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Sleep disturbances are important symptoms to monitor in people with bipolar disorder (BD) but the precise longitudinal relationships between sleep and mood remain unclear. We aimed to examine associations between stable and dynamic aspects of sleep and mood in people with BD, and assess individual differences in the strength of these associations.
Participants (N = 649) with BD-I (N = 400) and BD-II (N = 249) provided weekly self-reports of insomnia, depression and (hypo)mania symptoms using the True Colours online monitoring tool for 21 months. Dynamic structural equation models were used to examine the interplay between weekly reports of insomnia and mood. The effects of clinical and demographic characteristics on associations were also assessed.
Increased variability in insomnia symptoms was associated with increased mood variability. In the sample as a whole, we found strong evidence of bidirectional relationships between insomnia and depressive symptoms but only weak support for bidirectional relationships between insomnia and (hypo)manic symptoms. We found substantial variability between participants in the strength of prospective associations between insomnia and mood, which depended on age, gender, bipolar subtype, and a history of rapid cycling.
Our results highlight the importance of monitoring sleep in people with BD. However, researchers and clinicians investigating the association between sleep and mood should consider subgroup differences in this relationship. Advances in digital technology mean that intensive longitudinal data on sleep and mood are becoming increasingly available. Novel methods to analyse these data present an exciting opportunity for furthering our understanding of BD.
As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring.
The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed.
Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial’s DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report.
It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
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.
Much evidence – textual, material and documentary – points to slavery in the early and medieval Islamic Middle East (c. 600-1000 CE) as a social fact, persistent and multivalent. This is especially true for the urban landscape: the presence of enslaved and freed persons would have been impossible to miss. More difficult is the reconstruction of Middle Eastern agrarian slavery. This is a survey essay with particular reference to the early Abbasid Caliphate (c. 750-950) and select questions around which debate in modern scholarship has grown. One must comb medieval Arabic texts (literary and documentary) to reconstruct patterns of early Islamic-era enslavement; the organization and dynamics of slave commerce; the demands on slave and freed labor; and the (relative) social integration of the enslaved. The Arabic/Islamic library illuminates all manner of topics, religious and secular alike. Literary references to slavery and/or enslaved persons therein are plentiful and of a great variety. One has references in works of poetry and adab, an elastic term used for a variety of Arabic prose writings. Equally numerous are references in chronicles, biographical dictionaries, and works of geography and political thought. Medieval Arabic legal and religious writings provide a considerable number of references as well.
The feasibility of non-pharmacological public health interventions (NPIs) such as physical distancing or isolation at home to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in low-resource countries is unknown. Household survey data from 54 African countries were used to investigate the feasibility of SARS-CoV-2 NPIs in low-resource settings. Across the 54 countries, approximately 718 million people lived in households with ⩾6 individuals at home (median percentage of at-risk households 56% (95% confidence interval (CI), 51% to 60%)). Approximately 283 million people lived in households where ⩾3 people slept in a single room (median percentage of at-risk households 15% (95% CI, 13% to 19%)). An estimated 890 million Africans lack on-site water (71% (95% CI, 62% to 80%)), while 700 million people lacked in-home soap/washing facilities (56% (95% CI, 42% to 73%)). The median percentage of people without a refrigerator in the home was 79% (95% CI, 67% to 88%), while 45% (95% CI, 39% to 52%) shared toilet facilities with other households. Individuals in low-resource settings have substantial obstacles to implementing NPIs for mitigating SARS-CoV-2 transmission. These populations urgently need to be prioritised for coronavirus disease 2019 vaccination to prevent disease and to contain the global pandemic.
The use of Spratt’s dog cakes is well documented in the diaries and reminiscences of many early Antarctic expedition members. Commercially produced dog food was promoted by the likes of Spratt’s as an advanced form of animal nutrition and would have been of interest to expedition planners who were already concerned with the nutritional requirements of expedition members. An approximately 100-year-old dog cake recovered from Antarctica was compared by chemical analysis and spectroscopic methods with a series of model dog cakes and a commercial dog biscuit to determine the composition and calorific content. The presence of bone fragments within the dog cake was confirmed, whereas starch in the bulk matrix of the sample was consistent with being a mixture of wheat and oat flour, while only minimal fat or oil was present. Calorific content, while insufficient compared to a modern feed for high-performance dogs, would nonetheless have been a valuable addition to the use of dried or frozen whole meat such as seal, fish, or pemmican and contributed additional energy compared to meat alone.
The role of the Eurasian badger (Meles meles) as a wildlife host has complicated the management of bovine tuberculosis (bTB) in cattle. Badger ranging behaviour has previously been found to be altered by culling of badgers and has been suggested to increase the transmission of bTB either among badgers or between badgers and cattle. In 2014, a five-year bTB intervention research project in a 100 km2 area in Northern Ireland was initiated involving selective removal of dual path platform (DPP) VetTB (immunoassay) test positive badgers and vaccination followed by release of DPP test negative badgers (‘Test and Vaccinate or Remove’). Home range sizes, based on position data obtained from global positioning system collared badgers, were compared between the first year of the project, where no DPP test positive badgers were removed, and follow-up years 2–4 when DPP test positive badgers were removed. A total of 105 individual badgers were followed over 21 200 collar tracking nights. Using multivariable analyses, neither annual nor monthly home ranges differed significantly in size between years, suggesting they were not significantly altered by the bTB intervention that was applied in the study area.
Adults who were born preterm are at increased risk of hypertension and cardiovascular disease in later life. Infants born late preterm are the majority of preterm births; however, the effect of late preterm on risk of cardiovascular disease is unclear. The objective of this study was to assess whether vascular health and cardiac autonomic control differ in a group of late preterm newborn infants compared to a group of term-born infants.
A total of 35 healthy late preterm newborn infants, with normal growth (34–36 completed weeks’ gestation) and 139 term-born infants (37–42 weeks’ gestation) were compared in this study. Aortic wall thickening, assessed as aortic intima–media thickness (IMT) by high-resolution ultrasound, and cardiac autonomic control, assessed by heart rate variability, were measured during the first week of life. Postnatal age of full-term and late preterm infants at the time of the study was 5 days (standard deviation [SD] 5) and 4 days (SD 3), respectively.
Infants born late preterm show reduced aortic IMT (574 μm [SD 51] vs. 612 μm [SD 73]) and reduced heart rate variability [log total power 622.3 (606.5) ms2 vs. 1180. 6 (1114.3) ms2], compared to term infants. These associations remained even after adjustment for sex and birth weight.
Infants born late preterm show selective differences in markers of cardiovascular risk, with potentially beneficial differences in aortic wall thickness in contrast to potentially detrimental differences in autonomic control, when compared with term-born control infants. These findings provide pathophysiologic evidence to support an increased risk of hypertension and sudden cardiac death in individuals born late preterm.
The inhabitants of seventh-century Arabia mobilized for warfare in a manner new to that region of the Near East: the effort fell, albeit gradually, under central authority.1 Arabia had long been a highly variegated cultural zone, encompassing the Syrian Desert, southern Mesopotamia, and the Arabian Peninsula. Acting in tandem, largely nomadic tribal forces accepted the leadership of sedentary townsmen, the great number of whom belonged to the Quraysh, an influential tribe of two towns of the Hejaz region, Mecca and Medina. If Yemen and south Arabia had long known the rule of kings, and, hence, more formal military organization, only now did the central and northern stretches of the Peninsula and southern Syria experience what can thereby be considered as early state formation. The effort was driven by an equally untested set of ethical and spiritual teachings. A charismatic figure, Muḥammad ibn ʿAbdallāh (570–632), preached a strict monotheism; these teachings served as the seedbed of what would soon be known as Islam.
This consolidated case out of New York considered two independent appeals, both of which concerned testamentary trusts that awarded scholarships exclusively to male students. The first, Matter of Wilson, involved a 1969 testamentary trust (the “Wilson Trust”), which directed that trust income be applied to “[defray] the education and other expenses of the first year at college of five (5) young men who shall have graduated from the Canastota High School … as may be certified by the Superintendent of Schools.
How would judicial opinions change if the judges were to use feminist methods and perspectives when deciding cases? That is the question that various groups of scholars, working around the globe and mostly independently of each other, have taken up in a series of books of “shadow opinions” – literally, rewritten judicial decisions – using precedents, authorities, theories, and approaches that were in existence at the time of the original decision to reach radically different outcomes and often using saliently different reasoning. This global sociolegal movement toward critical opinion writing originated when a group of lawyers and law professors who called themselves the Women’s Court of Canada published a series of six rewritten decisions in 2008 in the Canadian Journal of Women and the Law. Inspired by that project, scholars have produced similar projects in the United Kingdom, Australia, the United States, Ireland, and New Zealand/Aotearoa. There is an international law feminist judgments project and a Scottish project. Other feminist judgments projects are underway in India, Africa, and Mexico.