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Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged antipsychotic use. RE KINECT, a real-world screening study of antipsychotic-treated outpatients, included patients with movements that were clinician-confirmed as possible TD (Cohort 2) and patients with no involuntary movements (Cohort 1). Baseline data from the patient rated EuroQoL 5-Dimension 5-Level questionnaire (EQ-5D-5L) and Sheehan Disability Scale (SDS) were analyzed to evaluate health related quality of life (Cohort 2 vs. Cohort 1) and the effects of possible TD on quality of life (Cohort 2).
Assessments included EQ-5D-5L utility score (0=equivalent to death to 1=perfect health); SDS total score (0=no impact to 30=highest impact); patient- and clinician-rated severity of possible TD in 4 body regions (0=none, 1=some, and 2=a lot; summary score, 0 to 8); and patient-rated impact of possible TD in 7 daily activities (0=none, 1=some, and 2=a lot; summary score, 0 to 14). Populations included Cohort 1 (N=450); full Cohort 2 (N=204); and limited Cohort 2 (N=111, patients who self-reported “some” or “a lot” of TD severity in ≥1 body region). Mean differences between Cohort 2 and Cohort 1 in EQ-5D-5L utility and SDS total scores were analyzed using a generalized linear regression model that was adjusted for potentially confounding factors (e.g., age, sex, psychiatric diagnosis). Associations between TD summary scores (severity, impact) and quality of life (EQ-5D-5L utility, SDS total) were analyzed using a regression model.
The mean score difference between full Cohort 2 (N=204) and Cohort 1 (N=450) was significant for EQ-5D-5L utility (-0.037; P<0.05 [adjusted analysis]) but not SDS total (0.267; P>0.05). However, when limited to Cohort 2 patients who self-reported “a lot” of TD severity (n=53) or impact (n=33), both EQ 5D 5L utility and SDS total scores were significantly worse than in Cohort 1 (P<0.05). Regression coefficients indicated significant associations between patient-rated impact and EQ 5D-5L utility in the full Cohort 2 (-0.021, P<0.001) and limited Cohort 2 (-0.024, P<0.001). A significant association was also found with patient rated severity in limited Cohort 2 (P<0.05), but not with clinician-rated severity. Similar results were found for SDS total score.
RE-KINECT patients were consistent in evaluating the severity and impact of TD, whether based on subjective assessments or standardized patient-reported instruments (EQ-5D-5L, SDS). Clinician-rated severity of TD may not always correlate with patient perceptions of the significance of TD. Patient self-assessments (focused on symptom impact) can be clinically relevant; incorporating such measures into everyday practice may provide a more comprehensive approach to TD assessment and management.
Application timing and environmental factors reportedly influence the efficacy of auxinic herbicides. In resistance-prone weed species such as Palmer amaranth (Amaranthus palmeri S. Watson), efficacy of auxinic herbicides recently adopted for use in resistant crops is of utmost importance to reduce selection pressure for herbicide-resistance traits. Growth chamber experiments were conducted comparing the interaction of different environmental effects with application time to determine the influence of these factors on visible phytotoxicity and hydrogen peroxide (H2O2) formation in A. palmeri. Temperature displayed a high degree of influence on 2,4-D and dicamba efficacy in general, with applications at the low-temperature treatment (31/20 C day/night) resulting in an increase in phytotoxicity compared with high-temperature treatments (41/30 C day/night). Application time across temperature treatments significantly affected 2,4-D–induced phytotoxicity, resulting in a ≥30% increase across rates with treatments at 4:00 PM compared with 8:00 AM. Temperature differential had a significant influence on dicamba efficacy based on visible phytotoxicity data, with a ≥46% increase with a high (37/20 C day/night) compared with a low differential (41/30 C day/night). Concentration of H2O2 in herbicide-treated plants was 34% higher under a high temperature differential compared with the low differential. Humidity treatments and application time interactions displayed undetected or inconsistent effects on visible phytotoxicity and H2O2 production. Overall, temperature-related influences seem to have the largest environmental effect on auxinic herbicides within conditions evaluated in this study. Leaf concentration of H2O2 appears to be generally correlated with phytotoxicity, providing a potentially useful tool in determining efficacy of auxinic herbicides in field settings.
Tardive dyskinesia (TD) is a hyperkinetic movement disorder associated with antipsychotic treatment. RE KINECT (NCT03062033), a real-world study of outpatients prescribed antipsychotics, was designed to identify the presence of possible TD and characterize the impact of involuntary movements on functioning and quality of life. Data from RE-KINECT were used to compare the impact of possible TD in patients with schizophrenia/schizoaffective disorder [SZD] versus mood/other psychiatric disorders [Mood].
Adults with ≥3months of lifetime exposure to antipsychotics and ≥1 psychiatric disorder were recruited. The presence of possible TD was based on clinicians’ observation of involuntary movements in 4 body regions (head, trunk, upper extremities, and lower extremities). Baseline outcomes included demographics, medication history, location/severity of abnormal movements, impact of abnormal movements on daily activities, the Sheehan Disability Scale (SDS), and the EuroQoL 5-Dimensional questionnaire (EQ-5D-5L).
Of 204 patients with clinician-confirmed possible TD, 111 (54.4%) had a SZD diagnosis and 93 (45.6%) had a mood/other psychiatric diagnosis. Significant differences found between groups (Mood vs SZD) included: mean age (56.9 vs 52.7 years; P=0.0263); male sex (33.3% vs 62.2%; P<0.0001); African-American race (7.5% vs 26.1%; P=0.0005); mean lifetime exposure to antipsychotics (9.5 vs 19.5 years; P<0.0001); and percentage of patients currently taking ≥2 psychiatric medications (93.5% vs 79.3%; P=0.0093). Based on clinician observation, there were no significant differences between diagnosis groups in the number of body regions impacted by abnormal movements, maximum severity score across all 4 regions, or patient awareness of possible TD. Over 30% of patients in both groups reported that involuntary movements had “some” or “a lot” of impact on their ability to continue usual activities, be productive, and socialize. No significant differences between the diagnosis groups (Mood vs SZD) were found for mean SDS total score (12.8 vs 10.8), SDS domain scores (work/school [4.1 vs 4.2], social life [4.3 vs 3.7], family life [4.1 vs 3.5]), EQ-5D-5L utility score (0.68 vs 0.74), or EQ-5D-5L health state VAS (64.8 vs 68.5).
In this cohort of outpatients with possible TD, those with Mood disorders were more likely to be older, female, and white than patients with SZD. The ability to function and quality of life were equally impaired in both groups. Further studies on the impact of TD are needed.
Funding Acknowledgements: Neurocrine Biosciences, Inc.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Tardive dyskinesia (TD) is associated with prolonged exposure to dopamine receptor blockers including antipsychotics. This registry describes the prevalence and impact of involuntary movements (possible TD) in a real-world population of patients taking antipsychotics.
RE-KINECT (NCT03062033) aims to enroll 1,000 patients from 70 US psychiatric practices. Adults with ≥3 months lifetime exposure to antipsychotic(s) and ≥1 psychiatric disorder are eligible for two-tier screening: informal observation, and then clinician observation of abnormal involuntary movements in general body regions (head/face, neck/trunk, upper/lower limbs) and confirmation of possible TD. Based on clinician assessment, patients are assigned to Cohort 1 or Cohort 2 (without or with abnormal involuntary movements, respectively). In both cohorts, the following baseline assessments are included: clinician’s assessment of clinical psychiatric severity, patient perceived health‐related quality of life (EuroQOL 5-Dimensions), social burden/disability questionnaire (Sheehan Disability Scale), and 12-month retrospective chart review ofmedical and treatment history. Cohort 2 also participate in 12-month longitudinal evaluation. Interim baseline data are available from four sites.
Baseline data are currently available for 116 patients—mean age, 49.6 years; female, 60.3%; schizophrenia/schizoaffective disorder, 32.8%; at least 1 mood disorder, 84.5%, and 10.4 years mean cumulative lifetime exposure to antipsychotic(s). The most concerning health condition for both cohorts is their mental health (69.0%), followed by physical activity and nutrition (33.6%). 32.8% of subjects had clinician confirmation of possible TD.
This novel registry aims to evaluate the real-world potential impact/burden of TD. Preliminary analyses suggest that TD is common in patients with schizophrenia and mood disorders taking antipsychotics. Further analyses will explore the burden of illness in this population.
This study was funded by Neurocrine Biosciences, Inc.
The efficacy of WSSA Group 4 herbicides has been reported to vary with dependence on the time of day the application is made, which may affect the value of this mechanism of action as a control option and resistance management tool for Palmer amaranth. The objectives of this research were to evaluate the effect of time of day for application on 2,4-D and dicamba translocation and whether or not altering translocation affected any existing variation in phytotoxicity seen across application time of day. Maximum translocation (Tmax) of [14C]2,4-D and [14C]dicamba out of the treated leaf was significantly increased 52% and 29% to 34% in one of two repeated experiments for each herbicide, respectively, with application at 7:00 AM compared with applications at 2:00 PM and/or 12:00 AM. Applications at 7:00 AM increased [14C]2,4-D distribution to roots and increased [14C]dicamba distribution above the treated leaf compared with other application timings. In phytotoxicity experiments, dicamba application at 8 h after exposure to darkness (HAED) resulted in significantly lower dry root biomass than dicamba application at 8 h after exposure to light (HAEL). Contrasts indicated that injury resulting from dicamba application at 8 HAEL, corresponding to midday, was significantly reduced with a root treatment of 5-[N-(3,4-dimethoxyphenylethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile hydrochloride (verapamil) compared with injury observed with dicamba application and a root treatment of verapamil at 8 HAED, which corresponded to dawn. Overall, time of application appears to potentially influence translocation of 2,4-D and dicamba. Furthermore, inhibition of translocation appears to somewhat influence variation in phytotoxicity across times of application. Therefore, translocation may be involved in the varying efficacy of WSSA Group 4 herbicides due to application time of day, which has implications for the use of this mechanism of action for effective control and resistance management of Palmer amaranth.
The Department of Materials and Metallurgical Engineering faculty at the South Dakota School of Mines and Technology (SDSM&T) has developed a unique undergraduate program that integrates research, extracurricular activities, and outreach experiences. A common thread throughout the program is an introduction to the artistic and historical background of metallurgical engineering. These activities use kinesthetic learning to promote student learning of metallurgical engineering, aspects often not traditionally included in engineering curricula. These programs are similar to those envisioned by the National Academy of Engineering in response to the changing needs of engineering. These are described in two visionary books published by the National Research Council.
A major focus of the program integrates blacksmithing activities with curricular, extracurricular, and outreach activities. All SDSM&T students are invited to a weekly blacksmithing activity called Hammer-in. Blacksmithing-related laboratories were added to the curriculum. Additionally, students developed a portable blacksmithing laboratory with faculty supervision. The laboratory has been taken to K-12 schools, including Native American schools on reservations, to reach out to regional students, thereby promoting interest in STEM careers. The success of these activities led to their incorporation into a National Science Foundation Research Experience for Undergraduate (REU) at SDSM&T called Back to the Future that focuses on understanding new technologies through historical antecedents. The SDSM&T students who participated in this REU used this experience as part of their junior/senior design courses. This program has increased enrollment in the department and has led to better learning outcomes for the students.
Cerianite-(Ce), ideally CeO2, occurs as rounded grains up to 5 μm across in a block of highly altered calcite carbonatite lava from the Kerimasi volcano, and as euhedral crystals up to 200 μm across in carbonatite-derived eluvial deposits in the Kisete and Loluni explosion craters in the Gregory Rift, northern Tanzania. X-ray powder diffraction data (a = 5.434(5) Å) and Raman spectroscopy (minor vibration modes at 184 and 571 cm—1 in addition to a strong signal at 449 cm—1) suggest the presence of essential amounts of large cations and oxygen vacancies in the Kisete material. Microprobe analyses reveal that the mineral contains both light and heavy trivalent rare earth elements (REE) (7.9-15.5 wt.% LREE2O3 and 4.9-9.7 wt.% HREE2O3), and that it is enriched in yttrium (7.1 — 14.5 wt.% Y2O3) and fluorine (2.2—3.5 wt.%). Single-crystal structure refinement of the mineral confirms a fluorite-type structure with a cation—anion distance of 2.3471(6) Å. The cerianite-(Ce) is considered to be a late-stage secondary mineral in the carbonatitic rocks.