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Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.
Using data from 9,421 individuals aged 8–21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation.
Externalizing was heritable (h2 = 0.46, p = 1 × 10−6), but not anxious-misery (h2 = 0.09, p = 0.183), fear (h2 = 0.04, p = 0.337), psychosis-spectrum (h2 = 0.00, p = 0.494), or general psychopathology (h2 = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρg = −0.412, p = 0.004), verbal reasoning (ρg = −0.485, p = 0.001), spatial reasoning (ρg = −0.426, p = 0.010), motor speed (ρg = 0.659, p = 1x10−4), verbal knowledge (ρg = −0.314, p = 0.002), and general cognitive ability (g)(ρg = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γg = −0.146, p = 0.004) and increasing environmental variance (γe = 0.059, p = 0.009) on externalizing.
Cognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults.
This paper presents a detailed investigation of the role played by the wave steepness in connection with the statistical properties of the surface elevation and fluid kinematics in irregular, directionally spread, deep-water wave fields initially given by a JONSWAP spectrum. Using ensembles of large wave fields obtained from fully nonlinear simulations, we first consider the statistical properties of the surface elevation. In that connection we determine the probability density functions (PDFs) of the surface and crest elevations for wave fields of relatively small to unprecedentedly large steepness, and compare them with theoretical results from the literature in order to establish the latter's accuracy. We then consider certain statistical aspects of the fluid kinematics found at the surface and of the fluid kinematics accompanying large crests, which to our knowledge marks the first investigation of these properties in the literature. We first determine the PDFs of the horizontal fluid velocities and accelerations as well as the vertical fluid acceleration at the surface. Next, we investigate the joint PDF of the surface elevation and each of the velocities and accelerations at the surface, and use it to determine the surface elevations for which the velocities and accelerations at the surface are large. We then present an analysis of the largest fluid velocities and accelerations found in the vicinity of large crests, and compute the PDFs of these quantities. Finally, we consider the PDFs of the location at which the largest velocities and accelerations occur relative to the crest.
After remission, antidepressants are often taken long term to prevent depressive relapse or recurrence. Whether psychological interventions can be a viable alternative or addition to antidepressants remains unclear.
To compare the effectiveness of psychological interventions as an alternative (including delivered when tapering antidepressants) or addition to antidepressants alone for preventing depressive relapse.
Embase, PubMed, the Cochrane Library and PsycINFO were searched from inception until 13 October 2019. Randomised controlled trials (RCTs) with previously depressed patients in (partial) remission where preventive psychological interventions with or without antidepressants (including tapering) were compared with antidepressant control were included. Data were extracted independently from published trials. A random-effects meta-analysis on time to relapse (hazard ratio, HR) and risk of relapse (risk ratio, RR) at the last point of follow-up was conducted. PROSPERO ID: CRD42017055301.
Among 11 included trials (n = 1559), we did not observe an increased risk of relapse for participants receiving a psychological intervention while tapering antidepressants versus antidepressants alone (RR = 1.02, 95% CI 0.84–1.25; P = 0.85). Psychological interventions added to antidepressants significantly reduced the risk of relapse (RR = 0.85, 95% CI 0.74–0.97; P = 0.01) compared with antidepressants alone.
This study found no evidence to suggest that adding a psychological intervention to tapering increases the risk of relapse when compared with antidepressants alone. Adding a psychological intervention to antidepressant use reduces relapse risk significantly versus antidepressants alone. As neither strategy is routinely implemented these findings are relevant for patients, clinicians and guideline developers.
Coalition governance divides policy-making influence across multiple parties, making it challenging for voters to accurately attribute responsibility for outcomes. We argue that many voters overcome this challenge by inferring parties’ policy-making influence using a simple heuristic model that integrates a number of readily available and cheaply obtained informational cues about parties (e.g., their roles in government and legislative seat shares)—while ignoring other cues that, while predictive of real-world influence, are not suitable for heuristic inference (e.g., median party status and bargaining power). Using original data from seven surveys in five countries, we show that voters’ attributions of parties’ policy-making influence are consistent with our proposed inferential strategy. Our findings suggest that while voters certainly have blind spots that cause them to misattribute policy responsibility in some situations, their attributions are generally sensible and consistent with the academic research on multiparty policy making.
Reconstructions of prehistoric vegetation composition help establish natural baselines, variability, and trajectories of forest dynamics before and during the emergence of intensive anthropogenic land use. Pollen–vegetation models (PVMs) enable such reconstructions from fossil pollen assemblages using process-based representations of taxon-specific pollen production and dispersal. However, several PVMs and variants now exist, and the sensitivity of vegetation inferences to PVM selection, variant, and calibration domain is poorly understood. Here, we compare the reconstructions, parameter estimates, and structure of a Bayesian hierarchical PVM, STEPPS, both to observations and to REVEALS, a widely used PVM, for the pre–Euro-American settlement-era vegetation in the northeastern United States (NEUS). We also compare NEUS-based STEPPS parameter estimates to those for the upper midwestern United States (UMW). Both PVMs predict the observed macroscale patterns of vegetation composition in the NEUS; however, reconstructions of minor taxa are less accurate and predictions for some taxa differ between PVMs. These differences can be attributed to intermodel differences in structure and parameter estimates. Estimates of pollen productivity from STEPPS broadly agree with estimates produced for use in REVEALS, while comparison between pollen dispersal parameter estimates shows no significant relationship. STEPPS parameter estimates are similar between the UMW and NEUS, suggesting that STEPPS parameter estimates are transferable between floristically similar regions and scales.
Visualisation of ideas and emergent designs is an essential ingredient in design practice. Sketching and CAD represent two widely used visualisation tools, each with complementary affordances that dictate their typical use during the design process. Sketching has affordances of fast and fluent visualisation whereas CAD affords easy modification of detailed designs. This paper proposes a hybrid tool, Digital Sketch Modelling, investigating the extent to which it can deliver complementary affordances of both sketching to CAD. Analysis of diary entries made by 62 postgraduate designers using sketching, digital sketch modelling and CAD within a design project forms the basis of the study. Results illustrate how digital sketching over crude 3d digital models, combined with benefits of digital image editing software enhance affordance for easy visualisation of ideas. Concurrently, the level of software used in Digital Sketch modelling led to fewer concerns over the level of difficulty to modify designs, enhancing the affordance for easy modification. As such we conclude Digital Sketch Modelling does combine affordances indicating its potential benefit in use between sketching and CAD.
Physical prototyping is critical activity in the produce development process, but the cost and time required to produce prototypes hinders it use in the design process. Hybrid prototyping through coupling LEGO and FDM printing is presented as an approach to address these issues. After establishing the separate design rules for FDM printing and LEGO, this paper created new set of rules called Design for Fabrication (DfF) for hybrid prototyping. These cover the three main considerations (Technical, Process, and Design) that the designer and process planning must include to practically implement LEGO and FDM hybrid prototyping. The DfF rules were considered in a prototype of a computer mouse. While the fabrication time was not reduced as expected, it showed that the rules could be practically implemented in a real-world example. Additional considerations were identified that are to be included in the DfF rules.
Further work is required to realise the predicted step-change reduction in fabrication time. The first approach is to leverage multiple printers to parallelise the printing. The second is to reduce fidelity while maintaining high fidelity in key regions of interest.
Cognitive impairment is a core feature of psychotic disorders, but the profile of impairment across adulthood, particularly in African-American populations, remains unclear.
Using cross-sectional data from a case–control study of African-American adults with affective (n = 59) and nonaffective (n = 68) psychotic disorders, we examined cognitive functioning between early and middle adulthood (ages 20–60) on measures of general cognitive ability, language, abstract reasoning, processing speed, executive function, verbal memory, and working memory.
Both affective and nonaffective psychosis patients showed substantial and widespread cognitive impairments. However, comparison of cognitive functioning between controls and psychosis groups throughout early (ages 20–40) and middle (ages 40–60) adulthood also revealed age-associated group differences. During early adulthood, the nonaffective psychosis group showed increasing impairments with age on measures of general cognitive ability and executive function, while the affective psychosis group showed increasing impairment on a measure of language ability. Impairments on other cognitive measures remained mostly stable, although decreasing impairments on measures of processing speed, memory and working memory were also observed.
These findings suggest similarities, but also differences in the profile of cognitive dysfunction in adults with affective and nonaffective psychotic disorders. Both affective and nonaffective patients showed substantial and relatively stable impairments across adulthood. The nonaffective group also showed increasing impairments with age in general and executive functions, and the affective group showed an increasing impairment in verbal functions, possibly suggesting different underlying etiopathogenic mechanisms.
The aim of this study was to investigate how innovation is defined with respect to new medicines.
MEDLINE, Embase, and EconLit databases were searched for articles published between January 1, 2010 and May 25, 2016 that described a relevant definition of innovation. Identified definitions were analyzed by mapping the concepts described onto a set of ten dimensions of innovation.
In total, thirty-six articles were included, and described a total of twenty-five different definitions of innovation. The most commonly occurring dimension was therapeutic benefit, with novelty and the availability of existing treatments the second and third most common dimensions. Overall, there was little agreement in the published literature on what characteristics of new medicines constitute rewardable innovation.
Alignment across countries and among regulators, health technology assessment bodies and payers would help manufacturers define research policies that can drive innovation, but may be challenging, as judgements about what aspects of innovation should be rewarded vary among stakeholders, and depend on political and societal factors.
Global social indicators have become a core point of interest of scholarship in law and other social sciences. The term ‘legitimacy’ is occasionally mentioned in this literature but without in-depth discussion. This paper aims to fill this gap by way of exploring the relationship between global social indicators and the concept of legitimacy. The crucial issue of such indicators is that, being drafted in a general fashion and based on a quantitative metric, they can be regarded as somehow ‘law-like’, thus raising questions about their legitimacy. This paper addresses these issues at both the general level of social theory and the operation of indicators in action.
Managerial devices are rapidly developing as a means for driving the legal performance of organisations, including those of states and corporations. This paper explores the managerial rationality underpinning global legal indicators, and the constraints they convey on institutional behaviour. In particular, it argues that indicators are better understood as part of a system of management control and distributed governance, which is steadily eroding state-centred forms of authority, including state law. In this context, legitimacy and reactivity are contingent to their cycle of production and implementation, which is fourfold: data-collecting, benchmarking, auditing and allocating incentives. Each process is meant to generate respectively subjectification, self-knowledge by comparison, accountability and stimulus for action. Indicators with higher degrees of legitimacy become entrenched in institutional practices and legal decision-making processes. The paper concludes that regulatory spaces where indicators unfold need critical and political scrutiny to expose their pernicious effects, undesirable uses and inevitable misuses.
The present paper argues that the Doing Business indicators, their legitimacy (their ability to be defended through some logic or justification arising from standards) and the wider notions of legitimacy (the standards) that they promulgate are all best understood as social or, better still, ‘econosociolegal’ constructions. It tracks their, primarily post-financial crisis, re-co-construction within and beyond the World Bank from servant of the private sector and discipliner of states to something approaching social champion. But it warns that the perceptions of legitimacy that have been generated by those indicators may well linger.
Many different indicators are used to monitor poverty and poverty-related deprivations. Two kinds of legitimacy worries may arise about any such indicator: one regarding its reliability as a measure of progress and another regarding the uses to which it is being put. This essay will touch upon both worries, beginning with the latter.