Model selection based on combined penalties for biomarker identification

The growing role of targeted medicine has led to an increased focus on the development of actionable biomarkers. Current penalized selection methods that are used to identify biomarker panels for classification in high-dimensional data, however, often result in highly complex panels that need careful pruning for practical use. In the framework of regularization methods, a penalty that is a weighted sum of the L₁ and L₀ norm has been proposed to account for the complexity of the resulting model. In practice, the limitation of this penalty is that the objective function is non-convex, non-smooth, the optimization is computationally intensive and the application to high-dimensional settings is challenging. In this paper, we propose a stepwise forward variable selection method which combines the L₀ with L₁ or L₂ norms. The penalized likelihood criterion that is used in the stepwise selection procedure results in more parsimonious models, keeping only the most relevant features. Simulation results and a real application show that our approach exhibits a comparable performance with common selection methods with respect to the prediction performance while minimizing the number of variables in the selected model resulting in a more parsimonious model as desired.     

Compound Heterozygosity for Hb Adana (HBA2: c.179G>A) and the –α3.7/αα Thalassemia Deletion in Greece: Clinical Phenotype and Genetic Counseling

Hb Adana (HBA2: c.179G>A) is found worldwide but is extremely rare and carriers are asymptomatic, with red cell indices similar to α⁺-thalassemia (α⁺-thal) carriers. First line screening tests are unable to detect the unstable hemoglobin (Hb). Coinheritance with the α-thal (–α^3.7) deletion is herein presented and the challenges involving genetic counseling of couples carrying the mutations are discussed.     

Pathological findings of Angiostrongylus vasorum infection in red foxes (Vulpes vulpes) from Central Italy,with the first report of a disseminated infection in this host species

In Europe, the red fox (Vulpes vulpes) is considered the reservoir of Angiostrongylus vasorum, nematode residing in the pulmonary arteries and right heart of dogs and many species of wild carnivores. Italy is considered one of the European countries where this nematode is actually spreading. Between May 2007 and November 2013, 62 foxes found dead in Central Italy were necropsied. Right heart and pulmonary arteries were opened and checked for the presence of adult parasites. Impression smears from sectioned lungs were examined for the presence of first-stage larvae, and samples of lungs were processed for histological examination. In order to detect eventual disseminated infections, samples of heart, pulmonary lymph nodes, liver, kidneys, and brain of foxes positive for A. vasorum at necropsy or lungs histological examination were processed for histological examination. An overall prevalence of 43.5 % was recorded. Light, mild, and severe lung lesions were detected in 33.3, 22.2, and 25.9 % of infected animals, respectively. Severe lesions were more frequent in animals younger than 12 months. In five infected foxes (18.5 %), no gross lesions were observed, while for three animals, angiostrongylosis was considered the cause of death. A case of disseminated angiostrongylosis was detected and another one was suspected. This is the firs report of disseminated angiostrongylosis in the fox.     

Correlation between myocardial enzyme serum levels and markers of inflammation with severity of coronary artery disease and Gensini score: A hospital-based,prospective study in Greek patients

Background

Our objective was to associate serum levels of myocardial enzymes and inflammatory biomarkers with severity of coronary artery disease (CAD).

Patients and methods

123 patients participated in our study, including 65 cases of acute myocardial infarction (MI), 27 cases of newly diagnosed CAD – without MI – and 31 controls. In all subjects, myocardial serum enzyme levels (creatine phosphokinase, aspartate aminotransferase, lactate dehydrogenase) and inflammatory indices (C-reactive protein, fibrinogen, white blood cells, and erythrocyte sedimentation rate) were measured. Patients were all submitted to coronary angiography and CAD severity was evaluated by Gensini score.

Results

Significant differences concerning enzyme serum levels and inflammatory indices were found to exist between the three study groups, being highest among patients with acute MI (p < 0.001). A significant association was demonstrated between Gensini score and serum enzyme levels as well as inflammatory biomarkers.

Conclusions

Our findings suggest that serum levels of myocardial enzymes and inflammatory indices correlate with CAD severity in Greek patients.