Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease

Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance

Different response to vitamin D supplementation of PVCs from RVOT and non-outflow tract RV regions

Abstract Background Recent publications have shown that premature ventricular contractions (PVCs)_ from the right ventricular outflow tract (RVOT) have a good response to vitamin D supplementation in patients that have a vitamin D deficiency. Purpose The present study aimed to compare the response to vitamin D supplementation of of 2 types of PVCs: from RVOT and from other RV areas outside RVOT Methods Our study included 16 patients from the Outpatient Clinic of the Rehabilitation Hospital, of whom all had vitamin D deficiency. Four patients had high PVC burden with an RV morphology other than RVOT and were matched 1:3 for age and sex with 12 patients with high PVC burden and RVOT morphology. Results Mean age was 26 years in both group and 33% were females. The mean 25-OH vitamin D value was 17.7±2.9 ng/ml in the non RVOT group and 21.6±5.3 ng/ml in the RVOT group. After 3±1.7 month of treatment with 2000–5000 U/day, 25 OH vitamin D increased to. 31.1±3.2. in the non-RVOT group and to 35.9±5.1 in the RVOT group. After treatment PVC burden decreased from 19956±2618 to 19399±3015 (NS) in the non-RVOT group and from 21057±9594 to 4249±2835 (p=0.0001) in the RVOT group. Conclusions After 3 months of vitamin D supplementation in patients with high burden PVC and vitamin D deficiency, the burden decreased significantly by more than 75% in the RVOT morphology group but not in the non- RVOT morphology group. Funding Acknowledgement Type of funding sources: None. PVC burden in the non RVOT groupPVC burden in the RVOT group </jats:sec

Combining tumor genome simulation with crowdsourcing to benchmark somatic single-nucleotide-variant detection

The detection of somatic mutations from cancer genome sequences is key to understanding the genetic basis of disease progression, patient survival and response to therapy. Benchmarking is needed for tool assessment and improvement but is complicated by a lack of gold standards, by extensive resource requirements and by difficulties in sharing personal genomic information. To resolve these issues, we launched the ICGC-TCGA DREAM Somatic Mutation Calling Challenge, a crowdsourced benchmark of somatic mutation detection algorithms. Here we report the BAMSurgeon tool for simulating cancer genomes and the results of 248 analyses of three in silico tumors created with it. Different algorithms exhibit characteristic error profiles, and, intriguingly, false positives show a trinucleotide profile very similar to one found in human tumors. Although the three simulated tumors differ in sequence contamination (deviation from normal cell sequence) and in subclonality, an ensemble of pipelines outperforms the best individual pipeline in all cases. BAMSurgeon is available at https://github.com/adamewing/bamsurgeon/

SeqControl:Process control for DNA sequencing

As high-throughput sequencing continues to increase in speed and throughput, routine clinical and industrial application draws closer. These 'production' settings will require enhanced quality monitoring and quality control to optimize output and reduce costs. We developed SeqControl, a framework for predicting sequencing quality and coverage using a set of 15 metrics describing overall coverage, coverage distribution, basewise coverage and basewise quality. Using whole-genome sequences of 27 prostate cancers and 26 normal references, we derived multivariate models that predict sequencing quality and depth. SeqControl robustly predicted how much sequencing was required to reach a given coverage depth (area under the curve (AUC) = 0.993), accurately classified clinically relevant formalin-fixed, paraffin-embedded samples, and made predictions from as little as one-eighth of a sequencing lane (AUC = 0.967). These techniques can be immediately incorporated into existing sequencing pipelines to monitor data quality in real time. SeqControl is available at http://labs.oicr.on.ca/Boutros-lab/software/SeqControl/.</p

Impact of chronic coronary syndromes on cardiovascular hospitalization and mortality: the ESC-EORP CICD-LT registry

Abstract Aims In Europe, global data on guideline adherence, geographic variations, and determinants of clinical events in patients with chronic coronary syndrome (CCS) remain suboptimal. The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischemic Cardiovascular Disease Long-Term (CICD-LT) registry is a prospective European registry, and was designed to describe the profile, management, and outcomes of patients with CCS across the ESC countries. Methods and results We aimed to investigate clinical events at 1-year follow-up from the ESC EORP CICD-LT registry. One-year outcomes of 6655 patients from the 9174 recruited in this European registry were analysed. Overall, 168 patients (2.5%) died, mostly from cardiovascular (CV) causes (n = 97, 1.5%). Northern Europe had the lowest CV mortality rate, while southern Europe had the highest (0.5 vs. 2.0%, P = 0.04). Women had a higher rate of CV mortality compared with men (2.0 vs. 1.3%, P = 0.02). During follow-up, 1606 patients (27.1%) were hospitalized at least once, predominantly for CV indications (n = 1220, 20.6%). Among the population with measured low-density lipoprotein-cholesterol level at 1 year, 1434 patients (66.5%) were above the recommended target. Age, history of atrial fibrillation, previous stroke, liver disease, chronic obstructive pulmonary disease or asthma, increased serum creatinine, and impaired left ventricular function were associated with an increased risk of CV death or hospitalization. Conclusion In the CICD registry, the majority of patients with CCS have uncontrolled CV-risk factors. The 1-year mortality rate is low, but these patients are frequently hospitalized for CV causes. Early identification of comorbidities may represent an opportunity for enhanced care and better outcomes. </jats:sec

Cohort profile. the ESC-EORP chronic ischemic cardiovascular disease long-term (CICD LT) registry

The European Society of cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischemic Cardiovascular Disease registry Long Term (CICD) aims to study the clinical profile, treatment modalities and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid and long term outcomes and their determinants in this population

The ESC-EORP Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry

Abstract Aims The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry aims to study the clinical profile, treatment modalities, and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular (CV) risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid- and long-term outcomes and their determinants in this population. Methods and results Nine thousand one hundred and seventy-four patients over 18 years with documented CICD defined by a history acute coronary syndrome with/without ST elevation, previous coronary revascularization, or stable coronary artery disease were enrolled between 1 May 2015 and 31 July 2018. Individual patient data on clinical profile, biology, and treatment modalities were collected across 154 centres from 20 ESC countries. Two years of follow-up is scheduled in order to determine the following clinical outcomes: all-cause and CV death, all-cause and CV hospitalizations, changes in medications, and quality of life using the EuroQol5D-5L score. Conclusion The CICD LT is an international registry of care and outcomes of patients hospitalized with CICD which will provide insights into the contemporary profile and management of patients with this common disease. </jats:sec