On the Distributional Characterization of Log-returns of a World Stock Index

In this paper we identify distributions which suitably fit log-returns of the world stock index (WSI) when these are expressed in units of different currencies. By searching for a best fit in the class of symmetric generalized hyperbolic distributions the maximum likelihood estimates appear to cluster in the neighborhood of those of the Student t distribution. This is confirmed on a high significance level under the likelihood ratio test.world stock index; benchmarked log-return; Student t distribution; symmetric generalized hyperbolic distribution

Less-expensive pricing and hedging of extreme-maturity interest rate derivatives and equity index options under the real-world measure

University of Technology Sydney. Faculty of Business.This thesis is practically oriented towards the pricing and hedging of long-dated interest rate derivatives and equity index options under Platen’s benchmark approach. It aims to be self-contained for convenience of the reader, including all proofs. Among leading banks and insurance companies there does not appear to exist a generally accepted methodology of accurately pricing and hedging such over-the-counter derivatives. This remains the case, despite significant efforts by academics and market practitioners since the early 1990s. This thesis revisits this problem in the light of empirical evidence in a much wider modelling framework than that provided by the classical risk neutral approach. The models considered in this thesis are specified by stochastic differential equations that describe the real-world dynamics of two market variables, namely the short rate and the volatility of the growth optimal portfolio (GOP). The latter is essentially a diversified equity index. This thesis assesses for these models their ability to generate reasonably accurate prices and hedges of typical interest rate term structure derivatives and equity index options. When the discounted GOP is modelled as a time-transformed squared Bessel process, fair prices differ from classical risk neutral prices, resulting in lower prices and lower values-at-risk of long-dated derivatives. Also, such models reflect well empirical market features, such as leptokurtic returns, the leverage effect and a stochastic, yet stationary, volatility structure of the equity index. The results of this analysis, which are contained in this thesis, have been supplemented by the publications of Fergusson and Platen [2006], Fergusson and Platen [2014a], Fergusson and Platen [2015b], Fergusson [2017a] and Fergusson [2017b] and the research reports of Fergusson and Platen [2013], Fergusson and Platen [2014b] and Fergusson and Platen [2015a]. In addition, as by-products of the work done in this thesis, the following papers have been published: Thompson et al. [2017], Calderin et al. [2017] and the following have been submitted to journals for publication: Fergusson and Platen [2014c], Fergusson and Platen [2017]. Finally, the following working papers are to be submitted to journals shortly: Fergusson [2017c], Fergusson [2017d], Fergusson [2017e]

Are undergraduates' expectations mirrored by graduates' realisations and employers' demands?

Innovation in teaching and learning in vocational university courses has involved mentoring schemes by industry to match the skills taught with the industry demands. However, an alternative way of ensuring university graduates are job ready involves an analysis of the job market destinations of graduates. The authors surveyed Curtin University undergraduates in the second semester of 2014 in respect of the actuarial science programme's attributes pertaining to skills and knowledge taught, the lecturers' expertise and the university's support for students. Additionally, the authors surveyed Curtin University graduates and examined employer advertisements with regards to the skills and knowledge required by graduates and employers. The results of our investigation highlight areas where Curtin University's actuarial programme can be better tailored to the demands of the workplace

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells

Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42020193027

Increased Urinary Angiotensin-Converting Enzyme 2 in Renal Transplant Patients with Diabetes

Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Depositional architecture, provenance, and tectonic/eustatic modulation of Miocene submarine fans in the Shikoku Basin: Results from Nankai Trough Seismogenic Zone Experiment

Seismostratigraphy, coring, and logging while drilling during Integrated Ocean Drilling Program Expeditions 319, 322, and 333 (Sites C0011/C0012) show three Miocene submarine fans in the NE Shikoku Basin, with broadly coeval deposits at Ocean Drilling Program Site 1177 and Deep Sea Drilling Project Site 297 (NW Shikoku Basin). The sediment dispersal patterns have major implications for paleogeographies at that time. The oldest, finer-grained (Kyushu) fan has sheet-like geometry; quartz-rich flows were fed mostly from an ancestral landmass in the East China Sea. During prolonged hemipelagic mud deposition at C0011-C0012 (~12.2 to 9.1 Ma), sand supply continued at Sites 1177 and 297. Sand delivery to much of the Shikoku Basin halted during a phase of sinistral strike slip to oblique plate motion, after which the Daiichi Zenisu Fan (~9.1 to 8.0 Ma) was fed by submarine channels. The youngest fan (Daini Zenisu; ~8.0 to 7.6 Ma) has sheet-like geometry with thick-bedded, coarse-grained pumiceous sandstones. The pumice fragments were fed from a mixed provenance that included the collision zone of the Izu-Bonin and Honshu Arcs. The shift from channelized to sheet-like flows was favored by renewal of relatively rapid northward subduction, which accentuated the trench as a bathymetric depression. Increased sand supply appears to correlate with long-term eustatic lowstands of sea level. The stratigraphic position and 3-D geometry of the sandbodies have important implications for subduction-related processes, including the potential for focused fluid flow and fluid overpressures above and below the plate boundary fault: In sheet-like sands, pathways for fluid flow have greater horizontal permeability compared with those in channel sands

Genome-Wide Meta-Analysis of Longitudinal Alcohol Consumption Across Youth and Early Adulthood

The public health burden of alcohol is unevenly distributed across the life course, with levels of use, abuse, and dependence increasing across adolescence and peaking in early adulthood. Here, we leverage this temporal patterning to search for common genetic variants predicting developmental trajectories of alcohol consumption. Comparable psychiatric evaluations measuring alcohol consumption were collected in three longitudinal community samples ( N = 2,126, obs = 12,166). Consumption-repeated measurements spanning adolescence and early adulthood were analyzed using linear mixed models, estimating individual consumption trajectories, which were then tested for association with Illumina 660W-Quad genotype data (866,099 SNPs after imputation and QC). Association results were combined across samples using standard meta-analysis methods. Four meta-analysis associations satisfied our pre-determined genome-wide significance criterion (FDR &lt; 0.1) and six others met our ‘suggestive’ criterion (FDR &lt;0.2). Genome-wide significant associations were highly biological plausible, including associations within GABA transporter 1, SLC6A1 (solute carrier family 6, member 1), and exonic hits in LOC100129340 (mitofusin-1-like). Pathway analyses elaborated single marker results, indicating significant enriched associations to intuitive biological mechanisms, including neurotransmission, xenobiotic pharmacodynamics, and nuclear hormone receptors (NHR). These findings underscore the value of combining longitudinal behavioral data and genome-wide genotype information in order to study developmental patterns and improve statistical power in genomic studies