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This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6–51 and HR = 7.0, 95% CI 1.5–33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88–1.5) or diabetes (HR = 1.1, 95% CI 0.9–1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84–20) or general population (SIR: 1.9, 95% CI 1.0–3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.
We analyse United States presidential appointee positions subject to Senate confirmation without a confirmed appointee in office. These “vacant” positions are byproducts of American constitutional design, shaped by the interplay of institutional politics. Using a novel dataset, we analyse appointee vacancies across executive branch departments and single-headed agencies from 1989 to 2013. We develop a theoretical model that uncovers the dynamics of vacancy onset and length. We then specify an empirical model and report results highlighting both position and principal–agent relations as critical to the politics of appointee vacancies. Conditional on high status positions reducing the frequency and duration of vacancies, we find important principal–agent considerations from a separation of powers perspective. Appointee positions in agencies ideologically divergent from the relevant Senate committee chair are vacant for less time than in ideologically proximal agencies. Importantly, this relationship strengthens as agency ideology diverges away from the chair and towards the chair’s party extreme.
Cyclonic storms (often called hurricanes, typhoons, or cyclones) often cause population declines in vulnerable bird species, and the intensity of these storms appears to be increasing due to climate change. Prior studies have reported short-term impacts of hurricanes on avifauna, but few have examined long-term impacts. Over two decades (1993–2018), we periodically surveyed a subspecies of West Indian Woodpecker Melanerpes superciliaris nyeanus on San Salvador, a small island in The Bahamas, to determine its distribution on the island, habitat use, and effects of hurricanes on abundance and population size. We conducted passive and playback surveys, supplemented with mist-netting. Woodpeckers were found only in the northern part of San Salvador, despite extensive surveys throughout other accessible areas of the island. Birds occupied areas with taller coppice adjacent to sabal palm Sabal palmetto groves, which were used for nesting. After hurricanes with >160 kph winds passed over San Salvador, woodpecker densities declined to 35–40% of pre-hurricane densities, but generally recovered back to pre-hurricane densities within 2–3 years. Based on an estimated density of woodpeckers within a ~1,400 ha occupied area, we calculated a population size of approximately 240 individuals (CI = 68-408). However, the population declined to far lower numbers immediately following hurricanes. Under IUCN Red List criteria, M. s. nyeanus classifies as ‘Critically Endangered’, and could be especially sensitive to future hurricanes if they occur at a high enough frequency or intensity to prevent the population from rebounding. Given the small size, isolation, and vulnerability of this population, we recommend preservation of the core habitat, continued monitoring, and further research. Our study shows that small, threatened bird populations can be resilient to the effects of hurricanes, but increased intensity of hurricanes, in combination with other threats, may limit this resilience in the future.
Prolonged survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on environmental surfaces and personal protective equipment may lead to these surfaces transmitting this pathogen to others. We sought to determine the effectiveness of a pulsed-xenon ultraviolet (PX-UV) disinfection system in reducing the load of SARS-CoV-2 on hard surfaces and N95 respirators.
Chamber slides and N95 respirator material were directly inoculated with SARS-CoV-2 and were exposed to different durations of PX-UV.
For hard surfaces, disinfection for 1, 2, and 5 minutes resulted in 3.53 log10, >4.54 log10, and >4.12 log10 reductions in viral load, respectively. For N95 respirators, disinfection for 5 minutes resulted in >4.79 log10 reduction in viral load. PX-UV significantly reduced SARS-CoV-2 on hard surfaces and N95 respirators.
With the potential to rapidly disinfectant environmental surfaces and N95 respirators, PX-UV devices are a promising technology to reduce environmental and personal protective equipment bioburden and to enhance both healthcare worker and patient safety by reducing the risk of exposure to SARS-CoV-2.
Lumateperone (lumateperone tosylate, ITI-007) is an investigational drug for the treatment of schizophrenia, bipolar depression, and other disorders. Lumateperone has a unique mechanism of action that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This may provide advantages in the treatment of the broad symptoms associated with schizophrenia, including negative and depression symptoms. In 2 previous placebo-controlled trials in patients with acute schizophrenia, lumateperone 42mg (ITI-007 60mg) demonstrated statistically significant improvement in the Positive and Negative Syndrome Scale (PANSS) Total score compared with placebo. In these studies, lumateperone was well tolerated with a safety profile similar to placebo. This open-label long-term study evaluated the safety and effectiveness of lumateperone 42mg in patients with schizophrenia and stable symptoms.
Patients with stable schizophrenia were treated for up to 1 year with lumateperone 42mg. Safety assessments included adverse events (AEs), body weight, laboratory parameters, and extrapyramidal symptoms (EPS)/motor symptom assessments. Efficacy analyses included evaluation of changes in PANSS Total score and in depression symptoms, as measured by the Calgary Depression Scale for Schizophrenia (CDSS).
In the 1-year open-label study, 602 patients received at least 1 dose of lumateperone 42mg; at the time of this interim analysis, 107 patients had completed 1 year of treatment. Only 4 TEAEs occurred in ≥5% of patients (weight decrease, dry mouth, headache and diarrhea); the majority of AEs were mild or moderate in intensity. Most metabolic parameters and mean prolactin levels decreased from SOC baseline, as did mean body weight and BMI. Based on AE reporting and EPS/motor symptom scales, lumateperone treatment was associated with minimal EPS risk. Lumateperone 42mg treatment was associated with significant reductions in PANSS Total score from baseline, with continuing PANSS improvement throughout the study. In patients with moderate-to-severe depression symptoms at baseline (CDSS>5), mean CDSS scores decreased from 7.4 (baseline) to 3.1 (Day 300); 60% of patients met CDSS response criteria (50% improvement from baseline) by Day 75 and this response rate was maintained through day 300. Similar magnitude of CDSS improvement was seen regardless of concurrent antidepressant therapy.
In long-term treatment, lumateperone was associated with minimal metabolic, EPS, and cardiovascular safety issues relative to current SOC antipsychotic therapy. Lumateperone improved schizophrenia symptoms with continued long-term treatment. In patients with moderate-to-severe depression symptoms at baseline, lumateperone treatment was associated with marked improvement in CDSS scores. These data are consistent with and extend data previously reported in placebo-controlled studies in patients with acute schizophrenia treated with lumateperone.
Supported by funding from Intra-Cellular Therapies, Inc.
Lumateperone (ITI-007) is in late-phase clinical development for schizophrenia. Lumateperone has a unique mechanism of action that modulates serotonin, dopamine, and glutamate neurotransmission. This pooled analysis of lumateperone in 3 randomized, double-blind, placebo-controlled studies was conducted to evaluate the safety and tolerability of lumateperone 42mg (ITI-007 60mg).
Data were pooled from the 3 controlled late-phase studies of lumateperone 42mg in patients with acute exacerbation of schizophrenia. Safety assessments of all patients who received at least one dose of any treatment included treatment-emergent adverse events (TEAEs), changes in laboratory parameters, extrapyramidal symptoms (EPS), and vital signs.
The safety population comprised 1,073 patients (placebo [n=412], lumateperone 42mg [n=406], risperidone [n=255]). TEAEs that occurred in the lumateperone 42mg group at a rate of ≥5% and twice placebo were somnolence/sedation (24.1% vs 10.0%) and dry mouth (5.9% vs 2.2%). Rates of discontinuation due to TEAEs with lumateperone 42mg (0.5%) were similar to placebo (0.5%) and lower than risperidone (4.7%). Mean change in weight and rates of EPS-related TEAEs were less for lumateperone 42mg and placebo patients than risperidone patients. Mean change from baseline in metabolic parameters were similar or smaller for lumateperone 42mg vs placebo. Mean changes were notably higher in risperidone patients vs lumateperone 42mg and placebo for glucose, cholesterol, triglycerides, and prolactin.
In this pooled analysis, lumateperone 42mg showed good tolerability with potential benefits over risperidone for metabolic, prolactin, and EPS risks. The only TEAE that occurred in >10% of lumateperone patients was somnolence/sedation, which was impacted by morning administration; in subsequent studies that administered lumateperone in the evening, somnolence/sedation rates were markedly reduced. These results suggest that lumateperone 42mg may be a promising new treatment for schizophrenia.
Supported by funding from Intra-Cellular Therapies, Inc.
Glyphosate-resistant (GR) canola is a widely grown crop across western Canada and has quickly become a prolific volunteer weed. Glyphosate-resistant soybean is rapidly gaining acreage in western Canada. Thus, there is a need to evaluate herbicide options to manage volunteer GR canola in GR soybean crops. We conducted an experiment to evaluate the efficacy of various PRE and POST herbicides applied sequentially to volunteer GR canola and to evaluate soybean injury caused by these herbicides. Trials were conducted across Saskatchewan and Manitoba in 2014 and 2015. All treatments provided a range of suppression (>70%) to control (>80%) of volunteer canola. All treatments with the exception of the glyphosate-treated control reduced aboveground canola biomass by an average of 96%. As well, canola seed contamination was reduced from 36% to less than 5% when a PRE and POST herbicide were both used. Moreover, all combinations of herbicides used had excellent crop safety (<10%). All PRE and POST herbicide combinations provided better control of volunteer canola compared with the glyphosate-only control, but tribenuron followed by bentazon and tribenuron followed by imazamox plus bentazon provided solutions that were low cost, currently available (registered in western Canada), and had the potential to minimize development of herbicide resistance in other weeds.
The climate crisis requires nations to achieve human well-being with low national levels of carbon emissions. Countries vary from one another dramatically in how effectively they convert resources into well-being, and some nations with low levels of emissions have relatively high objective and subjective well-being. We identify urgent research and policy agendas for four groups of countries with either low or high emissions and well-being indicators. Least studied are those with low well-being and high emissions. Understanding social and political barriers to switching from high-carbon to lower-carbon modes of production and consumption, and ways to overcome them, will be fundamental.
The main thesis of this article is that Kant’s concept of law is a non-positivistic one, notwithstanding the fact that his legal philosophy includes very strong positivistic elements. My argument takes as its point of departure the distinction of three elements, around which the debate between positivism and non-positivism turns: first, authoritative issuance, second, social efficacy, and, third, moral correctness. All positivistic theories are confined to the first two elements. As soon as a necessary connection between these first two elements and the third element, moral correctness, is established, the picture changes fundamentally. Positivism becomes non-positivism. There exist two kinds of connections between law and morality: classifying and qualifying connections. This distinction stems from different sorts of effects that moral defects give rise to. A classifying connection leads to the loss of legal validity, whereas a qualifying connection leads only to legal defectiveness. In Kant’s theory of law both connections are found. The qualifying connection is conspicuous throughout Kant’s theory of law, whereas the classifying connection, by contrast, is rare and well hidden. This will suffice to consider Kant as a representative of inclusive non-positivism.
In recent years, soybean acreage has increased significantly in western Canada. One of the challenges associated with growing soybean in western Canada is the control of volunteer glyphosate-resistant (GR) canola, because most soybean cultivars are also glyphosate resistant. The objective of this research was to determine the impact of soybean seeding rate and planting date on competition with volunteer canola. We also attempted to determine how high seeding rate could be raised while still being economically feasible for producers. Soybean was seeded at five different seeding rates (targeted 10, 20, 40, 80, and 160 plants m−2) and three planting dates (targeted mid-May, late May, and early June) at four sites across western Canada in 2014 and 2015. Soybean yield consistently increased with higher seeding rates, whereas volunteer canola biomass decreased. Planting date generally produced variable results across site-years. An economic analysis determined that the optimal rate was 40 to 60 plants m−2, depending on market price, and the optimal planting date range was from May 20 to June 1.
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
To determine the preliminary feasibility, acceptability, and effects of Meaning-Centered Grief Therapy (MCGT) for parents who lost a child to cancer.
Parents who lost a child to cancer and who were between six months and six years after loss and reporting elevated levels of prolonged grief were enrolled in open trials of MCGT, a manualized, one-on-one cognitive-behavioral-existential intervention that used psychoeducation, experiential exercises, and structured discussion to explore themes related to meaning, identity, purpose, and legacy. Parents completed 16 weekly sessions, 60–90 minutes in length, either in person or through videoconferencing. Parents were administered measures of prolonged grief disorder symptoms, meaning in life, and other assessments of psychological adjustment preintervention, mid-intervention, postintervention, and at three months postintervention. Descriptive data from both the in-person and videoconferencing open trial were pooled.
Eight of 11 (72%) enrolled parents started the MCGT intervention, and six of eight (75%) participants completed all 16 sessions. Participants provided positive feedback about MCGT. Results showed postintervention longitudinal improvements in prolonged grief (d = 1.70), sense of meaning (d = 2.11), depression (d = 0.84), hopelessness (d = 1.01), continuing bonds with their child (d = 1.26), posttraumatic growth (ds = 0.29–1.33), positive affect (d = 0.99), and various health-related quality of life domains (d = 0.46–0.71). Most treatment gains were either maintained or increased at the three-month follow-up assessment.
Significance of results
Overall, preliminary data suggest that this 16-session, manualized cognitive-behavioral-existential intervention is feasible, acceptable, and associated with transdiagnostic improvements in psychological functioning among parents who have lost a child to cancer. Future research should examine MCGT with a larger sample in a randomized controlled trial.
The OSU-FEI Electron Microscopy Collaboratory multiplies the number of individuals who can experience hands-on advanced microscopy techniques. The microscopy classroom allows up to 33 attendees to operate, individually and in real time, electron microscopes as if they were sitting in front of the actual instruments. The communications link, a fast backbone augmented by Internet2, allows various microscopes to be operated from the classroom or by collaborators in another city. This system transforms the training of new users from a one-person-at-a-time session with an expert operator to a group collaborative activity that can include users from around the world.
As the IAU heads towards its second century, many changes have simultaneously transformed Astronomy and the human condition world-wide. Amid the amazing recent discoveries of exoplanets, primeval galaxies, and gravitational radiation, the human condition on Earth has become blazingly interconnected, yet beset with ever-increasing problems of over-population, pollution, and never-ending wars. Fossil-fueled global climate change has begun to yield perilous consequences. And the displacement of people from war-torn nations has reached levels not seen since World War II.