Total Mastectomy or Breast Conservation Therapy? How Radiation Oncologist Accessibility Determines Treatment Choice and Quality: A SEER Data-base Analysis.

Mastectomy and breast conservation therapy (BCT) are equivalent in survival for treatment of early stage breast cancer. This study evaluated the impact of radiation oncologist accessibility on choice of breast conserving surgery (BCS) versus mastectomy, and the appropriate receipt of radiotherapy after BCS. In the National Cancer Institute Survival, Epidemiology, and End Results data base, the authors selected breast cancer cases from 2004 to 2008 with the following criteria: T2N1M0 or less, lobular or ductal histology, and treatment with simple or partial mastectomy. We combined the Health Resources and Services Administration Area Resource File to define average radiation oncologist density (ROD) by county over the same time period. We evaluated tumor characteristics, demographic information, and ROD with respect to BCS rates and receipt of radiation therapy after BCS in univariable and multivariable analyses. In 118,773 cases analyzed, mastectomy was performed 33.2% of the time relative to BCS. After adjustment for demographic and tumor variables, the odds of having BCS versus mastectomy were directly associated with ROD (multiplicative change in odds for a single unit increase in ROD [95% CI] = 1.02 [1.01-1.03]; p < 0.001). Adjuvant radiation therapy was not administered in 28.2% of BCS cases. When adjusting for demographic and tumor variables, the odds of having BCS without adjuvant radiation were inversely associated with ROD (0.95 [0.94-0.97]; p < 0.001). We observed a direct relationship between ROD and BCS rates independent of demographic and tumor variables, and an inverse trend for omission of radiotherapy after BCS. Access to radiation oncologists may represent an important factor in surgical choice and receiving appropriate BCT in early stage breast cancer.

Using a statistically calibrated biphasic finite element model of the human knee joint to identify robust designs for a meniscal substitute.

This paper describes a methodology for selecting a set of biomechanical engineering design variables to optimize the performance of an engineered meniscal substitute when implanted in a population of subjects whose characteristics can be specified stochastically. For the meniscal design problem where engineering variables include aspects of meniscal geometry and meniscal material properties, this method shows that meniscal designs having simultaneously large radial modulus and large circumferential modulus provide both low mean peak contact stress and small variability in peak contact stress when used in the specified subject population. The method also shows that the mean peak contact stress is relatively insensitive to meniscal permeability, so the permeability used in the manufacture of a meniscal substitute can be selected on the basis of manufacturing ease or cost. This is a multiple objective problem with the mean peak contact stress over the population of subjects and its variability both desired to be small. The problem is solved by using a predictor of the mean peak contact stress across the tibial plateau that was developed from experimentally measured peak contact stresses from two modalities. The first experimental modality provided computed peak contact stresses using a finite element computational simulator of the dynamic tibial contact stress during axial dynamic loading. A small number of meniscal designs with specified subject environmental inputs were selected to make computational runs and to provide training data for the predictor developed below. The second experimental modality consisted of measured peak contact stress from a set of cadaver knees. The cadaver measurements were used to bias-correct and calibrate the simulator output. Because the finite element simulator is expensive to evaluate, a rapidly computable (calibrated) Kriging predictor was used to explore extensively the contact stresses for a wide range of meniscal engineering inputs and subject variables. The predicted values were used to determine the Pareto optimal set of engineering inputs to minimize peak contact stresses in the targeted population of subjects.

Tekscan analysis programs (TAP) for quantifying dynamic contact mechanics.

This short communication provides details on customized Tekscan Analysis Programs (TAP) which extract comprehensive contact mechanics metrics from piezoelectric sensors in articulating joints across repeated loading cycles. The code provides functionality to identify regions of interest (ROI), compute contact mechanic metrics, and compare contact mechanics across multiple test conditions or knees. Further, the variability of identifying ROIs was quantified between seven different users and compared to an expert. Overall, the contribution of four variables were studied: two knee specimens; two points in the gait cycle; two averaging methods; and seven observers, to determine if variations in these values played a role in accurately quantifying the ROI. The relative error between the force ratio from each observer's ROI and the expert ROI was calculated as the output of interest. A multivariate linear mixed effects model was fit to the four variables for the relative error with an observer- and knee-specific random intercept. Results from the fitted model showed a statistically significant difference at the 0.05 level in the mean relative errors at the two gait points. Additionally, variability in the relative errors attributed to the observer, knee, and random errors was quantified. To reduce variability amongst users, by ensuring low inter-observer variability and increasing segmentation accuracy of knee contact mechanics, a training module and manual have been included as supplemental material. By sharing this code and training manual, we envisage that it can be used and modified to analyze outputs from a range of sensors, joints, and test conditions.

Circulating extracellular vesicle content reveals de novo DNA methyltransferase expression as a molecular method to predict septic shock.

Extracellular vesicles (EVs) are mRNA-containing cell fragments shed into circulation during pathophysiological events. DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) regulate gene expression by modifying DNA methylation and altering transcription. Sepsis is a systemic insult resulting in vascular dysfunction, which can lead to shock and death. We analysed plasma from ICU patients for circulating EV numbers, defined as particles isolated from 1 mL plasma at 21,000xg, and DNMTs mRNA content as prognostic markers of septic shock. Compared to plasma from critically ill patients with or without sepsis, plasma from septic shock patients contained more EVs per mL, expressed as total DNMTs mRNAs over 5 days, and more individual DNMT mRNAs at each day. A comparison of EV-DNMT1 (maintenance methylation) with EV-DNMT3A+DNMT3B (de novo methylation) expression correlated highly with severity, and EVs from septic shock patients carried more total DNMT mRNAs and more DNMT3A+DNMT3B mRNAs than control or sepsis EVs. Total plasma EVs also correlated with sepsis severity. EV-DNMT mRNAs load, when coupled with total plasma EV number, may be a novel method to diagnose septic shock upon ICU admittance and offer opportunities to more precisely intervene with standard therapy or other targeted interventions to regulate EV release and/or specific DNMT activity.

Evaluation of an in-vehicle monitoring system (IVMS) to reduce risky driving behaviors in commercial drivers: Comparison of in-cab warning lights and supervisory coaching with videos of driving behavior.

PROBLEM: Roadway incidents are the leading cause of work-related death in the United States. METHODS: The objective of this research was to evaluate whether two types of feedback from a commercially available in-vehicle monitoring system (IVMS) would reduce the incidence of risky driving behaviors in drivers from two companies. IVMS were installed in 315 vehicles representing the industries of local truck transportation and oil and gas support operations, and data were collected over an approximate two-year period in intervention and control groups. In one period, intervention group drivers were given feedback from in-cab warning lights from an IVMS that indicated occurrence of harsh vehicle maneuvers. In another period, intervention group drivers viewed video recordings of their risky driving behaviors with supervisors, and were coached by supervisors on safe driving practices. RESULTS: Risky driving behaviors declined significantly more during the period with coaching plus instant feedback with lights in comparison to the period with lights-only feedback (ORadj=0.61 95% CI 0.43-0.86; Holm-adjusted p=0.035) and the control group (ORadj=0.52 95% CI 0.33-0.82; Holm-adjusted p=0.032). Lights-only feedback was not found to be significantly different than the control group's decline from baseline (ORadj=0.86 95% CI 0.51-1.43; Holm-adjusted p>0.05). CONCLUSIONS: The largest decline in the rate of risky driving behaviors occurred when feedback included both supervisory coaching and lights. PRACTICAL APPLICATIONS: Supervisory coaching is an effective form of feedback to improve driving habits in the workplace. The potential advantages and limitations of this IVMS-based intervention program are discussed.