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1.
Robert C. Lynall J. Troy Blackburn Kevin M. Guskiewicz Stephen W. Marshall Prudence Plummer Jason P. Mihalik 《Journal of Science and Medicine in Sport》2019,22(5):503-508
Objectives
Despite evidence for increased musculoskeletal injury after concussion recovery, there is a lack of dynamic balance assessments that could inform management and research into this increased injury risk post-concussion. Our purpose was to identify tandem gait dynamic balance deficits in recreational athletes with a concussion history within the past 18-months compared to matched controls.Design
Cross-sectional, laboratory study.Methods
Fifteen participants with a concussion history (age: 19.7 ± 0.9 years; 9 females; median time since concussion 126 days, range 28–432 days), and 15 matched controls (19.7 ± 1.6 years; 9 females) with no recent concussion history participated. We measured center-of-pressure (COP) outcomes (velocity, path length, speed, dual-task cost) under 4 tandem gait conditions: (1) tandem gait, (2) tandem gait, eyes closed, (3) tandem gait, eyes open, cognitive distraction, and (4) tandem gait, eyes closed, cognitive distraction.Results
The concussion history group demonstrated slower tandem gait velocity compared to the control group (4.0 cm/s difference), thus velocity was used as a covariate when analyzing COP path length and speed. The concussion history group (23.5%) demonstrated greater COP speed dual-task cost than the control group (16.3%) during the eyes closed dual-task condition. No other comparisons were statistically significant.Conclusions
There may be subtle dynamic balance differences during tandem gait that are detectable after return-to-activity following concussion, but the clinical significance of these findings is unclear. Longitudinal investigations should identify acute movement deficits in varying visual and cognitive scenarios after concussion in comparison with recovery on traditional concussion assessment tools while also recording musculoskeletal injury outcomes. 相似文献2.
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E. Niclas Jonsson Rujia Xie Scott F. Marshall Rosalin H. Arends 《British journal of clinical pharmacology》2016,81(4):688-699
AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V
1), peripheral volume (V
2), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day–1, 2.71 l, 1.98 l, 0.371 l day–1, 8.03 μg day–1 and 27.7 ng ml–1, respectively. Inter‐individual variability (IIV) was included on CL, V
1, V
2 and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V
1 and V
2 significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit. 相似文献
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Nicole L. Stout DPT Justin C. Brown PhD Anna L. Schwartz PhD FNP Timothy F. Marshall PhD Anna M. Campbell PhD MBE Larissa Nekhlyudov MD MPH David S. Zucker MD PhD Karen M. Basen-Engquist PhD MPH Grace Campbell PhD MSW RN Jeffrey Meyerhardt MD MPH Andrea L. Cheville MD MSSE Kelley R. Covington MS Jennifer A. Ligibel MD Jonas M. Sokolof DO Kathryn H. Schmitz PhD MPH Catherine M. Alfano PhD 《Cancer》2020,126(12):2750-2758
10.
Mohamed E. Salem J. Nicholas Bodor Alberto Puccini Joanne Xiu Richard M. Goldberg Axel Grothey W. Michael Korn Anthony F. Shields William M Worrilow Edward S. Kim Heinz-Josef Lenz John L. Marshall Michael J. Hall 《International journal of cancer. Journal international du cancer》2020,147(10):2948-2956
Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI. 相似文献