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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
The aim of this study was to understand how and why relational welfare works to support young people who are not in employment, education or training (NEET). It builds on research discussing the limitations of work-first and human capital strategies in social policy while responding to calls for theory-driven insights into initiatives that move beyond employability and rapid employment. The material for this realist evaluation includes programme documents, fieldnotes and 75 interviews with practitioners and participants in community-based multicomponent initiatives delivered by Swedish municipalities. These data were scrutinised against programme theories while integrating literature on relational welfare as underpinned by co-creation and capability approaches. The results illustrate how flexible, challenging and coordinated programming strengthen beings and doings of young people in NEET situations while improving their wellbeing by overcoming isolation and forming a future orientation. The study provides guidance for supporting NEET-situated young people through a relational approach to welfare. It also offers a model against which local initiatives provided to a youth group high on the policy agenda can be mapped.
Guided by Pierre Bourdieu’s theoretical approaches of symbolic capital and symbolic violence, this article examines the everyday mechanisms of ‘otherising’ language practices in schools that reinforce racism against marginalised youths in Sweden. The empirical material is based on focus group discussions and individual in-depth interviews with youths with migrant backgrounds in Sweden. The stories told by the participants in this study indicate how young people with immigrant backgrounds are discursively racialised and otherised as a group that does not belong to Swedish society, through the articulation of negative opinions, attitudes, and ideologies as part of established colonial discourses. It is argued that the marginalisation of migrants in Sweden, which is a consequence of social policy, has even resulted in utilisation of a marginalised language — one that deviates from the majority language in several different ways.
A distinguishing feature of the bi-stable wake is that the wake persists in either of two preferred states for a sufficiently long time. Aiming to understand the persistence mechanism, this paper numerically investigates the airwake characteristics of the Chalmers ship model (CSM) using large eddy simulation with a wall-adapting local-eddy viscosity model and is complemented by experimental testings for validations. There are two cases of interest: (i) the baseline CSM with a sharp-edged superstructure front that induces massive boundary layer separation; (ii) the front-rounded (FR) CSM with suppressed flow separation. During a characteristic time ($t^*$) of 1142 (26.5 s), the baseline case has a frequently switching wake, whereas the FR wake maintains a stable asymmetric structure with only one switch attempt. To understand the different wake behaviours, the study starts by analysing wake flow structures, vortex cores and the wake dynamics, followed by investigating the instantaneous flow physics. Results suggest that the baseline wake has a weak bi-stable pattern, whereas the FR wake behaves similarly to a reflectional symmetry breaking state of a potential bi-stable wake. The wake switching is found to be driven by the tilting of (vertical-oriented) $z$-vorticity sheets from either side of the base toward the centre. This tilting behaviour is subjected to the high-magnitude vorticity that sheds from the upstream flow separation at the front sharp edges. With the sharp edges rounded in the FR case, the upstream vorticity is mitigated and the tilting effect is significantly reduced, leading to a more stable wake structure. The reasoning provided in the paper potentially explains the persistence mechanism of the bi-stable wake.
Assess effects on waist circumference from diet with or without cereal grains and with or without long-term physical exercise.
Background:
Elevated waist circumference is an indicator of increased abdominal fat storage and is accordingly associated with increased cardiovascular mortality. This is likely due to the association between lifestyle-induced changes in waist circumference and cardiovascular risk factors. Reductions in waist circumference may be facilitated by diet without cereal grains combined with long-term physical exercise.
Methods:
Two-year randomised controlled trial with factorial trial design in individuals at increased risk of cardiovascular disease with increased waist circumference. Participants were allocated diet based on current Swedish dietary guidelines with or without cereal grains (baseline diet information supported by monthly group sessions) and with or without physical exercise (pedometers and two initial months of weekly structured exercise followed by written prescription of physical activity) or control group. The primary outcome was the change in waist circumference.
Findings:
The greatest mean intervention group difference in the change in waist circumference among the 73 participants (47 women and 26 men aged 23–79 years) was at one year between participants allocated a diet without cereal grains and no exercise and participants allocated a diet with cereal grains and no exercise [M = −5.3 cm and −0.9 cm, respectively; mean difference = 4.4 cm, 4.0%, 95% CI (0.0%, 8.0%), P = 0.051, Cohen’s d = 0.75]. All group comparisons in the change in waist circumference were non-significant despite the greatest group difference being more than double that estimated in the pre-study power calculation. The non-significance was likely caused by too few participants and a greater than expected variability in the change in waist circumference. The greatest mean intervention group difference strengthens the possibility that dietary exclusion of cereal grains could be related to greater reduction in waist circumference.
Dysmyelination could be part of the pathophysiology of schizophrenia spectrum (SCZ) and bipolar disorders (BPD), yet few studies have examined myelination of the cerebral cortex. The ratio of T1- and T2-weighted magnetic resonance images (MRI) correlates with intracortical myelin. We investigated the T1w/T2w-ratio and its age trajectories in patients and healthy controls (CTR) and explored associations with antipsychotic medication use and psychotic symptoms.
Methods
Patients with SCZ (n = 64; mean age = 30.4 years, s.d. = 9.8), BPD (n = 91; mean age 31.0 years, s.d. = 10.2), and CTR (n = 155; mean age = 31.9 years, s.d. = 9.1) who participated in the TOP study (NORMENT, University of Oslo, Norway) were clinically assessed and scanned using a General Electric 3 T MRI system. T1w/T2w-ratio images were computed using an optimized pipeline with intensity normalization and field inhomogeneity correction. Vertex-wise regression models were used to compare groups and examine group × age interactions. In regions showing significant differences, we explored associations with antipsychotic medication use and psychotic symptoms.
Results
No main effect of diagnosis was found. However, age slopes of the T1w/T2w-ratio differed significantly between SCZ and CTR, predominantly in frontal and temporal lobe regions: Lower T1w/T2w-ratio values with higher age were found in CTR, but not in SCZ. Follow-up analyses revealed a more positive age slope in patients who were using antipsychotics and patients using higher chlorpromazine-equivalent doses.
Conclusions
While we found no evidence of reduced intracortical myelin in SCZ or BPD relative to CTR, different regional age trajectories in SCZ may suggest a promyelinating effect of antipsychotic medication.
The chapter introduces the material used for the study, that is, the Old Bailey Corpus (OBC) as well as the Old Bailey Online resource and the Proceedings that the OBC has been based on. The analytical frameworks adopted are also discussed, comprising the corpuslinguistic approach, and the historical sociopragmatics, the language variation and change, and the grammaticalization and pragmatic-semantic change frameworks. Attention is also paid to the late modern courtroom and to the issues of relevance to the study of past spoken interaction based on written records.
The chapter details how the activity type of the courtroom trial and the specific speaker roles, that is, judges, lawyers, defendants, victims, and witnesses, influence the use of intensifiers. Speaker roles, and thus the persuasive aims typical of them, have been found to be more important determiners than gender and social class. Witness and victims are typically found to amplify aspects such as reliability, probability, and blamelessness. Witnesses also amplify the good character of defedants, while the latter themselves maximize their innocence. Lawyers use intensifiers, in particular amplifiers, to elicit the strongest possible answers from witnesses. Lawyers’ most persuasive uses are found in the adversarial legal speeches, where they boost both their own points and their denials of the other side’s arguments.
This chapter provides an inventory of maximizer types and tokens attested in the data. Altogether 23 maximizers, covering both full and zero forms, were included in the study, totalling 9,488 relevant tokens; the four top-frequency items comprise perfectly, too, most and entirely. The diachronic distribution of the top seven maximizers across the period studied is discussed, with comparisons made between usage in the Late Modern English and the modern BNC trials data. The maximizers prove to be the only category of intensifiers increasing across the period studied; boosters and downtoners show declining rates of use. The semantic input domains of the maximizers are discussed, and the targets of intensification and the collocational features in usage patterns presented. Maximizers mainly modify adjectives and less so adverbs and verbs. Within the category of maximized adjectives, the category of Human Propensity dominates; within the maximized category of verbs, the material process types cover most of the uses. Finally, the collocates and semantic prosodies of the top seven maximizers are described, with attention paid to the situation-specific and relatively fixed uses.
In this theoretical background chapter, intensifiers are defined as degree-indicating devices and distinguished from items indicating similar and partly overlapping concepts such as quantification, emphasis, focus, and modality. They are subclassified into the categories of amplifiers (maximizers, boosters) and downtoners (moderators, diminishers, minimizers), with different semantic characteristics and effects. Formally, they are restricted to one-word adverbs, both with and without the -ly suffix. Their typical collocational associations and syntactic behaviour regarding preferred modified targets is dealt with. Their pragmatic distributions in different situational contexts is briefly touched on
This is the main methodology and first-results chapter. It opens with an introduction to the lexeme-based approach used for the investigation, contrasting this to previous, variationist approaches. The chapter proceeds to explain the data retrieval and screening processes and presents an overview of the data, the nearly 65,000 intensifier tokens found in the corpus, across the three main categories (maximizers, boosters, downtoners), and the descriptive results across time for the most frequent items. The word counts of the different sociopragmatic groups of speakers (divided by speakers’ role in the courtroom, gender and social class) are introduced, as well as the diachronic distribution of intensifiers across the genders and social classes. Results are presented within the descriptive statistics framework, but the chapter also briefly introduces the regression model, or the inferential, multivariate statistical method to be used in Chapters 8–11 to disentangle the complex interplay of the sociopragmatic variables of speakers on the use of intensifiers.
The boosters found in the Old Bailey Corpus (1720–1913) are documented in this chapter, with regard to their overall frequency distributions and usage patterns. This includes an overview of the entire inventory of 44 types and 47,613 tokens, which makes it the largest intensifier group in the data. Very is found to dominate the data, followed by far less frequent so and greatly as well as many fairly low-frequency items. Semantically, boosters are subdivided into originally quantitative (denoting amount: greatly, extent: widely) and qualitative types (e.g., denoting truth: very, perception: strikingly or evaluation: badly). Formally, the two most frequent types are unmarked adverbs (very, so); two other boosters prefer the suffixless form to a large extent (great, wide). The targets modified by boosters are mostly adjectives, followed by adverbs, while verbs and prepositional phrases are rare.
This chapter is devoted to downtoners, namely moderators, diminishers and minimizers, with the 19 attested types amounting to 7,874 examples. The dominant type a little constitutes 66 per cent of the occurrences and is followed by hardly with 13 per cent. The distribution of the five most frequent downtoners across the period studied is discussed, and compared to the BNC trials data. The decline in the use of diminisher a little accounts for the overall decline in the use of downtoners in the OBC data. The source terms of downtoners display a more varied spectrum of semantic shades than maximizers and boosters. There is also a greater variety of target categories than attested for boosters and maximizers: the otherwise most frequent targets adjectives are here outranked by prepositional phrases and verbs, with the latter standing out as the specialty of downtoners compared to all other intensifiers. They predominantly modify verbs of the material and mental process types; in the semantic classes of downtoned adjectives, the category of human propensity dominates. As for collocational profiles, for instance a little dominates in collocations with after, before and more.