Establishing Intra-Reliability and Normative Data in Physical Functioning Assessments: A Pilot Study

PURPOSE: Normative data ranges are not available for all functional balance tests for all age groups. The purpose is to establish intra-reliability and normative age-sensitive data ranges in a battery of functional balance-related measures including the modified Clinical Test for Sensory Integration and Balance (mCTSIB), One-legged Stance Test (OLST), Functional Reach Test (FRT), 30-second Sit-to-Stand Test (30STS), 1 O-meter Walk Test (10MWT), and Activities-specific Balance Confidence Scale (ABC Scale). METHODS: Ninety-two subjects (n =92), aged 19-87 years, were tested with each of these balance tests. Participants were randomly assigned the order in which to complete the six balance tests. Intra-rater reliability was established for the FRT, 30STS, and 10MWT using 10 subjects. Data were compiled into normative distributions into three age cohorts for all six tests, 19-39 years old, 40-59 years old, and 60 and older age ranges. Repeated-measure ANOVA was used to compare age cohorts for the FRT, 30STS, 10MWT, and ABC Scale. Bonferroni post hoc analysis was used to assess for statistically significant differences between age groups for the FRT, 30STS, 10MWT, and ABC Scale. Cross tab analysis was used to assess the frequencies of age group performances on the mCTSIB and OLST. RESULTS: Reliability was established for the FRT (ICC = 0.976), 30STS (ICC = 0.973), and 10MWT (ICC = 0.824). Reliability could not be statistically determined for the mCTSIB, OLST, and ABC Scale. The main findings of this study indicated that the differences in balance between different age categories were apparent among younger cohort groups (19-39 years and 40-59 years) and older-aged group (60-87 years). CONCLUSION: The results of the present study provide normative values for six balance tests for three age cohorts, 19-39 years old, 40-59 years old, and 60-87 years old. Intra-rater reliability was established for the FRT, 30STS, and 10MWT. Deterioration in balance appears to begin after people turn 60 years and older. The findings from this study can be used by clinicians and researchers when assessing balance capabilities of their clientele

Analysis of Separation Corridors for Visiting Vehicles from the International Space Station

The International Space Station (ISS) is a very dynamic vehicle with many operational constraints that affect its performance, operations, and vehicle lifetime. Most constraints are designed to alleviate various safety concerns that are a result of dynamic activities between the ISS and various Visiting Vehicles (VVs). One such constraint that has been in place for Russian Vehicle (RV) operations is the limitation placed on Solar Array (SA) positioning in order to prevent collisions during separation and subsequent relative motion of VVs. An unintended consequence of the SA constraint has been the impacts to the operational flexibility of the ISS resulting from the reduced power generation capability as well as from a reduction in the operational lifetime of various SA components. The purpose of this paper is to discuss the technique and the analysis that were applied in order to relax the SA constraints for RV undockings, thereby improving both the ISS operational flexibility and extending its lifetime for many years to come. This analysis focused on the effects of the dynamic motion that occur both prior to and following RV separations. The analysis involved a parametric approach in the conservative application of various initial conditions and assumptions. These included the use of the worst case minimum and maximum vehicle configurations, worst case initial attitudes and attitude rates, and the worst case docking port separation dynamics. Separations were calculated for multiple ISS docking ports, at varied deviations from the nominal undocking attitudes and included the use of two separate attitude control schemes: continuous free-drift and a post separation attitude hold. The analysis required numerical propagation of both the separation motion and the vehicle attitudes using 3-degree-of-freedom (DOF) relative motion equations coupled with rigid body rotational dynamics to generate a large set of separation trajectories

Coordination of Inpatient and Outpatient Care for Neurology Patients Undergoing Epilepsy Monitoring

ORGANIZING A SYSTEM TO CONSOLIDATE EPILEPSY REFERRALS TO AN OUTPATIENT NEUROLOGY PRACTICE An outpatient neurology practice was experiencing delayed or lost referrals for epilepsy monitoring. This delay was leading many patients to suffer unnecessary and unmanaged seizures and, in some cases, frequent trips to the emergency department. As a result, a team consisting of the neurology practice and neuro-navigators used baseline metrics to demonstrate the current state of the problem and conducted a root cause analysis that outlined several causes. A number of countermeasures were initiated with the goal of decreasing referral misses. Post the initiation of two KPIs, a significant improvement was noted in missed referrals. Next steps include sustaining the process by follow up KPIs to make sure the system is running effectively

Improving Highway Work Zone Safety

Highway work zones disrupt normal traffic flow and can create severe safety problems. Due to the rising needs in highway maintenance and construction in the United States, the number of work zones is increasing nationwide. With a total of 1,010 fatalities and more than 40,000 injuries occurring in 2006, improvements in work zone safety are necessary. The three primary objectives of this research project included: 1) to determine the effectiveness of a Portable Changeable Message Sign (PCMS) in reducing vehicle speeds on two-lane, rural highway work zones; 2) to determine the effectiveness of a Temporary Traffic Sign (TTS), (W20-1, “Road Work Ahead”); and 3) to determine motorists’ responses to the signage. To accomplish these objectives, field experiments were conducted at US-36 and US-73 in Seneca and Hiawatha, Kansas, respectively. During the field experiments, an evaluation of the effectiveness of the PCMS was conducted under three different conditions: 1) PCMS on; 2) PCMS off, but still visible; and 3) PCMS removed from the road and out of sight. The researchers also divided the vehicles into three classes (passenger car, truck, and semitrailer) and compared the mean speed change of these classes based on three different sign setups: PCMS on, PCMS off, and the use of the TTS (W20-1, “Road Work Ahead”). A survey was also conducted at the experimental work zones to obtain a general understanding of the motorists’ attitudes as they traveled through the construction areas. Based on the data analysis results, researchers concluded that the presence of the PCMS effectively reduced vehicle speeds on two-lane highway work zones. A slow speed is more likely to reduce the probability of a crash or the severity of a crash. In addition, researchers performed a univariate analysis of the variance test to determine if a significant interaction existed between motorists’ responses and the sign conditions. The results showed a significant interaction between the signs and passenger car vehicles

A case of advanced infantile myofibromatosis harboring a novel MYH10‐RET fusion

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137282/1/pbc26377_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137282/2/pbc26377.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137282/3/pbc26377-sup-0002-text.pd

Coordinate Gene Regulation during Hematopoiesis Is Related to Genomic Organization

Gene loci are found in nuclear subcompartments that are related to their expression status. For instance, silent genes are often localized to heterochromatin and the nuclear periphery, whereas active genes tend to be found in the nuclear center. Evidence also suggests that chromosomes may be specifically positioned within the nucleus; however, the nature of this organization and how it is achieved are not yet fully understood. To examine whether gene regulation is related to a discernible pattern of genomic organization, we analyzed the linear arrangement of co-regulated genes along chromosomes and determined the organization of chromosomes during the differentiation of a hematopoietic progenitor to erythroid and neutrophil cell types. Our analysis reveals that there is a significant tendency for co-regulated genes to be proximal, which is related to the association of homologous chromosomes and the spatial juxtaposition of lineage-specific gene domains. We suggest that proximity in the form of chromosomal gene distribution and homolog association may be the basis for organizing the genome for coordinate gene regulation during cellular differentiation

Acquired Resistance to KRAS (G12C) Inhibition in Cancer

BACKGROUND: Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS(G12C)). The mechanisms of acquired resistance to these therapies are currently unknown. METHODS: Among patients with KRAS(G12C) -mutant cancers treated with adagrasib monotherapy, we performed genomic and histologic analyses that compared pretreatment samples with those obtained after the development of resistance. Cell-based experiments were conducted to study mutations that confer resistance to KRAS(G12C) inhibitors. RESULTS: A total of 38 patients were included in this study: 27 with non-small-cell lung cancer, 10 with colorectal cancer, and 1 with appendiceal cancer. Putative mechanisms of resistance to adagrasib were detected in 17 patients (45% of the cohort), of whom 7 (18% of the cohort) had multiple coincident mechanisms. Acquired KRAS alterations included G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and high-level amplification of the KRAS(G12C) allele. Acquired bypass mechanisms of resistance included MET amplification; activating mutations in NRAS, BRAF, MAP2K1, and RET; oncogenic fusions involving ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function mutations in NF1 and PTEN. In two of nine patients with lung adenocarcinoma for whom paired tissue-biopsy samples were available, histologic transformation to squamous-cell carcinoma was observed without identification of any other resistance mechanisms. Using an in vitro deep mutational scanning screen, we systematically defined the landscape of KRAS mutations that confer resistance to KRAS(G12C) inhibitors. CONCLUSIONS: Diverse genomic and histologic mechanisms impart resistance to covalent KRAS(G12C) inhibitors, and new therapeutic strategies are required to delay and overcome this drug resistance in patients with cancer. (Funded by Mirati Therapeutics and others; ClinicalTrials.gov number, NCT03785249.)

No-till cropping systems in Oklahoma

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Testing mutual exclusivity of ETS rearranged prostate cancer

Prostate cancer is a clinically heterogeneous and multifocal disease. More than 80% of patients with prostate cancer harbor multiple geographically discrete cancer foci at the time of diagnosis. Emerging data suggest that these foci are molecularly distinct consistent with the hypothesis that they arise as independent clones. One of the strongest arguments is the heterogeneity observed in the status of E26 transformation specific (ETS) rearrangements between discrete tumor foci. The clonal evolution of individual prostate cancer foci based on recent studies demonstrates intertumoral heterogeneity with intratumoral homogeneity. The issue of multifocality and interfocal heterogeneity is important and has not been fully elucidated due to lack of the systematic evaluation of ETS rearrangements in multiple tumor sites. The current study investigates the frequency of multiple gene rearrangements within the same focus and between different cancer foci. Fluorescence in situ hybridization (FISH) assays were designed to detect the four most common recurrent ETS gene rearrangements. In a cohort of 88 men with localized prostate cancer, we found ERG, ETV1, and ETV5 rearrangements in 51% (44/86), 6% (5/85), and 1% (1/86), respectively. None of the cases demonstrated ETV4 rearrangements. Mutual exclusiveness of ETS rearrangements was observed in the majority of cases; however, in six cases, we discovered multiple ETS or 5′ fusion partner rearrangements within the same tumor focus. In conclusion, we provide further evidence for prostate cancer tumor heterogeneity with the identification of multiple concurrent gene rearrangements