Biology subjects

Blume, J.

Publications and source records attributed to Blume, J..

4 recordsLinked to original sources

bioRxiv2023

Evaluation of resampling-based inference for topological features of neuroimages

Many recent studies have demonstrated the inflated type 1 error rate of the original Gaussian random field (GRF) methods for inference of neuroimages and identified resampling (permutation and bootstrapping) methods that have better performance. There has been no evaluation of resampling procedures when using robust (sandwich) statistical images with different topological features (TF) used for neuroimaging inference. Here, we consider estimation of distributions TFs of a statistical image and evaluate resampling procedures that can be used when exchangeability is violated. We compare the methods using realistic simulations and study sex differences in life-span age-related changes in gray matter volume in the Nathan Kline Institute Rockland sample. We find that our proposed wild bootstrap and the commonly used permutation procedure perform well in sample sizes above 50 under realistic simulations with heteroskedasticity. The Rademacher wild bootstrap has fewer assumptions than the permutation and performs similarly in samples of 100 or more, so is valid in a broader range of conditions. We also evaluate the GRF-based pTFCE method and show that it has inflated error rates in samples less than 200. Our R package, pbj, is available on Github and allows the user to reproducibly implement various resampling-based group level neuroimage analyses.

neuroscience↗

bioRxiv2020

Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7.

Humanized mouse models have become increasingly valuable tools to study human hematopoiesis and infectious diseases. However, human T cell differentiation remains inefficient. We generated mice expressing human interleukin (IL-7), a critical growth and survival factor for T cells, under the control of murine IL-7 regulatory elements. After transfer of human cord blood-derived hematopoietic stem and progenitor cells, transgenic mice on the NSGW41 background, termed NSGW41hIL7, showed elevated and prolonged human cellularity in the thymus while maintaining physiological ratios of thymocyte subsets. As a consequence, numbers of functional human T cells in the periphery were increased without evidence for pathological lymphoproliferation or aberrant expansion of effector or memory-like T cells. We conclude that the novel NSGW41hIL7 strain represents an optimized mouse model for humanization to better understand human T cell differentiation in vivo and to generate a human immune system with a better approximation of human lymphocyte ratios.

immunology↗

bioRxiv2018

The GRE Over the Entire Range of Scores Lacks Predictive Ability for PhD Outcomes in the Biomedical Sciences

The association between GRE scores and academic success in graduate programs is currently of national interest. GRE scores are often assumed to be predictive of student success in graduate school. However, we found no such association in admission data from Vanderbilts Initiative for Maximizing Student Diversity (IMSD), which recruited historically underrepresented students for graduate study in the biomedical sciences at Vanderbilt University spanning a wide range of GRE scores. This study avoids the typical biases of most GRE investigations of performance where only high-achievers on the GRE were admitted. GRE scores, while collected at admission, were not used or consulted for admission decisions and comprise the full range of percentiles, from 1% to 91%. We report on the 29 students recruited to the Vanderbilt IMSD from 2007-2011 who have completed the program at this date. While the data set is not large, the predictive trends between GRE and long-term graduate outcomes (publications, first author publications, time to degree, predoctoral fellowship awards, and faculty evaluations) are remarkably null and there is sufficient precision to rule out even mild relationships between GRE and these outcomes. Career outcomes are encouraging; many students are in postdocs, and the rest are in stage-appropriate career environments for such a cohort, including tenure track faculty, biotech and entrepreneurship careers.

scientific communication and education↗

bioRxiv2018

Attenuated post-movement beta rebound in Parkinson’s disease to proprioceptive afferent feedback

Motor symptoms are defining traits in the diagnosis of Parkinsons disease (PD). A crucial component in motor function and control of movements is the integration of efferent signals from the motor network to the peripheral motor system, and afferent proprioceptive sensory feedback. Previous studies have indicated abnormal movement-related cortical oscillatory activity in PD, but the role of the proprioceptive afference on abnormal oscillatory activity in PD has not been elucidated. In the present study, we examine the role of proprioception by studying the cortical processing of proprioceptive stimulation in PD patients, ON/OFF levodopa medication, as compared to that of healthy controls (HC). We used a proprioceptive stimulator that generated precisely controlled passive movements of the index finger and measured the induced cortical oscillatory responses following the proprioceptive stimulation using magnetoencephalography (MEG). Both PD patients and HC showed a typical initial mu/beta-band (8-30 Hz) desynchronization during the passive movement. However, the subsequent beta rebound after the passive movement that was apparent in HC was much attenuated and almost absent in PD patients. Furthermore, we found no difference in the degree of beta rebound attenuation between patients ON and OFF levodopa medication. Our results hence demonstrate a disease-related deterioration in cortical processing of proprioceptive afference in PD, and further suggest that such disease-related loss of proprioceptive function is due to processes outside the dopaminergic system affected by levodopa medication.

neuroscience↗