Do we achieve LDL-cholesterol targets in routine clinical practice? Evidence from a tertiary care hospital in Sri Lanka

Background: Statins are widely used for primary and secondary prevention of cardiovascular disease (CVD). European Society of Cardiology / European Atherosclerosis Society (ESC/EAS) guidelines recommend LDL-cholesterol targets based on CVD risk.Objectives: This study aimed to determine whether LDL-cholesterol targets recommended by2016 ESC/EASare achieved in routine clinical practice.Methods: This paper is based on baseline data of patients recruited to a controlled clinical trial conducted at a tertiary care hospital. Participants have been on atorvastatin for >2 months. Demographic and clinical data were obtained using clinic records and interviewer administered questionnaires. LDL-cholesterol was assessed using Friedewald equation (when triglyceride was <400mg/dL) or by direct measurement (when triglyceride was ≥400mg/dL). Each participant’s CVD risk level and appropriate LDL-cholesterol target (very-high CVD risk:<70mg/dL; high CVD risk:<100mg/dL; low to moderate CVD risk:<115mg/dL) was determined according to 2016 ESC/EAS Guideline.Results: 101 patients were studied. (Women: 76.2%; mean-age: 61.2:±9.3years). Prevalence of coronary heart disease, ischaemic stroke, diabetes, hypertension and smoking was 30.7%, 4%, 77.2%, 80.2% and 4%, respectively. According to CVD risk level 80.2%, 15.8% and 4% were in very-high, high and moderate risk categories, respectively. Most were on atorvastatin 10mg (45.5%) followed by 20mg (43.6%), 40mg (8.9%), 30mg (1%) and 5mg (1%). Median duration of treatment was 41-months. Overall, only 12.9% had achieved target LDL-cholesterol (very-high risk: 7.4%; high risk: 37.5%, moderate risk: 25%; p=0.003). Men did better than women in achieving target LDL-cholesterol (men: 29.2%, women: 7.8%; p=006). There was no difference based on age, comorbidities or atorvastatin dose.Conclusions: In the study population majority has failed to achieve LDL-cholesterol targets recommended by 2016 ESC/EAS. Failure to achieve targets was more common among women and those having very-high CVD risk. Reason for suboptimal target achievement has to be studied further.Acknowledgement: Funded by University of Sri Jayewardenepura Research Grant (ASP/01/RE/MED/2015/54) and Ceylon College of Physicians Research Grant (2014)

Measurement of soil lead bioavailability and influence of soil types and properties:a review

Lead (Pb) is a widespread heavy metal which is harmful to human health, especially to young children. To provide a human health risk assessment that is more relevant to real conditions, Pb bioavailability in soils is increasingly employed in the assessment procedure. Both in vivo and in vitro measurements for lead bioavailability are available. In vivo models are time- consuming and expensive, while in vitro models are rapid, economic, reproducible, and reliable while involving more uncertainties. Uncertainties in various measurements create difficulties in accurately predicting Pb bioavailability, resulting in the unnecessary remediation of sites. In this critical review, we utilised available data from in vivo and in vitro studies to identify the key parameters influencing the in vitro measurements, and presented uncertainties existing in Pb bioavailability measurements. Soil type, properties and metal content are reported to influence lead bioavailability; however, the differences in methods for assessing bioavailability and the differences in Pb source limit one’s ability to conduct statistical analyses on influences of soil factors on Pb bioavailability. The information provided in the review is fundamentally useful for the measurement of bioavailability and risk assessment practices

Measurement of soil lead bioavailability and influence of soil types and properties:a review

Lead (Pb) is a widespread heavy metal which is harmful to human health, especially to young children. To provide a human health risk assessment that is more relevant to real conditions, Pb bioavailability in soils is increasingly employed in the assessment procedure. Both in vivo and in vitro measurements for lead bioavailability are available. In vivo models are time- consuming and expensive, while in vitro models are rapid, economic, reproducible, and reliable while involving more uncertainties. Uncertainties in various measurements create difficulties in accurately predicting Pb bioavailability, resulting in the unnecessary remediation of sites. In this critical review, we utilised available data from in vivo and in vitro studies to identify the key parameters influencing the in vitro measurements, and presented uncertainties existing in Pb bioavailability measurements. Soil type, properties and metal content are reported to influence lead bioavailability; however, the differences in methods for assessing bioavailability and the differences in Pb source limit one’s ability to conduct statistical analyses on influences of soil factors on Pb bioavailability. The information provided in the review is fundamentally useful for the measurement of bioavailability and risk assessment practices

A meta-analysis to correlate lead bioavailability and bioaccessibility and predict lead bioavailability

Defining the precise clean-up goals for lead (Pb) contaminated sites requires site-specific information on relative bioavailability data (RBA). While in vivo measurement is reliable but resource insensitive, in vitro approaches promise to provide high-throughput RBA predictions. One challenge on using in vitro bioaccessibility (BAc) to predict in vivo RBA is how to minimize the heterogeneities associated with in vivo-in vitro correlations (IVIVCs) stemming from various biomarkers (kidney, blood, liver, urinary and femur), in vitro approaches and studies. In this study, 252 paired RBA-BAc data were retrieved from 9 publications, and then a Bayesian hierarchical model was implemented to address these random effects. A generic linear model (RBA (%) = (0.87 ± 0.16) × BAc + (4.70 ± 2.47)) of the IVIVCs was identified. While the differences of the IVIVCs among the in vitro approaches were significant, the differences among biomarkers were relatively small. The established IVIVCs were then applied to predict Pb RBA of which an overall Pb RBA estimation was 0.49 ± 0.25. In particular the RBA in the residential land was the highest (0.58 ± 0.19), followed by house dust (0.46 ± 0.20) and mining/smelting soils (0.45 ± 0.31). This is a new attempt to: firstly, use a meta-analysis to correlate Pb RBA and BAc; and secondly, estimate Pb RBA in relation to soil types

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

Synthesis of earthworm trace metal uptake and bioaccumulation data: role of soil concentration, earthworm ecophysiology, and experimental design

Trace metals can be essential for organo-metallic structures and oxidation-reduction in metabolic processes or may cause acute or chronic toxicity at elevated concentrations. The uptake of trace metals by earthworms can cause transfer from immobilized pools in the soil to predators within terrestrial food chains. We report a synthesis and evaluation of uptake and bioaccumulation empirical data across different metals, earthworm genera, ecophysiological groups, soil properties, and experimental conditions (metal source, uptake duration, soil extraction method). Peer-reviewed datasets were extracted from manuscripts published before June 2019. The 56 studies contained 3513 soil-earthworm trace metal concentration paired data sets across 11 trace metals (As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sb, U, Zn). Across all field and laboratory experiments studied, the median concentrations of Hg, Pb, and Cd in earthworm tissues that were above concentrations known to be hazardous for consumption by small mammals and avian predators but not for Cu, Zn, Cr, Ni, and As. Power regressions show only Hg and Cd earthworm tissue concentrations were well-correlated with soil concentrations with R2 > 0.25. However, generalized linear mixed-effect models reveal that earthworm concentrations were significantly correlated with soil concentrations for log-transformed Hg, Cd, Cu, Zn, As, Sb (p < 0.05). Factors that significantly contributed to these relationships included earthworm genera, ecophysiological group, soil pH, and organic matter content. Moreover, spiking soils with metal salts, shortening the duration of exposure, and measuring exchangeable soil concentrations resulted in significantly higher trace metal uptake or greater bioaccumulation factors. Our results highlight that earthworms are able to consistently bioaccumulate toxic metals (Hg and Cd only) across field and laboratory conditions. However, future experiments should incorporate greater suites of trace metals, broader genera of earthworms, and more diverse laboratory and field settings to generate data to devise universal quantitative relationships between soil and earthworm tissue concentrations

Exploring the Use of a Care-Focused Approach to Foster Gender Inclusion in the Construction Industry in Australia

Construction engineering is one of the industries in Australia where researchers and practitioners attempt to close the gender gap via various policies and practices. However, even after some decades, the construction-engineering industry in Australia still reports low female participation, and the problem remains unsolved. Although a few studies have focused on finding why the current policies and practices fail to increase the female representation in male-dominant industries, there is very little use of an “inclusion lens” to identify how to retain women while enhancing their sense of inclusion at work. It is believed that unlike other concepts, such as diversity, equality, and equity, the subjective nature of the concept of “inclusion” necessitates a critical discussion to form a sound theoretical base. Although previous studies have provided conceptual and quantitative refinement of the inclusion constructs (i.e., fostering a sense of belongingness and acceptance of individual uniqueness), there is a lack of emphasis on theoretical and empirical explanations of or suggestions for a suitable mechanism to achieve workplace inclusion, especially in highly gendered workplace contexts. Hence, the purpose of this thesis is to explore the overarching esearch question: How can gender inclusion be achieved in the construction-engineering industry? To answer the research question, this study employed a constructivist, grounded-theory approach. Data were collected using in-depth interviews with 35 senior managers, human resources managers, and engineers working in engineering consultancy firms, construction firms, research and education organisations, government regulatory bodies, and a professional association in Australia. Three data-collection phases were carried out from December 2018 to January 2020. Concurrent data analysis was executed throughout the data-collection period