While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.

Seismic imaging in 3-D holds great potential for improving our understanding of ice sheet structure and dynamics. Conducting 3-D imaging in remote areas is simplified by using lightweight and logistically straightforward sources. We report results from controlled seismic source tests carried out near the West Antarctic Ice Sheet Divide investigating the characteristics of two types of surface seismic sources, Poulter shots and detonating cord, for use in both 2-D and 3-D seismic surveys on glaciers. Both source types produced strong basal P-wave and S-wave reflections and multiples recorded in three components. The Poulter shots had a higher amplitude for low frequencies (<10 Hz) and comparable amplitude at high frequencies (>50 Hz) relative to the detonating cord. Amplitudes, frequencies, speed of source set-up, and cost all suggested Poulter shots to be the preferred surface source compared to detonating cord for future 2-D and 3-D seismic surveys on glaciers.

We argue that Madole & Harden's distinction between shallow versus deep genetic causes can bring some clarity to causal claims arising from genome-wide association studies (GWASs). However, the authors argue that GWAS only finds shallow genetic causes, making GWAS commensurate with the environmental studies they hope to supplant. We also assess whether their distinction applies best to explanations or causes.

The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.

Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2; Gen2) at 18 years; HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP; quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.

Fluting is a technological and morphological hallmark of some of the most iconic North American Paleoindian stone points. Through decades of detailed artifact analyses and replication experiments, archaeologists have spent considerable effort reconstructing how flute removals were achieved, and they have explored possible explanations of why fluting was such an important aspect of early point technologies. However, the end of fluting has been less thoroughly researched. In southern North America, fluting is recognized as a diagnostic characteristic of Clovis points dating to approximately 13,000 cal yr BP, the earliest widespread use of fluting. One thousand years later, fluting occurs more variably in Dalton and is no longer useful as a diagnostic indicator. How did fluting change, and why did point makers eventually abandon fluting? In this article, we use traditional 2D measurements, geometric morphometric (GM) analysis of 3D models, and 2D GM of flute cross sections to compare Clovis and Dalton point flute and basal morphologies. The significant differences observed show that fluting in Clovis was highly standardized, suggesting that fluting may have functioned to improve projectile durability. Because Dalton points were used increasingly as knives and other types of tools, maximizing projectile functionality became less important. We propose that fluting in Dalton is a vestigial technological trait retained beyond its original functional usefulness.

Field studies were conducted to determine the effects of synthetic auxin herbicides at simulated exposure rates applied to ‘Covington’ sweetpotato propagation beds on the quality of nonrooted stem cuttings (slips). Treatments included diglycolamine salt of dicamba, 2,4-D choline plus nonionic surfactant (NIS), and 2,4-D choline plus glyphosate at 1/10, 1/33, or 1/66 of a 1X application rate (560 g ae ha−1 dicamba, 1,065 g ae ha−1 2,4-D choline, 1,130 g ae ha−1 glyphosate) applied at 2 or 4 wk after first slip harvest (WASH). Injury to sweetpotato 2 wk after treatment was greatest when herbicides were applied 2 WASH (21%) compared to 4 WASH (16%). More slip injury was caused by 2,4-D choline than by dicamba, and the addition of glyphosate did not increase injury over 2,4-D choline alone. Two weeks after the second application, sweetpotato slips were cut 2 cm above the soil surface and transplanted into production fields. In 2019, sweetpotato ground coverage 8 wk after transplanting was reduced 37% and 26% by the 1/10X rates of dicamba and 2,4-D choline plus NIS, respectively. Though dicamba caused less injury to propagation beds than 2,4-D choline with or without glyphosate, after transplanting, slips treated with 1/10X dicamba did not recover as quickly as those treated with 2,4-D choline. In 2020, sweetpotato ground coverage was 90% or greater for all treatments. Dicamba applied 2 WASH decreased marketable sweetpotato storage root yield by 59% compared to the nontreated check, whereas treatments including 2,4-D choline reduced marketable yield 22% to 29%. All herbicides applied at 4 WASH reduced marketable yield 31% to 36%. The addition of glyphosate to 2,4-D choline did not increase sweetpotato yield. Results indicate that caution should be taken when deciding whether to transplant sweetpotato slips that are suspected to have been exposed to dicamba or 2,4-D choline.

Field studies were conducted in North Carolina in 2018 and 2019 to determine sweetpotato tolerance to indaziflam and its effectiveness in controlling Palmer amaranth in sweetpotato. Treatments included indaziflam pre-transplant; 7 d after transplanting (DATr) or 14 DATr at 29, 44, 58, or 73 g ai ha−1; and checks (weedy and weed-free). Indaziflam applied postemergence caused transient foliar injury to sweetpotato. Indaziflam pretransplant caused less injury to sweetpotato than other application timings regardless of rate. Palmer amaranth control was greatest when indaziflam was applied pretransplant or 7 DATr. In a weed-free environment, sweetpotato marketable yield decreased as indaziflam application was delayed. No differences in storage root length to width ratio were observed.

The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

Exposure to glucocorticoid levels higher than appropriate for current developmental stages induces offspring metabolic dysfunction. Overfed/obese (OB) ewes and their fetuses display elevated blood cortisol, while fetal Adrenocorticotropic hormone (ACTH) remains unchanged. We hypothesized that OB pregnancies would show increased placental 11β hydroxysteroid dehydrogenase 2 (11β-HSD2) that converts maternal cortisol to fetal cortisone as it crosses the placenta and increased 11β-HSD system components responsible for peripheral tissue cortisol production, providing a mechanism for ACTH-independent increase in circulating fetal cortisol. Control ewes ate 100% National Research Council recommendations (CON) and OB ewes ate 150% CON diet from 60 days before conception until necropsy at day 135 gestation. At necropsy, maternal jugular and umbilical venous blood, fetal liver, perirenal fat, and cotyledonary tissues were harvested. Maternal plasma cortisol and fetal cortisol and cortisone were measured. Fetal liver, perirenal fat, cotyledonary 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PD), and 11β-HSD2 protein abundance were determined by Western blot. Maternal plasma cortisol, fetal plasma cortisol, and cortisone were higher in OB vs. CON (p < 0.01). 11β-HSD2 protein was greater (p < 0.05) in OB cotyledonary tissue than CON. 11β-HSD1 abundance increased (p < 0.05) in OB vs. CON fetal liver and perirenal fat. Fetal H6PD, an 11β-HSD1 cofactor, also increased (p < 0.05) in OB vs. CON perirenal fat and tended to be elevated in OB liver (p < 0.10). Our data provide evidence for increased 11β-HSD system components responsible for peripheral tissue cortisol production in fetal liver and adipose tissue, thereby providing a mechanism for an ACTH-independent increase in circulating fetal cortisol in OB fetuses.

Palmer amaranth is the most common and troublesome weed in North Carolina sweetpotato. Field studies were conducted in Clinton, NC, in 2016 and 2017 to determine the critical timing of Palmer amaranth removal in ‘Covington’ sweetpotato. Palmer amaranth was grown with sweetpotato from transplanting to 2, 3, 4, 5, 6, 7, 8, and 9 wk after transplanting (WAP) and maintained weed-free for the remainder of the season. Palmer amaranth height and shoot dry biomass increased as Palmer amaranth removal was delayed. Season-long competition by Palmer amaranth interference reduced marketable yields by 85% and 95% in 2016 and 2017, respectively. Sweetpotato yield loss displayed a strong inverse linear relationship with Palmer amaranth height. A 0.6% and 0.4% decrease in yield was observed for every centimeter of Palmer amaranth growth in 2016 and 2017, respectively. The critical timing for Palmer amaranth removal, based on 5% loss of marketable yield, was determined by fitting a log-logistic model to the relative yield data and was determined to be 2 WAP. These results show that Palmer amaranth is highly competitive with sweetpotato and should be managed as early as possible in the season. The requirement of an early critical timing of weed removal to prevent yield loss emphasizes the importance of early-season scouting and Palmer amaranth removal in sweetpotato fields. Any delay in removal can result in substantial yield reductions and fewer premium quality roots.

Field studies were conducted in 2016 and 2017 in Clinton, NC, to determine the interspecific and intraspecific interference of Palmer amaranth (Amaranthus palmeri S. Watson) or large crabgrass [Digitaria sanguinalis (L.) Scop.] in ‘Covington’ sweetpotato [Ipomoea batatas (L.) Lam.]. Amaranthus palmeri and D. sanguinalis were established 1 d after sweetpotato transplanting and maintained season-long at 0, 1, 2, 4, 8 and 0, 1, 2, 4, 16 plants m−1 of row in the presence and absence of sweetpotato, respectively. Predicted yield loss for sweetpotato was 35% to 76% for D. sanguinalis at 1 to 16 plants m−1 of row and 50% to 79% for A. palmeri at 1 to 8 plants m−1 of row. Weed dry biomass per meter of row increased linearly with increasing weed density. Individual dry biomass of A. palmeri and D. sanguinalis was not affected by weed density when grown in the presence of sweetpotato. When grown without sweetpotato, individual weed dry biomass decreased 71% and 62% from 1 to 4 plants m−1 row for A. palmeri and D. sanguinalis, respectively. Individual weed dry biomass was not affected above 4 plants m−1 row to the highest densities of 8 and 16 plants m−1 row for A. palmeri and D. sanguinalis, respectively.