Pointing to inclinations : Albertus Magnus' physiognomy as a scientific and theological nexus

This dissertation explores the physiognomy of Albertus Magnus, which is contained within his commentary on De animalibus, the three works on animals by Aristotle. This physiognomy provides an opportunity to demonstrate the medieval intellectual world view that the body and soul were connected, both theologically and medically. Albertus Magnus and his physiognomy also exemplify the reintroduction of physiognomy into Latin Christendom in the twelfth and thirteenth centuries through deep textual connections in physiognomy, medicine, and theories of the soul to the classical Mediterranean through the intermediary of the Islamic world. Physiognomies like that of Albertus Magnus also contribute to ideas of what constitutes a medieval scientia by building upon past scholarship on astrology, hagiography, and other aspects of the premodern world that have largely been rejected until recent decades.Includes bibliographical reference

Depression and health-adjusted life expectancy in the Canadian adult population: a descriptive study

Background: Few studies have evaluated the overall population health-related impact of depression in terms of losses to both premature mortality and health-related quality of life (HRQL). Purpose: To estimate health-adjusted life expectancy (HALE) for Canadian adults according to depression status

An epigenome-wide association study of sex-specific chronological ageing

Background Advanced age is associated with cognitive and physical decline and is a major risk factor for a multitude of disorders. There is also a gap in life expectancy between males and females. DNA methylation differences have been shown to be associated with both age and sex. Here, we investigate age-by-sex differences in blood-based DNA methylation in an unrelated cohort of 2586 individuals between the ages of 18 and 87 years, with replication in a further 4450 individuals between the ages of 18 and 93 years. Methods Linear regression models were applied, with stringent genome-wide significance thresholds (p < 3.6 x 10(-8)) used in both the discovery and replication data. A second, highly conservative mixed linear model method that better controls the false-positive rate was also applied, using the same genome-wide significance thresholds. Results Using the linear regression method, 52 autosomal and 597 X-linked CpG sites, mapping to 251 unique genes, replicated with concordant effect size directions in the age-by-sex interaction analysis. The site with the greatest difference mapped to GAGE10, an X-linked gene. Here, DNA methylation levels remained stable across the male adult age range (DNA methylation by age r = 0.02) but decreased across female adult age range (DNA methylation by age r = - 0.61). One site (cg23722529) with a significant age-by-sex interaction also had a quantitative trait locus (rs17321482) that is a genome-wide significant variant for prostate cancer. The mixed linear model method identified 11 CpG sites associated with the age-by-sex interaction. Conclusion The majority of differences in age-associated DNA methylation trajectories between sexes are present on the X chromosome. Several of these differences occur within genes that have been implicated in sexually dimorphic traits

Epigenetic prediction of complex traits and death

Funding: GS received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Genotyping and DNA methylation profiling of the GS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” ((STRADL) Reference 104036/Z/14/Z)). The LBC1936 is supported by Age UK (Disconnected Mind program) and the Medical Research Council (MR/M01311/1). Methylation typing was supported by Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. This work was conducted in the Centre for Cognitive Ageing and Cognitive Epidemiology, which is supported by the Medical Research Council and Biotechnology and Biological Sciences Research Council (MR/K026992/1), and which supports IJD. DLM and REM are supported by Alzheimer’s Research UK major project grant ARUK-PG2017B-10. This research was supported by Australian National Health and Medical Research Council (grants 1010374, 1046880, and 1113400) and by the Australian Research Council (DP160102400). PMV, NRW, and AFM are supported by the NHMRC Fellowship Scheme (1078037, 1078901, and 1083656). RFH and AJS are supported by funding from the Wellcome Trust 4-year PhD in Translational Neuroscience – training the next generation of basic neuroscientists to embrace clinical research [108890/Z/15/Z].Peer reviewedPublisher PD

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Australian Constitutional Convention 1973-1985: a guide to the archives

© 1998 Centre for Comparative Constitutional Studies, The University of MelbourneIntroduction to the collection: This collection provides researchers with records of the activities and achievements of the Australian Constitutional Convention (ACC) 1973-85, and the Australian Constitutional Convention Council which carried the Convention's work into the early 1990s. The collection also includes files dating from 1972 to 1973 recording preparations for the first Convention, and historical documents from the nineteenth century onwards relevant to the Australian Constitution and its review. The Convention met six times between 1973 and 1985. These plenary sessions were attended by delegates from Commonwealth, State and Territory Parliaments, local government representatives, and observers from the general public. Between these meetings, an energetic Chief Executive Officer, Secretariat, and various committees and consultants continued the research and deliberations of the Convention, and planned the next plenary session. Some of the State, Territory and Commonwealth delegations held separate meetings and circulated their own briefing notes as a Convention approached. The work and achievements of the Convention, and the context in which it operated, are set out further in the Historical Overview (pp. ). Records accumulated by the Convention Secretariat form the bulk of this collection. Over 500 files house records such as correspondence, submissions, minutes, working papers and reports. There are also bound volumes, audiotapes, videocassettes, photographs and other items. The collection includes records of attendance, debates and decisions at the plenary sessions, such as signed rolls of delegates and printed proceedings; and records of meetings of committees during the intervening months and years. Many of the files in the collection were compiled by Chief Executive Officer John Finemore, one of his assistants, or one of the research officers connected with the Secretariat. As the Secretariat was located in Melbourne, records of associated people such as secretaries to the Victorian Delegation have found their way into the collection, as has a set of files originally belonging to Victoria's A.R.B. McDonnell (Clerk of the Parliaments and Clerk of the Legislative Council) who became one of the clerks to the Convention. Although this collection is very extensive, it does not include all relevant records. Some related records are held at the Australian Archives (see pp. ). Researchers might also wish to consult State and Territory archives offices regarding any other records connected with the work of the ACC and delegations, and/or the Australian Constitutional Convention Council. The custodian of this collection is the Centre for Comparative Constitutional Studies (CCCS), at The University of Melbourne, and the collection is housed in the John Finemore Room in the University of Melbourne Law Library. Information about access to the collection is available at http://www.law.unimelb.edu.au/lrc/pub/rarebooks/finemore.cfm John Finemore's hand is evident throughout this collection. As Chief Executive Officer, he became the Convention's main spokesperson and point of contact. He corresponded with committee members, delegates and members of the public, oversaw the compilation of reference material and encouraged research. The richness of the ACC collection, and its survival, is largely attributable to John Finemore