the molecular techniques to accurately identify “true” heterozygotes in this study.

Multiple cases of ALS inhibitor-resistant weed biotypes are reported for many species, including wild mustard. The physiological extent and molecular basis of resistance to ALS inhibitors was compared in four biotypes of wild mustard from western Canada: a sulfonylurea (SU)-resistant (R) biotype from Manitoba detected in 1992; an SU (ethametsulfuron)-R biotype from Alberta detected in 1993 (metabolism-based resistance); an SU-R biotype from Manitoba detected in 2002; and a SU- and imidazolinone (IMI)-R biotype from Saskatchewan detected in 2002. Herbicide dose-response experiments confirmed that the two Manitoba biotypes were resistant to the SU herbicides ethametsulfuron and tribenuron : thifensulfuron mixture, whereas the Saskatchewan biotype was resistant to both SU herbicides and to imazethapyr, an IMI herbicide. Sequence analysis of theALSgene detected target site mutations in three of the four R biotypes, with amino acid substitutions Pro197(CCT) to Ser (TCT) [Domain A of the gene] in the two SU-R Manitoba biotypes and Trp574(TGG) to Leu (TTG) [Domain B] in the Saskatchewan biotype. The Alberta SU-R biotype had the sameALSnucleotide and amino acid sequence as the susceptible population at these two positions. Two heterozygous individuals [Trp574(Tt/gG)] were detected in the Saskatchewan biotype, and genetic segregation for nucleotide bases and resistance phenotype was consistent with single gene control. Nucleotide variation in neutral regions of theALSgene varied with biotype, with no variation in the two Manitoba biotypes, two variants in the Saskatchewan biotype, and 16 neutral nucleotide polymorphisms (0.9%) in the Alberta biotype. The occurrence of at least three different ALS inhibitor-R biotypes in this important weed species is likely to impact negatively on the use of ALS inhibitors, such as the IMIs, and serves as a warning for strict implementation of herbicide rotations to prevent or delay the evolution and spread of such populations.

Development of more comprehensive and cost-effective integrated weed management systems is required to facilitate greater integrated weed management adoption by farmers. A field experiment was conducted at two locations to determine the combined effects of seed date (April or May), seed rate (recommended or 150% of recommended), fertilizer timing (applied in fall or spring), and in-crop herbicide dose (50% or 100% of recommended) on weed growth and crop yield. This factorial set of treatments was applied in four consecutive years within a spring wheat–spring canola–spring wheat–spring canola rotation in a zero-till production system. Both wheat and canola phases of the rotation were grown each year. Weed biomass was often lower with May than with April seeding because more weeds were controlled with preplant glyphosate. However, despite fewer weeds being present with May seeding, wheat yield was only greater in 1 of 7 site-years, and canola yield was never greater with May compared with April seeding. Higher crop seed rates had a consistently positive effect on reducing weed growth and the weed seedbank. Crop yield was sometimes greater, and never lower, with higher seed rates. Fertilizer timing did not have a large effect on crop yield, but applying N in the spring compared with fall was less favorable for weeds as indicated by lower weed biomass and a 20% decrease in the weed seedbank. In-crop herbicides applied at 50% compared with 100% doses often resulted in similar weed biomass and crop yield, especially when higher crop seed rates were used. Indeed, the weed seedbank at the conclusion of the 4-yr experiment was not greater with the 50% compared with 100% herbicide dose at one of two locations. This study demonstrates the combined merits of early seeding (April), higher crop seed rates, and spring-applied fertilizer in conjunction with timely but limited herbicide use to manage weeds and maintain high crop yields in rotations containing wheat and canola.

Unintentional herbicide resistance gene stacking in canola may alter the sensitivity of volunteers to herbicides of alternative modes of action commonly used for their control. Greenhouse experiments were conducted to investigate the response of three single-herbicide–resistant (HR) cultivars (glyphosate, glufosinate, imidazolinone), one non-HR cultivar, and seven multiple (double or triple)–HR experimental lines to 2,4-D (amine and ester), MCPA ester, and metribuzin applied at the two- to three-leaf stage and of one non-HR and four HR cultivars (glyphosate, glufosinate, imidazolinone, bromoxynil) to 2,4-D amine applied at two growth stages (two- to three-leaf stage and five- to six-leaf stage). All canola cultivars or lines treated at the two- to three-leaf stage responded similarly to increasing doses of each of the three herbicides. At the five- to six-leaf stage, however, the bromoxynil HR cultivar was less sensitive to 2,4-D than the other cultivars. The results of this study suggest that canola with multiple-herbicide–resistance traits does not differ from cultivars that are non-HR or single HR in its sensitivity to herbicides commonly used to control volunteers. All volunteers, whether non-HR, single HR, or multiple HR, should be treated when plants are most sensitive to herbicides (two- to four-leaf stage) to reduce their interference against crops and their perpetuation of gene flow.

Growth chamber studies were conducted to ex- amine the soil residual properties of DPX-A7881, a new sulfonylurea herbicide. The phytotoxic residue levels in the soil were determined by a lentil radicle bioassay. The duration of activity was prolonged in soil adjusted to pH 7.6 and 8.1 relative to more acidic levels. The rate of breakdown in the soil was enhanced with increased temperature and soil mois- ture content; a significant temperature by moisture inter- action was noted over the duration of the incubation period. The dissipation of DPX-A7881 in soil obeyed first-order kinetics in both studies. An accelerated rate of breakdown in unsterilized versus sterilized soil (pH 7.6) indicated that microbial degradation was an important factor affecting the persistence in alkaline soils. Herbicide residues in the soil caused a reduction in taproot length and number of primary lateral roots of canola seedlings 15 days after plant- ing but there were no other morphological effects observed on the root. The secondary laterals, however, had generally recovered by this time. Nomenclature: DPX-A7881, 2- (((((4