Proactively Investigating “Limits of use” with Medical Device Manufacturers – An Example Case: Robotic Surgery

AbstractThis paper presents an exploration of strategies undertaken by a consortium of clinical teams and manufacturers to proactively prepare and support use of new categories of medical devices. Potential avenues of exploration include leveraging other domains, such as the US Space program, providing innovative methods of training and research and development in known areas of concern such as systems integration. By a commitment to creating a safer system, we are committing to providing safer care to patients. We believe incorporating the ‘lessons learned’ from the largest possible set of real-world scenarios, into the design and use of medical devices, will accelerate success

Quantitative Analysis of Shallow Earthquake Sequences and Regional Earthquake Behavior: Implications for Earthquake Forecasting

This study is a quantitative investigation and characterization of earthquake sequences in the Central Volcanic Region (CVR) of New Zealand, and several regions in New Zealand and Southern California. We introduce CURATE, a new declustering algorithm that uses rate as the primary indicator of an earthquake sequence, and we show it has appreciable utility for analyzing seismicity. The algorithm is applied to the CVR and other regions around New Zealand. These regions are also compared with the Southern California earthquake catalogue. There is a variety of behavior within these regions, with areas that experience larger mainshock-aftershock (MS-AS) sequences having distinctly different general sequence parameters than those of more swarm dominated regions. The analysis of the declustered catalog shows that Lake Taupo and at least three other North Island regions have correlated variations in rate over periods of ~5 years. These increases in rate are not due to individual large sequences, but are instead caused by a general increase in earthquake and sequence occurrence. The most obvious increase in rate across the four North Island subsets follows the 1995-1996 magmatic eruption at Ruapehu volcano. The fact that these increases are geographically widespread and occur over years at a time suggests that the variations may reflect changes in the subduction system or a broad tectonic process. We examine basic sequence parameters of swarms and MS-AS sequences to provide better information for earthquake forecasting models. Like MS-AS sequences, swarm sequences contain a large amount of decay (decreasing rate) throughout their duration. We have tested this decay and found that 89% of MS-AS sequences and 55% of swarm sequences are better fit with an Omori's law decay than a linear rate. This result will be important to future efforts to forecast lower magnitude ranges or swarm prone areas like the CVR. To look at what types of process may drive individual sequences and may be associated with the rate changes, we examined a series of swarms that occurred to the South of Lake Taupo in 2009. We relocated these earthquakes using double-difference method, hypoDD, to obtain more accurate relative locations and depths. These swarms occur in an area about 20x20 km. They do not show systematic migration between sequences. The last swarm in the series is located in the most resistive area of the Tokaanu geothermal region and had two M =4.4 earthquakes within just four hours of each other. The earthquakes in this swarm have an accelerating rate of occurrence leading up to the first M = 4.4 earthquakes, which migrate upward in depth. The locations of earthquakes following the M = 4.4 event expand away from it at a rate consistent with fluid diffusion. Our statistical investigation of triggering due to large global (M ≥ 7) and regional earthquakes (M ≥ 6) concludes that more detailed (waveform level) investigation of individual sequences will be necessary to conclusively identify triggering, but sequence catalogs may be useful in identifying potential targets for those investigations. We also analyzed the probability that a series of swarms in the central Southern Alps were triggered by the 2009 Dusky Sound Mw = 7.8 and the 2010 Darfield Mw = 7.1 earthquake. There is less than a one-percent chance that the observed sequences occurred randomly in time. The triggered swarms do not show a significant difference to the swarms occurring in that region at other times in the 1.5-year catalog. Waveform cross-correlation was performed on this central Southern Alps earthquake catalog by a fellow PhD student Carolin Boese, and reveals that individual swarms are often composed of a single waveform family or multiple waveform families in addition to earthquakes that did not show waveform similarities. The existence of earthquakes that do not share waveform similarity in the same swarm (2.5 km radius) as a waveform family indicates that similar waveform groups may be unique in their location, but do not necessarily necessitate a unique trigger or driver. In addition to these triggered swarms in the Southern Alps we have also identified two swarms that are potentially triggered by slow-slip earthquakes along the Hikurangi margin in 2009 and 2010. The sequence catalogs generated by the CURATE method may be an ideal tool for searching for earthquake sequences triggered by slow-slip

Safer Systems, Safer Care: Bringing the Tools and Strategies to Clinical Service Areas Through Applied Patient Safety Programs

AbstractAlong with creating and supporting a trained network of Patient Safety Managers across the U.S. Veterans Health Administration, the National Center for Patient Safety brings an increased, shared awareness of patient safety goals and strategies to disciplines of healthcare, beginning with the biomedical engineers at VHA facilities. This presentation outlines a ‘roadmap’ for the journey to high reliability healthcare and shares the training approach and results to date. This roadmap is modelled after that used at NASA and contains four development phases beginning with an awareness of human limitations and ending with proactive analysis to anticipate causes of safety episodes. The goal of the roadmap is to systematically ensure the care given to patients is done as safely as possible by incorporating best practices from mature industries

Weaving Indigenous and Western Science Knowledges Through a Land-Based Field Course at Bkejwanong Territory (Laurentian Great Lakes)

In response to a growing interest in building Indigenous-led educational experiences, we codeveloped a land-based field course that wove Indigenous ways of knowing together with Western ecological concepts. The spirit of the course was the one rooted in varied ways of knowing nature, on the land, the water, and the culture—to see the Great Lakes from an Anishinaabe perspective. Situated in the heart of the Laurentian Great Lakes Basin at Bkejwanong Territory (Walpole Island First Nation), in the Traditional Territory of the Three Fires Confederacy of First Nations (Ojibwe, Odawa, and Potawatomi) on Turtle Island (North America), this inaugural undergraduate university course was led by an Indigenous instructor with contributions from non-Indigenous science faculty from the university and local community knowledge keepers. Here, we describe our journey in cocreating land-based teaching modules with Indigenous scholars and scholars at the University of Windsor, Ontario, Canada. We focused on experiences that exposed students to traditional ways of knowing nature, and reflections were used as the main teaching pedagogy. The course offered daily perspectives and activities across land and water and examined dimensions of biodiversity as sacred beings and medicine. Outcomes and indicators of success were driven by the individual’s reflection and evaluation on their own growth, as expressed through a final project aimed at bridging knowledges, supporting community initiatives or both. This case is designed to offer an example that has potential for application to many other contexts where community-faculty partnerships and land-based learning opportunities are availabl

Embryonic Exposures to Perfluorooctanesulfonic Acid (PFOS) Disrupt Pancreatic Organogenesis in the Zebrafish, Danio rerio

Perfluorooctanesulfonic acid (PFOS) is a ubiquitous environmental contaminant, previously 16 utilized as a non-stick application for consumer products and firefighting foam. It can cross the 17 placenta, and has been repeatedly associated with increased risk for diabetes in epidemiological 18 studies. Here, we sought to establish the hazard posed by embryonic PFOS exposures on the 19 developing pancreas in a model vertebrate embryo, and develop criteria for an adverse outcome 20 pathway (AOP) framework to study the developmental origins of metabolic dysfunction. 21 Zebrafish (Danio rerio) embryos were exposed to 16, 32, or 64 μM PFOS beginning at the mid-22 blastula transition. We assessed embryo health, size, and islet morphology in Tg(insulin-GFP) 23 embryos at 48, 96 and 168 hpf, and pancreas length in Tg(ptf1a-GFP) embryos at 96 and 168 24 hpf. QPCR was used to measure gene expression of endocrine and exocrine hormones, digestive 25 peptides, and transcription factors to determine whether these could be used as a predictive 26 measure in an AOP. Embryos exposed to PFOS showed anomalous islet morphology and 27 decreased islet size and pancreas length in a U-shaped dose-response curve, which resemble 28 congenital defects associated with increased risk for diabetes in humans. Expression of genes 29 encoding islet hormones and exocrine digestive peptides followed a similar pattern, as did total 30 larval growth. Our results demonstrate that embryonic PFOS exposures can disrupt pancreatic 31 organogenesis in ways that mimic human congenital defects known to predispose individuals to 32 diabetes; however, future study of the association between these defects and metabolic 33 dysfunction are needed to establish an improved AOP framework

Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model

The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio). Using endogenously expressed fluorescent protein markers for developing zebrafish beta cells and exocrine pancreas tissue, we documented differences in islet area and incidence rates of islet morphological variants in zebrafish embryos between 48 and 96 h post fertilization (hpf), raised under control conditions commonly used in embryotoxicity assays. We identified critical windows for chemical exposures during which increased incidences of endocrine pancreas abnormalities were observed following exposure to cyclopamine (2–12 hpf), Mono-2-ethylhexyl phthalate (MEHP) (3–48 hpf), and Perfluorooctanesulfonic acid (PFOS) (3–48 hpf). Both islet area and length of the exocrine pancreas were sensitive to oxidative stress from exposure to the oxidant tert-butyl hydroperoxide during a highly proliferative critical window (72 hpf). Finally, pancreatic dysmorphogenesis following developmental exposures is discussed with respect to human disease

Path cover number, maximum nullity, and zero forcing number of oriented graphs and other simple digraphs

An oriented graph is a simple digraph obtained from a simple graph by choosing exactly one of the two arcs (u,v)(u,v) or (v,u)(v,u) to replace each edge {u,v}{u,v}. A simple digraph describes the zero-nonzero pattern of off-diagonal entries of a family of (not necessarily symmetric) matrices. The minimum rank of a simple digraph is the minimum rank of this family of matrices; maximum nullity is defined analogously. The simple digraph zero forcing number and path cover number are related parameters. We establish bounds on the range of possible values of all these parameters for oriented graphs, establish connections between the values of these parameters for a simple graph GG, for various orientations G→G→ and for the doubly directed digraph of GG, and establish an upper bound on the number of arcs in a simple digraph in terms of the zero forcing number