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There are many structural problems facing the UK at present, from a weakened National Health Service to deeply ingrained inequality. These challenges extend through society to clinical practice and have an impact on current mental health research, which was in a perilous state even before the coronavirus pandemic hit. In this editorial, a group of psychiatric researchers who currently sit on the Academic Faculty of the Royal College of Psychiatrists and represent the breadth of research in mental health from across the UK discuss the challenges faced in academic mental health research. They reflect on the need for additional investment in the specialty and ask whether this is a turning point for the future of mental health research.
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.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
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.
Results
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.
Conclusions
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.
Ethnohistoric accounts indicate that the people of Australia's Channel Country engaged in activities rarely recorded elsewhere on the continent, including food storage, aquaculture and possible cultivation, yet there has been little archaeological fieldwork to verify these accounts. Here, the authors report on a collaborative research project initiated by the Mithaka people addressing this lack of archaeological investigation. The results show that Mithaka Country has a substantial and diverse archaeological record, including numerous large stone quarries, multiple ritual structures and substantial dwellings. Our archaeological research revealed unknown aspects, such as the scale of Mithaka quarrying, which could stimulate re-evaluation of Aboriginal socio-economic systems in parts of ancient Australia.
James VI and I was the first king personally to act as a judge in both Scotland and England. He was also the last king to sit as a judge in either country. Although James did not sit as a judge frequently, he did so on several occasions. James’s ideas about the king as a judge were disseminated in his speeches and printed works. This material has not been used by historians, despite the importance contemporaries attached to some of James’s appearances as a judge. This paper investigates James’s judicial role. It compares both James’s judicial activity in his two realms and James’s ideas of the king as judge to his practice of judging.
The distribution of genetic diversity in invasive plant populations can have important management implications. Alligatorweed [Alternanthera philoxeroides (Mart.) Griseb.] was introduced into the United States around 1900 and has since spread throughout much of the southern United States and California. A successful biological control program was initiated in the late 1960s that reduced A. philoxeroides in the southern United States, although control has varied geographically. The degree to which variation among genotypes may be responsible for variation in control efficacy has not been well studied due to a lack of genetic data. We sampled 373 plants from 90 sites across the United States and genotyped all samples at three chloroplast regions to help inform future management efforts. Consistent with clonal spread, there was high differentiation between sites, yet we found six haplotypes and high haplotype diversity (mean h = 0.48) across states, suggesting this plant has been introduced multiple times. Two of the haplotypes correspond to previously described biotypes that differ in their susceptibility to herbicides and herbivory. The geographic distribution of the three common haplotypes varied by latitude and longitude, while the other haplotypes were widespread or localized to one or a few sites. All the haplotypes we screened are hexaploid (6n = 102), which may enhance biological control. Future studies can use these genetic data to determine whether genotypes differ in their invasiveness or respond differently to control measures. Some states, for instance, have mainly a single haplotype that may respond more uniformly to a single control strategy, whereas other states may require a variety of control strategies. These data will also provide the basis for identifying the source regions in South America, which may lead to the discovery of new biological control agents more closely matched to particular genotypes.
If law and legal systems may be said to grow and develop in a way analogous to natural organisms, the shape into which they grow is not predetermined, but is fashioned by the choices and actions of individuals who present questions for lawyers to resolve, and by the intellectual choices made by lawyers, lawmakers, and judges, when faced with how to deal with new problems. In recent years, historians have become increasingly interested in exploring how legal development has been shaped by networks of particular individuals and groups, and by the connections are made between different ideas and concepts. Whether law changes as a result of litigation initiated in the courtroom or through legislation, the form which it takes may be shaped by the groups of people initiating the change, by the networks of legal intermediaries – whether lawyers or legislators – who are tasked with implementing it, and by the wider community networks with whose expectations the law must cohere.
Scholars of comparative constitution-making and direct democracy agree that economic conditions affect public support for constitutional reform but disagree as to how. Prospect theory suggests both approaches may be correct, depending on the political and economic context in which voters operate. Fourteen states periodically ask their citizens whether to call a state constitutional convention, making this the oldest form of direct democracy in the United States. We test our theory in preelection polls in two of these states and a survey experiment. According to the results, negative perceptions of economic and government performance increase support for conventions when voters view them as opportunities to correct problems. On the other hand, if a convention represents a chance to improve on an acceptable status quo, voters with positive performance evaluations become more supportive. Our findings contribute to the heuristics literature and inform normative debates over direct democracy and popular constitutionalism.
Network and Connections in Legal History examines networks of lawyers, legislators and litigators, and how they shaped legal development in Britain and the world. It explores how particular networks of lawyers - from Scotland to East Florida and India - shaped the culture of the forums in which they operated, and how personal connections could be crucial in pressuring the legislature to institute reform - as with twentieth century feminist campaigns. It explores the transmission of legal ideas; what happened to those ideas was not predetermined, but when new connections were made, they could assume a new life. In some cases, new thinkers made intellectual connections not previously conceived, in others it was the new purposes to which ideas and practices were applied which made them adapt. This book shows how networks and connections between people and places have shaped the way that legal ideas and practices are transmitted across time and space.
Bulachite specimens from Cap Garonne, France, comprise two intimately mixed hydrated aluminium arsenate minerals with the same Al:As ratio of 2:1 and with different water contents. The crystal structures of both minerals have been solved using data from low-dose electron diffraction tomography combined with synchrotron powder X-ray diffraction. One of the minerals has the same powder X-ray diffraction pattern (PXRD) as for published bulachite. It has orthorhombic symmetry, space group Pnma with unit-cell parameters a = 15.3994(3), b = 17.6598(3), c = 7.8083(1) Å and Z = 4, with the formula [Al6(AsO4)3(OH)9(H2O)4]⋅2H2O. The second mineral is a higher hydrate with composition [Al6(AsO4)3(OH)9(H2O)4]⋅8H2O. It has the same Pnma space group and unit-cell parameters a = 19.855(4), b = 17.6933(11) and c = 7.7799(5) Å i.e. almost the same b and c parameters but a much larger a parameter. The structures are based on polyhedral layers, parallel to (100), of composition [Al6(AsO4)3(OH)9(H2O)4] and with H-bonded H2O between the layers. The layers contain [001] spiral chains of edge-shared octahedra, decorated with corner connected AsO4 tetrahedra that are the same as in the mineral liskeardite. The spiral chains are joined together by octahedral edge-sharing to form layers parallel to (100). Synchrotron PXRD patterns collected at different temperatures during heating of the specimen show that the higher-hydrate mineral starts transforming to bulachite when heated to 50°C, and the transformation is complete between 75 and 100°C.
As uncertainty remains about whether clinical response influences cognitive function after electroconvulsive therapy (ECT) for depression, we examined the effect of remission status on cognitive function in depressed patients 4 months after a course of ECT.
Method
A secondary analysis was undertaken on participants completing a randomised controlled trial of ketamine augmentation of ECT for depression who were categorised by remission status (MADRS ⩽10 v. >10) 4 months after ECT. Cognition was assessed with self-rated memory and neuropsychological tests of anterograde verbal and visual memory, autobiographical memory, verbal fluency and working memory. Patients were assessed through the study, healthy controls on a single occasion, and compared using analysis of variance.
Results
At 4-month follow-up, remitted patients (N = 18) had a mean MADRS depression score of 3.8 (95% CI 2.2–5.4) compared with 27.2 (23.0–31.5) in non-remitted patients (N = 19), with no significant baseline differences between the two groups. Patients were impaired on all cognitive measures at baseline. There was no deterioration, with some measures improving, 4-months after ECT, at which time remitted patients had significantly improved self-rated memory, anterograde verbal memory and category verbal fluency compared with those remaining depressed. Self-rated memory correlated with category fluency and autobiographical memory at follow-up.
Conclusions
We found no evidence of persistent impairment of cognition after ECT. Achieving remission improved subjective memory and verbal memory recall, but other aspects of cognitive function were not influenced by remission status. Self-rated memory may be useful to monitor the effects of ECT on longer-term memory.
We study the term in the eddy energy budget of continuously stratified quasigeostrophic turbulence that is responsible for energy extraction by eddies from the background mean flow. This term is a quadratic form, and we derive Euler–Lagrange equations describing its eigenfunctions and eigenvalues, the former being orthogonal in the energy inner product and the latter being real. The eigenvalues correspond to the instantaneous energy growth rate of the associated eigenfunction. We find analytical solutions in the Eady problem. We formulate a spectral method for computing eigenfunctions and eigenvalues, and compute solutions in Phillips-type and Charney-type problems. In all problems, instantaneous growth is possible at all horizontal scales in both inviscid problems and in problems with linear Ekman friction. We conjecture that transient growth at small scales is matched by linear transfer to decaying modes with the same horizontal structure, and we provide simulations supporting the plausibility of this hypothesis. In Charney-type problems, where the linear problem has exponentially growing modes at small scales, we expect net energy extraction from the mean flow to be unavoidable, with an associated nonlinear transfer of energy to dissipation.
The Earth is a powerful organic chemist, transforming vast quantities of carbon through complex processes, leading to diverse suites of products that include the fossil fuels upon which modern societies depend. When exploring how the Earth operates as an organic chemist, it is tempting to turn to how organic reactions are traditionally studied in chemistry labs. While highly informative, especially in terms of insights gained into reaction mechanisms, this approach can also be a source of frustration, as many of the reactants and conditions employed in chemistry labs have few or no parallels to geologic processes. The primary goal of this chapter is to provide examples of predicting thermodynamic influences and using the predictions to design experiments that reveal the mechanisms of how reactions occur at the elevated temperatures and pressures encountered in the Earth. This work is ongoing, and we hope this chapter will inspire numerous and diverse experimental and theoretical advances in hydrothermal organic geochemistry.