We performed a retrospective outcome study of 199 patients who underwent resective epilepsy surgery from 1998 to 2012 and had a minimum of one-year follow-up at the University Hospitals Leuven. Our ...aim was to assess seizure outcome, prognostic factors for seizure outcome and complication rate. Good seizure outcome after surgery was 38 % at 5 years and 34 % at 10 years follow-up. Good seizure outcome over the previous year at last follow-up, however, was 77 %, which could be explained by the ‘running-down phenomenon’, i.e. seizure freedom after initial recurrent epilepsy in 32 % of the patients, mainly after temporal lobe surgery. Good seizure outcome for at least 1 year at the last visit was 82 % for temporal and 62 % for extra-temporal lobe interventions. Other variables predictive of a good seizure outcome were not identified. Permanent complications of epilepsy surgery were observed in 31 %. The most important were word finding difficulties (22 %), depression (18 %) and memory deficits (12 %). In conclusion, epilepsy surgery is an excellent treatment option for selected patients, with a good seizure outcome in around 80 % of patients and complications in about 30 %.
A key challenge in the field of HIV-1 protein evolution is the identification of coevolving amino acids at the molecular level. In the past decades, many sequence-based methods have been designed to ...detect position-specific coevolution within and between different proteins. However, an ensemble coevolution system that integrates different methods to improve the detection of HIV-1 protein coevolution has not been developed.
We integrated 27 sequence-based prediction methods published between 2004 and 2013 into an ensemble coevolution system. This system allowed combinations of different sequence-based methods for coevolution predictions. Using HIV-1 protein structures and experimental data, we evaluated the performance of individual and combined sequence-based methods in the prediction of HIV-1 intra- and inter-protein coevolution. We showed that sequence-based methods clustered according to their methodology, and a combination of four methods outperformed any of the 27 individual methods. This four-method combination estimated that HIV-1 intra-protein coevolving positions were mainly located in functional domains and physically contacted with each other in the protein tertiary structures. In the analysis of HIV-1 inter-protein coevolving positions between Gag and protease, protease drug resistance positions near the active site mostly coevolved with Gag cleavage positions (V128, S373-T375, A431, F448-P453) and Gag C-terminal positions (S489-Q500) under selective pressure of protease inhibitors.
This study presents a new ensemble coevolution system which detects position-specific coevolution using combinations of 27 different sequence-based methods. Our findings highlight key coevolving residues within HIV-1 structural proteins and between Gag and protease, shedding light on HIV-1 intra- and inter-protein coevolution.
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