Engineering Disease Resistance through Generation of an iPSC-derived P. Maniculatus Chimera

The goal of this project is to develop methods to manipulate the genome of Peromyscus maniculatus for the future eradication of diseases such as Hantavirus and Lyme disease that this species can transmit to humans. The initial thrust of this project is to generate induced pluripotent stem cells (iPSCs) from P. maniculatus mouse embryonic fibroblasts (MEFs) using an engineered Sendai Virus vector system. The Sendai Virus vector is a non-integrating viral vector that delivers four transcription factors necessary to reprogram normal somatic cells to a pluripotent, stem cell-like state. Subsequent, a plasmid will be used to insert DNA into the genome of the iPSC that codes for a fluorescent protein. In the future, the fluorescence will be used to confirm that Mus musculus cells are able to combine with the P. maniculatus cells in a chimeric blastocyst. Because many notable diseases are transmissible to humans from P. maniculatus, the genetic manipulation and creation of a disease resistant P. maniculatus using iPSCs could help to eradicate the spread of these diseases.

Functional Comparison of Six-Minute Walk Tests Between Shod and Minimalist Footwear Individuals in Mid-Life: A Preliminary Pilot Study Analysis

Research has shown that wearing minimalistic footwear can increase intrinsic and extrinsic foot muscle size and strength,although the effect of transitioning from shod to minimalist footwear on gait functionality–such as performance on a six-minute walk test–is not well documented. PURPOSE: We observed the differences in a six-minute functional walk test between mid-life (45yrs-65yrs) individuals who transitioned to minimalist footwear (MF) over a fourteen month period compared to habitually shod (HS) individuals. METHODS: Twenty mid-life individuals participated in this study. Participants were randomly assigned to either the MF (n=8, age= 56.5 ± 5.18 yrs, height= 162.71 ± 7.69 cm, weight= 82.71 ± 16.24 kg,) or HS (n=12, age= 57.36 ± 5.43 yrs, height= 162.91 ± 7.44 cm, weight= 73.48 ± 15.65 kg) group. MF participants were coached through a nine-week training to safely transition to MF. Participants assigned to the HS group were instructed to continue normal activity. Each participant underwent a data collection at 1 week, 9 weeks, 8 months, and 14 months. At each data collection, the individual was instructed to walk as far as possible around a set track for 6 minutes. Every lap around the track was 208 feet and partial laps were measured to the distance completed. RESULTS: A repeated measures ANOVA indicated a significant increase in distance walked at 8 months (1703.5 ± 190.2 ft, p=0.009) and 14 months (1708.1 ± 181.1 ft, p=0.025) compared to week 1 (1634.6 ± 194.7 ft). There was no significant difference between groups in the increase in walking distance (p=0.950). Significant covariates were biological sex (p=0.007) and height (p=0.034). CONCLUSION: Overall, participants in the study increased walking distance in the six-minute walk test regardless of group. Therefore, minimalist shoes do not appear to affect gait functionality in mid-life adults during the six-minute walk test

Engineering Disease Resistance through Generation of an iPSC-derived P. Maniculatus Chimera

The goal of this project is to develop methods to manipulate the genome of Peromyscus maniculatus for the future eradication of diseases such as Hantavirus and Lyme disease that this species can transmit to humans. The initial thrust of this project is to generate induced pluripotent stem cells (iPSCs) from P. maniculatus mouse embryonic fibroblasts (MEFs) using an engineered Sendai Virus vector system. The Sendai Virus vector is a non-integrating viral vector that delivers four transcription factors necessary to reprogram normal somatic cells to a pluripotent, stem cell-like state. Subsequent, a plasmid will be used to insert DNA into the genome of the iPSC that codes for a fluorescent protein. In the future, the fluorescence will be used to confirm that Mus musculus cells are able to combine with the P. maniculatus cells in a chimeric blastocyst. Because many notable diseases are transmissible to humans from P. maniculatus, the genetic manipulation and creation of a disease resistant P. maniculatus using iPSCs could help to eradicate the spread of these diseases.

Real-time motion analytics during brain MRI improve data quality and reduce costs

Head motion systematically distorts clinical and research MRI data. Motion artifacts have biased findings from many structural and functional brain MRI studies. An effective way to remove motion artifacts is to exclude MRI data frames affected by head motion. However, such post-hoc frame censoring can lead to data loss rates of 50% or more in our pediatric patient cohorts. Hence, many scanner operators collect additional 'buffer data', an expensive practice that, by itself, does not guarantee sufficient high-quality MRI data for a given participant. Therefore, we developed an easy-to-setup, easy-to-use Framewise Integrated Real-time MRI Monitoring (FIRMM) software suite that provides scanner operators with head motion analytics in real-time, allowing them to scan each subject until the desired amount of low-movement data has been collected. Our analyses show that using FIRMM to identify the ideal scan time for each person can reduce total brain MRI scan times and associated costs by 50% or more

Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study

BackgroundTo better characterize short- term and long- term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD).MethodsPatients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long- term pancreatic function, recurrence, and survival) were collected.ResultsSixty- five patients from 18 institutions with a median age of 13 years (4 months- 22 years) and a median (IQR) follow- up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30- day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non- SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival.ConclusionThis is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156233/2/pbc28425.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156233/1/pbc28425_am.pd

Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study

Background: To better characterize short-term and long-term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD). Methods: Patients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long-term pancreatic function, recurrence, and survival) were collected. Results: Sixty-five patients from 18 institutions with a median age of 13 years (4 months-22 years) and a median (IQR) follow-up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30-day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non-SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival. Conclusion: This is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr