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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.
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.
We present the case of a 17-year-old boy with a cardiac venous malformation. This case highlights the diagnostic challenges of such tumours and demonstrates the potential efficacy of a watch-and-wait management approach.
The goal of this study was to examine the mental health needs of children and youth who present to the emergency department (ED) for mental health care and to describe the type of, and satisfaction with, follow-up mental health services accessed.
Methods
A 6-month to 1.5-year prospective cohort study was conducted in three Canadian pediatric EDs and one general ED, with a 1-month follow-up post-ED discharge. Measures included 1) clinician rating of mental health needs, 2) patient and caregiver self-reports of follow-up services, and 3) interviews regarding follow-up satisfaction. Data analysis included descriptive statistics and the Fisher’s exact test to compare sites.
Results
The cohort consisted of 373 children and youth (61.1% female; mean age 15.1 years, 1.5 standard deviation). The main reason for ED presentations was a mental health crisis. The three most frequent areas of need requiring action were mood (43.8%), suicide risk (37.4%), and parent-child relational problems (34.6%). During the ED visit, 21.6% of patients received medical clearance, 40.9% received a psychiatric consult, and 19.4% were admitted to inpatient psychiatric care. At the 1-month post-ED visit, 84.3% of patients/caregivers received mental health follow-up. Ratings of service recommendations were generally positive, as 60.9% of patients obtained the recommended follow-up care and 13.9% were wait-listed.
Conclusions
Children and youth and their families presenting to the ED with mental health needs had substantial clinical morbidity, were connected with services, were satisfied with their ED visit, and accessed follow-up care within 1-month with some variability.
Marguerite Bay, situated between the subpolar glacial regime of the northern Antarctic Peninsula and the polar glacial regime of West Antarctica, is ideally located to test various models of glacial and glacial-marine sedimentation and specific scenarios of late Wisconsin ice sheet expansion. Piston cores and single-channel seismic reflection data were collected during the Deep Freeze 85 and 86 expeditions to determine the late Quaternary history of the area. Seismic data in the bay show a rugged seafloor, with numerous deep troughs and a very thin layer of sediment over crystalline basement or older sediments. Glacial erosion is important in modifying existing features, although the ultimate repository of the eroded material is not known; it is not found within the bay. The piston cores are topped by diatomaceous muds, which are underlain by terrigenous muds and muddy gravels that imply deposition beneath an ice shelf. Basal tills were penetrated at three sites, reflecting deposition by a grounded marine ice sheet. A reconstruction of the glacial history of Marguerite Bay since the last glacial maximum shows grounded ice filling the bay in late Wisconsin time. Rising sea level caused an uncoupling of the ice sheet and slow retreat of an ice shelf throughout the Holocene.
We carried out a cross-sectional study to assess cognitive function in a sample of adult CHD patients, within the Functioning in Adult Congenital Heart Disease study London. The association between cognitive functioning and disease complexity was examined.
Methods
A total of 310 patients participated in this study. Patients were classified into four structural complexity groups – tetralogy of Fallot, transposition of the great arteries, single ventricle, and simple conditions. Each patient underwent neuropsychological assessment to evaluate cognitive function, including memory and executive function, and completed questionnaires to assess depression and anxiety.
Results
Among all, 41% of the sample showed impaired performance (>1.5 SD below the normative mean) on at least three tests of cognitive function compared with established normative data. This was higher than the 8% that was expected in a normal population. The sample exhibited significant deficits in divided attention, motor function, and executive functioning. There was a significant group difference in divided attention (F=5.01, p=0.002) and the mean total composite score (F=5.19, p=0.002) between different structural complexity groups, with the simple group displaying better cognitive function.
Conclusion
The results indicate that many adult CHD patients display impaired cognitive function relative to a healthy population, which differs in relation to disease complexity. These findings may have implications for clinical decision making in this group of patients during childhood. Possible mechanisms underlying these deficits and how they may be reduced or prevented are discussed; however, further work is needed to draw conclusive judgements.
This book presents a wide range of new research on many aspects of naval strategy in the early modern and modern periods. Among the themes covered are the problems of naval manpower, the nature of naval leadership and naval officers, intelligence, naval training and education, and strategic thinking and planning. The book is notable for giving extensive consideration to navies other than those ofBritain, its empire and the United States. It explores a number of fascinating subjects including how financial difficulties frustrated the attempts by Louis XIV's ministers to build a strong navy; how the absence of centralised power in the Dutch Republic had important consequences for Dutch naval power; how Hitler's relationship with his admirals severely affected German naval strategy during the Second World War; and many more besides. The book is a Festschrift in honour of John B. Hattendorf, for more than thirty years Ernest J. King Professor of Maritime History at the US Naval War College and an influential figure in naval affairs worldwide.
N.A.M. Rodger is Senior Research Fellow at All Souls College, Oxford.
J. Ross Dancy is Assistant Professor of Military History at Sam Houston State University.
Benjamin Darnell is a D.Phil. candidate at New College, Oxford.
Evan Wilson is Caird Senior Research Fellow at the National Maritime Museum, Greenwich.
Contributors: Tim Benbow, Peter John Brobst, Jaap R. Bruijn, Olivier Chaline, J. Ross Dancy, Benjamin Darnell, James Goldrick, Agustín Guimerá, Paul Kennedy, Keizo Kitagawa, Roger Knight, Andrew D. Lambert, George C. Peden, Carla Rahn Phillips, Werner Rahn, Paul M. Ramsey, Duncan Redford, N.A.M. Rodger, Jakob Seerup, Matthew S. Seligmann, Geoffrey Till, Evan Wilson
Clinical databases in congenital and paediatric cardiac care provide a foundation for quality improvement, research, policy evaluations and public reporting. Structured audits verifying data integrity allow database users to be confident in these endeavours. We report on the initial audit of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry.
Materials and methods
Participants reviewed the entire registry to determine key fields for audit, and defined major and minor discrepancies for the audited variables. In-person audits at the eight initial participating centres were conducted during a 12-month period. The data coordinating centre randomly selected intensive care encounters for review at each site. The audit consisted of source data verification and blinded chart abstraction, comparing findings by the auditors with those entered in the database. We also assessed completeness and timeliness of case submission. Quantitative evaluation of completeness, accuracy, and timeliness of case submission is reported.
Results
We audited 434 encounters and 29,476 data fields. The aggregate overall accuracy was 99.1%, and the major discrepancy rate was 0.62%. Across hospitals, the overall accuracy ranged from 96.3 to 99.5%, and the major discrepancy rate ranged from 0.3 to 0.9%; seven of the eight hospitals submitted >90% of cases within 1 month of hospital discharge. There was no evidence for selective case omission.
Conclusions
Based on a rigorous audit process, data submitted to the PC4 clinical registry appear complete, accurate, and timely. The collaborative will maintain ongoing efforts to verify the integrity of the data to promote science that advances quality improvement efforts.
