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Compare quetiapine+antidepressant (AD) with lithium+AD, and quetiapine monotherapy with lithium+AD in open, rater-blinded treatment.
Patients with treatment resistant depression (Thase et al 1997 stage 1 and 2) with severity of MADRS ≥25 received: quetiapine XR 300mg/day plus AD (SSRIs or venlafaxine) (n=229), lithium (monitored to between 0.6 to 1.0 meq/l) plus AD (n=221) or quetiapine XR alone (300mg/day) (n=225) for 6 weeks. Primary efficacy measure was change from baseline in MADRS total score. The pre-specified non-inferiority limit was 3 points on the MADRS.
Fewer patients discontinued on quetiapine+AD (15.2%) than lithium+AD (20.5%) and quetiapine monotherapy (21.5%). Quetiapine+AD and quetiapine monotherapy, were not inferior to lithium+AD in the primary (per protocol) analysis with a mean difference (97.5%CI) on the MADRS of -2.32 (-4.6 to -0.05) favouring add-on quetiapine and -0.97 (-3.24 to 1.31) favouring quetiapine monotherapy. This mandated superiority testing on the modified ITT population showing no significant difference at endpoint.
In a post hoc analysis discounting multiplicity, quetiapine+AD was significantly more effective than lithium+AD on the MADRS change from baseline, p=0.046. The advantage was observed at day 4 (p=0.007) and persisted throughout. Efficacy was supported by CGI-I (p=0.07). Quetiapine+AD showed a numerically greater advantage over lithium+AD in those with two failed treatments (Stage 2) rather than one (Stage 1).
Quetiapine+AD and quetiapine monotherapy, were non-inferior to lithium+AD in treatment resistant depression. There was an early significant and persistent efficacy advantage on MADRS for quetiapine augmentation compared with lithium augmentation of SSRI or venlafaxine treatment.
To evaluate risperidone long-acting injectable (RLAI) versus placebo in prevention of mood episodes in adults with bipolar I disorder.
A 12-week open-label period with RLAI (N=585) was followed by an 18-month randomized, double-blind period with RLAI (25, 37.5 or 50 mg/2 weeks; N=137) or placebo (N=140); a third group (N=138) was randomized to olanzapine for reference and exploratory comparisons. Primary efficacy endpoint: time to relapse of any mood episode for risperidone LAI vs. placebo in the double-blind period (Kaplan-Meier analysis). Relapse was defined by criteria including DSM diagnosis, further treatment, hospitalisation, or Clinical Global Impression score ≥4 combined with YMRS or MADRS >12.
Dosing was fixed during the double-blind period at patients’ final open-label dose (25 mg, 66%; 37.5 mg, 31%; 50 mg, 4%). Time to recurrence (any mood episode) was longer with RLAI versus placebo (log-rank test stratified by region and patient type, p=0.062; stratified by region only, p=0.032); the difference was significant for time to recurrence of elevated mood episodes (p=0.005) but not depressive episodes (p=0.587). Discontinuations due to adverse events (AEs) occurred in 2% of patients in the open-label period, and 4% and 1% in the RLAI and placebo groups, respectively, in the double-blind period. The most frequently reported AE in the open-label period was insomnia (15%). During double-blind treatment, the most frequently reported AEs with RLAI were weight increased (24%; placebo, 9%) and insomnia (16%; placebo, 17%).
Type of recurrence
Type of episode, n (%)
Risperidone LAI (N=135)
All mood episodes
Elevated mood episode
RLAI significantly delayed time to relapse of elevated mood episodes and was well tolerated.
Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication's efficacy. Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics. This post-hoc analysis assessed supplementation of olanzapine long-acting injection (olanzapine-LAI) with oral olanzapine.
Subjects and methods
We used 12 months of data from an open-label, single-arm extension study of patients with schizophrenia or schizoaffective disorder (N = 931) treated with olanzapine-LAI. The prevalence, duration, time to first supplementation, and best predictors of oral supplementation were assessed.
Oral supplementation occurred in 21% of patients for a median of 31 days with mean modal dose of 10.8 mg/day. Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients (47 vs. 97 days, p < 0.001). Best predictors of oral supplementation included a more severe illness profile at baseline, lower olanzapine-LAI dose prior to oral supplementation, supervised living arrangements, and being African-American.
Supplementation of olanzapine-LAI appears to be infrequent, of relatively short duration, and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse.
This chapter presents a number of contact zones in the spectrum of violence, zones around which the fears, anxieties, concerns and aspirations provoked by instances of violence and their representation were concentrated. I discuss the following scenes of violence: The War Against Time; Apocalypse; The Anxiety of Remembrance; Abomination; The Nonhuman World; Spectacle. These zones do not constitute categories of violence but, like violence itself, are porous and mimetic. The temporal focus of the survey covers some six centuries, from the pre-Islamic sixth century to the twelfth century and the Crusades.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Studies to evaluate the effect of application time of day (TOD) and protoporphyrinogen IX oxidase (PPO)-inhibiting herbicide–resistant Palmer amaranth on the efficacy of commonly used herbicides was conducted in Tennessee in 2017 and 2018. Treatments of fomesafen, lactofen, acifluorfen, paraquat, glufosinate, glufosinate plus fomesafen, paraquat plus fomesafen, and paraquat plus metribuzin were applied to PPO-resistant (PPO-R) and PPO-susceptible (PPO-S) Palmer amaranth at sunrise and midday. Control of Palmer amaranth with acifluorfen, glufosinate, and glufosinate plus fomesafen was greater with the midday application. However, control of Palmer amaranth with paraquat-based treatments was greater with the sunrise application. TOD effects on PPO-inhibiting herbicides and paraquat-based treatments were more prominent for the PPO-R Palmer amaranth biotype. The TOD effect observed when applying glufosinate in early morning hours on PPO-S Palmer amaranth can be minimized by adding fomesafen to the tank mix. However, this strategy did not provide consistent performance on PPO-R Palmer amaranth. The percentages of living Palmer amaranth plants and control were greater when paraquat plus metribuzin was applied to both biotypes. These results highlight the necessity of at least two effective herbicide sites of action for POST applications intended for controlling PPO-R Palmer amaranth. In addition, the timing of herbicide applications can affect their activity in both PPO-R and PPO-S Palmer amaranth populations.
Chronic spontaneous urticaria (CSU) has been associated with depression and can have an impact on quality of life. Therefore, researchers have suggested the potential utility of psychological interventions for targeting depression among CSU patients. Psychological interventions that may hold the most promise are those that are brief and easily transportable, such as brief behavioural activation treatment for depression. We report results of a preliminary investigation of an uncontrolled open trial of a one-session behavioural activation treatment for depression designed for patients with CSU (BATD-CSU) at a university-based allergy and immunology clinic. Participants were 11 females with chronic, poorly controlled urticaria and symptoms of depression. Following the completion of pretreatment questionnaires, participants were administered BATD-CSU primarily by non-mental health professionals trained and supervised in its delivery. One month post-BATD-CSU, participants completed follow-up questionnaires. Participants exhibited significant reductions in depression severity, avoidance/rumination, and work/school impairment. BATD-CSU was also associated with improvements in urticaria control one month post-treatment. Moreover, five of nine patients reported reliable and clinically significant improvement on at least one outcome. Results demonstrate that BATD-CSU may have benefits for CSU patients even when consisting of one session and delivered by professionals with limited background in psychological interventions, thus speaking to its feasibility and transportability.
Swimming propagules (embryos and larvae) are a critical component of the life histories of benthic marine animals. Larvae that feed (planktotrophic) have been assumed to swim faster, disperse farther and have more complex behavioural patterns than non-feeding (lecithotrophic) larvae. However, a number of recent studies challenge these early assumptions, suggesting a need to revisit them more formally. The current review presents a quantitative analysis of swimming speed and body size in planktotrophic and lecithotrophic propagules across five major marine phyla (Porifera, Cnidaria, Annelida, Mollusca and Echinodermata). Results of the comparative study showed that swimming speed differences among ciliated propagules can be driven by taxonomy, adult mobility (motile vs sessile) and/or larval nutritional mode. On a phylogenetic level, distinct patterns emerge across phyla and life stages, whereby planktotrophic propagules swim faster in some of them, and lecithotrophic propagules swim faster in others. Interestingly, adults with sessile and sedentary lifestyles produce propagules that swam faster than the propagules produced by motile adults. Understanding similarities and differences among marine propagules associated with different reproductive strategies and adult lifestyles are significant from ecological, evolutionary and applied perspectives. Patterns of swimming can directly impact the dispersal/recruitment potential with incidence on the design of larval rearing methods and marine protected areas.
Protoporphyrinogen IX oxidase (PPO)–inhibiting herbicides (WSSA Group 14) have been used in agronomic row crops for over 50 yr. Broadleaf weeds, including glyphosate-resistant Palmer amaranth, have been controlled by this herbicide site of action PRE and POST. Recently, Palmer amaranth populations were reported resistant to PPO inhibitors in 2011 in Arkansas, in 2015 in Tennessee, and in 2016 in Illinois. Historically, the mechanism for this resistance involves the deletion of a glycine at position 210 (ΔG210) in a PPO enzyme encoded by the PPX2 gene; however, the ΔG210 deletion did not explain all PPO inhibitor–resistant Palmer amaranth in Tennessee populations. Recently, two new mutations within PPX2 (R128G, R128M) that confer resistance to PPO inhibitors were identified in Palmer amaranth. Therefore, research is needed to document the presence and distribution of the three known mutations that confer PPO inhibitor resistance in Tennessee. In 2017, a survey was conducted in 18 fields with Palmer amaranth to determine whether resistance existed and the prevalence of each known mutation in each field. Fomesafen was applied at 265 g ai ha–1 to Palmer amaranth infestations within each field to select for resistant weeds for later analysis. Where resistance was described (70% of surviving plants), the ΔG210 mutation was detected in 47% of resistant plants. The R128G mutation accounted for 42% of resistance, similar to the frequency of the ΔG210 mutation. The R128M mutation was less frequent than the other two mutations, accounting for only 10% of the resistance. All mutations detected in this study were heterozygous. Additionally, no more than one of the three PPX2 mutations were detected in an individual surviving plant. Similar to previous research, about 70% of PPO resistance was accounted for by these three known mutations, leaving about 30% of resistance not characterized in Tennessee populations. Survivors not showing the three known PPO mutations suggest that other resistance mechanisms are present.
Recently, several incidents of glyphosate failure on junglerice [Echinochloa colona (L.) Link] have been reported in the midsouthern United States, specifically in Mississippi and Tennessee. Research was conducted to measure the magnitude of glyphosate resistance and to determine the mechanism(s) of resistance to glyphosate in E. colona populations from Mississippi and Tennessee. ED50 (dose required to reduce plant growth by 50%) values for a resistant MSGR4 biotype, a resistant TNGR population, and a known susceptible MSGS population were 0.8, 1.62, and 0.23 kg ae ha−1 of glyphosate, respectively. The resistance index calculated from the these ED50 values indicated that the MSGR4 biotype and TNGR population were 4- and 7-fold, respectively, resistant to glyphosate relative to the MSGS population. The absorption patterns of [14C]glyphosate in the TNGR and MSGS populations were similar. However, the MSGS population translocated 13% more [14C]glyphosate out of the treated leaf compared with the TNGR population at 48 h after treatment. EPSPS gene sequence analyses of TNGR E. colona indicated no evidence of any point mutations, but several resistant biotypes, including MSGR4, possessed a single-nucleotide substitution of T for C at codon 106 position, resulting in a proline-to-serine substitution (CCA to TCA). Results from quantitative polymerase chain reaction analyses suggested that there was no amplification of the EPSPS gene in the resistant populations and biotypes. Thus, the mechanism of resistance in the MSGR population (and associated biotypes) is, in part, due to a target-site mutation at the 106 loci of the EPSPS gene, while reduced translocation of glyphosate was found to confer glyphosate resistance in the TNGR population.
Teaching undergraduate students, mentoring graduate students, and generating publishable research are distinct tasks for many political scientists. This article highlights lessons for merging these activities through experiences from an initiative that sparked a series of collaborative-research projects focused on opinions about crime and punishment in the United States. This article describes three collaborative projects conducted between 2015 and 2017 to demonstrate how to merge undergraduate teaching, graduate training, and producing research. By participating in these projects, students learned about social-scientific research through hands-on experiences designing experiments, collecting and analyzing original data, and reporting empirical findings to a public audience. This approach is an effective way to engage students and generate research that can advance professional goals.
Giant electromagnetic pulses (EMP) generated during the interaction of high-power lasers with solid targets can seriously degrade electrical measurements and equipment. EMP emission is caused by the acceleration of hot electrons inside the target, which produce radiation across a wide band from DC to terahertz frequencies. Improved understanding and control of EMP is vital as we enter a new era of high repetition rate, high intensity lasers (e.g. the Extreme Light Infrastructure). We present recent data from the VULCAN laser facility that demonstrates how EMP can be readily and effectively reduced. Characterization of the EMP was achieved using B-dot and D-dot probes that took measurements for a range of different target and laser parameters. We demonstrate that target stalk geometry, material composition, geodesic path length and foil surface area can all play a significant role in the reduction of EMP. A combination of electromagnetic wave and 3D particle-in-cell simulations is used to inform our conclusions about the effects of stalk geometry on EMP, providing an opportunity for comparison with existing charge separation models.
A study was conducted to evaluate the response of glyphosate- and dicamba-tolerant (GDT) soybean and weed control from cover crop different termination intervals before and after soybean planting. Cover crop biomass was highest when terminated at planting, decreased with the 7- and 14-d preplant (DPP) and day-after-planting (DAP) timings, and again at the 14 DPP and DAP timings. Glyphosate+dicamba provided total control of cover crops by 21 DAP. Cover crop termination timing did not influence soybean population or yield. Palmer amaranth control at the 21 and 28 d after termination (DAT) was 97% to 99%. Differences in Palmer amaranth control were not detected among herbicide programs or termination intervals at the end of season rating, and all treatments provided ≥97% control. Although differences in Palmer amaranth control were not apparent at the end of the season, the delay in cover crop affected the number of days until 10-cm Palmer amaranth was present. When utilizing a wheat+hairy vetch cover crop in DGT soybeans, producers should delay cover crop termination until 11 to 14 DPP and make at least one POST application of glyphosate+dicamba+an additional herbicide mode of action (MOA) to maximize Palmer amaranth control and soybean yields.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Some 25% of women and 8% of men in the United States have experienced childhood sexual abuse (CSA) before the age of 18. For these individuals, healthcare visits and interactions can be retraumatizing due to perceived similarities to past abuse (e.g., pain, undressing, lack of control). However, no prior studies have provided formal qualitative analyses regarding CSA survivors' reactions to cancer treatment. Therefore, our study's objective was to identify key themes pertaining to CSA survivors' cancer treatment experiences.
Male and female members of the Amazon Mechanical Turk (N = 159, mean age = 44.27 years, SD = 10.02) participated in an anonymous online survey study. The inclusion criteria included reporting: history of CSA; a diagnosis of colorectal, gynecological, breast, or skin cancer; and experience of triggers and/or difficulties during cancer treatment. Participants' responses to open-ended questions were analyzed using inductive thematic analysis.
We identified two primary themes describing CSA survivors' experiences: Theme 1: treatment-related triggers (key subthemes: procedure-related, provider-related, and emotional triggers); and Theme 2: questioning the meaning of cumulative trauma (e.g., “Why me again?”).
Significance of results:
For CSA survivors, cancer and its treatment can trigger thoughts and emotions associated with the original abuse as well as negative evaluations of themselves, the world, and their future. Our findings are consistent with past research on CSA survivors' experiences in non-cancer healthcare settings and add to the literature by highlighting their struggles during cancer treatment. The present results can inform further research on trauma survivors' reactions to cancer treatment and give cancer care providers the context they need to understand and sensitively serve a substantial yet often overlooked patient group.
A study to evaluate the effect of application time of day (TOD) on the efficacy of five burndown herbicides was conducted in Alabama and Tennessee. Treatments of 2,4-D, dicamba, glufosinate, paraquat, and saflufenacil were applied at sunrise, midday, or sunset to a native population of horseweed and analyzed separately. Control of glyphosate-resistant (GR) horseweed with 2,4-D, dicamba, glufosinate, and saflufenacil was greatest from the midday application. Percentage of living horseweed counts for all of these herbicides followed a similar pattern. Control from paraquat was lowest at the midday timing and greatest from the sunset application with surviving horseweed plant populations reflecting those control ratings. Application TOD significantly affected all of the herbicides in this research. Applications of 2,4-D, dicamba, glufosinate, and saflufenacil are more efficacious when applied during the middle portion of the day, while paraquat is more efficacious when applied at sunset for maximum horseweed control.
A rare, intact Viking boat burial in western Scotland contained a rich assemblage of grave goods, providing clues to the identity and origins of both the interred individual and the people who gathered to create the site. The burial evokes the mundane and the exotic, past and present, as well as local, national and international identities. Isotopic analysis of the teeth hints at a possible Scandinavian origin for the deceased, while Scottish, Irish and Scandinavian connections are attested by the grave goods. Weapons indicate a warrior of high status; other objects imply connections to daily life, cooking and work, farming and food production. The burial site is itself rich in symbolic associations, being close to a Neolithic burial cairn, the stones of which may have been incorporated into the grave.