The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

OBJECTIVES/SPECIFIC AIMS: Background: Delirium is a well described form of acute brain organ dysfunction characterized by decreased or increased movement, changes in attention and concentration as well as perceptual disturbances (i.e., hallucinations) and delusions. Catatonia, a neuropsychiatric syndrome traditionally described in patients with severe psychiatric illness, can present as phenotypically similar to delirium and is characterized by increased, decreased and/or abnormal movements, staring, rigidity, and mutism. Delirium and catatonia can co-occur in the setting of medical illness, but no studies have explored this relationship by age. Our objective was to assess whether advancing age and the presence of catatonia are associated with delirium. METHODS/STUDY POPULATION: Methods: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Measures of association (OR) were assessed with a simple logistic regression model with catatonia as the independent variable and delirium as the dependent variable. Effect measure modification by age was assessed using a Likelihood ratio test. RESULTS/ANTICIPATED RESULTS: Results: We enrolled 136 medical and surgical critically ill patients with 452 matched (concomitant) delirium and catatonia assessments. Median age was 59 years (IQR: 52–68). In our cohort of 136 patients, 58 patients (43%) had delirium only, 4 (3%) had catatonia only, 42 (31%) had both delirium and catatonia, and 32 (24%) had neither. Age was significantly associated with prevalent delirium (i.e., increasing age associated with decreased risk for delirium) (p=0.04) after adjusting for catatonia severity. Catatonia was significantly associated with prevalent delirium (p<0.0001) after adjusting for age. Peak delirium risk was for patients aged 55 years with 3 or more catatonic signs, who had 53.4 times the odds of delirium (95% CI: 16.06, 176.75) than those with no catatonic signs. Patients 70 years and older with 3 or more catatonia features had half this risk. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Catatonia is significantly associated with prevalent delirium even after controlling for age. These data support an inverted U-shape risk of delirium after adjusting for catatonia. This relationship and its clinical ramifications need to be examined in a larger sample, including patients with dementia. Additionally, we need to assess which acute brain syndrome (delirium or catatonia) develops first.

Field and laboratory experiments were conducted in 1983 and 1984 to compare the degradation of dichlormid (2,2-dichloro-N,N-di-2-prophenylacetamide), dietholate (O,O-diethyl O-phenylphosphorothioate), EPTC (S-ethyl dipropyl carbamothioate), and butylate [S-ethyl bis(2-methylpropyl) carbamothioate] in soils that had or had not been previously treated with each chemical. EPTC + dichlormid, butylate + dichlormid, EPTC + dichlormid + dietholate, or butylate + dichlormid + dietholate were applied annually for 4 yr to field plots to establish treatment histories. Butylate and EPTC degradation was enhanced in soils with previous histories of butylate and EPTC, respectively. Degradation rates of dietholate were equivalent in untreated soils or soils previously treated with EPTC + dietholate or butylate + dietholate.

All herbicide treatments controlled the initial stand of Canada thistle [Cirsium arvense (L.) Scop.] and musk thistle (Carduus nutans L.) on a subirrigated range site. Annual retreatment controlled seedlings and the few plants that emerged from surviving root remnants after the first application. Average perennial grass production on unfertilized, herbicide-treated plots increased 110, 314, and 212%/yr over unfertilized check plots during the 3-yr period of treatment, i.e., 960, 3450, and 4300 kg/ha, respectively. Grasses did not fully reoccupy the site at the end of 3 consecutive yr of excellent thistle and forb control. The increase in grass production varied considerably among several herbicide treatments that controlled thistles equally. Grass production in the third year was greater under the 3,6-dichloropicolinic acid and 2,4-D [(2,4-dichlorophenoxy)acetic acid] treatment series than all other treatments. Ammonium nitrate enhanced the recovery of grass damaged by certain herbicides, but favored the competitive ability of the thistle more than that of the grasses.

Field research was conducted during the summers of 1981 and 1982 in order to determine relative infection and population increase of lesion nematodes (Pratylenchus spp.) on seven weed species that commonly occur in field-bean (Phaseolus vulgaris L.) fields in western Nebraska. Weeds were grown at three densities with and without fieldbeans. A representative sample of the root systems from plants in each plot was removed in August and the nematodes were extracted and counted. No difference in nematode infection rate was found among weed population levels. Nematodes per gram of dry root were not different in weeds grown with or without fieldbeans. Weeds grown with fieldbeans had smaller root systems, and consequently total nematodes per root system were less than in weeds grown in the absence of fieldbeans. There was a significant difference among most weed species when nematodes per gram of dry root were estimated. Hairy nightshade (Solanum sarachoides Sendt. ♯3 SOLSA) and barnyardgrass [Echinochloa crus-galli (L.) ♯ ECHCG] supported the highest numbers of nematodes per g oven-dry roots, redroot pigweed (Amaranthus retroflexus L. ♯ AMARE) and common cocklebur (Xanthium pensylvanicum Wallr. ♯ XANPE) had least numbers of nematodes/g oven-dry roots, and infestation levels on other weed species were variable but generally intermediate.

Field studies were conducted to determine the influence of annual herbicide treatments plus cultivation on weed populations and corn yields in ridge-till corn during a 3-yr period at Mitchell, NE, and a 7-yr period at North Platte, NE. When the experiment was initiated at North Platte, no weeds were present before corn planting. It took 4 yr before triazine-resistant kochia became a problem before corn planting in plots treated with atrazine, but these were controlled by other operations prior to corn harvest. In the cultivated check, green foxtail densities before harvest increased from 0 in 1985 to 32 plants 100 m−2 in 1991. Annual applications of dicamba plus 2,4-D 10 d early preplant followed by cultivation controlled triazine-resistant kochia and velvetleaf, but common lambsquarters, nightshade species, and green foxtail increased. Volunteer corn was controlled with cultivation. After 3 yr at Mitchell, the annual weed population increased 10-fold in the cultivated check. Thus, corn yields were reduced 64% with two cultivations compared with an annual early preplant application of dicamba plus 2,4-D followed by alachlor plus cyanazine PRE and two cultivations. With two cultivations under low annual weed populations at North Platte, grain yield from the cultivated check treatment was not different from annual treatments of herbicides after 7 yr. Metolachlor plus atrazine occasionally caused a reduction in corn grain yields.

Effectiveness of rotary hoeing with cultivation and comparison of an in-row cultivator with a standard row-crop cultivator were determined in dry edible bean. The effectiveness of in-row cultivation conducted at various timings and frequencies was examined. The in-row cultivator was more effective in reducing weed populations than the standard cultivator, although at least two mechanical weeding operations were needed to reduce weed populations to levels of the herbicide check (EPTC [S-ethyl dipropyl carbamothioate] plus ethalfluralin). When the in-row cultivation was delayed until the second trifoliolate stage or later, weed populations were greater than those in the herbicide check. In situations with high weed populations, rotary hoeing prior to cultivation was required to reduce weed populations to levels similar to the herbicide check. An in-row cultivator has potential to improve mechanical weed control options in a crop such as dry edible bean. The types of adjustments made in combination with soil textures, soil moisture, and operator experience affect overall weed control. Thus, it is expected that the level of weed control will vary from year to year and even field to field for the same operator.

Formulated and technical grade HOE-39866 [ammonium-(3-amino-3-carboxypropyl) methylphosphinate] at concentrations of 10–1, 10–2, and 10–3M were applied to leaf blade tissues of nonreproductive adult redroot pigweed (Amaranthus retroflexus L. # AMARE) and fall panicum (Panicum dichotomiflorum Michx. # PANDI). Tissues were sampled at regular intervals after treatment and prepared for light microscopic examination. The major response of both species involved rupture and contortion of the interveinal mesophyll cells with concomitant disorganization of the bundle sheath cells. Rapid epidermal collapse occurred in redroot pigweed but not in fall panicum. The absence of adjuvants resulted in nonuniform symptom expression as herbicide droplets accumulated in depressions and along leaf margins. No other adjuvant-specific effect was observed. Herbicide concentration did not alter the final response but the time-to-expression increased as concentration decreased.

Field studies were conducted in 1999, 2000, and 2001 to evaluate broadleaf weed control in glyphosate-resistant cotton by glyphosate plus CGA 362622 applied postemergence. Treatments included 560 and 1,120 g ai/ha glyphosate-isopropylamine alone or in mixtures with CGA 362622 at 3.8 and 7.5 g ai/ha, and CGA 362622 at 7.5 g/ha alone. Cotton injury 7 d after treatment (DAT) was 3 to 11% from glyphosate alone and 16 to 24% from glyphosate plus CGA 362622. Injury 28 DAT with CGA 362622 or herbicide mixtures did not exceed 6%. Broadleaf weed control by herbicide mixtures was generally more consistent than control from either herbicide applied alone. Glyphosate plus CGA 362622 controlled common cocklebur and smooth pigweed better than glyphosate alone. In most instances, the mixtures also controlled common ragweed, common lambsquarters, ivyleaf morningglory, pitted morningglory, and tall morningglory better than glyphosate applied alone. Common cocklebur and smooth pigweed were controlled at least 85% by all treatments. CGA 362622 did not control spurred anoda or jimsonweed. Cotton yields generally reflected weed control. According to these results, glyphosate plus CGA 362622 mixtures can consistently control many broadleaf weeds in cotton.

Field and greenhouse studies were conducted to evaluate mesotrione alone and in combinations with low rates of atrazine and bentazon for control of yellow and purple nutsedge. Mesotrione alone at rates of 105 to 210 g ai/ha controlled yellow nutsedge 43 to 70%. Mixtures of mesotrione with atrazine at 280 g ai/ha did not always improve yellow nutsedge control over that by mesotrione alone, but increasing atrazine to 560 g ai/ha in these mixtures generally provided more consistent control of yellow nutsedge. Mesotrione at 105 g ai/ha mixed with bentazon at 280 or 560 g ai/ha controlled yellow nutsedge 88% or greater which was similar to control from the standard halosulfuron at 36 g ai/ha. Mesotrione, atrazine, and bentazon alone did not control purple nutsedge. Mixtures of mesotrione plus bentazon, however, did improve control of purple nutsedge over either herbicide applied alone, but this control was not considered commercially acceptable.

Field studies were conducted in 1999, 2000, and 2001 to investigate weed control and glyphosate-resistant corn tolerance to postemergence applications of mesotrione at 70, 105, and 140 g ai/ha applied with and without glyphosate at 560 g ai/ha. Mesotrione alone and mixed with glyphosate controlled smooth pigweed greater than 97% and common lambsquarters 93 to 99%. Control of common ragweed and morningglory species was variable. Common ragweed control was generally best when mesotrione was applied at 105 or 140 g/ha, and control increased only in 2000 with the addition of glyphosate. Giant foxtail control was below 25% with all rates of mesotrione, but mixtures of mesotrione plus glyphosate controlled giant foxtail 65 to 75%. Mesotrione injured glyphosate-resistant corn 4 to 24% when averaged over glyphosate rates, and injury was usually increased by higher mesotrione rates, with rainfall after herbicide applications, and in mixtures with glyphosate. Injury was transient and did not reduce corn yields. Mesotrione injury on glyphosate-resistant corn was confirmed in the greenhouse, where all mesotrione treatments reduced glyphosate-resistant corn biomass 9 to 23% compared with the nontreated check.

Field studies were conducted to determine if mesotrione alone or in combinations with other corn herbicides would control horseweed and other winter annual weeds associated with no-till corn. Mesotrione alone controlled horseweed 52 to 80% by 3 wk after treatment (WAT); however, by 7 WAT control diminished to between 37 to 68%, depending on mesotrione rate. Mesotrione at 0.16 kg ai/ha plus atrazine at 0.28 kg ai/ha controlled 99% of horseweed and annual bluegrass and 88% of yellow woodsorrel. Combinations of mesotrione at 0.16 kg/ha plus acetochlor at 1.79 kg ai/ha plus 1.12 kg ai/ha glyphosate (trimethylsulfonium salt of glyphosate) or 0.7 kg ai/ha paraquat provided 93% or greater control of all three weed species. Glyphosate alone also controlled all weed species 97 to 99%, while paraquat alone provided 99% control of annual bluegrass, 72% control of horseweed, and 36% control of yellow woodsorrel. Mixtures of paraquat plus acetochlor improved control of horseweed (93%) and yellow woodsorrel (73%) over control with either herbicide applied alone.

Field and greenhouse studies were conducted near Painter, VA, in 1999, 2000, and 2001 to evaluate mesotrione postemergence for control of horsenettle in corn. Mesotrione at 105 g ai/ha controlled horsenettle at least 80% in all studies, and in 2001, after two consecutive annual applications, mesotrione controlled horsenettle up to 91%. Additions of primisulfuron, dicamba, and 2,4-D to mesotrione did not increase horsenettle control. Occasionally, combinations of dicamba with mesotrione controlled horsenettle less than did mesotrione alone, and primisulfuron combinations with mesotrione delayed or reduced development of bleaching symptoms associated with mesotrione. Initial horsenettle response to mesotrione was increased by addition of 280 g ai/ha atrazine; however, late-season horsenettle control was not improved by atrazine. Two consecutive annual applications of mesotrione alone decreased horsenettle biomass > 89%. Treatments of primisulfuron plus dicamba, primisulfuron plus CGA 152005 plus dicamba, and 2,4-D plus dicamba provided similar horsenettle control and biomass reductions as did 105 g/ha mesotrione alone.