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The importance of the accurate recording and monitoring of the occurrence of disease is well recognized. There is a long history of the establishment of disease registers and this is also the case for congenital anomaly registers. This chapter provides an overview of 2 congenital anomaly register networks, focusing on factors that lead to the successful operating of a register and the main uses of their data.
Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity.
We analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators.
Affective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data.
Affective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.
Richard Topcliffe (1531–1604) was the most infamous torturer of Elizabethan England. He was also a professional reader. Historians of the book are interested in how repressive regimes read the books of their enemies. This essay identifies a number of books that contain Topcliffe's marginalia and have not previously been studied by scholars. It argues that Topcliffe's reading was forensic in nature, and was utilized directly by the Elizabethan regime in its campaign against Catholicism. This investigation reveals the connection between racking and reading, and demonstrates the ways in which Topcliffe's reading legitimated state-authorized violence.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Objective: White matter (WM) microstructural changes are
increasingly recognized as a mechanism of age-related cognitive differences.
This study examined the associations between patterns of WM microstructure and
cognitive performance on the University of California, San Francisco (UCSF)
Brain Health Assessment (BHA) subtests of memory (Favorites), executive
functions and speed (Match), and visuospatial skills (Line Orientation) within a
sample of older adults. Method: Fractional anisotropy (FA) in WM
tracts and BHA performance were examined in 84 older adults diagnosed as
neurologically healthy (47), with mild cognitive impairment (19), or with
dementia (18). The relationships between FA and subtest performances were
evaluated using regression analyses. We then explored whether regional WM
predicted performance after accounting for variance explained by global FA.
Results: Memory performance was associated with FA of the
fornix and the superior cerebellar peduncle; and executive functions and speed,
with the body of the corpus callosum. The fornix–memory association and
the corpus callosum–executive association remained significant after
accounting for global FA. Neither tract-based nor global FA was associated with
visuospatial performance. Conclusions: Memory and executive
functions are associated with different patterns of WM diffusivity. Findings add
insight into WM alterations underlying age- and disease-related cognitive
We propose the concept of the “Fish Revolution” to demarcate the dramatic increase in North Atlantic fisheries after AD 1500, which led to a 15-fold increase of cod (Gadus morhua) catch volumes and likely a tripling of fish protein to the European market. We consider three key questions: (1) What were the environmental parameters of the Fish Revolution? (2) What were the globalising effects of the Fish Revolution? (3) What were the consequences of the Fish Revolution for fishing communities? While these questions would have been considered unknowable a decade or two ago, methodological developments in marine environmental history and historical ecology have moved information about both supply and demand into the realm of the discernible. Although much research remains to be done, we conclude that this was a major event in the history of resource extraction from the sea, mediated by forces of climate change and globalisation, and is likely to provide a fruitful agenda for future multidisciplinary research.
1. Introduction. Let ω be an irrational number. It is well known that there exists a positive real number h such that the inequality
has infinitely many solutions in coprime integers a and c. A theorem of Hurwitz asserts that the set of all such numbers h is a closed set with supremum √5. Various proofs of these results are known, among them one by Ford (1), in which he makes use of properties of the modular group. This approach suggests the following generalization.