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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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
A 2018 workshop on the White Mountain Apache Tribe lands in Arizona examined ways to enhance investigations into cultural property crime (CPC) through applications of rapidly evolving methods from archaeological science. CPC (also looting, graverobbing) refers to unauthorized damage, removal, or trafficking in materials possessing blends of communal, aesthetic, and scientific values. The Fort Apache workshop integrated four generally partitioned domains of CPC expertise: (1) theories of perpetrators’ motivations and methods; (2) recommended practice in sustaining public and community opposition to CPC; (3) tactics and strategies for documenting, investigating, and prosecuting CPC; and (4) forensic sedimentology—uses of biophysical sciences to link sediments from implicated persons and objects to crime scenes. Forensic sedimentology served as the touchstone for dialogues among experts in criminology, archaeological sciences, law enforcement, and heritage stewardship. Field visits to CPC crime scenes and workshop deliberations identified pathways toward integrating CPC theory and practice with forensic sedimentology’s potent battery of analytic methods.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Recent discussion and research has pointed to the changing functions of archdeacons within the Church of England as the role has become expanded to combine both the traditional statutory functions with flexible and visionary leadership skills within a changing church. This study draws on data collected in 2009 from 186 active and retired male archdeacons in order to assess the psychological profile established by that time. Compared with the psychological profile of 626 clergymen, male archdeacons were much more likely to prefer the SJ temperament (60 per cent compared with 31 per cent), a temperament ideally suited for effective administration of the statutory functions. As a consequence, preference for intuition was lower among male archdeacons (38 per cent compared with 62 per cent), as was preference for perceiving (9 per cent compared with 32 per cent), qualities core for flexibility and visionary leadership.
High definition video from a towed camera system was used to describe the deep-sea benthic habitats within an elongate depression located at the western margin of Rockall Bank in the Hatton–Rockall Basin. At depths greater than 1190 m, an extensive area (10 km long by 1.5 km wide) of what appeared to be reduced sediments, bacterial mats and flocculent matter indicated possible cold-seep habitat. Plumes of sediment-rich fluid were observed alongside raised elongate features that gave topographic relief to the otherwise flat seafloor. In the deepest section of the depression (1215 m) dense flocculent matter was observed suspended in the water column, in places obscuring the seabed. Away from the bacterial mats, the habitat changed rapidly to sediments dominated by tube-dwelling polychaete worms and then to deep-sea sedimentary habitats more typical for the water depth (sponges and burrowing megafauna in areas of gentle slopes, and coral gardens on steeper slopes).
The partial skull of a lion from Natodomeri, northwest Kenya is described. The Natodomeri sites are correlated with Member I of the Kibish Formation, dated to between 195 ka and ca. 205 ka. The skull is remarkable for its very great size, equivalent to the largest cave lions (Panthera spelaea [Goldfuss, 1810]) of Pleistocene Eurasia and much larger than any previously known lion from Africa, living or fossil. We hypothesize that this individual represents a previously unknown population or subspecies of lion present in the late Middle and Late Pleistocene of eastern Africa rather than being an indication of climate-driven size increase in lions of that time. This raises questions regarding the extent of our understanding of the pattern and causes of lion evolution in the Late Pleistocene.
This volume explores the diverse ways in which the Book of Psalms profoundly influenced medieval English literature and culture, through a series of connected overviews and special case studies. A number of recent studies have highlighted the Psalter's reception in Early Modern English (and wider European culture), while three monographs by contributors to this volume offer focused studies of the Psalter in individual periods of medieval English literature: Jane Toswell's The Anglo-Saxon Psalter, Annie Sutherland's English Psalms in the Middle Ages: 1300–1450and Michael P. Kuczynski's Prophetic Song: The Psalms as Moral Discourse in Late Medieval England. But as yet no single study has sought to offer a comprehensive survey of English responses to the Book of Psalms from the conversion of the Anglo-Saxons to the cusp of the Reformation. By bringing work by experts on both Old and Middle English literature into dialogue, this volume breaks down the traditional disciplinary binaries of pre- and post-Conquest English, late medieval and Early Modern, as well as emphasizing the complex and fascinating relationship between Latin and the vernacular languages of England. In order to encourage the reader to make connections both across and within these various periods and languages, the book is arranged thematically rather than chronologically, with three sections designed to offer a variety of perspectives on the Psalms and medieval English literature.
Section I (Translation) focuses on the development of English psalm translation from its beginnings in Old English interlinear glosses in Latin psalters through the multilingual psalters of the Anglo-Norman era to the stand-alone vernacular psalters of the fourteenth and fifteenth centuries. Concentrating on the Psalter as a book, this section charts the emergence of English as a scriptural language in the medieval period.
Section II (Adaptation) considers how medieval English prose and verse writers draw on the Psalms as a source of literary inspiration. Demonstrating how the Psalter could be adapted and redeployed within the context of medieval worship and prayer, it begins with a discussion of the first adaptation of the entire Psalter into English verse, before turning to a consideration of the development of the abbreviated psalter tradition. This section also addresses the wider influence of psalmic language and imagery on Old English praise and lament poetry, and on Middle English alliterative verse.
The Book of Psalms had a profound impact on English literature from the Anglo-Saxon to the late medieval period. This collection examines the various ways in which they shaped medieval English thoughtand contributed to the emergence of an English literary canon. It brings into dialogue experts on both Old and Middle English literature, thus breaking down the traditional disciplinary binaries of both pre- and post-Conquest English and late medieval and Early Modern, as well as emphasizing the complex and fascinating relationship between Latin and the vernacular languages of England. Its three main themes, translation, adaptation and voice, enable a rich variety of perspectives on the Psalms and medieval English literature to emerge.
Tamara Atkin is Senior Lecturer in Late Medieval and Early Renaissance Literature at Queen Mary University of London; Francis Leneghan is Associate Professor of Old English at The University of Oxford and a Fellow of St Cross College, Oxford.
Contributors: Daniel Anlezark, Mark Faulkner, Vincent Gillespie, Michael P. Kuczynski, David Lawton, Francis Leneghan, Jane Roberts, Mike Rodman Jones, Elizabeth Solopova, Lynn Staley, AnnieSutherland, Jane Toswell, Katherine Zieman.