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Sleep and circadian timing shifts later during adolescence, conflicting with early school start times, and resulting in circadian misalignment. Although circadian misalignment has been linked to depression, substance use, and altered reward function, a paucity of experimental studies precludes the determination of causality. Here we tested, for the first time, whether experimentally-imposed circadian misalignment alters the neural response to monetary reward and/or response inhibition.
Healthy adolescents (n = 25, ages 13–17) completed two in-lab sleep schedules in counterbalanced order: An ‘aligned’ condition based on typical summer sleep-wake times (0000–0930) and a ‘misaligned’ condition mimicking earlier school year sleep-wake times (2000–0530). Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward (morning only) and response inhibition (morning and afternoon) tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively.
Bilateral ventral striatal (VS) activation during reward outcome was lower during the Misaligned condition after accounting for the prior night's total sleep time. Bilateral VS activation during reward anticipation was lower during the Misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the Misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan.
Our findings provide novel experimental evidence that circadian misalignment analogous to that resulting from school schedules may have measurable impacts on healthy adolescents' reward processing and inhibition of prepotent responses.
Aripiprazole has demonstrated efficacy for the treatment of paediatric patients (10–17 years) with a manic or mixed episode associated with bipolar I disorder in a clinical trial that utilised the Young Mania Rating Scale (YMRS) Total score as the primary outcome measure.
This analysis evaluated the profile of discrete symptom response using the YMRS and other measures.
Post-hoc analysis of individual items of the YMRS and the parent or subject version of the General Behaviour Inventory (GBI) Mania and Depression scales using data from a 4-week, double-blind, randomised trial that compared aripiprazole (10 or 30 mg/day, n = 197) with placebo (n = 99).
In total, 296 patients were randomised; 80% completed the study. Significant decreases at Week 4 (p < 0.05) were seen in eight YMRS items: elevated mood, increased motor activity/energy, need for sleep, irritability, speech (rate and amount), language/thought disorder, abnormal thought content and disruptive/aggressive behaviour. For the GBI, effect sizes for parent-reported mania items were medium to large (for example, 0.41 for ‘depressed but high energy’ to 0.78 for ‘rage combined with unusually happy’) but were consistently small on subject self-reported items of mania and depression and, for the overall scale, had the poorest agreement with clinician ratings.
Aripiprazole demonstrated improvements in some of the more troublesome symptoms of paediatric patients with bipolar I disorder experiencing an acute manic or mixed episode. Of note, irritability and aggression showed large treatment effects on both clinician and parent-reported measures, but less so for subject-reported measures.
Anxiety is the most prevalent psychological disorder among youth, and even following treatment, it confers risk for anxiety relapse and the development of depression. Anxiety disorders are associated with heightened response to negative affective stimuli in the brain networks that underlie emotion processing. One factor that can attenuate the symptoms of anxiety and depression in high-risk youth is parental warmth. The current study investigates whether parental warmth helps to protect against future anxiety and depressive symptoms in adolescents with histories of anxiety and whether neural functioning in the brain regions that are implicated in emotion processing and regulation can account for this link. Following treatment for anxiety disorder (Time 1), 30 adolescents (M age = 11.58, SD = 1.26) reported on maternal warmth, and 2 years later (Time 2) they participated in a functional neuroimaging task where they listened to prerecorded criticism and neutral statements from a parent. Higher maternal warmth predicted lower neural activation during criticism, compared with the response during neutral statements, in the left amygdala, bilateral insula, subgenual anterior cingulate (sgACC), right ventrolateral prefrontal cortex, and anterior cingulate cortex. Maternal warmth was associated with adolescents’ anxiety and depressive symptoms due to the indirect effects of sgACC activation, suggesting that parenting may attenuate risk for internalizing through its effects on brain function.
A geochemical and biostratigraphic approach has been applied to investigate the spatial and stratigraphic variability of Palaeogene sandstones from key wells in Taranaki Basin, New Zealand. Chronostratigraphic control is predominantly based on miospore zonation, while differences in the composition of Paleocene and Eocene sandstones are supported by geochemical evidence. Stratigraphic changes are manifested by a significant decrease in Na2O across the New Zealand miospore PM3b/MH1 early Eocene zonal boundary, at approximately 53.5 Ma. The change in Na2O is associated with a decrease in baseline concentrations of many other major (MnO, CaO, TiO2) and trace elements, and is interpreted to reflect a significant change in sandstone maturity. Paleocene sandstones are characterized by abundant plagioclase (albite and locally Na–Ca plagioclase), significant biotite and a range of heavy minerals, while Eocene sandstones are typically quartzose, with K-feldspar dominant over plagioclase, low mica contents and rare heavy minerals comprising a resistant suite. This change could reflect a change in provenance from local plutonic basement during the Paleocene Epoch to relatively quartz- and K-feldspar-rich granitic sources during Eocene time. However, significant quartz enrichment of Eocene sediment was also likely due to transportation reworking/winnowing along the palaeoshoreface and enhanced chemical weathering, driven in part by long-term global warming associated with the Early Eocene Climatic Optimum. The broad-ranging changes in major-element composition overprint local variations in sediment provenance, which are only detectable from the immobile trace-element geochemistry.
When open-cut mines are eventually abandoned, they leave a large hole with sloping sides. The hole fills with rain water, and there is also contaminated run-off from surrounding land, that moves through the rock and eventually through the sloping sides of the abandoned mine. This paper considers a two-dimensional unsteady model motivated by this leaching flow through the rock and into the rain-water reservoir. The stability of the interface between the two fluids is analysed in the inviscid limit. A viscous Boussinesq model is also presented, and a closed-form solution is presented to this problem, after it has been linearized in a manner consistent with Boussinesq theory. That solution suggests that the interfacial zone is effectively neutrally stable as it evolves in time. However, an asymptotic theory in the interfacial region shows the interface to be unstable. In addition, the nonlinear Boussinesq model is solved using a spectral method. Interfacial travelling waves and roll-up are observed and discussed, and compared against the predictions of asymptotic Boussinesq theory.
Trauma exposure is associated with development of depression and anxiety; yet, some individuals are resilient to these trauma-associated effects. Differentiating mechanisms underlying development of negative affect and resilience following trauma is critical for developing effective interventions. One pathway through which trauma could exert its effects on negative affect is reward-learning networks. In this study, we examined relationships among lifetime trauma, reward-learning network function, and emotional states in young adults.
One hundred eleven young adults self-reported trauma and emotional states and underwent functional magnetic resonance imaging during a monetary reward task. Trauma-associated neural activation and functional connectivity were analyzed during reward prediction error (RPE). Relationships between trauma-associated neural functioning and affective and anxiety symptoms were examined.
Number of traumatic events was associated with greater ventral anterior cingulate cortex (vACC) activation, and lower vACC connectivity with the right insula, frontopolar, inferior parietal, and temporoparietal regions, during RPE. Lower trauma-associated vACC connectivity with frontoparietal regions implicated in regulatory and decision-making processes was associated with heightened affective and anxiety symptoms; lower vACC connectivity with insular regions implicated in interoception was associated with lower affective and anxiety symptoms.
In a young adult sample, two pathways linked the impact of trauma on reward-learning networks with higher v. lower negative affective and anxiety symptoms. The disconnection between vACC and regions implicated in decision-making and self-referential processes may reflect aberrant regulatory but appropriate self-focused mechanisms, respectively, conferring risk for v. resilience against negative affective and anxiety symptoms.
Alcohol use is commonly initiated during adolescence, with earlier onset known to increase the risk for alcohol use disorder (AUD). Altered function in neural reward circuitry is thought to increase the risk for AUD. To test the hypothesis that adolescent alcohol misuse primes the brain for alcohol-related psychopathology in early adulthood, we examined whether adolescent alcohol consumption rates predicted reward responsivity in the ventral striatum (VS), and in turn, AUD symptoms in adulthood.
A total of 139 low income, racially diverse urban males reported on their alcohol use at ages 11, 12, 15, and 17; completed self-reports of personality, psychiatric interviews, and a functional magnetic resonance imaging (fMRI) scan at age 20; and completed a psychiatric interview at age 22. We measured adolescent alcohol use trajectories using latent growth curve modeling and measured neural responses to monetary reward using a VS region of interest. We tested indirect effects of adolescent alcohol use on AUD symptoms at age 22 via VS reward-related reactivity at age 20.
Greater acceleration in adolescent alcohol use predicted increased VS response during reward anticipation at age 20. VS reactivity to reward anticipation at age 20 predicted AUD symptoms at age 22, over and above concurrent symptoms. Accelerated adolescent alcohol use predicted AUD symptoms in early adulthood via greater VS reactivity to reward anticipation.
Prospective findings support a pathway through which adolescent alcohol use increases the risk for AUD in early adulthood by impacting reward-related neural functioning. These results highlight increased VS reward-related reactivity as a biomarker for AUD vulnerability.
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.
There is now ample evidence that the quality of early attachment experiences shapes expectations for supportive and responsive care and ultimately serves to scaffold adaptation to the salient tasks of development. Nonetheless, few studies have identified neural mechanisms that might give rise to these associations. Using a moderately large sample of low-income male participants recruited during infancy (N = 171), we studied the predictive significance of attachment insecurity and disorganization at age 18 months (as measured in the Strange Situation Procedure) for patterns of neural activation to reward and loss at age 20 years (assessed during a reward-based task as part of a functional magnetic resonance imaging scan). Results indicated that individuals with a history of insecure attachment showed hyperactivity in (a) reward- and emotion-related (e.g., basal ganglia and amygdala) structures and (b) emotion regulation and self-referential processing (cortical midline structures) in response to positive and negative outcomes (and anticipation of those outcomes). Further, the neural activation of individuals with a history of disorganized attachment suggested that they had greater emotional reactivity in anticipation of reward and employed greater cognitive control when negative outcomes were encountered. Overall, results suggest that the quality of early attachments has lasting impacts on brain function and reward processing.
Previous studies demonstrate that boys' monoamine oxidase A (MAOA) genotype interacts with adverse rearing environments in early childhood, including punitive discipline, to predict later antisocial behavior. Yet the mechanisms by which MAOA and punitive parenting interact during childhood to amplify risk for antisocial behavior are not well understood. In the present study, hostile attributional bias and aggressive response generation during middle childhood, salient aspects of maladaptive social information processing, were tested as possible mediators of this relation in a sample of 187 low-income men followed prospectively from infancy into early adulthood. Given racial–ethnic variation in MAOA allele frequencies, analyses were conducted separately by race. In both African American and Caucasian men, those with the low-activity MAOA allele who experienced more punitive discipline at age 1.5 generated more aggressive responses to perceived threat at age 10 relative to men with the high-activity variant. In the African American subsample only, formal mediation analyses indicated a marginally significant indirect effect of maternal punitiveness on adult arrest records via aggressive response generation in middle childhood. The findings suggest that maladaptive social information processing may be an important mechanism underlying the association between MAOA × Parenting interactions and antisocial behavior in early adulthood. The present study extends previous work in the field by demonstrating that MAOA and harsh parenting assessed in early childhood interact to not only predict antisocial behavior in early adulthood, but also predict social information processing, a well-established social–cognitive correlate of antisocial behavior.
Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth.
LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables.
Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%.
These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.
We propose a novel developmentally informed framework to push research beyond a focus on comorbidity between discrete diagnostic categories and to move toward research based on the well-validated dimensional and hierarchical structure of psychopathology. For example, a large body of research speaks to the validity and utility of the internalizing and externalizing spectra as organizing constructs for research on common forms of psychopathology. The internalizing and externalizing spectra act as powerful explanatory variables that channel the psychopathological effects of genetic and environmental risk factors, predict adaptive functioning, and account for the likelihood of disorder-level manifestations of psychopathology. As such, our proposed theoretical framework uses the internalizing and externalizing spectra as central constructs to guide future psychopathology research across the life span. The framework is particularly flexible, because any of the facets or factors from the dimensional and hierarchical structure of psychopathology can form the focus of research. We describe the utility and strengths of this framework for developmental psychopathology in particular and explore avenues for future research.
The time-varying flow in which fluid is withdrawn from or added to a reservoir of infinite or arbitrary finite depth through a point sink or source of variable strength beneath a free surface is considered. Backed up by some analytic work, a numerical method is used, and the results are compared with previous work on steady and unsteady flows. In the case of withdrawal for an impulsively started flow, it is found that the critical flow rate increases with reservoir depth, although it changes little as the depth increases beyond double the sink submergence depth. The largest flow rate at which steady solutions can evolve in source flows follows a similar pattern although at a considerably higher value. Simulations indicate that some of the previously calculated steady state solutions at higher flow rates may be unstable, if they exist at all.
Original studies published over the last decade regarding time trends in dementia report mixed results. The aims of the present study were to use linked administrative health data for the province of Saskatchewan for the period 2005/2006 to 2012/2013 to: (1) examine simultaneous temporal trends in annual age- and sex-specific dementia incidence and prevalence among individuals aged 45 and older, and (2) stratify the changes in incidence over time by database of identification.
Using a population-based retrospective cohort study design, data were extracted from seven provincial administrative health databases linked by a unique anonymized identification number. Individuals 45 years and older at first identification of dementia between April 1, 2005 and March 31, 2013 were included, based on case definition criteria met within any one of four administrative health databases (hospital, physician, prescription drug, and long-term care).
Between 2005/2006 and 2012/2013, the 12-month age-standardized incidence rate of dementia declined significantly by 11.07% and the 12-month age-standardized prevalence increased significantly by 30.54%. The number of incident cases decreased from 3,389 to 3,270 and the number of prevalent cases increased from 8,795 to 13,012. Incidence rate reductions were observed in every database of identification.
We observed a simultaneous trend of decreasing incidence and increasing prevalence of dementia over a relatively short 8-year time period from 2005/2006 to 2012/2013. These trends indicate that the average survival time of dementia is lengthening. Continued observation of these time trends is warranted given the short study period.
The steady, axisymmetric flow induced by a point sink (or source) submerged in an inviscid fluid of infinite depth is computed and the resulting deformation of the free surface is obtained. The effect of surface tension on the free surface is determined and is the new component of this work. The maximum Froude numbers at which steady solutions exist are computed. It is found that the determining factor in reaching the critical flow changes as more surface tension is included. If there is zero or a very small amount of surface tension, the limiting factor appears to be the formation of small wavelets on the free surface; but, as the surface tension increases, this is replaced by a tendency for the lowest point on the free surface to descend sharply as the Froude number is increased.
Parasites are detrimental to host fitness and therefore should strongly select for host defence mechanisms. Yet, hosts vary considerably in their observed parasite loads. One notable source of inter-individual variation in parasitism is host sex. Such variation could be caused by the immunomodulatory effects of gonadal steroids. Here we assess the influence of gonadal steroids on the ability of guppies (Poecilia reticulata) to defend themselves against a common and deleterious parasite (Gyrodactylus turnbulli). Adult male guppies underwent 31 days of artificial demasculinization with the androgen receptor-antagonist flutamide, or feminization with a combination of flutamide and the synthetic oestrogen 17 β-estradiol, and their parasite loads were compared over time to untreated males and females. Both demasculinized and feminized male guppies had lower G. turnbulli loads than the untreated males and females, but this effect appeared to be mainly the result of demasculinization, with feminization having no additional measurable effect. Furthermore, demasculinized males, feminized males and untreated females all suffered lower Gyrodactylus-induced mortality than untreated males. Together, these results suggest that androgens reduce the ability of guppies to control parasite loads, and modulate resistance to and survival from infection. We discuss the relevance of these findings for understanding constraints on the evolution of resistance in guppies and other vertebrates.
The effect of Hybrid stage 1 palliation for hypoplastic left heart syndrome on right ventricular function is unknown. We sought to compare right ventricular function in normal neonates and those with hypoplastic left heart syndrome before Hybrid palliation and to assess the effect of Hybrid palliation on right ventricular function, using the right ventricular myocardial performance index and the ratio of systolic and diastolic durations.
We carried out a retrospective review of echocardiographic data on 23 infants with hypoplastic left heart syndrome who underwent Hybrid palliation and 35 normal controls. Data were acquired before Hybrid and after Hybrid palliation – post 1, 0–4 days; post 2, 1 week; post 3, 2–3 weeks; post 4, 1–1.5 months following Hybrid palliation.
Myocardial performance index and ratio of systolic and diastolic durations were higher in the pre-Hybrid hypoplastic left heart syndrome group (n=23) – 0.47±0.16 versus 0.25±0.07, p<0.001; 1.59±0.44 versus 1.09±0.14, p<0.0001 – compared with controls (n=35). There was no significant change in the myocardial performance index at any of the post-Hybrid time points. Ratio of systolic and diastolic durations increased significantly 2 weeks after Hybrid – post 3: 2.08±0.62 and post 4: 2.21±0.45 versus pre: 1.59±0.44, p=0.043 and 0.003. There were no significant differences in parameters between sub-groups of infants who died (n=10) and survivors (n=13).
Right ventricular myocardial performance index and ratio of systolic and diastolic durations were significantly higher in infants with hypoplastic left heart syndrome before intervention compared with controls. The ratio of systolic and diastolic durations increased significantly 2 weeks after Hybrid palliation. Our data suggest that infants with hypoplastic left heart syndrome have right ventricular dysfunction before intervention, which worsens over 2 weeks after Hybrid palliation.
Both maternal obesity and disordered mood have adverse effects on pregnancy outcome. We hypothesized that maternal very severe obesity (SO) is associated with increased anxiety and depression (A&D) symptoms during pregnancy, with adverse effects on gestational weight gain (GWG), postpartum mood and postpartum weight retention (PPWR) and explored any mediation by circulating glucocorticoids.
We measured A&D symptoms with validated questionnaires at weeks 17 and 28 of pregnancy and 3 months postpartum in 135 lean [body mass index (BMI) ⩽25 kg/m2] and 222 SO (BMI ⩾40 kg/m2) pregnant women. Fasting serum cortisol was measured by radioimmunoassay; GWG and PPWR were recorded.
A&D symptoms were higher in the SO group during pregnancy and postpartum despite adjusting for multiple confounders including previous mental health diagnosis (p < 0.05), and were non-linearly correlated with total GWG (anxiety R2 = 0.06, p = 0.037; depression R2 = 0.09, p = 0.001). In the SO group only, increased maternal anxiety (β = 0.33, p = 0.03) and depression (β = 0.19, p = 0.04) symptoms at week 17 of pregnancy were associated with increased PPWR, independent of total GWG and breastfeeding. Anxiety symptoms at week 28 of pregnancy, but not depression, were non-linearly correlated with serum cortisol level at week 36 of pregnancy (R2 = 0.06, p = 0.02). Cortisol did not mediate the link between A&D symptoms and GWG.
Maternal SO was associated with increased A&D symptoms, and with adverse effects on GWG and PPWR independent of circulating glucocorticoids. Strategies to optimize GWG and postpartum weight management in SO women should include assessment and management of maternal mood in early pregnancy.