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Champion, K.

Publications and source records attributed to Champion, K..

2 recordsLinked to original sources

An Oscillatory Mechanism for Multi-level Storage in Short-term Memory

Oscillatory activity is commonly observed during the maintenance of information in short-term memory, but its role remains unclear. Non-oscillatory models of short-term memory storage are able to encode stimulus identity through their spatial patterns of activity, but are typically limited to either an all-or-none representation of stimulus amplitude or exhibit a biologically implausible exact-tuning condition. Here, we demonstrate a simple phase-locking mechanism by which oscillatory input enables a circuit to generate persistent or sequential activity patterns that encode information not only in their location but also in their discretely graded amplitudes. SignificanceA core observation in many memory systems and tasks is the presence of oscillations during memory maintenance. Here, we demonstrate a mechanism for the accumulation and storage of information in short-term memory in which oscillatory activity enables a solution to long-standing challenges in modeling the persistent neural activity underlying working memory. These challenges include the ability to encode information with low firing rates, multi-level storage of stimulus amplitude without extreme fine tuning, and multi-level storage of information in sequential activity. Altogether, this work proposes a new class of models for the storage of information in working memory, a new potential role for brain oscillations, and a novel dynamical mechanism for multi-stability.

neuroscience

Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms

Identification of genomic mutations by molecular testing plays an important role in diagnosis, prognosis, and treatment of myeloid neoplasms. Next-generation sequencing (NGS) is an efficient method for simultaneous detection of clinically significant genomic mutations with high sensitivity. However, due to lack of standard NGS protocols, the application of NGS for hematologic malignancies into clinical settings remains limited. We report development and validation of a 48-gene NGS panel for molecular profiling of myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. A bioinformatics pipeline that was developed in-house was used to detect single nucleotide variations (SNVs), insertions/deletions (indels), and FLT3 internal tandem duplications (FLT3-ITD). An analytical validation study was performed on 184 unique specimens for variants with allele frequencies [≥]5%. Variants identified by the 48-gene panel were compared to those identified by a 35-gene hematologic neoplasms panel using an additional 137 unique specimens. The developed assay was applied to a large cohort (n=2,053) of patients with suspected myeloid neoplasms. Analytical validation yielded 99.6% sensitivity (95% CI: 98.9-99.9%) and 100% specificity (95% CI: 100%). Concordance of variants detected by the 2 tested panels was 100%. Among patients with suspected myeloid neoplasms (n=2,053), 54.5% patients harbored at least one clinically significant mutation: 77% in AML patients, 48% in MDS, and 45% in MPN. Together, these findings demonstrate that the assay can identify mutations associated with diagnosis, prognosis, and treatment options of myeloid neoplasms.

cancer biology