ISA Associate

Abstract In the military, combat wound infections can progress rapidly to life-threatening sepsis. Discovery of effective small molecule drugs to prevent and/or treat sepsis is a priority. To identify potential sepsis drug candidates, we used an optimized larval zebrafish model of endotoxicity/sepsis (Philip et al., 2017) to screen commercial libraries of U.S. Food and Drug Administration (FDA)- approved drugs and other active pharmaceutical ingredients (API) known to affect pathways implicated in the initiation and progression of sepsis in humans (i.e., inflammation, mitochondrial dysfunction, coagulation, and apoptosis). We induced endotoxicity in 3- and 5-day post fertilization larval zebrafish (characterized by mortality and tail fin edema (vascular leakage)) by immersion exposure toPseudomonas aeruginosa60 μg/mL lipopolysaccharide (LPS) for 24 hours, then screened for the rescue potential of 644 selected drugs simultaneously with LPS at 10 μM. After LPS exposure, we used a neurobehavioral assay (light-dark test) to further evaluate rescue from endotoxicity and to determine possible off-target drug side effects. We identified 29 drugs with > 60% rescue of tail edema and mortality. Three drugs (Ketanserin, Tegaserod, and Brexpiprazole) produced 100% rescue and did not differ from the controls in the light-dark test, suggesting a lack of off-target neurobehavioral effects. Further testing of these three drugs at a nearly 100% lethal concentration ofKlebsiella pneumoniaeLPS (45 μg/mL) showed 100% rescue from mortality and 88%-100% mitigation against tail edema. The success of the three identified drugs in a zebrafish endotoxicity/sepsis model warrants further evaluation in mammalian sepsis models.

Abstract Graphite is a quasi-brittle material that has recently become of great interest to designs of advanced nuclear reactors due to its excellent thermal and neutronic properties. When designing graphite core components for reactors, engineers must analyze the components for structural adequacy. Graphite is a quasi-brittle material with complex failure behavior. Of particular interest to this paper is the disparate flaw failure mode that results in low strength failures in some portion of graphite specimens. The nature of disparate flaws and their impact on the failure probability distribution of graphite is explored. To this end, historic data and literature is reviewed. The American Society of Mechanical Engineers Boiler and Pressure Vessel Code (ASME BPVC) contains a set of rules to aid in the design and qualification of graphite core components. The current manner in which the ASME BPVC attempts to account for disparate flaws within the full assessment and its derivation is discussed. This method is shown to have a number of problems. Alternative methods for the handling of disparate flaws are provided and the benefits of each potential method is assessed. Based on the review of disparate flaw behavior and the methods by which they may be accounted for, the authors propose a path forward which allows reactor designs to have accuracy in estimated material reliability curves without the need for excessive testing or unrealistic conservatism.

FigureWith presidential campaigns in full swing, it's safe to say the future of healthcare will take up a fair share of the national conversation for the next several months, with topics such as Medicaid expansion, reproductive health, and persistent healthcare workforce challenges at the forefront. As patient advocates, physician associates/assistants (PAs) have an obligation to engage in the national conversation, but we also have a duty to ensure that progress on PA-led policy continues at the state level. Discourse during a presidential election year has a way of sucking up all the oxygen, but in states across the country, active legislation remains before many legislatures. Although perhaps not as headline-grabbing as many of the pressing national priorities, the changes PAs are seeking to state laws would have a significant effect on how healthcare is delivered in communities throughout our country. For example, in 2024, our profession is well positioned to make significant headway on the PA Licensure Compact. By the close of 2023, three states—Utah, Delaware, and Wisconsin—had enacted the PA Compact, and legislation had been introduced in Maine, Michigan, New York, Ohio, Vermont, and Washington state. This progress demonstrates the power of partnerships, as collaboration with the Federation of State Medical Boards and the Council of State Governments was key to this strong start. The PA Licensure Compact, like other PA practice law modernizations, is a long overdue and commonsense way to make healthcare delivery in our country more efficient. After the compact is operational, licensed PAs will be able to make a single application for privileges to practice (in person or via telemedicine) in any state that has joined the compact, without the need to apply for licensure in each state. This would significantly reduce administrative burdens and may reduce licensing fees for PAs. However, most importantly, it would reduce delays in providing patient care and increase patient access. After seven states have adopted the compact model legislation, the compact will be activated and will begin the process to become operational. Historically, this process has taken 18 to 24 months after activation for other professions. The PA Compact is completely optional—PAs may use the compact to obtain privileges to practice in all states in which they wish to practice, or they may continue to obtain single-state licenses. Furthermore, the PA Compact will not change scope of practice—PAs using the compact must still abide by the state laws and regulations in the states in which they practice. The PA Compact also would establish a multistate data system that will enhance public protection by facilitating the sharing of licensure and disciplinary information across compact member states. Increased licensure portability is an urgent need for PAs who travel or relocate regularly, including military spouses. With an active interstate PA compact, a practicing PA can maintain licensure and avoid licensing-related downtime between jobs, as long as relevant states are members of the compact. For more information on the PA Compact, including updates on where your state is in the process, visit pacompact.org. I urge PAs who are not involved in advocacy to reach out to your state chapters. Breaking through the noise of an election year requires a loud, united PA voice. Every email, call, or meeting can make a difference.

Folusho Ogunfiditimi is president of the American Academy of Physician Associates, based in Alexandria, Va., and administrator of practice management for Florida Health Care Plans in Daytona Beach, Fla. The author has disclosed no potential conflicts of interest, financial or otherwise.

Although allopathic (MD) and osteopathic (DO) students have similar curricular requirements, little is known about differences in MD and DO preparedness for obstetrics and gynecology (OB/GYN) residency. To assess differences in experiences and confidence of MD vs DO students who matched to OB/GYN. This cross-sectional survey study was open to all fourth-year medical students who matched to OB/GYN in the United States in April 2021. The survey included demographic data, clinical experiences, confidence (5-point sliding scale), and a 11-item knowledge test. Survey responses were compared to assess for disparities in experiences and confidence. Survey response rate was 72.0% (1057 of 1469) students matched to OB/GYN postgraduate year 1 positions. Of the 871 MD and 175 DO responding students, MDs were more likely to have clerkships ≥6 weeks (78.1% vs 15.4%; P<.001) and a home sub-internship (92.0% vs 53.4%; P<.001). DOs reported more hands-on experiences with procedures (MD median=35 [20-35] vs DO median=40 [25-65]; P=.002). There was no difference in self-reported confidence in knowledge, technical skills, or having a realistic sense of internship, and no difference in baseline knowledge test scores. DOs felt less confident about their medical school preparation (aOR 0.40; 95% CI 0.25-0.66; P<.001) and were more likely to perceive inequity of residency preparation (aOR 1.88; 95% CI 1.18-3.00; P=.002). MD students matched to US OB/GYN residency programs reported longer clerkship and more home sub-internships, while DO students reported more hands-on experiences. Despite reporting similar confidence in knowledge and skills, DO students felt less prepared for internship.

Abstract The ASME Code, Section III, provides rules for the evaluation of cyclic loading that include evaluations of fatigue. These rules were first developed in the 1960s along with the original development of Section III. Since then, technology and analytical advancements have improved our understanding of the fatigue phenomenon. As an example, the developments in environmentally assisted fatigue (EAF) have become a major consideration in the low-cycle fatigue for light water reactors and plant life extension. Fatigue usage has an outsized impact on the overall cost and complexity of nuclear plants, which goes beyond just the qualification of ASME components. For example, pipe break locations, pipe whip restraints, and inservice inspections are, in part, based on fatigue analysis results. Therefore, it is important that fatigue analyses provide the most realistic assessment of fatigue with appropriate conservatism. The Section III Standards Committee has been working to keep the Code up to date with the latest research, analysis tools and fatigue data. In 2017, a Fatigue Steering Committee was formed to provide a venue for stakeholders to identify and coordinate development of updated fatigue design criteria, analysis methods, and their associated physical and thermo-mechanical properties for application to Section III of the ASME BPV Code. The stakeholders include many international organizations including the Japan Society of Mechanical Engineers. Many PVP papers have been used as the basis for the Fatigue Action Plan items. The Steering Committee completed its work in 2019 with the adoption of a Fatigue Action Plan, which provided a vision for advanced fatigue approaches. The Fatigue Action Plan recommended specific Code actions and activities to guide and coordinate the Code actions in the area of fatigue. This paper outlines the overall Fatigue Action Plan and provides an update on the implementation progress. Section III has already accomplished several actions on the Fatigue Action Plan by publishing numerous Code Cases and Code revisions that have improved the analysis tools available to designers to address fatigue. This paper provides an overview and introduction to these Code Cases and other tools for designers. The Fatigue Action Plan was largely based on addressing the need for the light water reactor fleet to address low cycle thermal fatigue. The Committee also recognizes that going forward the Fatigue Action Plan must address the needs of the growing advanced reactor community as well as other users of the Code. The paper discusses these needs and Section III plans to meet these future needs.

Abstract The U.S. Department of Energy has recently completed a research program to support the development of the compact heat exchanger (CHX) for use in high temperature advanced reactors. The project was executed by an Integrated Research Project (IRP) and includes team members from the University of Wisconsin–Madison, University of Michigan, Georgia Institute of Technology, University of Idaho, North Carolina State University, Oregon State University, Electric Power Research Institute, MPR Associates, and heat exchangers manufacturers CompRex and Vacuum Process Engineering. The objective of the research was to enable the use of compact heat exchanger designs in high temperature advanced reactor service in order to improve plant efficiency and economics. A necessary step for achieving this objective is to ensure that the ASME Boiler and Pressure Vessel Code, Section III has rules for the construction of CHXs for nuclear service. However, construction rules alone are not sufficient to deploy a compact heat exchanger in an advanced reactor. ASME Section XI Rules for the Inservice Inspection (ISI) of a heat exchanger in an operating nuclear reactor will be required, and mostly likely ISI will be conducted in according with ASME Section XI, Division 2, Reliability and Integrity Management (RIM) methodology, which is a non-deterministic, technology neutral, approach to inservice inspection. Since a RIM based ISI program is developed by an owner considering the entire reactor technology safety case, owners will need specific information regarding the performance, failure modes, reliability, and inspection options for compact heat exchangers. Previously, ICONE27-1139 provided strategies for inservice inspection of compact heat exchanger that outlined how an owner can use the planned IRP research to support the development of an ISI program that includes compact heat exchangers. Now that the IRP research is completed, this paper updates the earlier strategy to reflect the results of the research. Failure mechanisms for compact heat exchanger are unique and not widely understood. The IRP has studied the failure mechanisms, monitoring and inspection technologies and this research may be used to enable an owner/operator of an advanced nuclear reactor to develop a RIM based inservice program.

This paper analyzes price gaps in the Ukrainian stock market for the case of UX index over the period 2009–2018. Using different statistical tests (Student’s t-tests, ANOVA, Mann-Whitney test) and regression analysis with dummy variables, as well as modified cumulative approach and trading simulation, the authors test a number of hypotheses searching for price patterns and abnormal market behavior related to price gaps: there is seasonality in price gaps (H1); price gaps generate statistical anomalies in the Ukrainian stock market (H2); upward gaps generate price patterns in the Ukrainian stock market (H3) and downward gaps generate price patterns in the Ukrainian stock market (H4). Overall results are consistent with the Efficient Market Hypothesis: there is no seasonality in price gaps and in most cases there is no evidences of price patterns or abnormal price behavior after the gaps in the Ukrainian stock market. Nevertheless, the authors find very strong and convincing evidences in favor of momentum effect on the days of negative gaps. These observations are confirmed by trading simulations: trading strategy based on detected price pattern generates profits and demonstrates overall efficiency, which is against the market efficiency. These results can be interesting both for academicians (further evidences against market efficiency) and practitioners (real and effective trading strategy to generate profits in the Ukrainian market market).