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Disorders involving compulsivity, fear, and anxiety are linked to beliefs that the world is less predictable. We lack a mechanistic explanation for how such beliefs arise. Here, we test a hypothesis that in people with compulsivity, fear, and anxiety, learning a probabilistic mapping between actions and environmental states is compromised.
In Study 1 (n = 174), we designed a novel online task that isolated state transition learning from other facets of learning and planning. To determine whether this impairment is due to learning that is too fast or too slow, we estimated state transition learning rates by fitting computational models to two independent datasets, which tested learning in environments in which state transitions were either stable (Study 2: n = 1413) or changing (Study 3: n = 192).
Study 1 established that individuals with higher levels of compulsivity are more likely to demonstrate an impairment in state transition learning. Preliminary evidence here linked this impairment to a common factor comprising compulsivity and fear. Studies 2 and 3 showed that compulsivity is associated with learning that is too fast when it should be slow (i.e. when state transition are stable) and too slow when it should be fast (i.e. when state transitions change).
Together, these findings indicate that compulsivity is associated with a dysregulation of state transition learning, wherein the rate of learning is not well adapted to the task environment. Thus, dysregulated state transition learning might provide a key target for therapeutic intervention in compulsivity.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Herbicide-resistant (HR) kochia is a growing problem in the Great Plains region of Canada and the United States (U.S.). Resistance to up to four herbicide sites of action, including photosystem II inhibitors, acetolactate synthase inhibitors, synthetic auxins, and the 5-enolpyruvylshikimate-3-phosphate synthase inhibitor glyphosate have been reported in many areas of this region. Despite being present in the U.S. since 1993/1994, auxinic-HR kochia is a recent and growing phenomenon in Canada. This study was designed to characterize (a) the level of resistance and (b) patterns of cross-resistance to dicamba and fluroxypyr in 12 putative auxinic-HR kochia populations from western Canada. The incidence of dicamba-resistant individuals ranged among populations from 0% to 85%, while fluroxypyr-resistant individuals ranged from 0% to 45%. In whole-plant dose-response bioassays, the populations exhibited up to 6.5-fold resistance to dicamba and up to 51.5-fold resistance to fluroxypyr based on visible injury 28 days after application. Based on plant survival estimates, the populations exhibited up to 3.7-fold resistance to dicamba and up to 72.5-fold resistance to fluroxypyr. Multiple patterns of synthetic auxin resistance were observed, where one population from Cypress County, Alberta was resistant to dicamba but not fluroxypyr, while another from Rocky View County, Alberta was resistant to fluroxypyr but not dicamba based on single-dose population screening and dose-response bioassays. These results suggest that multiple mechanisms may confer resistance to dicamba and/or fluroxypyr in Canadian kochia populations. Further research is warranted to determine these mechanisms. Farmers are urged to adopt proactive non-chemical weed management tools in an effort to preserve efficacy of the remaining herbicide options available for control of HR kochia.
Pain, fatigue and anxiety are common features of fibromyalgia and ME/CFS and significantly impact quality of life. Aetiology is poorly defined but dysfunctional inflammatory, autonomic and interoceptive (sensing of internal bodily signals) processes are implicated.
To investigate how altered interoception relates to baseline expression of pain, fatigue and anxiety symptoms in fibromyalgia and ME/CFS and in response to an inflammatory challenge.
Sixty-five patients with fibromyalgia and/or ME/CFS diagnosis and 26 matched controls underwent baseline assessment: pressure-pain thresholds and self-report questionnaires assessing pain, fatigue and anxiety severity. Participants received injections of typhoid (inflammatory challenge) or saline (placebo) in a randomised, double-blind, crossover design, before completing heartbeat tracking tasks. Three interoception dimensions were examined: subjective sensibility, objective accuracy and metacognitive awareness. Interoceptive trait prediction error was calculated as discrepancy between accuracy and sensibility.
Patients with fibromyalgia and ME/CFS had significantly higher interoceptive sensibility and trait prediction error, despite no differences in interoceptive accuracy. Interoceptive sensibility and trait prediction error correlated with all self-report pain, fatigue and anxiety measures, and with lower pain thresholds. Anxiety mediated the positive-predictive relationships between pain (Visual Analogue Scale and Widespread Pain Index), fatigue impact and interoceptive sensibility. After inflammatory challenge, metacognitive awareness correlated with baseline self-reported symptom measures and lower pain thresholds.
This is the first study investigating interoceptive dimensions in patients with fibromyalgia and ME/CFS, which were found to be dysregulated and differentially influenced by inflammatory mechanisms. Interoceptive processes may represent a new potential target for diagnostic and therapeutic investigation in these poorly understood conditions.
This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care.
We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted.
Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions.
When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.
Incremental prediction of aggression from callous–unemotional (CU) traits is well established, but cross-cultural replication and studies of young children are needed. Little is understood about the contribution of CU traits in children who are already aggressive. We addressed these issues in prospective studies in the United Kingdom and Colombia. In a UK epidemiological cohort, CU traits and aggression were assessed at age 3.5 years, and aggression at 5.0 years by mothers (N = 687) and partners (N = 397). In a Colombian general population sample, CU traits were assessed at age 3.5 years and aggression at 3.5 and 5.0 years by mother report (N = 220). Analyses consistently showed prediction of age-5.0 aggression by age-3.5 CU traits controlling for age-3.5 aggression. Associations between age-3.5 CU traits and age-5.0 aggression were moderated by aggression at 3.5 years, with UK interaction terms, same informant, β = .07 p = .014 cross-informant, β = .14 p = .002, and in Colombia, β = .09 p = .128. The interactions arose from stronger associations between CU traits and later aggression in those already aggressive. Our findings with preschoolers replicated across culturally diverse settings imply a major role for CU traits in the maintenance and amplification of already established aggression, and cast doubt on their contribution to its origins.
When Hurricane Harvey struck the coastline of Texas in 2017, it caused 88 fatalities and over US $125 billion in damage, along with increased emergency department visits in Houston and in cities receiving hurricane evacuees, such as the Dallas-Fort Worth metroplex (DFW).
This study explored demographic indicators of vulnerability for patients from the Hurricane Harvey impact area who sought medical care in Houston and in DFW. The objectives were to characterize the vulnerability of affected populations presenting locally, as well as those presenting away from home, and to determine whether more vulnerable communities were more likely to seek medical care locally or elsewhere.
We used syndromic surveillance data alongside the Centers for Disease Control and Prevention Social Vulnerability Index to calculate the percentage of patients seeking care locally by zip code tabulation area. We used this variable to fit a spatial lag regression model, controlling for population density and flood extent.
Communities with more patients presenting for medical care locally were significantly clustered and tended to have greater socioeconomic vulnerability, lower household composition vulnerability, and more extensive flooding.
These findings suggest that populations remaining in place during a natural disaster event may have needs related to income, education, and employment, while evacuees may have more needs related to age, disability, and single-parent household status.
This paper introduces and demonstrates the use of quantum computers for asset–liability management (ALM). A summary of historical and current practices in ALM used by actuaries is given showing how the challenges have previously been met. We give an insight into what ALM may be like in the immediate future demonstrating how quantum computers can be used for ALM. A quantum algorithm for optimising ALM calculations is presented and tested using a quantum computer. We conclude that the discovery of the strange world of quantum mechanics has the potential to create investment management efficiencies. This in turn may lead to lower capital requirements for shareholders and lower premiums and higher insured retirement incomes for policyholders.
Childhood maltreatment is associated with altered neural reactivity during autobiographical memory (ABM) recall and a pattern of overgeneral memory (OGM). Altered ABM and OGM have been linked with psychopathology and poorer social functioning. The present study investigated the association between altered ABM and subsequent socio-emotional functioning (measured two years later) in a sample of adolescents with (N = 20; maltreatment group, MT) and without (N = 17; non-MT group) documented childhood maltreatment histories.
At baseline, adolescents (aged 12.6 ± 1.45 years) were administered the Autobiographical Memory Test to measure OGM. Participants also recalled specific ABMs in response to emotionally valenced cue words during functional MRI. Adolescents in both groups underwent assessments measuring depressive symptoms and prosocial behavior at both timepoints. Regression analyses were carried out to predict outcome measures at follow-up controlling for baseline levels.
In the MT group, greater OGM at baseline significantly predicted reduced prosocial behavior at follow-up and showed a trend level association with elevated depressive symptoms. Patterns of altered ABM-related brain activity did not significantly predict future psycho-social functioning.
The current findings highlight the potential value of OGM as a cognitive mechanism that could be targeted to reduce risk of depression in adolescents with prior histories of maltreatment.
Attitudes, and in some cases legislation, make it decreasingly acceptable to admit people younger than 18 years to adult psychiatric inpatient units. One strategy to reduce the number of under 18s admitted to adult psychiatric units is the commissioning of specialist Child and Adolescent Mental Health (CAMHS) inpatient units.
Map the flow of admissions toacute adult psychiatric inpatient units and paediatric medical units in the years before and after the opening of specialist CAMHS inpatient units.
Determine if opening CAMHS inpatient increases or decreases the flow of admissions to acute adult psychiatric inpatient units and paediatric medical units
Analysis of statewide admission data for under 18s to specialist CAMHS inpatient units, acute adult psychiatric inpatient units, and paediatric medical units for the period January 2001 to December 2013 in New South Wales, Australia.
Five of 8 health districts experienced an increase in juvenile admissions to adult units in the year of opening a CAMHS unit. Admissions to related paediatric medical units increased in 3 of 7 health districts. Admissions to adult and paediatric units rose with time but there was no interaction between time and health district type (with/without CAMHS unit).
Opening CAMHS units may temporarily increase the number of juveniles admitted to adult units, but does not influence the flow of patients to non-CAMHS facilities in the longer term. CAMHS units appear to fulfil an additional as opposed to replacement role in the care pathway for young people with mental illness.
The aim of this study was to analyze pharmacy functionality, or the volume of operational pharmacies, among areas in North Carolina and South Carolina affected by Hurricane Florence.
Using geographic information system software and data from the Federal Emergency Management Agency and Healthcare Ready, we computed, mapped, and analyzed pharmacy functionality measures for the period of September 12, 2018, through September 20, 2018, among counties in North Carolina and South Carolina to examine health-care–related disaster readiness for and response to Hurricane Florence.
In the Hurricane Florence-impacted region, counties located along the coast had the most suboptimal pharmacy functionality, whereas counties located more centrally within North Carolina and South Carolina had more optimal pharmacy functionality throughout the disaster. Generally, functionality was high at Hurricane Florence’s landfall on September 14, 2018, for which operating pharmacy capacity was reported at 85% in North Carolina and 88% in South Carolina. Both states had the lowest functionality on September 16, 2018, at 71% for North Carolina and 62% for South Carolina.
During the Hurricane Florence event, suboptimal pharmacy functionality was detected for coastal areas and during the disaster response period. Hurricane readiness plans and infrastructure strengthening should be emphasized for community pharmacies in hurricane-prone areas.
Increasing fluorination of organosilyl nitrile solvents improves ionic conductivities of lithium salt electrolytes, resulting from higher values of salt dissociation. Ionic conductivities at 298 K range from 1.5 to 3.2 mS/cm for LiPF6 salt concentrations at 0.6 or 0.7 M. The authors also report on solvent blend electrolytes where the fluoroorganosilyl (FOS) nitrile solvent is mixed with ethylene carbonate and diethyl carbonate. Ionic conductivities of the FOS solvent/carbonate blend electrolytes increase achieving ionic conductivities at 298 K of 5.5–6.3 mS/cm and salt dissociation values ranging from 0.42 to 0.45. Salt dissociation generally decreases with increasing temperature.
Fomesafen is a protoporphyrinogen oxidase–inhibitor herbicide with an alternative mode of action that provides PRE weed control in strawberry [Fragaria×ananassa (Weston) Duchesne ex Rozier (pro sp.) [chiloensis×virginiana]] produced in a plasticulture setting in Florida. Plasticulture mulch could decrease fomesafen dissipation and increase crop injury in rotational crops. Field experiments were conducted in Balm, FL, to investigate fomesafen persistence and movement in soil in Florida strawberry systems for the 2014/2015 and 2015/2016 production cycles. Treatments included fomesafen preplant at 0, 0.42, and 0.84 kg ai ha−1. Soil samples were taken under the plastic from plots treated with fomesafen at 0.42 kg ha−1 throughout the production cycle. Fomesafen did not injure strawberry or decrease yield. Fomesafen concentration data for the 0.0- to 0.1-m soil depth were described using a three-parameter logistic function. The fomesafen 50% dissipation times were 37 and 47 d for the 2014/2015 and 2015/2016 production cycles, respectively. At the end of the study, fomesafen was last detected in the 0.0- to 0.1-m depth soil at 167 and 194 d after treatment in the 2014/2015 and 2015/2016 production cycles, respectively. Fomesafen concentration was less than 25 ppb on any sampling date for 0.1- to 0.2-m and 0.2- to 0.3-m depths. Fomesafen concentration decreased significantly after strawberry was transplanted and likely leached during overhead and drip irrigation used during the crop establishment.
Self-screening using an electronic version of the Malnutrition Universal Screening Tool (‘MUST’) has been developed but its implementation requires investigation. A total of 100 outpatients (mean age 50 (sd 16) years; 57 % male) self-screened with an electronic version of ‘MUST’ and were then screened by a healthcare professional (HCP) to assess concurrent validity. Ease of use, time to self-screen and prevalence of malnutrition were also assessed. A further twenty outpatients (mean age 54 (sd 15) years; 55 % male) examined preference between self- screening with paper and electronic versions of ‘MUST’. For the three-category classification of ‘MUST’ (low, medium and high risk), agreement between electronic self-screening and HCP screening was 94 % (κ=0·74, se 0·092; P<0·001). For the two-category classification (low risk; medium+high risk) agreement was 96 % (κ=0·82, se 0·085; P<0·001), comparable with the previously reported paper-based self-screening. In all, 15 % of patients categorised themselves ‘at risk’ of malnutrition (5 % medium, 10 % high). Electronic self-screening took 3 min (sd 1·2 min), 40 % faster than previously reported for the paper-based version. Patients found the tool easy or very easy to understand (99 %) and complete (98 %). Patients that assessed both tools found the electronic tool easier to complete (65 %) and preferred it (55 %) to the paper version. Electronic self-screening using ‘MUST’ in a heterogeneous group of hospital outpatients is acceptable, user-friendly and has ‘substantial to almost-perfect’ agreement with HCP screening. The electronic format appears to be as agreeable and often the preferred format when compared with the validated paper-based ‘MUST’ self-screening tool.
Broadleaf species escape current integrated weed management strategies in strawberry [Fragaria×ananassa (Weston) Duchesne ex Rozier (pro sp.) [chiloensis×virginiana]] production. Clopyralid is a registered POST control option, but current application timings provide suppression of only some species. Earlier clopyralid application timings may increase spray coverage to weeds at the planting hole, but strawberry plant tolerance to applications shortly after transplant is unknown. The objectives of the study were to determine the degree of clopyralid tolerance when applied to mature strawberry plants according to current management strategies, whether clopyralid absorption and translocation were involved in the tolerance response demonstrated by mature strawberry plants, and whether clopyralid could be safely applied to immature strawberry plants shortly after transplant. Clopyralid caused no damage when applied to mature strawberry plants and did not affect crop height, number of crowns, flowers, immature berries, or yield. Maximal strawberry absorption of radiolabeled clopyralid was 82% of the recovered radioactivity and reached peak (90%) absorption at 15 h. Maximal total translocation of radioactivity from the treated leaf was 17% and reached peak translocation at 52 h. Translocation was primarily to the new leaves and reproductive structures. In the early-application experiment, damage induced by clopyralid for all application timings reached 0 by 8 wk after treatment. Across all timings, maximal damage at 140 g ha−1 was 17% when applied 14 d after transplant (DATr) and 56% at 28 g ha−1 when applied at 21 DATr. Clopyralid dose did not affect the number of crowns, aboveground biomass, or yield. There was some stunting in plant height (3%) by the high labeled dose of clopyralid. Labeled dose clopyralid applications appear safe for application timings closer to strawberry transplant, though considerations of leaf cupping should be taken under consideration for label changes.
Recent findings highlight that there are prenatal risks for affective disorders that are mediated by glucocorticoid mechanisms, and may be specific to females. There is also evidence of sex differences in prenatal programming mechanisms and developmental psychopathology, whereby effects are in opposite directions in males and females. As birth weight is a risk for affective disorders, we sought to investigate whether maternal prenatal cortisol may have sex-specific effects on fetal growth. Participants were 241 mothers selected from the Wirral Child Health and Development Study (WCHADS) cohort (n=1233) using a psychosocial risk stratifier, so that responses could be weighted back to the general population. Mothers provided saliva samples, which were assayed for cortisol, at home over 2 days at 32 weeks gestation (on waking, 30-min post-waking and during the evening). Measures of infant birth weight (corrected for gestational age) were taken from hospital records. General population estimates of associations between variables were obtained using inverse probability weights. Maternal log of the area under the curve cortisol predicted infant birth weight in a sex-dependent manner (interaction term P=0.029). There was a positive and statistically significant association between prenatal cortisol in males, and a negative association in females that was not statistically significant. A sex interaction in the same direction was evident when using the waking (P=0.015), and 30-min post-waking (P=0.013) cortisol, but not the evening measure. There was no interaction between prenatal cortisol and sex to predict gestational age. Our findings add to an emerging literature that suggests that there may be sex-specific mechanisms that underpin fetal programming.