Chikungunya Outbreak Risks after the 2014 Outbreak, Dominican Republic.

The 2014 chikungunya outbreak in the Dominican Republic resulted in intense local transmission, with high postoutbreak seroprevalence. The resulting population immunity will likely minimize risk for another large outbreak through 2035, but changes in population behavior or environmental conditions or emergence of different virus strains could lead to increased transmission

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Current and emerging developments in subseasonal to decadal prediction

Weather and climate variations of subseasonal to decadal timescales can have enormous social, economic and environmental impacts, making skillful predictions on these timescales a valuable tool for decision makers. As such, there is a growing interest in the scientific, operational and applications communities in developing forecasts to improve our foreknowledge of extreme events. On subseasonal to seasonal (S2S) timescales, these include high-impact meteorological events such as tropical cyclones, extratropical storms, floods, droughts, and heat and cold waves. On seasonal to decadal (S2D) timescales, while the focus remains broadly similar (e.g., on precipitation, surface and upper ocean temperatures and their effects on the probabilities of high-impact meteorological events), understanding the roles of internal and externally-forced variability such as anthropogenic warming in forecasts also becomes important. The S2S and S2D communities share common scientific and technical challenges. These include forecast initialization and ensemble generation; initialization shock and drift; understanding the onset of model systematic errors; bias correct, calibration and forecast quality assessment; model resolution; atmosphere-ocean coupling; sources and expectations for predictability; and linking research, operational forecasting, and end user needs. In September 2018 a coordinated pair of international conferences, framed by the above challenges, was organized jointly by the World Climate Research Programme (WCRP) and the World Weather Research Prograame (WWRP). These conferences surveyed the state of S2S and S2D prediction, ongoing research, and future needs, providing an ideal basis for synthesizing current and emerging developments in these areas that promise to enhance future operational services. This article provides such a synthesis

Establishing a Framework to Transition High Frequency Oscillations to Routine Clinical Care in Patients with Focal Epilepsy

High frequency oscillations (HFOs), characteristic oscillations observable using electroencephalography (EEG), are a promising and specific marker of the epileptogenic zone (EZ). However, there remain several obstacles to the implementation of HFOs as a prospective tool in the treatment of epilepsy. The identification of HFOs lacks universal standards and demands large time commitments from epileptologists. Therefore, this work involved the implementation and validation of novel frameworks for identifying HFOs, and for evaluating these HFOs as markers of the EZ. An epoched framework was implemented to facilitate the visual identification of HFOs, through which poor reliability was observed between reviewers. Furthermore, it was found that the temporal efficiency of visually evaluating HFOs within the epoched framework marked a substantial improvement over previously reported evaluation times. Using generalizability theory, it was then extended to determine effective methods of achieving highly reliable visual HFO evaluations, which included averaging ratings from at least 12 visual reviewers, or employing a training paradigm to increase the correlation of the ratings across reviewers. A novel surrogate marker (uGIC) of HFO activity was implemented and found to be correlated with HFOs detected algorithmically at low or high thresholds, all of which were found to be markers of the seizure onset zone overall. A retrospective framework was implemented to improve the accuracy of delineating the margins of resection with respect to EEG electrodes. A deformable method of image co-registration and a hybrid method of estimating electrode shift were shown to more effectively compensate for post-surgical shifts in brain anatomy. Resecting the uGIC or detected HFOs were found to have a positive effect on seizure freedom. Notably, the inclusion of lower-threshold oscillations was beneficial in facilitating the visual evaluation of HFOs, and in the identification of the EZ. Together, the findings of the studies undertaken herein provide a comprehensive framework to serve as the basis for transitioning high frequency oscillations to a feasible and meaningful part of the routine pre-surgical work-up in patients with focal epilepsy