The imperial cult and the individual : the negotiation of Augustus' private worship during his lifetime at Rome

This dissertation argues for a reevaluation of the imperial cult in Rome. It demonstrates that worship of the living Augustus began in private acts which progressed into public rituals after his senate-decreed divinity in 14 CE. Scenes of private worship, preserved in architecture, poetry, and the city's topography, as well as private images of the emperor anticipate Augustus' public cult as a divus (deified emperor). The chapters show how the climate in Rome allowed for the private articulation of Augustus' living cult, and then address specific aspects of his worship: sacrifice, cult places, and cultic statues. This argument expands our understanding of Augustus' divinity in Rome to include worship of the vivus (living emperor), and demonstrates how this worship transitioned into public cult. No less importantly, it challenges lingering modern assumptions about the boundaries between divinity and humanity as these played out around the figure of the emperor in early imperial Rome.Includes bibliographical reference

Combined effect of ammonia stress and cell line age on CHO cell derived VRC01 monoclonal antibody glycosylation

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Development of a measure of model fidelity for mental health Crisis Resolution Teams

Background Crisis Resolution Teams (CRTs) provide short-term intensive home treatment to people experiencing mental health crisis. Trial evidence suggests CRTs can be effective at reducing hospital admissions and increasing satisfaction with acute care. When scaled up to national level however, CRT implementation and outcomes have been variable. We aimed to develop and test a fidelity scale to assess adherence to a model of best practice for CRTs, based on best available evidence. Methods A concept mapping process was used to develop a CRT fidelity scale. Participants (n = 68) from a range of stakeholder groups prioritised and grouped statements (n = 72) about important components of the CRT model, generated from a literature review, national survey and qualitative interviews. These data were analysed using Ariadne software and the resultant cluster solution informed item selection for a CRT fidelity scale. Operational criteria and scoring anchor points were developed for each item. The CORE CRT fidelity scale was then piloted in 75 CRTs in the UK to assess the range of scores achieved and feasibility for use in a 1-day fidelity review process. Trained reviewers (n = 16) rated CRT service fidelity in a vignette exercise to test the scale’s inter-rater reliability. Results There were high levels of agreement within and between stakeholder groups regarding the most important components of the CRT model. A 39-item measure of CRT model fidelity was developed. Piloting indicated that the scale was feasible for use to assess CRT model fidelity and had good face validity. The wide range of item scores and total scores across CRT services in the pilot demonstrate the measure can distinguish lower and higher fidelity services. Moderately good inter-rater reliability was found, with an estimated correlation between individual ratings of 0.65 (95% CI: 0.54 to 0.76). Conclusions The CORE CRT Fidelity Scale has been developed through a rigorous and systematic process. Promising initial testing indicates its value in assessing adherence to a model of CRT best practice and to support service improvement monitoring and planning. Further research is required to establish its psychometric properties and international applicability

Profiling movement quality and gait characteristics according to body-mass index in children (9–11 y)

Obese children move less and with greater difficulty than their normal-weight counterparts. Whilst the effect of high BMI on cardiovascular fitness is well known, the effect on movement quality characteristics during a standardised fitness test has not been investigated. The aims of this study were, to characterise the movement quality of children performing the multi-stage fitness test (MSFT), and, report how movement quality characteristics cluster according to weight status. One hundred and three children (10.3 ± 0.6 y, 1.42 ± 0.08 m, 37.8 ± 9.3 kg, BMI; 18.5 ± 3.3 kg m2) performed the MSFT whilst wearing an ankle mounted accelerometer. BMI groups were used to classify children as underweight (UW), normal weight (NW), overweight (OW) and obese (OB). Characteristics of movement were profiled using a clustering algorithm. Spearman’s rho was used to assess relationship with BMI group, and a Mann-Whitney U test was used to assess differences between BMI groups. Obese children had significantly lower spectral purity than every other group and significantly lower time to exhaustion (TTE) than UW and NW children (P < 0.05). BMI was clustered with stride profile and TTE with spectral purity. Significant negative correlations (P < 0.05) were found between BMI and TTE (r = −0.25), spectral purity (r = −0.24), integrated acceleration (r = −0.22), stride angle (r = −0.23) and stride variability (r = −0.22). This was the first study to report the spectral purity of children’s gait. Further analysis unveiled key performance characteristics that differed between BMI groups. These were (i) representative of children’s performance during the MSFT and, (ii) significantly negatively correlated with BMI

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Cholesterol Dependent Activity of the Adenosine A2A Receptor Is Modulated via the Cholesterol Consensus Motif

Background: Membrane cholesterol dysregulation has been shown to alter the activity of the adenosine A2A receptor (A2AR), a G protein-coupled receptor, thereby implicating cholesterol levels in diseases such as Alzheimer&rsquo;s and Parkinson&rsquo;s. A limited number of A2AR crystal structures show the receptor interacting with cholesterol, as such molecular simulations are often used to predict cholesterol interaction sites. Methods: Here, we use experimental methods to determine whether a specific interaction between amino acid side chains in the cholesterol consensus motif (CCM) of full length, wild-type human A2AR, and cholesterol modulates activity of the receptor by testing the effects of mutational changes on functional consequences, including ligand binding, G protein coupling, and downstream activation of cyclic AMP. Results and conclusions: Our data, taken with previously published studies, support a model of receptor state-dependent binding between cholesterol and the CCM, whereby cholesterol facilitates both G protein coupling and downstream signaling of A2AR

Two New Instruments to Calibrate the Visible Sky

Construction of the Facility Lidar for Astronomical Measurement of Extinction (FLAME) and the Astronomical Extinction SpectroPhotometer (AESoP) is nearing completion. FLAME is a 0.5m multi-wavelength backscatter lidar operating at the first three Nd:YAG harmonics and measuring with high precision and accuracy the Rayleigh backscatter from the middle stratosphere. AESoP is a 100mm diameter objective stellar spectroradiometer, the throughput of which is carefully calibrated to NIST radiometric standards. Together they form the core of the mobile instrument suite being amalgamated by the UNM Measurement Astrophysics group to characterize and calibrate atmospheric extinction at observatory sites. The first task of this instrument suite will be to help create a new set of standard stars radiometrically calibrated to NIST standards. Initially this will be done for bright stars across the wavelength range 350nm to 1050nm at 1nm spectral resolution with measurement accuracy better than 1% per spectral resolution element by calibration to NIST silicon detectors. The byproduct of these measurements is calibrated atmospheric transmission along the line of sight to the standard star