Atrial Fibrillation and the Prognostic Performance of Biomarkers in Heart Failure

BACKGROUND: Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide, C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin, co-peptin, growth differentiation factor-15, soluble Suppressor of Tumorigenicitiy (sST2), galectin-3, and procalcitonin plasma concentrations were measured in a prospective, multicenter study of adults with HF. AF was defined as a previous history of AF, and/or presence of AF/flutter on baseline 12-lead electrocardiogram. The primary outcome was the composite of HF-hospitalization or all-cause mortality at 2 years. RESULTS: Among 1099 patients (age 62 +/- 12years, 28% female), 261(24%) patients had AF. Above-median concentrations of all biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for galectin-3 and sST2. In considering NT-proBNP for additive risk stratification, sST2 (adjusted hazard ratio [AHR]1.85, 95%confidence interval [C.I.] 1.17-2.91) and galectin-3 (AHR1.85, 95%C.I. 1.09-2.45) were independently associated with increased primary outcome only in the presence of AF. The prognostic performance of sST2 was also stronger in AF for all-cause mortality (AF: AHR2.82, 95%C.I. 1.26-6.21; non-AF: AHR1.78, 95% C.I. 1.14-2.76 without AF), while galectin-3 predicted HF-hospitalization only in AF (AHR1.64, 95%C.I. 1.03-2.62). CONCLUSIONS: AF modified the prognostic utility of selected guideline-endorsed HF-biomarkers. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF

Development of a Stepping Force Analgesic Meter for a Rat Arthritic Model

Behavioural assessment of experimental pain is an essential method for analysing and measuring pain levels. Rodent models, which are widely used in behavioural tests, are often subject to external forces and stressful manipulations that cause variability of the parameters measured during the experiment. Therefore, these parameters may be inappropriate as indicators of pain. In this article, a stepping-force analgesimeter was designed to investigate the variations in the stepping force of rats in response to pain induction. The proposed apparatus incorporates new features, namely an infrared charge-coupled device (CCD) camera and a data acquisition system. The camera was able to capture the locomotion of the rats and synchronise the stepping force concurrently so that each step could be identified. Inter-day and intra-day precision and accuracy of each channel (there were a total of eight channels in the analgesimeter and each channel was connected to one load cell and one amplifier) were studied using different standard load weights. The validation studies for each channel also showed convincing results whereby intra-day and inter-day precision were less than 1% and accuracy was 99.36–100.36%. Consequently, an in vivo test was carried out using 16 rats (eight females and eight males). The rats were allowed to randomly walk across the sensor tunnel (the area that contained eight channels) and the stepping force and locomotion were recorded. A non-expert, but from a related research domain, was asked to differentiate the peaks of the front and hind paw, respectively. The results showed that of the total movement generated by the rats, 50.27 ± 3.90% in the case of the male rats and 62.20 ± 6.12% in that of the female rats had more than two peaks, a finding which does not substantiate the assumptions made in previous studies. This study also showed that there was a need to use the video display frame to distinguish between the front and hind paws in the case of 48.80 ± 4.01% of the male rats and 66.76 ± 5.35% of the female rats. Evidently the assumption held by current researchers regarding stepping force measurement is not realistic in terms of application, and as this study has shown, the use of a video display frame is essential for the identification of the front and hind paws through the peak signals

Diagnostic Accuracy of the Electrocardiogram for Heart Failure With Reduced or Preserved Ejection Fraction

Current heart failure (HF) guidelines recommend electrocardiography (ECG) as an essential initial investigation in a patient's workup. 1 However, these recommendations were based on studies primarily including patients with HF with reduced ejection fraction (HFrEF). 1 , 2 , 3 Guidelines do not distinguish HFrEF from HF with preserved and mid-range ejection fraction (HFpEF and HFmrEF) in their ECG recommendations. We hypothesized that a normal ECG does not exclude HFpEF and has a considerably lower sensitivity for diagnosing HFpEF than HFrEF

Genome-Wide Association Meta-analysis Identifies Novel Variants Associated With Fasting Plasma Glucose in East Asians

Fasting plasma glucose (FPG) has been recognized as an important indicator for the overall glycemic state preceding the onset of metabolic diseases. So far, most indentified genome-wide association loci for FPG were derived from populations with European ancestry, with a few exceptions. To extend a thorough catalog for FPG loci, we conducted meta-analyses of 13 genome-wide association studies in up to 24,740 nondiabetic subjects with East Asian ancestry. Follow-up replication analyses in up to an additional 21,345 participants identified three new FPG loci reaching genome-wide significance in or near PDK1-RAPGEF4, KANK1, and IGF1R. Our results could provide additional insight into the genetic variation implicated in fasting glucose regulation

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression1,2, is known for its association with fasting glucose levels3,4. The evidence of an association with T2D for PEPD5 and HNF4A6,7 has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D

Clinical Studies in HFE haemochromatosis

© 2018 Sim Yee OngHFE haemochromatosis is the most common iron overload disease. Since the discovery of the HFE gene is 1996, it is readily diagnosed using a genetic test rather than using liver biopsies. It is an autosomal recessive disease and the most common form of HFE haemochromatosis is homozygosity for p.C282Y. Homozygosity for this substitution accounts for more than 90% of haemochromatosis in Australia. Excessive iron accumulates due to malfunction of the HFE protein that leads to excess iron absorption. As a result, excess iron builds up in various organs including liver, joints, heart, pancreas, pituitary gland and skin, that may cause end-organ damage including liver cirrhosis, cardiac failure, diabetes mellitus, hypopituitarism and skin pigmentation. Symptomatically, fatigue and arthralgia are the major complaints reported by patients with haemochromatosis. This disease is easily treatable, as the blood contains a significant proportion of the body’s iron, so excess iron can be removed via the blood through phlebotomy. Multiple studies have found that individuals with high total body iron, defined by serum ferritin of more than 1000ug/L, have the highest risk of developing complications including liver cirrhosis. In the last decade, some have suggested that patients with elevated body iron but with serum ferritin less than 1000ug/L, here defined as moderate iron overload, might not need treatment, as they might not have symptomatic manifestations of the disease. However, there have been no randomised controlled trials to examine the treatment benefits for individuals with moderately elevated iron. To answer this question, a randomised controlled trial (Mi-Iron) was conducted which was the major aim of my PhD to examine if removing excess iron would have an impact on patient-reported outcomes, particularly fatigue, as well as liver fibrosis and oxidative stress. This demonstrated that with treatment, there was an improvement in fatigue and its cognitive subcomponent, and the affect component of the arthritis score. There was also an improvement in the liver fibrosis marker, Hepascore, and oxidative stress marker plasma F2-isoprostane, by removing excess iron in this cohort when compared to the control group who did not have iron reduction. These results, therefore, support current guidelines that all patients with haemochromatosis with elevated serum ferritin should have phlebotomy to return body iron levels to normal levels. In the second clinical study, the relationship of serum ferritin with non-invasive markers of liver fibrosis including transient elastography, Hepascore, aspartate aminotransaminase (AST) to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) to assess for liver fibrosis and cirrhosis in HFE p.C282Y homozygotes was examined. This study was conceived due to the shift from using liver biopsy to the increasing use of non-invasive techniques to assess liver fibrosis and cirrhosis. This showed that there was a linear relationship of serum ferritin with Hepascore, indicating that higher body iron is associated with more advanced liver fibrosis and cirrhosis. This relationship was also found for APRI and FIB-4 scores. These findings are important as they provide extra information in utilising these scores to assess liver fibrosis and cirrhosis in haemochromatosis. In the third study, the hand joint arthritis in people with haemochromatosis was examined. Arthralgia is one of the major complaints of individuals with haemochromatosis and is often one of the earliest symptoms of haemochromatosis. It is often difficult to differentiate between haemochromatosis arthropathy and osteoarthritis in the hands. The second and third metacarpophalangeal joints are described to be more commonly affected in individuals with haemochromatosis. By examining the data from HealthIron, a haemochromatosis cohort extracted from a population study that assessed the burden of disease due to iron overload, I found that there was an increase in first metacarpophalangeal joint abnormalities in those with HFE p.C282Y homozygosity, comparable to the frequency of involvement of second and third metacarpophalangeal joints

Deep learning Convolutional Neural Network for Unconstrained License Plate Recognition

The evolve of neural networks algorithm into deep learning convolutional neural networks seems like the next generation for object detection. This algorithm works has a significantly better accuracy and did not tied to any particular aspect ratio. License plate and traffic signs detection and recognition have a number of different applications relevant for transportation systems, such as traffic monitoring, detection of stolen vehicles, driver navigation support or any statistical research. An exponential increase in number of vehicles necessitates the use of automated systems to maintain vehicle information. The information is highly required for both management of traffic as well as reduction of crime. Number plate recognition is an effective way for automatic vehicle identification. A number of methods have been proposed, but only for particular cases and working under constraints (e.g. known text direction or high resolution). Deep learning convolutional neural networks work well especially in handles occlusion/rotation better, therefore we believe this approach is able to provide a better solution to the unconstrained license plate recognition problem

Deep learning Convolutional Neural Network for Unconstrained License Plate Recognition

The evolve of neural networks algorithm into deep learning convolutional neural networks seems like the next generation for object detection. This algorithm works has a significantly better accuracy and did not tied to any particular aspect ratio. License plate and traffic signs detection and recognition have a number of different applications relevant for transportation systems, such as traffic monitoring, detection of stolen vehicles, driver navigation support or any statistical research. An exponential increase in number of vehicles necessitates the use of automated systems to maintain vehicle information. The information is highly required for both management of traffic as well as reduction of crime. Number plate recognition is an effective way for automatic vehicle identification. A number of methods have been proposed, but only for particular cases and working under constraints (e.g. known text direction or high resolution). Deep learning convolutional neural networks work well especially in handles occlusion/rotation better, therefore we believe this approach is able to provide a better solution to the unconstrained license plate recognition problem

Performance evaluation of CPF approved trustee stocks.

The main objective of this study is to provide a better understanding of the performance of CPF approved trustee stocks and their difference from non-trustee stocks.This study is divided into two main sections. In the first, we will use the DBS CPF Approved Trustee Stocks Index as a proxy to trustee stock performance. The index is compared against the market index, SES All-Singapore Index. Risk return ratios such as Coefficient of Variance, Sharpe Index and Treynor Index are then used to compare the performance of the two indices. In the second section this study, 64 trustee stock companies were chosen and their financial ratios from year 1994 to 1996 were collected