Epidemiological transition: a historical analysis of immigration patterns by country of origin (1861-1986) related to circulatory system diseases and all-cause mortality in twentieth-century Australia.

Background And Objectives: Circulatory system disease (CSD) patterns vary over time and between countries, related to lifestyle risk factors, associated in turn with socioeconomic circumstances. Current global CSD epidemics in developing economies are similar in scale to those observed previously in the USA and Australasia. Australia exhibits an important macroeconomic phenomenon as a rapidly transitioning economy with high immigration throughout the nineteenth and twentieth centuries.

Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection.

TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients.

The Value of Technology to Support Dyadic Caregiving for Individuals Living With Heart Failure: Qualitative Descriptive Study.

Background: The demand for health services to meet the chronic health needs of the aging population is significant and remains unmet because of the limited supply of clinical resources. Specifically, in managing heart failure (HF), digital health sought to address this gap during the COVID-19 pandemic but highlighted an access issue for those who could not use technology-mediated health care services without the support of their informal caregivers (ICs). The complexity of managing HF symptoms and recurrent exacerbations requires many patients to comanage their illness with their ICs in a care dyad, working together to optimize patient outcomes and health-related quality of life.

Comparative Analysis of Swept-Source Optical Coherence Tomography and Partial Coherence Interferometry Biometers in the Prediction of Cataract Surgery Refractive Outcomes.

Purpose: To compare the accuracy of pre-operative corneal measurements obtained with four devices, and the refractive outcomes of two optical biometers.

Setting: Private practice.

Design: Retrospective.

A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove.

Proprotein convertase (PC) subtilisin kexin type 9 (PCSK9) inhibits the clearance of low density lipoprotein (LDL) cholesterol from plasma by directly interacting with the LDL receptor (LDLR). As the interaction promotes elevated plasma LDL cholesterol levels and a predisposition to cardiovascular disease (CVD), it has attracted much interest as a therapeutic target. While anti-PCSK9 monoclonal antibodies have been successful in the treatment of hypercholesteremia by decreasing CVD risk, their high cost and a requirement for injection have prohibited widespread use.

A neural network analysis of Lifeways cross-generation imputed data.

Objectives: Neural networks are a powerful statistical tool that use nonlinear regression type models to obtain predictions. Their use in the Lifeways cross-generation study that examined body mass index (BMI) of children, among other measures, is explored here. Our aim is to predict the BMI of children from that of their parents and maternal and paternal grandparents.

Happy birthday? An observational study.

Background: Previous studies show contradictory findings on the relationship between birthday and deathday, in particular whether people postpone death until after their birthday. We examine the phenomenon in eight groups of famous people.

Methods: Birthday and deathday for the following groups were recorded: British prime ministers, US presidents, Academy Award best actor, best female actor, best director, Nobel Prize winners, Wimbledon men's and ladies' singles winners, all from when records began.

The value of serial metal ion levels in following up patients with metal-on-metal hip arthroplasty.

Background: The sensitivity of cobalt (Co) and chromium (Cr) ion-levels in detecting poorly performing metal-on-metal hip implants is low. This study proposes that serial changes in ion-levels are a more accurate marker of arthroplasties at risk.

Methods: Serial metal ion-levels and implant data of 285 patients with ASR resurfacing or replacement were studied.

Body mass index is associated with the maternal lines but height is heritable across family lines in the Lifeways Cross-Generation Cohort Study.

Objectives: Overweight and obesity is a problem in children in particular and determining pathways of transmission is important in prevention. We aimed to examine associations for body mass index (BMI) across three generations of the same families.

Participants: Members of 556 families in the Lifeways Cross-Generation Cohort Study 2001-2014.

MRI findings following metal on metal hip arthroplasty and their relationship with metal ion levels and acetabular inclination angles.

Following the global recall of all ASR metal on metal hip products, our aim was to correlate MRI findings with acetabular inclination angles and metal ion levels in patients with these implants. Both cobalt and chromium levels were significantly higher in the presence of a periprosthetic fluid collection. There was no association between the presence of a periprosthetic mass, bone marrow oedema, trochanteric bursitis or greater levels of abductor muscle destruction for cobalt or chromium.

Optical ray tracing-guided myopic laser in situ keratomileusis: 1-year clinical outcomes.

Purpose: To compare the safety, efficacy, and predictability of laser in situ keratomileusis treatments at 1 year postprocedure using a novel geometric ray tracing algorithm with outcomes of treatments using wavefront-optimized, wavefront-guided, and topography-guided ablation profiles of an excimer laser (WaveLight GmbH, Erlangen, Germany; Alcon Laboratories, Fort Worth, TX, USA).

Setting: Wellington Eye Clinic, Dublin, Ireland.

Design: Retrospective comparative case series.

The effect of acetabular inclination on metal ion levels following metal-on-metal hip arthroplasty.

Acetabular inclination angles have been suggested as a principal determinant of circulating metal ion levels in metal-on-metal hip arthroplasties. We aimed to determine whether inclination angle correlates with ion levels in arthroplasties using the Articular Surface Replacement (ASR) system. Patients undergoing ASR arthroplasties had blood metal ion levels and radiograph analysis performed a mean of 3.

Predictability of corneal flap thickness in laser in situ keratomileusis using a 200 kHz femtosecond laser.

Purpose: To compare the intended versus the resultant thickness of laser in situ keratomileusis (LASIK) flaps created with a new femtosecond laser and to report the 3-month postoperative refractive outcomes.

Setting: Wellington Eye Clinic, Dublin, Ireland.

Design: Retrospective consecutive case series.

Body mass index and height over three generations: evidence from the Lifeways cross-generational cohort study.

Background: Obesity and its measure of body mass index are strongly determined by parental body size. Debate continues as to whether both parents contribute equally to offspring body mass which is key to understanding the aetiology of the disease. The aim of this study was to use cohort data from three generations of one family to examine the relative maternal and paternal associations with offspring body mass index and how these associations compare with family height to demonstrate evidence of genetic or environmental cross-generational transmission.

Bovine tuberculosis and udder health in Irish dairy herds.

The association between bovine tuberculosis (TB) infection status based on results from the single intradermal comparative tuberculin test (SICTT) and milk production has been described in dairy cows in TB-infected herds in Ireland. The biological basis was uncertain, but could be related to increased TB susceptibility among lower producing dairy cows. In this study, the relationship between somatic cell count (as an objective measure of udder health) and SICTT reactivity (as a proxy for TB infection status) was investigated.

Spatial clustering of TB-infected cattle herds prior to and following proactive badger removal.

Bovine tuberculosis (TB) is primarily a disease of cattle. In both Ireland and the UK, badgers (Meles meles) are an important wildlife reservoir of infection. This paper examined the hypothesis that TB is spatially correlated in cattle herds, established the range of correlation and the effect, if any, of proactive badger removal on this.

Bovine tuberculosis and milk production in infected dairy herds in Ireland.

This study describes the relationship between bovine tuberculosis (TB) and milk yield in TB-infected dairy herds in Ireland. The study had two objectives: to determine whether cows detected as TB reactors (and thus subject to immediate slaughter) were likely to be the higher milk-producing cows, and to determine whether subclinical TB infection was associated with reduced milk production at or around the time of disclosure (detection). All Irish dairy herds restricted from trading between the 1(st) June 2004 and the 31(st) May 2005 as a result of two or more TB reactors by the Single Intradermal Comparative Tuberculin Test (SICTT) were considered for study.

Estimating the extent of spatial association of Mycobacterium bovis infection in badgers in Ireland.

Mycobacterium bovis infects the wildlife species badgers Meles meles who are linked with the spread of the associated disease tuberculosis (TB) in cattle. Control of livestock infections depends in part on the spatial and social structure of the wildlife host. Here we describe spatial association of M.

A long-term observational study of the impact of badger removal on herd restrictions due to bovine TB in the Irish midlands during 1989--2004.

An observational study was carried out, using data collected from four areas in the Irish midlands, between 1989 and 2004, to critically evaluate the long-term effects of proactive badger culling and to provide insights into reactive badger culling tuberculosis (TB) prevalence in cattle. Confirmed cattle herd TB incidence is the outcome measure used throughout. Relative to reactive culling, proactive badger culling was associated with a decrease in incidence in each of the 16 years of observation, which encompassed periods of both intensive and less-intensive badger removal.

Phase I trial of phenoxodiol delivered by continuous intravenous infusion in patients with solid cancer.

Background: Phenoxodiol is a multi-pathway initiator of apoptosis with broad anti-tumor activity and high specificity for tumor cells. Its biochemical effects are particularly suited to reversal of chemo-resistance, and the drug is being developed as a chemo-sensitizer of standard chemotherapeutics in solid cancers. This phase I, single-center trial was conducted to test a continuous intravenous dosing regimen of phenoxodiol in patients with late-stage, solid tumors to determine toxicity, pharmacokinetics, and preliminary efficacy.

Repeated measurement of the gas exchange threshold: relative size of measurement and biological variabilities.

If an individual's gas exchange threshold (GET) is measured on several separate occasions, without a change in aerobic fitness, a random variability will be observed. However, it is not known how much of this variability is biologically determined and how much results from variability in the calibration and measurement processes. The statistical re-sampling technique of Bootstrapping was used to estimate the variability of the GET on a single occasion.

Flavonoid compounds in maintenance of prostate health and prevention and treatment of cancer.

Compounds based on a flavonoid (di-phenolic) ring structure are emerging as a potentially important new class of pharmaceutical compounds with a broad range of biological activities, most prominent of which are their potential role as anticancer agents. These compounds exert a wide range of upregulating and downregulating effects on signal transduction processes within cells in both plants and animals. The observation that human communities, which consume large quantities of these compounds (legume-based vegetarian diets), have a lower incidence of many degenerative diseases and some cancers has led to the speculation that these compounds, or synthetic analogs, may be of therapeutic value.

The impact of badger removal on the control of tuberculosis in cattle herds in Ireland.

In Ireland, the herd prevalence of bovine tuberculosis has remained stable for several decades, and in common with several other countries, progress towards eradication has stalled. There is evidence in support of the potential role of infected badgers (Meles meles, a protected species) in bovine tuberculosis in Ireland and Britain. However, this evidence on its own has not been sufficient to prove disease causation.

Models for estimating the change-point in gas exchange data.

In subjects undertaking an incremental exercise test to exhaustion, the onset of metabolic acidosis can be detected by an increased rate of carbon dioxide output (VCO2) relative to the rate of increase of oxygen uptake (VO2). To locate the change-point (the gas exchange threshold) in such subjects, a two-line regression model relating these two quantities has been used, where the location of the change-point is unknown. We argue that statistical models where the change-point is set on time (rather than VO2) are more appropriate.