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)

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

Cardiac rhabdomyoma leading to an early neonatal death

(Key words: cardiac rhabdomyoma, neonate

Data from: The Genome sequence of a widespread apex predator, the golden eagle (Aquila chrysaetos)

Biologists routinely use molecular markers to identify conservation units, to quantify genetic connectivity, to estimate population sizes, and to identify targets of selection. Many imperiled eagle populations require such efforts and would benefit from enhanced genomic resources. We sequenced, assembled, and annotated the first eagle genome using DNA from a male golden eagle (Aquila chrysaetos) captured in western North America. We constructed genomic libraries that were sequenced using Illumina technology and assembled the high-quality data to a depth of ~40x coverage. The genome assembly includes 2,552 scaffolds >10 Kb and 415 scaffolds >1.2 Mb. We annotated 16,571 genes that are involved in myriad biological processes, including such disparate traits as beak formation and color vision. We also identified repetitive regions spanning 92 Mb (~6% of the assembly), including LINES, SINES, LTR-RTs and DNA transposons. The mitochondrial genome encompasses 17,332 bp and is ~91% identical to the Mountain Hawk-Eagle (Nisaetus nipalensis). Finally, the data reveal that several anonymous microsatellites commonly used for population studies are embedded within protein-coding genes and thus may not have evolved in a neutral fashion. Because the genome sequence includes ~800,000 novel polymorphisms, markers can now be chosen based on their proximity to functional genes involved in migration, carnivory, and other biological processes

transposable elements_repeatmasker_kmer70-v2-min200-scaffolds.fa

############################ ###### RepeatMasker ######## ############################ ## RepeatMasker version 4.0.2 ## RepeatMaskerLibrary-20130422 version ## command: RepeatMasker -nolow -no_is -norna -dir . \ -lib RepeatMaskerLib.embl.lib \ kmer70-v2-min200-scaffolds.fa ## output files: repeatmasker_kmer70-v2-min200-scaffolds.fa.masked repeatmasker_kmer70-v2-min200-scaffolds.fa.tb

Abus de confiance : diversité des actes de détournement

Panorama Droit pénal des affaire

transposable elements_RepeatProteinMask output_ge_v2_all

############################ ##### RepeatProteinMask #### ############################ ## version: 4.0.2 ## command: RepeatProteinMask -noLowSimple -pvalue 1e-4 -engine abblast kmer70-v2-min200-scaffolds.fa ## output files: ge_v2_all.anno