Project description:Student-centered pedagogies increase learning and retention. Quantifying change in both student learning gains and student perception of their experience allows faculty to evaluate curricular transformation more fully. Student buy-in, particularly how much students value and enjoy the active learning process, has been positively associated with engagement in active learning and increased learning gains. We hypothesize that as the frequency of students who have successfully completed the course increases in the student population, current students may be more likely to buy-in to the curriculum because this common experience could create a sense of community. We measured learning gains and attitudes during the transformation of an introductory biology course at a small, liberal arts college using our novel curriculum, Integrating Biology and Inquiry Skills (IBIS). Students perceived substantial learning gains in response to this curriculum, and concept assessments confirmed these gains. Over time, buy-in increased with each successive cohort, as demonstrated by the results of multiple assessment instruments, and students increasingly attributed specific components of the curriculum to their learning. These findings support our hypothesis and should encourage the adoption of curricular transformation using IBIS or other student-centered approaches.
Project description:The neural mechanism underlying preparation for tasks that vary in difficulty has not been explored. This functional magnetic resonance imaging study manipulated task difficulty by varying the working memory (WM) load of the n-back task. Each n-back task block was preceded by a preparation period involving a screen that indicated the level of difficulty of the upcoming task. Consistent with previous work, activation in some brain regions depended on WM load in the task. These regions were used as regions of interest for the univariate and multivariate (classification) analyses of preparation periods. The findings were that the patterns of brain activation during task preparation contain information about the upcoming task difficulty. (1) A support vector machine classifier was able to decode the n-back task difficulty from the patterns of brain activation during task preparation. Those individuals whose activation patterns for anticipated 1- versus 2- versus 3-back conditions were classified with higher accuracy showed better behavioral performance on the task, suggesting that task performance depends on task preparation. (2) Left inferior frontal gyrus, intraparietal sulcus, and anterior cingulate cortex parametrically decreased activation as anticipated task difficulty increased. Taken together, these results suggest dynamic involvement of the WM network not only during WM task performance, but also during task preparation.
Project description:ObjectiveTo obtain medical records, family interviews, and death-related reports of sudden unexpected death in epilepsy (SUDEP) cases to better understand SUDEP.MethodsAll cases referred to the North American SUDEP Registry (NASR) between October 2011 and June 2018 were reviewed; cause of death was determined by consensus review. Available medical records, death scene investigation reports, autopsy reports, and next-of-kin interviews were reviewed for all cases of SUDEP. Seizure type, EEG, MRI, and SUDEP classification were adjudicated by 2 epileptologists.ResultsThere were 237 definite and probable cases of SUDEP among 530 NASR participants. SUDEP decedents had a median age of 26 (range 1-70) years at death, and 38% were female. In 143 with sufficient information, 40% had generalized and 60% had focal epilepsy. SUDEP affected the full spectrum of epilepsies, from benign epilepsy with centrotemporal spikes (n = 3, 1%) to intractable epileptic encephalopathies (n = 27, 11%). Most (93%) SUDEPs were unwitnessed; 70% occurred during apparent sleep; and 69% of patients were prone. Only 37% of cases of SUDEP took their last dose of antiseizure medications (ASMs). Reported lifetime generalized tonic-clonic seizures (GTCS) were <10 in 33% and 0 in 4%.ConclusionsNASR participants commonly have clinical features that have been previously been associated with SUDEP risk such as young adult age, ASM nonadherence, and frequent GTCS. However, a sizeable minority of SUDEP occurred in patients thought to be treatment responsive or to have benign epilepsies. These results emphasize the importance of SUDEP education across the spectrum of epilepsy severities. We aim to make NASR data and biospecimens available for researchers to advance SUDEP understanding and prevention.
Project description:Adoptive therapy with chimeric antigen receptor (CAR)-redirected T cells showed spectacular efficacy in the treatment of leukemia in recent early phase trials. Patient's T cells were ex vivo genetically engineered with a CAR, amplified and re-administered to the patient. While T cells mediating the primary response were predominantly of young effector and central memory phenotype, repetitive antigen engagement irreversible triggers T cell maturation leaving late memory cells with the KLRG1(+) CD57(+) CD7(-) CCR7(-) phenotype in the long-term. These cells preferentially accumulate in the periphery, are hypo-responsive upon TCR engagement and prone to activation-induced cell death. A recent report indicates that those T cells can be rescued by CAR provided CD28 and OX40 (CD134) stimulation. We discuss the strategy with respect to prolong the anti-tumor response and to improve the over-all efficacy of adoptive cell therapy.
Project description:ObjectiveTo identify the molecular signaling pathways underlying sudden unexpected death in epilepsy (SUDEP) and high-risk SUDEP compared to control patients with epilepsy.MethodsFor proteomics analyses, we evaluated the hippocampus and frontal cortex from microdissected postmortem brain tissue of 12 patients with SUDEP and 14 with non-SUDEP epilepsy. For transcriptomics analyses, we evaluated hippocampus and temporal cortex surgical brain tissue from patients with mesial temporal lobe epilepsy: 6 low-risk and 8 high-risk SUDEP as determined by a short (<50 seconds) or prolonged (≥50 seconds) postictal generalized EEG suppression (PGES) that may indicate severely depressed brain activity impairing respiration, arousal, and protective reflexes.ResultsIn autopsy hippocampus and cortex, we observed no proteomic differences between patients with SUDEP and those with non-SUDEP epilepsy, contrasting with our previously reported robust differences between epilepsy and controls without epilepsy. Transcriptomics in hippocampus and cortex from patients with surgical epilepsy segregated by PGES identified 55 differentially expressed genes (37 protein-coding, 15 long noncoding RNAs, 3 pending) in hippocampus.ConclusionThe SUDEP proteome and high-risk SUDEP transcriptome were similar to those in other patients with epilepsy in hippocampus and cortex, consistent with diverse epilepsy syndromes and comorbid conditions associated with SUDEP. Studies with larger cohorts and different epilepsy syndromes, as well as additional anatomic regions, may identify molecular mechanisms of SUDEP.
Project description:Several potential pathophysiologic phenomena, including "cerebral shutdown," are postulated to be responsible for SUDEP. Since the evidence for a seizure-related mechanism is strong, a poor understanding of the physiology of human seizure termination is a major handicap. However, rather than a failure of a single homeostatic mechanism, such as postictal arousal, it may be a "perfect storm" created by the lining up of a several factors that lead to death.
Project description:Populations often contain discrete classes or morphs (e.g., sexual dimorphisms, wing dimorphisms, trophic dimorphisms) characterized by distinct patterns of trait expression. In quantitative genetic analyses, the different morphs can be considered as different environments within which traits are expressed. Genetic variances and covariances can then be estimated independently for each morph or in a combined analysis. In the latter case, morphs can be considered as separate environments in a bivariate analysis or entered as fixed effects in a univariate analysis. Although a common approach, we demonstrate that the latter produces downwardly biased estimates of additive genetic variance and heritability unless the quantitative genetic architecture of the traits concerned is perfectly correlated between the morphs. This result is derived for four widely used quantitative genetic variance partitioning methods. Given that theory predicts the evolution of genotype-by-environment (morph) interactions as a consequence of selection favoring different trait combinations in each morph, we argue that perfect correlations between the genetic architectures of the different morphs are unlikely. A sampling of the recent literature indicates that the majority of researchers studying traits expressed in different morphs recognize this and do estimate morph-specific quantitative genetic architecture. However, ca. 16% of the studies in our sample utilized only univariate, fixed-effects models. We caution against this approach and recommend that it be used only if supported by evidence that the genetic architectures of the different morphs do not differ.
Project description:We consider the privacy-preserving computation of node influence in distributed social networks, as measured by egocentric betweenness centrality (EBC). Motivated by modern communication networks spanning multiple providers, we show for the first time how multiple mutually-distrusting parties can successfully compute node EBC while revealing only differentially-private information about their internal network connections. A theoretical utility analysis upper bounds a primary source of private EBC error—private release of ego networks—with high probability. Empirical results demonstrate practical applicability with a low 1.07 relative error achievable at strong privacy budget Electronic supplementary material The online version of this chapter (10.1007/978-3-030-47436-2_12) contains supplementary material, which is available to authorized users.
Project description:Various cell lines including clones of MDAH-041 cells were karyotypically defined by SKY. Two replicates of each line was harvested from one flask of cells.
Project description:Rationale: Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk. We aimed to determine if electroclinical seizure features worsen from seizure to seizure within a cluster and possible associations between GCS clusters, markers of seizure severity, and SUDEP risk. Methods: Patients were consecutive, prospectively consented participants with drug-resistant epilepsy from a multi-center study. Seizure clusters were defined as two or more GCS in a 24-h period during the recording of prolonged video-electroencephalography in the Epilepsy monitoring unit (EMU). We measured heart rate variability (HRV), pulse oximetry, plethysmography, postictal generalized electroencephalographic suppression (PGES), and electroencephalography (EEG) recovery duration. A linear mixed effects model was used to study the difference between the first and subsequent seizures, with a level of significance set at p < 0.05. Results: We identified 112 GCS clusters in 105 patients with 285 seizures. GCS lasted on average 48.7 ± 19 s (mean 49, range 2-137). PGES emerged in 184 (64.6%) seizures and postconvulsive central apnea (PCCA) was present in 38 (13.3%) seizures. Changes in seizure features from seizure to seizure such as seizure and convulsive phase durations appeared random. In grouped analysis, some seizure features underwent significant deterioration, whereas others improved. Clonic phase and postconvulsive central apnea (PCCA) were significantly shorter in the fourth seizure compared to the first. By contrast, duration of decerebrate posturing and ictal central apnea were longer. Four SUDEP cases in the cluster cohort were reported on follow-up. Conclusion: Seizure clusters show variable changes from seizure to seizure. Although clusters may reflect epilepsy severity, they alone may be unrelated to SUDEP risk. We suggest a stochastic nature to SUDEP occurrence, where seizure clusters may be more likely to contribute to SUDEP if an underlying progressive tendency toward SUDEP has matured toward a critical SUDEP threshold.