Incorporating Human Factors Analysis and Classification System (HFACS) Into Analysis of Reported Near Misses and Incidents in Radiation Oncology.

PURPOSE: Human factors analysis and classification system (HFACS) is a framework for investigation into causation of human errors. We herein assess whether radiation oncology professionals, with brief training, can conduct HFACS on reported near misses or safety incidents (NMSIs) in a reliable (eg, with a high level of agreement) and practical (eg, timely and with user satisfaction) manner. METHODS AND MATERIALS: We adapted a classical HFACS framework by selecting and modifying main headings, subheadings, and nano-codes that were most likely to apply to radiation oncology settings. The final modified HFACS included 3 main headings, 8 subheadings, and 20 nano-codes. The modified HFACS was first tested in a simulated trial on 8 NMSI and was analyzed by 5 to 10 radiation oncology professionals, with 2 endpoints: (1) agreement among participants at the main-heading, subheading, and nano-code level, and (2) time to complete the analysis. We then performed a prospective trial integrating this approach into a weekly NMSI review meeting, with 10 NMSIs analyzed by 8 to 13 radiation oncology professionals with the same endpoints, while also collecting survey data on participants' satisfaction. RESULTS: In the simulated trial, agreement among participants was 85% on the main headings, 73% on the subheadings, and 70% on the nano-codes. Participants needed, on average, 16.4 minutes (standard deviation, 5.7 minutes) to complete an analysis. In the prospective trial, agreement between participants was 81% on the main headings, 75% on the subheadings, and 74% on the nano-codes. Participants needed, on average, 8.3 minutes (standard deviation, 4.7 minutes) to complete an analysis. The average satisfaction with the proposed HFACS approach was 3.9 (standard deviation 1.0) on a scale from 1 to 5. CONCLUSIONS: This study demonstrates that, after relatively brief training, radiation oncology professionals were able to perform HFACS analysis in a reliable and timely manner and with a relatively high level of satisfaction.

Clinical indications for, and the future of, circulating tumor cells.

Circulating tumor cells (CTCs) are cells that have detached from the primary tumor and entered circulation with potential to initiate a site of metastasis. Currently, CTC detection using CellSearch is cleared by the Food and Drug Administration for monitoring metastatic breast, prostate, and colorectal cancers as a prognostic biomarker for progression-free and overall survival. Accumulating evidence suggests CTCs have similar prognostic value in other metastatic and non-metastatic settings. Current research efforts are focused on extending the utility of CTCs beyond a prognostic biomarker to help guide clinical decision-making. These include using CTCs as a screening tool for diagnosis, liquid biopsy for molecular profiling, predictive biomarker to specific therapies, and monitoring tool to assess response and guide changes to treatment. CTCs have unique advantages vs circulating tumor DNA in this endeavor. Indications for CTCs in daily practice will expand as isolation techniques improve and clinical studies validating their utility continue to grow.

Differential effects of buffer pH on Ca(2+)-induced ROS emission with inhibited mitochondrial complexes I and III.

Excessive mitochondrial reactive oxygen species (ROS) emission is a critical component in the etiology of ischemic injury. Complex I and complex III of the electron transport chain are considered the primary sources of ROS emission during cardiac ischemia and reperfusion (IR) injury. Several factors modulate ischemic ROS emission, such as an increase in extra-matrix Ca(2+), a decrease in extra-matrix pH, and a change in substrate utilization. Here we examined the combined effects of these factors on ROS emission from respiratory complexes I and III under conditions of simulated IR injury. Guinea pig heart mitochondria were suspended in experimental buffer at a given pH and incubated with or without CaCl2. Mitochondria were then treated with either pyruvate, a complex I substrate, followed by rotenone, a complex I inhibitor, or succinate, a complex II substrate, followed by antimycin A, a complex III inhibitor. H2O2 release rate and matrix volume were compared with and without adding CaCl2 and at pH 7.15, 6.9, or 6.5 with pyruvate + rotenone or succinate + antimycin A to simulate conditions that may occur during in vivo cardiac IR injury. We found a large increase in H2O2 release with high [CaCl2] and pyruvate + rotenone at pH 6.9, but not at pHs 7.15 or 6.5. Large increases in H2O2 release rate also occurred at each pH with high [CaCl2] and succinate + antimycin A, with the highest levels observed at pH 7.15. The increases in H2O2 release were associated with significant mitochondrial swelling, and both H2O2 release and swelling were abolished by cyclosporine A, a desensitizer of the mitochondrial permeability transition pore (mPTP). These results indicate that ROS production by complex I and by complex III is differently affected by buffer pH and Ca(2+) loading with mPTP opening. The study suggests that changes in the levels of cytosolic Ca(2+) and pH during IR alter the relative amounts of ROS produced at mitochondrial respiratory complex I and complex III.

Rhizobial plasmids that cause impaired symbiotic nitrogen fixation and enhanced host invasion.

The genetic rules that dictate legume-rhizobium compatibility have been investigated for decades, but the causes of incompatibility occurring at late stages of the nodulation process are not well understood. An evaluation of naturally diverse legume (genus Medicago) and rhizobium (genus Sinorhizobium) isolates has revealed numerous instances in which Sinorhizobium strains induce and occupy nodules that are only minimally beneficial to certain Medicago hosts. Using these ineffective strain-host pairs, we identified gain-of-compatibility (GOC) rhizobial variants. We show that GOC variants arise by loss of specific large accessory plasmids, which we call HR plasmids due to their effect on symbiotic host range. Transfer of HR plasmids to a symbiotically effective rhizobium strain can convert it to incompatibility, indicating that HR plasmids can act autonomously in diverse strain backgrounds. We provide evidence that HR plasmids may encode machinery for their horizontal transfer. On hosts in which HR plasmids impair N fixation, the plasmids also enhance competitiveness for nodule occupancy, showing that naturally occurring, transferrable accessory genes can convert beneficial rhizobia to a more exploitative lifestyle. This observation raises important questions about agricultural management, the ecological stability of mutualisms, and the genetic factors that distinguish beneficial symbionts from parasites.