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Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
Many U.S. states have proposed policies that restrict bathroom access to an individual’s birth sex. These policies have had widespread effects on safety for transgender and gender-nonconforming people, as well as on state economies. In this registered report, we assessed the role of disgust in support for policies that restrict transgender bathroom access. We found that sensitivity to pathogen disgust was positively associated with support for bathroom restrictions; sexual and injury disgust were unrelated. We also examined the role of disgust-driven moral concerns, known as purity concerns, as well as harm-related moral concerns in support for bathroom restrictions. While concerns about harm to cisgender and transgender people predicted support for bathroom restrictions, purity was a much stronger predictor. Also, purity partially mediated the link between pathogen disgust and support for bathroom restrictions, even after accounting for harm concerns. Findings and implications are discussed.
What causes people to see their political attitudes in a moral light? One answer is that attitude moralization results from associating one’s attitude stance with feelings of disgust. To test the possibility that disgust moralizes, the current study used a high-powered preregistered design looking at within-person change in moral conviction paired with an experimental manipulation of disgust or anger (versus control). Results from the preregistered analyses found that we successfully induced anger but not disgust; however, our manipulation had no effect on moral conviction. Additional exploratory analyses investigating whether emotion and harm predicted increases in moral conviction over time found that neither disgust, anger, nor sadness had an effect on moralization, whereas perceptions of harm did predict moralization. Our findings are discussed in terms of their implications for current theory and research into attitude moralization.
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.
Subjective cognitive difficulties are common in mental illness and have a negative impact on role functioning. Little is understood about subjective cognition and the longitudinal relationship with depression and anxiety symptoms in young people.
To examine the relationship between changes in levels of depression and anxiety and changes in subjective cognitive functioning over 3 months in help-seeking youth.
This was a cohort study of 656 youth aged 12–25 years attending Australian headspace primary mental health services. Subjective changes in cognitive functioning (rated as better, same, worse) reported after 3 months of treatment was assessed using the Neuropsychological Symptom Self-Report. Multivariate multinomial logistic regression analysis was conducted to evaluate the impact of baseline levels of and changes in depression (nine-item Patient Health Questionnaire; PHQ9) and anxiety symptoms (seven-item Generalised Anxiety Disorder scale; GAD7) on changes in subjective cognitive function at follow-up while controlling for covariates.
With a one-point reduction in PHQ9 at follow-up, there was an estimated 11–18% increase in ratings of better subjective cognitive functioning at follow-up, relative to stable cognitive functioning. A one-point increase in PHQ9 from baseline to follow-up was associated with 7–14% increase in ratings of worse subjective cognitive functioning over 3 months, relative to stable cognitive functioning. A similar attenuated pattern of findings was observed for the GAD7.
A clear association exists between subjective cognitive functioning outcomes and changes in self-reported severity of affective symptoms in young people over the first 3 months of treatment. Understanding the timing and mechanisms of these associations is needed to tailor treatment.
This study used data from 12 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and United States; N = 1,315) to investigate bidirectional associations between parental warmth and control, and child externalizing and internalizing behaviors. In addition, the extent to which these associations held across mothers and fathers and across cultures with differing normative levels of parent warmth and control were examined. Mothers, fathers, and children completed measures when children were ages 8 to 13. Multiple-group autoregressive cross-lagged structural equation models revealed that evocative child-driven effects of externalizing and internalizing behavior on warmth and control are ubiquitous across development, cultures, mothers, and fathers. Results also reveal that parenting effects on child externalizing and internalizing behaviors, though rarer than child effects, extend into adolescence when examined separately in mothers and fathers. Father-based parent effects were more frequent than mother effects. Most parent- and child-driven effects appear to emerge consistently across cultures. The rare culture-specific parenting effects suggested that occasionally the effects of parenting behaviors that run counter to cultural norms may be delayed in rendering their protective effect against deleterious child outcomes.
Southern crabgrass [Digitaria ciliaris (Retz.) Koeler] is an annual grass weed that commonly infests turfgrass, roadsides, wastelands, and cropping systems throughout the southeastern United States. Two biotypes of D. ciliaris (R1 and R2) with known resistance to cyclohexanediones (DIMs) and aryloxyphenoxypropionates (FOPs) previously collected from sod production fields in Georgia were compared with a separate susceptible biotype (S) collected from Alabama for the responses to pinoxaden and to explore the possible mechanisms of resistance. Increasing rates of pinoxaden (0.1 to 23.5 kg ha−1) were evaluated for control of R1, R2, and S. The resistant biotypes, R1 and R2, were resistant to pinoxaden relative to S. The S biotype was completely controlled at rates of 11.8 and 23.5 kg ha−1, resulting in no aboveground biomass at 14 d after treatment. Pinoxaden rates at which tiller length and aboveground biomass would be reduced 50% (I50) and 90% (I90) for R1, R2, and S ranged from 7.2 to 13.2 kg ha−1, 6.9 to 8.6 kg ha−1, and 0.7 to 2.1 kg ha−1, respectively, for tiller length, and 7.7 to 10.2 kg ha−1, 7.2 to 7.9 kg ha−1, and 1.6 to 2.3 kg ha−1, respectively, for aboveground biomass. Prior selection pressure from DIM and FOP herbicides could result in the evolution of D. ciliaris cross-resistance to pinoxaden herbicides. Amplification of the carboxyl-transferase domain of the plastidic ACCase by standard PCR identified a point mutation resulting in an Ile-1781-Leu amino acid substitution only for the resistant biotype, R1. Further cloning of PCR product surrounding the 1781 region yielded two distinct ACCase gene sequences, Ile-1781 and Leu-1781. The amino acid substitution, Ile-1781-Leu in both resistant biotypes (R1 and R2), however, was revealed by next-generation sequencing of RNA using Illumina platform. A point mutation in the Ile-1781 codon leading to herbicide insensitivity in the ACCase enzyme has been previously reported in other grass species. Our research confirms that the Ile-1781-Leu substitution is present in pinoxaden-resistant D. ciliaris.
Fine fescues (Festuca spp.) are cool-season grasses used in low-maintenance turf areas. Mesotrione is a PRE and early-POST herbicide used during establishment of most cool-season turfgrasses, excluding fine fescues. Currently, efforts are being made to breed for increased tolerance to mesotrione in fine fescues to enhance weed control during establishment. This study was conducted to evaluate the association of foliar and root uptake of [14C]mesotrione with the tolerance of three lines each of Chewings fescue [Festuca rubra ssp. commutata Gaudin; syn. F. rubra ssp. fallax (Thuill.) Nyman], hard fescue [Festuca trachyphylla (Hack.) Hack.], and strong creeping red fescue (Festuca rubra L. ssp. rubra) lines. From a rate-titration experiment, the hierarchical rank of species for mesotrione tolerance from highest to lowest was: hard > Chewings > strong creeping red fescue. The hierarchical rank of species for foliar uptake from highest to lowest was: Chewings > strong creeping red > hard fescue. Translocation of foliar-absorbed 14C was not associated with differential tolerance levels of the three species. Root absorption was comparable among species, but differences between lines were detected within the species. The most susceptible lines of Chewings and strong creeping red fescue exhibited greater root uptake than lines with greater tolerance. Hard fescue translocated the least amount of root-absorbed radioactivity to shoots, while Chewings and strong creeping red fescues were comparable.
Proximal environments could facilitate smoking cessation among low-income smokers by making cessation appealing to strive for and tenable.
We sought to examine how home smoking rules and proximal environmental factors such as other household members' and peers' smoking behaviors and attitudes related to low-income smokers' past quit attempts, readiness, and self-efficacy to quit.
This analysis used data from Offering Proactive Treatment Intervention (OPT-IN) (randomized control trial of proactive tobacco cessation outreach) baseline survey, which was completed by 2,406 participants in 2011/12. We tested the associations between predictors (home smoking rules and proximal environmental factors) and outcomes (past-year quit attempts, readiness to quit, and quitting self-efficacy).
Smokers who lived in homes with more restrictive household smoking rules, and/or reported having ‘important others’ who would be supportive of their quitting, were more likely to report having made a quit attempt in the past year, had greater readiness to quit, and greater self-efficacy related to quitting.
Adjustments to proximal environments, including strengthening household smoking rules, might encourage cessation even if other household members are smokers.
Experiments were initiated to characterize a waterhemp population (CHR) discovered in a central Illinois corn field after it was not controlled by the 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor topramezone. Field experiments conducted during 2014–2015 indicated that acetolactate synthase (ALS)-, protoporphyrinogen oxidase (PPO)-, photosystem II (PSII)-, and HPPD-inhibiting herbicides and the synthetic auxin 2,4-D did not control the CHR population. Laboratory experiments confirmed target site–based resistance mechanisms to ALS- and PPO-inhibiting herbicides. Herbicide doses required to reduce dry biomass 50% (GR50) were determined in greenhouse dose–response experiments, and indicated 16-fold resistance to the HPPD inhibitor mesotrione, 9.5-fold resistance to the synthetic auxin 2,4-D, and 252-fold resistance to the PSII inhibitor atrazine. Complementary results from field, laboratory, and greenhouse investigations indicate that the CHR population has evolved resistance to herbicides from five sites of action (SOAs): ALS-, PPO-, PSII-, and HPPD-inhibiting herbicides and 2,4-D. Herbicide use history for the field in which CHR was discovered indicates no previous use of 2,4-D.
Here, we report that a marine sandworm Nereis virens jaw protein, Nvjp1, nucleates hemozoin with similar activity as the native parasite hemozoin protein, HisRPII. X-ray diffraction and scanning electron microscopy confirm the identity of the hemozoin produced from Nvjp1-containing reactions. Finally, we observed that nAl assembled with hemozoin from Nvjp1 reactions has a substantially higher energetic output when compared to analogous thermite from the synthetic standard or HisRPII-nucleated hemozoin. Our results demonstrate that a marine sandworm protein can nucleate malaria pigment and set the stage for engineering recombinant hemozoin production for nanoenergetic applications.
This study examined the interplay between a polygenic composite and cortisol activity as moderators of the mediational pathway among family adversity, youth negative emotional reactivity to family conflict, and their psychological problems. The longitudinal design contained three annual measurement occasions with 279 adolescents (Mean age = 13.0 years) and their parents. Latent difference score analyses indicated that observational ratings of adversity in interparental and parent–child interactions at Wave 1 predicted increases in a multimethod, multi-informant assessment of youth negative emotional reactivity to family conflict from Waves 1 to 2. Changes in youth negative emotional reactivity, in turn, predicted increases in a multi-informant (i.e., parents, adolescent, and teacher) assessment of psychological problems from Waves 1 to 3. Consistent with differential susceptibility theory, the association between family adversity and negative emotional reactivity was stronger for adolescents who carried more sensitivity alleles in a polygenic composite consisting of 5-HTTLPR, DRD4 VNTR, and BDNF polymorphisms. Analyses of adolescent cortisol in the period surrounding a family disagreement task at Wave 1 revealed that overall cortisol output, rather than cortisol reactivity, served as an endophenotype of the polygenic composite. Overall cortisol output was specifically associated with polygenic plasticity and moderated the association between family adversity and youth negative emotional reactivity in the same for better or for worse manner as the genetic composite. Finally, moderator-mediated-moderation analyses indicated that the moderating role of the polygenic plasticity composite was mediated by the moderating role of adolescent cortisol output in the association between family adversity and their emotional reactivity.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
While previous studies have identified relationships between hippocampal volumes and memory performance in schizophrenia, these relationships are not apparent in healthy individuals. Further, few studies have examined the role of hippocampal subfields in illness-related memory deficits, and no study has examined potential differences across varying illness stages. The current study aimed to investigate whether individuals with early and established psychosis exhibited differential relationships between visuospatial associative memory and hippocampal subfield volumes.
Measurements of visuospatial associative memory performance and grey matter volume were obtained from 52 individuals with a chronic schizophrenia-spectrum disorder, 28 youth with recent-onset psychosis, 52 older healthy controls, and 28 younger healthy controls.
Both chronic and recent-onset patients had impaired visuospatial associative memory performance, however, only chronic patients showed hippocampal subfield volume loss. Both chronic and recent-onset patients demonstrated relationships between visuospatial associative memory performance and hippocampal subfield volumes in the CA4/dentate gyrus and the stratum that were not observed in older healthy controls. There were no group by volume interactions when chronic and recent-onset patients were compared.
The current study extends the findings of previous studies by identifying particular hippocampal subfields, including the hippocampal stratum layers and the dentate gyrus, that appear to be related to visuospatial associative memory ability in individuals with both chronic and first-episode psychosis.
Using multilevel models, we examined mother-, father-, and child-reported (N = 1,336 families) externalizing behavior problem trajectories from age 7 to 14 in nine countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States). The intercept and slope of children's externalizing behavior trajectories varied both across individuals within culture and across cultures, and the variance was larger at the individual level than at the culture level. Mothers’ and children's endorsement of aggression as well as mothers’ authoritarian attitudes predicted higher age 8 intercepts of child externalizing behaviors. Furthermore, prediction from individual-level endorsement of aggression and authoritarian attitudes to more child externalizing behaviors was augmented by prediction from cultural-level endorsement of aggression and authoritarian attitudes, respectively. Cultures in which father-reported endorsement of aggression was higher and both mother- and father-reported authoritarian attitudes were higher also reported more child externalizing behavior problems at age 8. Among fathers, greater attributions regarding uncontrollable success in caregiving situations were associated with steeper declines in externalizing over time. Understanding cultural-level as well as individual-level correlates of children's externalizing behavior offers potential insights into prevention and intervention efforts that can be more effectively targeted at individual children and parents as well as targeted at changing cultural norms that increase the risk of children's and adolescents’ externalizing behavior.
Use of ketamine in the prehospital setting may be advantageous due to its potent analgesic and sedative properties and favorable risk profile. Use in the military setting has demonstrated both efficacy and safety for pain relief. The purpose of this study was to assess ketamine training, use, and perceptions in the civilian setting among nationally certified paramedics (NRPs) in the United States.
A cross-sectional survey of NRPs was performed. The electronic questionnaire assessed paramedic training, authorization, use, and perceptions of ketamine. Included in the analysis were completed surveys of paramedics who held one or more state paramedic credentials, indicated “patient care provider” as their primary role, and worked in non-military settings. Descriptive statistics were calculated.
A total of 14,739 responses were obtained (response rate=23%), of which 10,737 (73%) met inclusion criteria and constituted the study cohort. Over one-half (53%) of paramedics reported learning about ketamine during their initial paramedic training. Meanwhile, 42% reported seeking ketamine-related education on their own. Of all respondents, only 33% (3,421/10,737) were authorized by protocol to use ketamine. Most commonly authorized uses included pain management (55%), rapid sequence intubation (RSI; 72%), and chemical restraint/sedation (72%). One-third of authorized providers (1,107/3,350) had never administered ketamine, with another 32% (1,070/3,350) having administered ketamine less than five times in their career. Ketamine was perceived to be safe and effective as the vast majority reported that they were comfortable with the use of ketamine (94%) and would, in similar situations (95%), use it again.
This was the first large, national survey to assess ketamine training, use, and perceptions among paramedics in the civilian prehospital setting. While training related to ketamine use was commonly reported among paramedics, few were authorized to administer the drug by their agency’s protocols. Of those authorized to use ketamine, most paramedics had limited experience administering the drug. Future research is needed to determine why the prevalence of ketamine use is low and to assess the safety and efficacy of ketamine use in the prehospital setting.
BucklandDM, CroweRP, CashRE, GondekS, MalusoP, SirajuddinS, SmithER, DangerfieldP, ShapiroG, WankaC, PanchalAR, SaraniB. Ketamine in the Prehospital Environment: A National Survey of Paramedics in the United States. Prehosp Disaster Med. 2018;33(1):23–28.
The Foodborne Diseases Active Surveillance Network (FoodNet) conducts population-based surveillance for Campylobacter infection. For 2010 through 2015, we compared patients with Campylobacter jejuni with patients with infections caused by other Campylobacter species. Campylobacter coli patients were more often >40 years of age (OR = 1·4), Asian (OR = 2·3), or Black (OR = 1·7), and more likely to live in an urban area (OR = 1·2), report international travel (OR = 1·5), and have infection in autumn or winter (OR = 1·2). Campylobacter upsaliensis patients were more likely female (OR = 1·6), Hispanic (OR = 1·6), have a blood isolate (OR = 2·8), and have an infection in autumn or winter (OR = 1·7). Campylobacter lari patients were more likely to be >40 years of age (OR = 2·9) and have an infection in autumn or winter (OR = 1·7). Campylobacter fetus patients were more likely male (OR = 3·1), hospitalized (OR = 3·5), and have a blood isolate (OR = 44·1). International travel was associated with antimicrobial-resistant C. jejuni (OR = 12·5) and C. coli (OR = 12) infections. Species-level data are useful in understanding epidemiology, sources, and resistance of infections.
Using data from 1,177 families in eight countries (Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States), we tested a conceptual model of direct effects of childhood family adversity on subsequent externalizing behaviors as well as indirect effects through psychological mediators. When children were 9 years old, mothers and fathers reported on financial difficulties and their use of corporal punishment, and children reported perceptions of their parents’ rejection. When children were 10 years old, they completed a computerized battery of tasks assessing reward sensitivity and impulse control and responded to questions about hypothetical social provocations to assess their hostile attributions and proclivity for aggressive responding. When children were 12 years old, they reported on their externalizing behavior. Multigroup structural equation models revealed that across all eight countries, childhood family adversity had direct effects on externalizing behaviors 3 years later, and childhood family adversity had indirect effects on externalizing behavior through psychological mediators. The findings suggest ways in which family-level adversity poses risk for children's subsequent development of problems at psychological and behavioral levels, situated within diverse cultural contexts.
With 30 threatened species (14 categorized as Critically Endangered and 16 as Endangered, sensu IUCN), Coccothrinax (c. 54 species) is the flagship palm genus for conservation in the Caribbean Island Biodiversity Hotspot. Coccothrinax has its centre of taxonomic diversity in these islands, with c. 51 endemic species. We present a conservation framework for the 14 Critically Endangered species, found in Cuba, Haiti or the Dominican Republic. Only two species (C. jimenezii, C. montana) occur in more than one country (Haiti and the Dominican Republic). Immediate threats include oil drilling and nickel mining, intrusion of saline water into soil, urban and agricultural development, low population recruitment, uncontrolled fires, interspecific hybridization, and unsustainable ethnobotanical practices. Coccothrinax bermudezii, C. borhidiana, C. crinita ssp. crinita, C. leonis and C. spissa are not conserved in protected areas. Coccothrinax bermudezii, C. jimenezii, C. leonis and C. nipensis are not part of ex situ collections. Based on results from a conservation project targeting C. jimenezii, we recommend international cooperation between the three range states to implement integrative conservation management plans, plant exploration initiatives, taxonomic revisions, outreach, and fundraising. The ultimate aim of this review is to provide baseline information that will develop conservation synergy among relevant parties working on Coccothrinax conservation in Cuba, Haiti and the Dominican Republic. Such collaborations could also benefit through partnerships with botanists working in other countries.