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In the history of Western music, no single figure has been as closely tied to the Enlightenment as Beethoven: he is regarded as the composer who embodies ideals such as freedom and humanism that many celebrate as the Enlightenment's legacy. This view, however, rests on a very narrow conception of the Enlightenment that aggressively stresses secularism and political liberalism. More recent historical research has shown that the Enlightenment's outlook on political and religious issues was more diverse and nuanced than traditional accounts have depicted it. The essays in this volume consider how new ways of thinking about the Enlightenment can alter the way we understand Beethoven and his music. By rethinking Beethoven and the Enlightenment, this book questions the Beethoven we know in both the popular and scholarly imagination and redefines the role the composer plays in the history of Western music.
This study compares outcomes of open versus percutaneous tracheostomies in coronavirus disease 2019 patients to guide clinical decision-making based on disease severity.
Methods
A retrospective cohort study using the 2020 National Readmissions Database identified 4810 coronavirus disease 2019 patients (International Statistical Classification of Diseases and Related Health Problems 10th Revision code U071) who underwent tracheostomy. Of these, 2061 had open and 2749 had percutaneous tracheostomies. Patient demographics, severity (All Patient Refined-Diagnosis Related Groups) and outcomes (mortality, readmission, complications) were analysed using chi-squared tests, both overall and by severity.
Results
Mortality was higher in the percutaneous group (29.25 per cent) compared to the open group (26.35 per cent) (p = 0.0265). For severe cases (All Patient Refined-Diagnosis Related Groups 3–4), open tracheostomies had significantly lower mortality, readmission and complication rates (p < 0.05).
Conclusion
Open tracheostomies are associated with better outcomes in severe coronavirus disease 2019 cases. Percutaneous tracheostomies are effective in mild cases, but patient selection and procedural planning should consider disease severity. Future research should validate these findings.
Recurrent methicillin-susceptible Staphylococcus aureus colonization following successful decolonization in a neonatal intensive care unit (NICU) has been observed. Of 17 recolonization events, 53% were due to concordant strains; 19 different spa types were identified. Results of this study support sources of re-acquisition both intrinsic and extrinsic to the NICU.
Auditory verbal hallucinations (AVHs) in schizophrenia have been suggested to arise from failure of corollary discharge mechanisms to correctly predict and suppress self-initiated inner speech. However, it is unclear whether such dysfunction is related to motor preparation of inner speech during which sensorimotor predictions are formed. The contingent negative variation (CNV) is a slow-going negative event-related potential that occurs prior to executing an action. A recent meta-analysis has revealed a large effect for CNV blunting in schizophrenia. Given that inner speech, similar to overt speech, has been shown to be preceded by a CNV, the present study tested the notion that AVHs are associated with inner speech-specific motor preparation deficits.
Objectives
The present study aimed to provide a useful framework for directly testing the long-held idea that AVHs may be related to inner speech-specific CNV blunting in patients with schizophrenia. This may hold promise for a reliable biomarker of AVHs.
Methods
Hallucinating (n=52) and non-hallucinating (n=45) patients with schizophrenia, along with matched healthy controls (n=42), participated in a novel electroencephalographic (EEG) paradigm. In the Active condition, they were asked to imagine a single phoneme at a cue moment while, precisely at the same time, being presented with an auditory probe. In the Passive condition, they were asked to passively listen to the auditory probes. The amplitude of the CNV preceding the production of inner speech was examined.
Results
Healthy controls showed a larger CNV amplitude (p = .002, d = .50) in the Active compared to the Passive condition, replicating previous results of a CNV preceding inner speech. However, both patient groups did not show a difference between the two conditions (p > .05). Importantly, a repeated measure ANOVA revealed a significant interaction effect (p = .007, ηp2 = .05). Follow-up contrasts showed that healthy controls exhibited a larger CNV amplitude in the Active condition than both the hallucinating (p = .013, d = .52) and non-hallucinating patients (p < .001, d = .88). No difference was found between the two patient groups (p = .320, d = .20).
Conclusions
The results indicated that motor preparation of inner speech in schizophrenia was disrupted. While the production of inner speech resulted in a larger CNV than passive listening in healthy controls, which was indicative of the involvement of motor planning, patients exhibited markedly blunted motor preparatory activity to inner speech. This may reflect dysfunction in the formation of corollary discharges. Interestingly, the deficits did not differ between hallucinating and non-hallucinating patients. Future work is needed to elucidate the specificity of inner speech-specific motor preparation deficits with AVHs. Overall, this study provides evidence in support of atypical inner speech monitoring in schizophrenia.
Fatigue and insomnia, potentially induced by inflammation, are distressing symptoms experienced by colorectal cancer (CRC) survivors. Emerging evidence suggests that besides the nutritional quality and quantity, also the timing, frequency and regularity of dietary intake (chrono-nutrition) could be important for alleviating these symptoms. We investigated longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in CRC survivors. In a prospective cohort of 459 stage I-III CRC survivors, four repeated measurements were performed between 6 weeks and 24 months post-treatment. Chrono-nutrition variables included meal energy contribution, frequency (a maximum of six meals could be reported each day), irregularity and time window (TW) of energetic intake, operationalised based on 7-d dietary records. Outcomes included sleep quality, fatigue and plasma concentrations of inflammatory markers. Longitudinal associations of chrono-nutrition variables with outcomes from 6 weeks until 24 months post-treatment were analysed by confounder-adjusted linear mixed models, including hybrid models to disentangle intra-individual changes from inter-individual differences over time. An hour longer TW of energetic intake between individuals was associated with less fatigue (β: −6·1; 95 % CI (−8·8, −3·3)) and insomnia (β: −4·8; 95 % CI (−7·4, −2·1)). A higher meal frequency of on average 0·6 meals/d between individuals was associated with less fatigue (β: −3·7; 95 % CI (−6·6, −0·8)). An hour increase in TW of energetic intake within individuals was associated with less insomnia (β: −3·0; 95 % CI (−5·2, −0·8)) and inflammation (β: −0·1; 95 % CI (−0·1, 0·0)). Our results suggest that longer TWs of energetic intake and higher meal frequencies may be associated with less fatigue, insomnia and inflammation among CRC survivors. Future studies with larger contrasts in chrono-nutrition variables are needed to confirm these findings.
For successful human-artificial intelligence (AI) collaboration in design, human designers must properly use AI input. Some factors affecting that use are designers’ self-confidence and competence and those variables' impact on reliance on AI. This work studies how designers’ self-confidence before and during teamwork and overall competence are associated with their performance as teammates, measured by AI reliance and overall team score. Results show that designers’ self-confidence and competence have very different impacts on their collaborative performance depending on the accuracy of AI.
Student's t test is valid for statistical inference under the normality assumption or asymptotically. By contrast, although the bootstrap t test was proposed in 1993, it is seldom adopted in medical research. We aim to demonstrate that the bootstrap t test outperforms Student's t test under normality in data. Using random data samples from normal distributions, we evaluated the testing performance, in terms of true-positive rate (TPR) and false-positive rate and diagnostic abilities, in terms of the area under the curve (AUC), of the bootstrap t test and Student's t test. We explore the AUC of both tests with varying sample size and coefficient of variation. We compare the testing outcomes using the COVID-19 serial interval (SI) data in Shenzhen and Hong Kong, China, for demonstration. With fixed TPR, the bootstrap t test maintained the equivalent accuracy in TPR, but significantly improved the true-negative rate from the Student's t test. With varying TPR, the diagnostic ability of bootstrap t test outperformed or equivalently performed as Student's t test in terms of the AUC. The equivalent performances are possible but rarely occur in practice. We find that the bootstrap t test outperforms by successfully detecting the difference in COVID-19 SI, which is defined as the time interval between consecutive transmission generations, due to sex and non-pharmaceutical interventions against the Student's t test. We demonstrated that the bootstrap t test outperforms Student's t test, and it is recommended to replace Student's t test in medical data analysis regardless of sample size.
It is important to understand the temporal trend of the paediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load to estimate the transmission potential of children in schools and communities. We determined the differences in SARS-CoV-2 viral load dynamics between nasopharyngeal samples of infected asymptomatic and symptomatic children. Serial cycle threshold values of SARS-CoV-2 from the nasopharynx of a cohort of infected children were collected for analysis. Among 17 infected children, 10 (58.8%) were symptomatic. Symptomatic children, when compared to asymptomatic children, had higher viral loads (mean cycle threshold on day 7 of illness 28.6 vs. 36.7, P = 0.02). Peak SARS-CoV-2 viral loads occurred around day 2 of illness in infected children. Although we were unable to directly demonstrate infectivity, the detection of significant amount of virus in the upper airway of asymptomatic children suggest that they have the potential to shed and transmit SARS-CoV-2. Our study highlights the importance of contact tracing and screening for SARS-CoV-2 in children with epidemiological risk factors regardless of their symptom status, in order to improve containment of the virus in the community, including educational settings.
There is compelling evidence for gradient effects of household income on school readiness. Potential mechanisms are described, yet the growth curve trajectory of maternal mental health in a child's early life has not been thoroughly investigated. We aimed to examine the relationships between household incomes, maternal mental health trajectories from antenatal to the postnatal period, and school readiness.
Methods
Prospective data from 505 mother–child dyads in a birth cohort in Singapore were used, including household income, repeated measures of maternal mental health from pregnancy to 2-years postpartum, and a range of child behavioural, socio-emotional and cognitive outcomes from 2 to 6 years of age. Antenatal mental health and its trajectory were tested as mediators in the latent growth curve models.
Results
Household income was a robust predictor of antenatal maternal mental health and all child outcomes. Between children from the bottom and top household income quartiles, four dimensions of school readiness skills differed by a range of 0.52 (95% Cl: 0.23, 0.67) to 1.21 s.d. (95% CI: 1.02, 1.40). Thirty-eight percent of pregnant mothers in this cohort were found to have perinatal depressive and anxiety symptoms in the subclinical and clinical ranges. Poorer school readiness skills were found in children of these mothers when compared to those of mothers with little or no symptoms. After adjustment of unmeasured confounding on the indirect effect, antenatal maternal mental health provided a robust mediating path between household income and multiple school readiness outcomes (χ2 126.05, df 63, p < 0.001; RMSEA = 0.031, CFI = 0.980, SRMR = 0.034).
Conclusions
Pregnant mothers with mental health symptoms, particularly those from economically-challenged households, are potential targets for intervention to level the playing field of their children.
Studies have shown that mental health problems during pregnancy have adverse effects on fetal growth. The impact of depressive and anxiety symptoms during pregnancy on the fetus have not yet been examined in Singapore.
Objectives:
To examine the association between mental health problems during the second trimester of pregnancy on the quality of the pregnancy, reflected by birth weight and birth length of the newborn.
Aims:
This study aims to understand the importance of mental health during pregnancy on the development of the child in an Asian population.
Methods:
Preliminary data of a prospective cohort study of pregnant women (GUSTO), were followed from pregnancy onwards. At 26 weeks of the pregnancy, the Edinburgh Postnatal Depression Scale (EPDS), the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI) were administered. Data on birth parameters were collected from medical records.
Results:
Linear regression analyses of preliminary data show negative correlations between depressive symptoms measured with EPDS (n = 1025, P = 0.54), BDI (n = 1012, P = 0.001), and anxiety symptoms measured with STAI (n = 1023, P = 0.002) and birth length (corrected for gestational age and gender). No associations were found for birth weight.
Conclusions:
There is an association between depressive and anxiety symptoms reported at the end of the second trimester of the pregnancy and birth length, but not birth weight, of the newborn. As it is known that fetal length increases mainly in the second trimester, it suggests that stress of the mother influences the development of the fetus during this trimester.
Mental health stigma is a multidimensional concept that encompasses many different themes and definitions. Public stigma is defined as the degree to which the general public holds negative views and discriminates against a specific group.
Objective
To understand the context and correlates of stigma in multi-ethnic Singapore.
Aims
The current study aimed to (i) explore the factor structure of the Depression Stigma Scale and the Social Distance Scale using an exploratory structural equation modelling approach and (ii) examine the correlates of the identified dimensions of stigma in the general population of Singapore.
Methods
Data for the current study came from a larger nation-wide cross-sectional study of mental health literacy conducted in Singapore. All respondents were administered the Personal and Perceived scales of the Depression Stigma Scale and the Social Distance scale to measure personal stigma and social distance respectively.
Results
The findings from the factor analysis revealed that personal stigma formed two distinct dimensions comprising “Weak-not-Sick” and “Dangerous/Unpredictable” components while social distance stigma items loaded strongly into a single factor. Those of Malay and Indian ethnicity, lower education, lower income status and those who were administered the depression and alcohol abuse vignette were significantly associated with higher weak-not-sick scores. Those of Indian ethnicity, 6 years of education and below, lower income status and those who were administered the alcohol abuse vignette were significantly associated with higher dangerous/unpredictable scores.
Conclusion
There is a need for well-planned and culturally relevant anti-stigma campaigns in this population.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Method
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Results
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
Conclusion
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
The second Singapore Mental Health Study (SMHS) – a nationwide, cross-sectional, epidemiological survey - was initiated in 2016 with the intent of tracking the state of mental health of the general population in Singapore. The study employed the same methodology as the first survey initiated in 2010. The SMHS 2016 aimed to (i) establish the 12-month and lifetime prevalence and correlates of major depressive disorder (MDD), dysthymia, bipolar disorder, generalised anxiety disorder (GAD), obsessive compulsive disorder (OCD) and alcohol use disorder (AUD) (which included alcohol abuse and dependence) and (ii) compare the prevalence of these disorders with reference to data from the SMHS 2010.
Methods
Door-to-door household surveys were conducted with adult Singapore residents aged 18 years and above from 2016 to 2018 (n = 6126) which yielded a response rate of 69.0%. The subjects were randomly selected using a disproportionate stratified sampling method and assessed using World Health Organization Composite International Diagnostic Interview version 3.0 (WHO-CIDI 3.0). The diagnoses of lifetime and 12-month selected mental disorders including MDD, dysthymia, bipolar disorder, GAD, OCD, and AUD (alcohol abuse and alcohol dependence), were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
Results
The lifetime prevalence of at least one mood, anxiety or alcohol use disorder was 13.9% in the adult population. MDD had the highest lifetime prevalence (6.3%) followed by alcohol abuse (4.1%). The 12-month prevalence of any DSM-IV mental disorders was 6.5%. OCD had the highest 12-month prevalence (2.9%) followed by MDD (2.3%). Lifetime and 12-month prevalence of mental disorders assessed in SMHS 2016 (13.8% and 6.4%) was significantly higher than that in SMHS 2010 (12.0% and 4.4%). A significant increase was observed in the prevalence of lifetime GAD (0.9% to 1.6%) and alcohol abuse (3.1% to 4.1%). The 12-month prevalence of GAD (0.8% vs. 0.4%) and OCD (2.9% vs. 1.1%) was significantly higher in SMHS 2016 as compared to SMHS 2010.
Conclusions
The high prevalence of OCD and the increase across the two surveys needs to be tackled at a population level both in terms of creating awareness of the disorder and the need for early treatment. Youth emerge as a vulnerable group who are more likely to be associated with mental disorders and thus targeted interventions in this group with a focus on youth friendly and accessible care centres may lead to earlier detection and treatment of mental disorders.
This article analyses Euripides’ mythopoetics in what survives of the first quarter of his fragmentary Hypsipyle: prologue, parodos, and first episode. It examines Euripides’ innovation in joining two myths (the Seven Against Thebes and the story of Hypsipyle and the Argonauts) into one, and the representation of Hypsipyle herself. In her private moments, the thoughts that preoccupy her mind are focused on other-places and other-times, in vivid contrast to the naturalistically presented world of the present where, as a slave, she must interact with men. Euripides uses the language of serving (θɛραπɛύɛιν) and doing a ‘favour’ (χάρις), as well as the word ἐρῆμος (‘lonely,’ ‘deserted’) and homoeophonic language (e.g. Argo and Argos) to indicate that, in helping the Argives, Hypsipyle repeats typologically her hospitality to the Argonauts. There is a circularity in Hypsipyle's story that creates suspense, since by doing a favour for the Argive leader, she is reunited with the sons she bore to Argonauts’ leader, who themselves are sent to find her by their grandfather whom she saved; and by losing the infant in her care (Opheltes, later named Archemorus), she is reunited with her former infants. By the end of Hypsipyle's first conversation with Amphiaraus, Euripides has invented a theme of ‘parallel worlds’ that he will resolve at the play's end.
The Single Ventricle Reconstruction trial randomised neonates with hypoplastic left heart syndrome to a systemic-to-pulmonary-artery shunt strategy. Patients received care according to usual institutional practice. We analysed practice variation at the Stage II surgery to attempt to identify areas for decreased variation and process control improvement.
Methods
Prospectively collected data were available in the Single Ventricle Reconstruction public-use database. Practice variation across 14 centres was described for 397 patients who underwent Stage II surgery. Data are centre-level specific and reported as interquartile ranges across all centres, unless otherwise specified.
Results
Preoperative Stage II median age and weight across centres were 5.4 months (interquartile range 4.9–5.7) and 5.7 kg (5.5–6.1), with 70% performed electively. Most patients had pre-Stage-II cardiac catheterisation (98.5–100%). Digoxin was used by 11/14 centres in 25% of patients (23–31%), and 81% had some oral feeds (68–84%). The majority of the centres (86%) performed a bidirectional Glenn versus hemi-Fontan. Median cardiopulmonary bypass time was 96 minutes (75–113). In aggregate, 26% of patients had deep hypothermic circulatory arrest >10 minutes. In 13/14 centres using deep hypothermic circulatory arrest, 12.5% of patients exceeded 10 minutes (8–32%). Seven centres extubated 5% of patients (2–40) in the operating room. Postoperatively, ICU length of stay was 4.8 days (4.0–5.3) and total length of stay was 7.5 days (6–10).
Conclusions
In the Single Ventricle Reconstruction Trial, practice varied widely among centres for nearly all perioperative factors surrounding Stage II. Further analysis may facilitate establishing best practices by identifying the impact of practice variation.
By contrast to infantile spinal muscular atrophy, which usually links to deletions in the SMN genes, fetal onset motor neuron disease is poorly reported. We collected a series of twelve cases of fetal arthrogryposis (16-31 weeks gestational age) with fetal motor neuron disease and excluded infectious diseases, lysosomal storage disease and neuroaxonal dystrophy. Of these twelve, 3 were thought to be ischemic in nature with microvascular alterations and systemic or central nervous system ischemic injury. The remaining 9 all displayed marked reduction in anterior horn motor neurons. Of these 9, four demonstrated mineralised neurons, four demonstrated either neuronal loss or cavitation in the globus pallidus, and in two, degenerating neurons were detectable in the brainstem or globus pallidus. Specific sequencing of SMN1 was performed in 6 of 9 and was reported as normal. Whole exome sequencing was performed in 4 without definitive diagnosis. We conclude that fetal motor neuron disease can be distinguished from ischemic injury, is morphologically heterogeneous, may affect the globus pallidus and is rarely linked to SMN1 mutations.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.
Methods:
The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.
Results:
The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.
Conclusions:
Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.
The quality of prenatal maternal mental health, from psychological stress and depressive symptoms to anxiety and other nonpsychotic mental disorders, profoundly affects fetal neurodevelopment. Despite the evidence for the influence of positive mental well-being on health, there is, to our knowledge, no research examining the possible effects of positive antenatal mental health on the development of the offspring. Using exploratory bifactor analysis, this prospective study (n = 1,066) demonstrated the feasibility of using common psychiatric screening tools to examine the effect of positive maternal mental health. Antenatal mental health was assessed during 26th week of pregnancy. The effects on offspring were assessed when the child was 12, 18, and 24 months old. Results showed that positive antenatal mental health was uniquely associated with the offspring's cognitive, language and parentally rated competences. This study shows that the effects of positive maternal mental health are likely to be specific and distinct from the sheer absence of symptoms of depression or anxiety.