Optimizing Cybersecurity Risk in Medical Cyber-Physical Devices

Medical devices are increasingly connected, both to cyber networks and to sensors collecting data from physical stimuli. These cyber-physical systems pose a new host of deadly security risks that traditional notions of cybersecurity struggle to take into account. Previously, we could predict how algorithms would function as they drew on defined inputs. But cyber-physical systems draw on unbounded inputs from the real world. Moreover, with wide networks of cyber-physical medical devices, a single cybersecurity breach could pose lethal dangers to masses of patients. The U.S. Food and Drug Administration (FDA) is tasked with regulating medical devices to ensure safety and effectiveness, but its regulatory approach—designed decades ago to regulate traditional medical hardware—is ill-suited to the unique problems of cybersecurity. Because perfect cybersecurity is impossible and every cybersecurity improvement entails costs to affordability and health, designers need standards that balance costs and benefits to inform the optimal level of risk. The FDA, however, conducts limited cost-benefit analyses, believing that its authorizing statute forbids consideration of economic costs. We draw on statutory text and case law to show that this belief is mistaken and that the FDA can and should conduct cost-benefit analyses to ensure safety and effectiveness, especially in the context of cybersecurity. We describe three approaches the FDA could take to implement this analysis as a practical matter. Of these three, we recommend an approach modeled after the Federal Trade Commission’s cost-benefit test. Regardless of the specific approach the FDA chooses, however, the critical point is that the agency must weigh costs and benefits to ensure the right level of cybersecurity. Until then, medical device designers will face continued uncertainty as cybersecurity threats become increasingly dangerous

Transitions in Gambling Participation During Late Adolescence and Young Adulthood

Purpose: The purpose of this study was to examine transitions in gambling participation from late adolescence into emerging adulthood and to identify factors (i.e., gender, race, intervention status, lunch status, conduct disorder, parental monitoring, neighborhood environment, and substance use) that might influence these transitions. Methods: Markov modeling was used to describe the movement between past-year gambling states (i.e., nongambling and gambling) across 5 years. Annual data on the past-year gambling behavior and substance use were collected from 515 young men and women starting at the age of 17 years. Results: Past-year gambling declined from 51% prevalence at the age of 17 years to 21% prevalence at the age of 22 years. Participants who reported no past-year gambling at a particular annual assessment had more than an 80% probability of also reporting no past-year gambling at the following assessment. Men were 1.07–2.82 times more likely than women to transition from past-year nongambling to gambling year to year, and women were 1.27–5.26 times more likely than men to transition from past-year gambling to nongambling year to year. In addition, gender and past-year tobacco use interacted such that men who used tobacco were most likely (and men who did not use tobacco least likely) to gamble at baseline. Conclusions: Transition rates between gambling states appear to be relatively stable over time from late adolescence into emerging adulthood; however, men and those who engage in substance use may be at an increased risk of gambling participation

Transitions in Gambling Participation During Late Adolescence and Young Adulthood

Purpose: The purpose of this study was to examine transitions in gambling participation from late adolescence into emerging adulthood and to identify factors (i.e., gender, race, intervention status, lunch status, conduct disorder, parental monitoring, neighborhood environment, and substance use) that might influence these transitions. Methods: Markov modeling was used to describe the movement between past-year gambling states (i.e., nongambling and gambling) across 5 years. Annual data on the past-year gambling behavior and substance use were collected from 515 young men and women starting at the age of 17 years. Results: Past-year gambling declined from 51% prevalence at the age of 17 years to 21% prevalence at the age of 22 years. Participants who reported no past-year gambling at a particular annual assessment had more than an 80% probability of also reporting no past-year gambling at the following assessment. Men were 1.07–2.82 times more likely than women to transition from past-year nongambling to gambling year to year, and women were 1.27–5.26 times more likely than men to transition from past-year gambling to nongambling year to year. In addition, gender and past-year tobacco use interacted such that men who used tobacco were most likely (and men who did not use tobacco least likely) to gamble at baseline. Conclusions: Transition rates between gambling states appear to be relatively stable over time from late adolescence into emerging adulthood; however, men and those who engage in substance use may be at an increased risk of gambling participation

NASA's GreenLab Research Facility: A Guide for a Self-Sustainable Renewable Energy Ecosystem

There is a large gap between the production and demand for energy from alternative fuel and alternative renewable energy sources. The sustainability of humanity, as we know it, directly depends on the ability to secure affordable fuel, food, and freshwater. NASA Glenn Research Center (Glenn) has initiated a laboratory pilot study on using biofuels as viable alternative fuel resources for the field of aviation, as well as utilizing wind and solar technology as alternative renewable energy resources. The GreenLab Research Facility focuses on optimizing biomass feedstock using algae and halophytes as the next generation of renewable aviation fuels. The unique approach in this facility helps achieve optimal biomass feedstock through climatic adaptation of balanced ecosystems that do not use freshwater, compete with food crops, or use arable land. In addition, the GreenLab Research Facility is powered, in part, by alternative and renewable energy sources, reducing the major environmental impact of present electricity sources. The ultimate goal is to have a 100 percent clean energy laboratory that, when combined with biomass feedstock research, has the framework in place for a self-sustainable renewable energy ecosystem that can be duplicated anywhere in the world and can potentially be used to mitigate the shortage of food, fuel, and water. This paper describes the GreenLab Research Facility at Glenn and its power and energy sources, and provides recommendations for worldwide expansion and adoption of the facility s concept

A Flanking Gene Problem Leads to the Discovery of a Gprc5b Splice Variant Predominantly Expressed in C57Bl/6J Mouse Brain and in Maturing Neurons

Gprc5b, a retinoic acid-inducible orphan G protein-coupled receptor (GPCR), is a member of the group C metabotropic glutamate receptor family proteins possibly involved in non-canonical Wnt signaling. Many GPCR transcripts are alternatively spliced, which diversifies this class of proteins in their cell- and tissue-specific signaling, regulatory and/or pharmacological properties. We previously generated p97FE65 isoform-specific knockout mice that showed learning/memory deficits. In this study, we further characterized the 97FE65 null mice using cDNA microarray and RT-PCR analyses.We discovered a novel brain-specific C-terminal splice variant of Gprc5b, Gprc5b_v2, which was differentially expressed in p97FE65 wild type and null mouse brains. The null mice were generated in 129/Sv ES cells, and backcrossed to C57Bl/6J for ten generations. We found that expression of Gprc5b_v2 mRNA in the brains of p97FE65 null mice was dramatically down-regulated (more than 20 fold) compared to their wild type littermates. However, expression profiles of Gprc5b variants and SNP analysis surrounding the FE65 locus suggest that the down-regulation is unlikely due to the altered FE65 function, but rather is caused by gene retention from the 129/Sv ES cells. Consistently, in contrast to ubiquitously expressed Gprc5b_v1, Gprc5b_v2 was predominantly expressed in the brain tissues of C57Bl/6J mice. The alternative splicing of the 3' terminal exon also altered the protein coding sequences, giving rise to the characteristic C-termini. Levels of Gprc5b_v2 mRNA were increased during neuronal maturation, paralleling the expression of synaptic proteins. Overexpression of both Gprc5b variants stimulated neurite-like outgrowth in a neuroblastoma cell line.Our results suggest that Gprc5b-v2 may play a role during brain maturation and in matured brain, possibly through the regulation of neuronal morphology and protein-protein interaction. This study also highlights the fact that unexpected gene retention following repeated backcrosses can lead to important biological consequences

The Effect of Growth Environment and Salinity on Lipid Production and Composition of Salicornia virginica

Finding a viable and sustainable source of renewable energy is a global task. Biofuels as a renewable energy source can potentially be a viable option for sustaining long-term energy needs. Biodiesel from halophytes shows great promise due to their ability to serve not only as a fuel source, but a food source as well. Halophytes are one of the few biomass plant species that can tolerate a wide range of saline conditions. We investigate the feasibility of using the halophyte, Salicornia virginica as a biofuel source by conducting a series of experiments utilizing various growth and salinity conditions. The goal is to determine if the saline content of Salicornia virginica in our indoor growth vs outdoor growth conditions has an influence on lipid recovery and total biomass composition. We focused on using standard lipid extraction protocols and characterization methods to evaluate twelve Salicornia virginica samples under six saline values ranging from freshwater to seawater and two growth conditions. The overall goal is to develop an optimal lipid extraction protocol for Salicornia virginica and potentially apply this protocol to halophytes in general

Multi-donor × elite-based populations reveal QTL for low-lodging wheat

Low-lodging high-yielding wheat germplasm and SNP-tagged novel alleles for lodging were identified in a process that involved selecting donors through functional phenotyping for underlying traits with a designed phenotypic screen, and a crossing strategy involving multiple-donor × elite populations

Roles for a Lipid Phosphatase in the Activation of its Opposing Lipid Kinase

Fig4 is a phosphoinositide phosphatase that converts PI3,5P2 to PI3P. Paradoxically, mutation of Fig4 results in lower PI3,5P2, indicating that Fig4 is also required for PI3,5P2 production. Fig4 promotes elevation of PI3,5P2, in part, through stabilization of a protein complex that includes its opposing lipid kinase, Fab1, and the scaffold protein Vac14. Here we show that multiple regions of Fig4 contribute to its roles in the elevation of PI3,5P2: Its catalytic site, an N-terminal disease-related surface, and a C-terminal region. We show that mutation of the Fig4 catalytic site enhances the formation of the Fab1-Vac14-Fig4 complex, and reduces the ability to elevate PI3,5P2. This suggests that independent of its lipid phosphatase function, the active site plays a role in the Fab1-Vac14-Fig4 complex. We also show that the N-terminal disease-related surface contributes to the elevation of PI3,5P2 and promotes Fig4 association with Vac14 in a manner that requires the Fig4 C-terminus. We find that the Fig4 C-terminus alone interacts with Vac14 in vivo and retains some functions of full-length Fig4. Thus, a subset of Fig4 functions are independent of its phosphatase domain and at least three regions of Fig4 play roles in the function of the Fab1-Vac14-Fig4 complex

PatientExploreR: an extensible application for dynamic visualization of patient clinical history from electronic health records in the OMOP common data model.

MotivationElectronic health records (EHRs) are quickly becoming omnipresent in healthcare, but interoperability issues and technical demands limit their use for biomedical and clinical research. Interactive and flexible software that interfaces directly with EHR data structured around a common data model (CDM) could accelerate more EHR-based research by making the data more accessible to researchers who lack computational expertise and/or domain knowledge.ResultsWe present PatientExploreR, an extensible application built on the R/Shiny framework that interfaces with a relational database of EHR data in the Observational Medical Outcomes Partnership CDM format. PatientExploreR produces patient-level interactive and dynamic reports and facilitates visualization of clinical data without any programming required. It allows researchers to easily construct and export patient cohorts from the EHR for analysis with other software. This application could enable easier exploration of patient-level data for physicians and researchers. PatientExploreR can incorporate EHR data from any institution that employs the CDM for users with approved access. The software code is free and open source under the MIT license, enabling institutions to install and users to expand and modify the application for their own purposes.Availability and implementationPatientExploreR can be freely obtained from GitHub: https://github.com/BenGlicksberg/PatientExploreR. We provide instructions for how researchers with approved access to their institutional EHR can use this package. We also release an open sandbox server of synthesized patient data for users without EHR access to explore: http://patientexplorer.ucsf.edu.Supplementary informationSupplementary data are available at Bioinformatics online

Netrin-3 Avoidance and Mitotic Inhibition in \u3cem\u3eTetrahymena thermophila\u3c/em\u3e Involves Intracellular Calcium and Serine/Threonine Kinase Activity

Netrins are a family of signaling proteins ubiquitously expressed throughout the animal kingdom. While netrin-1 has been well characterized, other netrins, such as netrin-3, remain less well understood. In our current study, we characterize the behavior of two netrin-3 peptides, one derived from the N-terminal and one derived from the C-terminal of netrin-3. Both peptides cause avoidance behavior and mitotic inhibition in Tetrahymena thermophila at concentrations as low as 0.5 micrograms (μg) per milliliter. These effects can be reversed by addition of the calcium chelator, EGTA; the intracellular calcium chelator, BAPTA-AM, or the serine/threonine kinase inhibitor, apigenin. The broad spectrum tyrosine kinase inhibitor, genistein, has no effect on netrin-3 signaling, indicating that netrin-3 signaling in this organism uses a different pathway than the previously described netrin-1 pathway. Further studies will allow us to better describe the netrin-3 signaling pathway in this organism