Analysis of Safety-Critical Computer Failures in Medical Devices

Incidents due to malfunctioning medical devices are a major cause of serious injury and death in the United States. During 2006–2011, 5,294 recalls and around 1.2 million adverse events were reported to the U.S. Food and Drug Administration (FDA). Almost 23% of these recalls were due to computer-related failures, of which around 94% presented medium-to-high risk of severe health consequences (such as serious injury or death) to patients. This paper investigates the causes of failures in computer-based medical devices and their impact on patients, by analyzing human-written descriptions of recalls and adverse event reports, obtained from public FDA databases. We characterize computer-related failures by deriving fault classes, failure modes, recovery actions, and number of devices affected by the recalls. This analysis is used as a basis for identifying safety issues in life-critical medical devices and providing insights on the future challenges in the design of safety-critical medical devices.Princeton/MARCO / 2009-DT-2049Stanford/DTRA / 27451040-49741-AOpe

Intra-aortic balloon pump inserted through the subclavian artery: A minimally invasive approach to mechanical support in the ambulatory end-stage heart failure patient

ObjectiveIntra-aortic balloon pumps are traditionally inserted through the femoral artery, limiting the patient's mobility. We used alternate approaches of intra-aortic balloon pump insertion to provide temporary and minimally invasive support for patients with decompensating, end-stage heart failure. The present study describes the outcomes with closed-chest, transthoracic intra-aortic balloon pumps by way of the subclavian artery.MethodsDuring a 3-year period, 20 patients underwent subclavian artery–intra-aortic balloon pump in the setting of end-stage heart failure. The balloon was inserted through a polytetrafluoroethylene graft sutured to the right subclavian artery in 19 patients (95%) and to the left subclavian artery in 1 patient (5%). The goal of support was to bridge to transplantation in 17 patients (85%) and bridge to recovery in 3 patients (15%). The primary outcome measure was death during subclavian artery–intra-aortic balloon pump support. The secondary outcomes included survival to the intended endpoint of bridge to transplantation/bridge to recovery, complications during subclavian artery–intra-aortic balloon pump support (eg, stroke, limb ischemia, brachial plexus injury, dissection, bleeding requiring reoperation, and device-related infection), emergent surgery for worsening heart failure, and ambulation during intra-aortic balloon pump support.ResultsThe duration of balloon support ranged from 3 to 48 days (mean, 17.3 ± 13.1 days). No patients died during subclavian artery–intra-aortic balloon pump support. Of the 20 patients, 14 (70%) were successfully bridged to transplant or left ventricular-assist device. Two patients (10%) required emergent left ventricular-assist device for worsening heart failure.ConclusionsAn intra-aortic balloon pump inserted through the subclavian artery is a simple, minimally invasive approach to mechanical support and is associated with limited morbidity and facilitates ambulation in patients with end-stage heart failure

Safety Implications of Robotic Surgery: A Study of 13 Years of FDA Data on da Vinci Surgical Systems

Robotic surgical systems are intended to enable surgeons to perform minimally invasive operations with increased vision, precision, dexterity, and control, and to reduce the rate of injuries, blood loss, length of hospital stay, and post-operative complications. Recently, concerns regarding the safety and effectiveness of robot-assisted surgeries have heightened as an increased number of adverse events associated with the surgical robots have been reported to the U.S. Food and Drug Administration (FDA). Our study focuses on the analysis of the adverse events and recalls of da Vinci surgical systems, collected by the FDA over a period of 13 years from 2000 to 2012. We use the data on deaths, injuries, and robot malfunctions, combined with the technical problems and corresponding recovery actions taken by the company (provided by the recalls), together with systematic accident analysis using a tool called CAST. Using an automated natural language parsing tool trained with domain-specific dictionaries and part-of-speech and negation taggers, we extracted valuable information on the potential causes of robotic accidents in order to understand the effectiveness of using robotic devices for different minimally invasive procedures. We found that despite the increasing number of procedures being done with the da Vinci surgical system, a significant number of malfunctions and system downtimes with potentially adverse impacts on patients are being experienced. We provide insights on the use of existing state-of-the-art technologies for enhancing safety in future robotic surgical systems.National Science Foundation (NSF CNS10-18503 CISE); IBM Corporation; Infosys LtdOpe

Imaging and Quantification of Myocardial Perfusion Using Real-Time Three-Dimensional Echocardiography

ObjectivesWe tested the feasibility of real-time three-dimensional echocardiographic (RT3DE) perfusion imaging and developed and validated an algorithm for volumetric analysis of myocardial contrast inflow. The study included three protocols wherein perfusion was measured: 1) in an ex-vivo model of controlled global coronary flow, 2) in an in-vivo model during regional perfusion variations, and 3) in humans during pharmacologically induced hyperemia.BackgroundThe RT3DE technology offers an opportunity for myocardial perfusion imaging without multi-slice reconstruction and repeated contrast maneuvers.MethodsElectrocardiographically triggered harmonic RT3DE datasets were acquired (Philips 7500) while infusion of Definity was initiated and reached a steady state. Protocol 1 was performed in nine isolated rabbit hearts and included three coronary flow levels. In protocol 2, changes in regional perfusion caused by partial left anterior descending artery occlusion were measured in five pigs. In protocol 3, adenosine-induced changes in perfusion were measured in eight normal volunteers. Myocardial video-intensity (MVI) was measured over time in three-dimensional (3D) slices to calculate peak contrast inflow rate (PCIR). In pigs, PCIR was measured on a regional basis and validated against microspheres.ResultsThe RT3DE imaging allowed selection of slices for perfusion analysis in rabbit hearts, pigs, and humans. Administration of contrast resulted in clearly visible and quantifiable changes in MVI. In rabbits, The PCIR progressively decreased with coronary flow (p < 0.0001). In pigs, coronary occlusion caused a 59 ± 26% decrease in PCIR exclusively in the left anterior descending artery territory (p < 0.05) in agreement with microspheres. In humans, adenosine increased PCIR to 198 ± 57% of baseline (p < 0.05).ConclusionsContrast-enhanced RT3DE imaging provides the basis for volumetric imaging and quantification of myocardial perfusion

Live 3-Dimensional Transesophageal Echocardiography Initial Experience Using the Fully-Sampled Matrix Array Probe

ObjectivesOur study goals were to evaluate the 3-dimensional matrix array transesophageal echocardiographic (3D-MTEE) probe by assessing the image quality of native valves and other intracardiac structures.BackgroundBecause 3-dimensional transesophageal echocardiography with gated rotational acquisition is not used routinely as the result of artifacts, lengthy acquisition, and processing, a 3D-MTEE probe was developed (Philips Medical Systems, Andover, Massachusetts).MethodsIn 211 patients, 3D-MTEE zoom images of the mitral valve (MV), aortic valve, tricuspid valve, interatrial septum, and left atrial appendage were obtained, followed by a left ventricular wide-angled acquisition. Images were reviewed and graded off-line (Xcelera with QLAB software, Philips Medical Systems).ResultsExcellent visualization of the MV (85% to 91% for all scallops of both MV leaflets), interatrial septum (84%), left atrial appendage (86%), and left ventricle (77%) was observed. Native aortic and tricuspid valves were optimally visualized only in 18% and 11% of patients, respectively.ConclusionsThe use of 3D-MTEE imaging, which is feasible in most patients, provides superb imaging of native MVs, which makes this modality an excellent choice for MV surgical planning and guidance of percutaneous interventions. Optimal aortic and tricuspid valve imaging will depend on further technological developments. Fast acquisition and immediate online display will facilitate wider acceptance and routine use in clinical practice

Проектирование автоматизированной системы дожимной насосной станции

Целью данной выпускной квалификационной работы является разработка автоматизированной системы управления ДНС с использованием современного оборудования для увеличения производительности и надежности станции, а также снижения затрат на обслуживание. В ходе работы будет выполнено исследование и проектирование автоматизированной системы дожимной насосной станции.The purpose of this final qualifying work is the development of an automated control system for CSN using modern equipment to increase plant performance and reliability, as well as reduce maintenance costs. In the course of work, research and design of an automated system of a booster pumping station will be performed

Regional Inequality in India in the 1990s: A District-Level View

This paper examines changes in regional inequality in India in the 1990s, using data for 210 of India's districts, spread across nine states. It provides a finer-grained quantitative analysis of growth patterns than has hitherto been attempted for India. The methodology is that of cross-section growth regressions, which seek to explain longer-run growth rates in terms of initial conditions of development. By identifying these connections, the study seeks to illuminate the role of aspects of physical infrastructure, financial development and human capital in influencing regional patterns of growth. In turn, this may have implications for government policies at the national and state levels. We find no evidence for divergence, but evidence for growth convergence in some cases, dependent on initial conditions. The district level results are supportive of the importance of literacy, and access to finance and roads. The methodology can be used to identify districts which may require additional policy intervention along these dimensions, as well as districts where the performance is worse than the average, even after conditioning on development measures, suggesting other causes of backwardness

What do we know about chronic kidney disease in India: first report of the Indian CKD registry

<p>Abstract</p> <p>Background</p> <p>There are no national data on the magnitude and pattern of chronic kidney disease (CKD) in India. The Indian CKD Registry documents the demographics, etiological spectrum, practice patterns, variations and special characteristics.</p> <p>Methods</p> <p>Data was collected for this cross-sectional study in a standardized format according to predetermined criteria. Of the 52,273 adult patients, 35.5%, 27.9%, 25.6% and 11% patients came from South, North, West and East zones respectively.</p> <p>Results</p> <p>The mean age was 50.1 ± 14.6 years, with M:F ratio of 70:30. Patients from North Zone were younger and those from the East Zone older. Diabetic nephropathy was the commonest cause (31%), followed by CKD of undetermined etiology (16%), chronic glomerulonephritis (14%) and hypertensive nephrosclerosis (13%). About 48% cases presented in Stage V; they were younger than those in Stages III-IV. Diabetic nephropathy patients were older, more likely to present in earlier stages of CKD and had a higher frequency of males; whereas those with CKD of unexplained etiology were younger, had more females and more frequently presented in Stage V. Patients in lower income groups had more advanced CKD at presentation. Patients presenting to public sector hospitals were poorer, younger, and more frequently had CKD of unknown etiology.</p> <p>Conclusions</p> <p>This report confirms the emergence of diabetic nephropathy as the pre-eminent cause in India. Patients with CKD of unknown etiology are younger, poorer and more likely to present with advanced CKD. There were some geographic variations.</p

UBR2 of the N-End Rule Pathway Is Required for Chromosome Stability via Histone Ubiquitylation in Spermatocytes and Somatic Cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells