Towards Better Integration of Surrogate Models and Optimizers

Surrogate-Assisted Evolutionary Algorithms (SAEAs) have been proven to be very effective in solving (synthetic and real-world) computationally expensive optimization problems with a limited number of function evaluations. The two main components of SAEAs are: the surrogate model and the evolutionary optimizer, both of which use parameters to control their respective behavior. These parameters are likely to interact closely, and hence the exploitation of any such relationships may lead to the design of an enhanced SAEA. In this chapter, as a first step, we focus on Kriging and the Efficient Global Optimization (EGO) framework. We discuss potentially profitable ways of a better integration of model and optimizer. Furthermore, we investigate in depth how different parameters of the model and the optimizer impact optimization results. In particular, we determine whether there are any interactions between these parameters, and how the problem characteristics impact optimization results. In the experimental study, we use the popular Black-Box Optimization Benchmarking (BBOB) testbed. Interestingly, the analysis finds no evidence for significant interactions between model and optimizer parameters, but independently their performance has a significant interaction with the objective function. Based on our results, we make recommendations on how best to configure EGO

Potassium channel gene mutations rarely cause atrial fibrillation

BACKGROUND: Mutations in several potassium channel subunits have been associated with rare forms of atrial fibrillation. In order to explore the role of potassium channels in inherited typical forms of the arrhythmia, we have screened a cohort of patients from a referral clinic for mutations in the channel subunit genes implicated in the arrhythmia. We sought to determine if mutations in KCNJ2 and KCNE1-5 are a common cause of atrial fibrillation. METHODS: Serial patients with lone atrial fibrillation or atrial fibrillation with hypertension were enrolled between June 1, 2001 and January 6, 2005. Each patient underwent a standardized interview and physical examination. An electrocardiogram, echocardiogram and blood sample for genetic analysis were also obtained. Patients with a family history of AF were screened for mutations in KCNJ2 and KCNE1-5 using automated sequencing. RESULTS: 96 patients with familial atrial fibrillation were enrolled. Eighty-three patients had lone atrial fibrillation and 13 had atrial fibrillation and hypertension. Patients had a mean age of 56 years at enrollment and 46 years at onset of atrial fibrillation. Eighty-one percent of patients had paroxysmal atrial fibrillation at enrollment. Unlike patients with an activating mutation in KCNQ1, the patients had a normal QT(c )interval with a mean of 412 ± 42 ms. Echocardiography revealed a normal mean ejection fraction of 62.0 ± 7.2 % and mean left atrial dimension of 39.9 ± 7.0 mm. A number of common polymorphisms in KCNJ2 and KCNE1-5 were identified, but no mutations were detected. CONCLUSION: Mutations in KCNJ2 and KCNE1-5 rarely cause typical atrial fibrillation in a referral clinic population

Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA)

In a population-based cohort study of middle-aged people in Central Europe, Stefan Kääb and colleagues find an association between electrocardiographic early repolarization pattern and mortality risk

Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006)

The 4q12 Amplicon in Malignant Peripheral Nerve Sheath Tumors: Consequences on Gene Expression and Implications for Sunitinib Treatment

Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive tumors which originate from Schwann cells and develop in about 10% of neurofibromatosis type 1 (NF1) patients. The five year survival rate is poor and more effective therapies are needed. Sunitinib is a drug targeting receptor tyrosine kinases (RTK) like PDGFRα, c-Kit and VEGFR-2. These genes are structurally related and cluster on chromosomal segment 4q12.) was present in MPNST cell lines suggesting an autocrine loop. We show that VEGF triggered signal transduction via the MAPK pathway, which could be blocked by sunitinib. might serve as predictive markers for efficacy of sunitinib