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With increasing concerns over global climate change caused by GHG emissions, carbon capture and storage (CCS) has become imperative for coal based power plants. Meanwhile, with the development and deployment of hybrid vehicles, electric vehicles, and alternative fuel vehicles, GHG reduction efforts in the power industry can also benefit the transportation sector. Power plants with H2 co-production capability can contribute significantly in such development trends because H2 powered fuel cell hybrid vehicles are very promising for future " zero emissions vehicles" This work investigates the thermodynamic performance and cost advantage of employing advanced technologies currently under development for central power plants that (1) employ coal and biomass as feed stock; (2) co-produce power and high purity H2; (3) capture most of the CO2 evolved within the plants. Two system designs are developed: the first " base" case is an integrated gasification combined cycle (IGCC) system consisting of commercially ready technologies; the second " advanced" case is an integrated gasification fuel cell (IGFC) system. The feedstock employed consists of Utah bituminous coal along with two typical biomass resources, corn stover and cereal straw. The IGFC plant produces significantly higher amount of electricity for the same amounts of feedstock and H2 export while the cost of producing the H2 using a cost of electricity of 135/MWh is 1178/tonne for the IGFC case versus 2620/tonne for the IGCC case. © 2011 Elsevier Ltd.

Integrated gasification fuel cell (IGFC) systems that combine coal gasification and solid oxide fuel cells (SOFC) are promising for highly efficient and environmentally sensitive utilization of coal for power production. Most IGFC system analysis efforts performed to-date have employed non-dimensional SOFC models, which predict SOFC performance based upon global mass and energy balances that do not resolve important intrinsic constraints of SOFC operation, such as the limits of internal temperatures and species concentrations. In this work, a detailed dimensional planar SOFC model is applied in IGFC system analysis to investigate these constraints and their implications and effects on the system performance. The analysis results further confirm the need for employing a dimensional SOFC model in IGFC system design. To maintain the SOFC internal temperature within a safe operating range, the required cooling air flow rate is much larger than that predicted by the non-dimensional SOFC model, which results in a larger air compressor design and operating power that significantly reduces the system efficiency. Options to mitigate the challenges introduced by considering the intrinsic constraints of SOFC operation in the analyses and improve IGFC design and operation have also been investigated. Novel design concepts that include staged SOFC stacks and cascading air flow can achieve a system efficiency that is close to that of the baseline analyses, which did not consider the intrinsic SOFC limitations. © 2011 Elsevier B.V. All rights reserved.

Integrated gasification fuel cell (IGFC) technology combining coal gasification and solid oxide fuel cell (SOFC) is believed to be the only viable solution to achieving U.S. Department of Energy (DOE)'s performance goal for next generation coal-based power plants, producing electricity at 60% efficiency (coal HHV-AC) while capturing more than 90% of the evolved CO2. Achieving this goal is challenging even with high performance SOFCs; design concepts published to date have not demonstrated this performance goal. In this work an IGFC system concept consisting of catalytic hydro-gasification, proven low-temperature gas cleaning and hybrid fuel cell-gas turbine power block (with SOFC operating at about 10 bar) is introduced. The system is demonstrating an electricity efficiency greater than 60% (coal HHV basis), with more than 90% of the carbon present in the syngas separated as CO2 amenable to sequestration. A unique characteristic of the system is recycling de-carbonized, humidified anode exhaust back to the catalytic hydro-gasifier for improved energy integration. Alternative designs where: (1) anode exhaust is recycled directly back to SOFC stacks, (2) SOFC stack operating pressure is reduced to near atmospheric and (3) methanation reactor in the reactor/expander topping cycle is removed, have also been investigated and the system design and performance differences are discussed. © 2010 Elsevier B.V.

A novel process configuration consisting of integrating the air separation unit with a H2 separation membrane reactor (HSMR) in a coal gasification based coproduction facility with near zero emissions is described. The plant utilizes an air separation unit operating at elevated pressure to produce an Intermediate Pressure (IP) N2 stream in addition to the O2 required by the coal gasifier. The syngas produced by the gasifier after cleanup is supplied to the membrane reactor which produces H2 by shifting the carbon monoxide while simultaneously separating the fy. The IP N2 is used as sweep gas to assist in the separation of the H 2 diffusing across the membrane walls by decreasing the partial pressure of the H2 on the permeate side. The total pressure of gases on the permeate side may thus be increased such that the H2 / N 2 mixture may be fed directly to the gas turbines at the required pressure without requiring cooling and compression of the HT. An added advantage is that the total pressure differential across the membrane wall is reduced. The N2 in the fuel gas functions both as a thermal diluent for reducing the formation of nitrogen oxides and as additional motive fluid for expansion in the turbine. The carbon dioxide rich gas (non-permeate) leaving the membrane reactor after catalytic oxidation of the residual combustibles constitutes the carbon capture stream which may be further compressed and pipelined for CO2 sequestration. High purity H2 may be coproduced for export from a portion of the H2-N2 stream leaving the HSMR utilizing a Pressure Swing Adsorption (PSA) unit. The techno-economic advantages of such a coproduction facility are addressed. Copyright © 2006 by ASME.

The goal of the U.S. Department of Energy's (DOE's) FutureGen project initiative is to develop and demonstrate technology for ultra clean 21st century energy plants that effectively remove environmental concerns associated with the use of fossil fuels for producing electricity, and simultaneously develop highly efficient and cost-effective power plants. The design optimization of an advanced FutureGen plant consisting of an advanced transport reactor (ATR) for coal gasification to generate syngas to fuel an integrated solid oxide fuel cell (SOFC) combined cycle is presented. The overall plant analysis of a baseline system design is performed by identifying the major factors effecting plant performance; these major factors being identified by a strategy consisting of the application of design of experiments (DOEx). A steady state simulation tool is used to perform sensitivity analysis to verify the factors identified through DOEx, and then to perform parametric analysis to identify optimum values for maximum system efficiency. Modifications to baseline system design are made to attain higher system efficiency and to lower the negative impact of reducing the SOFC operating pressure on system efficiency. © 2006.

An advanced coal based power plant system that has an electrical efficiency of 60% on an HHV basis is defined. The solid oxide fuel cell (SOFC) hybrid has been shown to be an essential requirement in order to achieve such a high efficiency. The coal is gasified utilizing a high pressure air-blown advanced transport reactor (ATR). A thermo-economic analysis of this integrated gasification fuel cell (IGFC) plant is performed by comparing it to an integrated gasification combined cycle (IGCC) plant that utilizes a gas turbine combined cycle for power generation. Results of this thermo-economic analysis indicate that the required "break even" cost of the SOFC system is $400/kW on an installed cost basis such that the cost of electricity of IGFC plant is the same as that of the IGCC plant. Coproduction of H2 and capture of carbon emissions may be incorporated in the design without causing a major thermal penalty on the system performance when high temperature separation membranes are employed. An O2-blown gasifier is required for such applications. The technology development needs are addressed. Copyright © 2005 by ASME.

The operation of solid oxide fuel cells on various fuels, such as natural gas, biogas and gases derived from biomass or coal gasification and distillate fuel reforming has been an active area of SOFC research in recent years. In this study, we develop a theoretical understanding and thermodynamic simulation capability for investigation of an integrated SOFC reformer system operating on various fuels. The theoretical understanding and simulation results suggest that significant thermal management challenges may result from the use of different types of fuels in the same integrated fuel cell reformer system. Syngas derived from coal is simulated according to specifications from high-temperature entrained bed coal gasifiers. Diesel syngas is approximated from data obtained in a previous NFCRC study of JP-8 and diesel operation of the integrated 25 kW SOFC reformer system. The syngas streams consist of mixtures of hydrogen, carbon monoxide, carbon dioxide, methane and nitrogen. Although the SOFC can tolerate a wide variety in fuel composition, the current analyses suggest that performance of integrated SOFC reformer systems may require significant operating condition changes and/or system design changes in order to operate well on this variety of fuels. © 2005 Elsevier B.V. All rights reserved.

The power generation community faces a major challenge: to protect the environment while producing a plentiful supply of clean low-cost energy. "21st Century Energy Plants" (Vision 21 Plants) have been proposed and conceptualized to meet the energy and environmental challenges. The solid oxide fuel cell and intercooled gas turbine (SOFC-ICGT) hybrid cycle introduced in this work is one example of a Vision 21 Plant. The system includes an internal-reforming tubular-SOFC, an intercooled gas turbine, a humidifier, and other auxiliary components. A recently developed thermodynamic analysis computer code entitled advanced power systems analyses tools (APSAT) was applied to analyze the system performance of the SOFC-ICGT cycle. Sensitivity analyses of several major system parameters were studied to identify the key development needs and design and operating improvements for this hybrid cycle. A novel optimization strategy including a design of experiments (DOEx) approach is proposed and applied to the hybrid system. Using this optimization strategy, a system electrical efficiency higher than 75% (net ac/lower heating value (LHV)) could be achieved when the system was designed to operate under a high operating pressure (50bara) and with a low percent excess air (EA) (55%) in the SOFC. © 2003 Elsevier B.V. All rights reserved.

Under the sponsorship of the U.S. Department of Energy/National Energy Technology Laboratory, a multi-disciplinary team led by the Advanced Power and Energy Program of the University of California at Irvine is defining the system engineering issues associated with the integration of key components and subsystems into power plant systems that meet performance and emission goals of the Vision 21 program. Earlier tasks of the program have narrowed down the myriad of fuel processing, power generation, and emission control technologies to selected scenarios that identify those combinations having the potential to achieve the Vision 21 program goals of high efficiency and minimized environmental impact while using fossil fuels. These analyses have been extended to consider coal gasification processes combined with the advanced power cycles previously identified. The technology levels considered are based on projected technical and manufacturing advances being made in industry and on advances identified in current and future government supported research. Examples of systems included in these advanced cycles are solid oxide fuel cells, advanced cycle gas turbines, membrane separation of gases and oxygen-enhanced combustion.

Under the sponsorship of the U.S. Department of Energy/National Energy Technology Laboratory, a multi-disciplinary team led by the Advanced Power and Energy Program of the University of California at Irvine is defining the system engineering issues associated with the integration of key components and subsystems into power plant systems that meet performance and emission goals of the Vision 21 program. Earlier tasks of the program have narrowed down the myriad of fuel processing, power generation, and emission control technologies to selected scenarios that identify those combinations having the potential to achieve the Vision 21 program goals of high efficiency and minimized environmental impact while using fossil fuels. These analyses have been extended to consider coal gasification processes combined with the advanced power cycles previously identified. The technology levels considered are based on projected technical and manufacturing advances being made in industry and on advances identified in current and future government supported research. Examples of systems included in these advanced cycles are solid oxide fuel cells, advanced cycle gas turbines, membrane separation of gases and oxygen-enhanced combustion.

The goals of a research program recently completed at the University of California, Irvine were to develop analysis strategy for solid oxide fuel cell (SOFC) based systems, to apply the analysis strategy to tubular SOFC hybrid systems and to identify promising hybrid configurations. A pressurized tubular SOFC combined with an intercooled-reheat gas turbine (SureCell™ cycle) is chosen as the base cycle over which improvements are sought. The humid air turbine (HAT) cycle features are incorporated to the base cycle resulting in the SOFC-HAT hybrid cycle which shows an efficiency of 69.05 percent while the base cycle has an efficiency of 66.23 percent. Exergy analysis identified the superior efficiency performance of the SOFC component. Therefore, an additional cycle variation added a second SOFC component followed by a low pressure combustor in place of the reheat combustor of the gas turbine of the SOFC-HAT hybrid. The resulting dual SOFC-HAT hybrid has a thermal efficiency of 75.98 percent. The single SOFC-HAT hybrid gives the lowest cost of electricity (3.54¢/kW-hr) while the dual SOFC-HAT hybrid has the highest cost of electricity (4.02¢ /kW-hr) among the three cycles with natural gas priced at $3/GJ. The dual SOFC-HAT hybrid plant cost is calculated to be significantly higher because the fraction of power produced by the SOFC(s) is significantly higher than that in the other cases on the basis of $1100/kw initial cost for the SOFC. The dual SOFC-HAT hybrid can only be justified in favor of the single SOFC-HAT hybrid when the price of natural gas is greater than $14/GJ or if a severe carbon tax on the order of $180/ton of CO2 is imposed while natural gas price remains at $3/GJ. Copyright © 2003 by ASME.

The emergence of fuel cell systems and hybrid fuel cell systems requires the evolution of analysis strategies for evaluating thermodynamic performance and directing design and development. A description and application of the recently developed tool for analyzing tubular SOFC based systems is presented. The capabilities of this tool include an analytical model for the tubular SOFC derived from first principles and the secondary equipment required to analyze hybrid power plants. Examples of such secondary equipment are gas turbine, reformer, partial oxidation reactor, shift reactor, humidifier, steam turbines, compressor, gas expander, heat exchanger, and pump. A "controller" is included which is essential for modeling systems to automatically iterate in order to meet the desired process or system design criteria. Another important capability that is included is to be able to arrange the various components or modules as defined by the user in order to configure different hybrid systems. Analysis of the hybrid cycle as originally proposed by Westinghouse (SureCellm) indicates that the thermal efficiency of the cycle is quite insensitive to the pressure ratio, increasing from 65.5 percent to 66.6 percent on a lower calorific value of the fuel as the pressure ratio decreases from 15 to 6.5.

The goals of a research program recently completed at the University of California, Irvine were to develop analysis strategy for Solid Oxide Fuel Cell (SOFC) based systems, to apply the analysis strategy to tubular SOFC hybrid systems and to identify promising hybrid configurations. A pressurized tubular SOFC combined with an intercooled-reheat gas turbine (SureCell ™ cycle) is chosen as the Base Cycle over which improvements are sought. The humid air turbine (HAT) cycle features are incorporated to the Base Cycle resulting in the SOFC-HAT hybrid cycle which shows an efficiency of 69.05% while the Base Cycle has an efficiency of 66.23%. Exergy analysis identified the superior efficiency performance of the SOFC component. Therefore, an additional cycle variation added a second SOFC component followed by a low pressure combustor in place of the reheat combustor of the gas turbine of the SOFC-HAT hybrid. The resulting Dual SOFC-HAT hybrid has a thermal efficiency of 75.98%. The Single SOFC-HAT hybrid gives the lowest cost of electricity (3.54¢/kW-hr) while the Dual SOFC-HAT hybrid has the highest cost of electricity (4.02¢/kW-hr) among the three cycles with natural gas priced at $3/GJ. The Dual SOFC-HAT hybrid plant cost is calculated to be significantly higher because the fraction of power produced by the SOFC(s) is significantly higher than that in the other cases on the basis of $1100/kw initial cost for the SOFC. The Dual SOFC-HAT hybrid can only be justified in favor of the Single SOFC-HAT hybrid when price of natural gas is greater than $14/GJ or ffa severe carbon tax on the order of $180/ton of CO2 is imposed while natural gas price remains at $3/GJ. Copyright © 2001 by ASME.

Objective: Observational studies assessing the association of combination therapy of metformin and sulfonylurea on all-cause and/or cardiovascular mortality in type 2 diabetes have shown conflicting results. We therefore evaluated the effects of combination therapy of sulfonylureas and metformin on the risk of all-cause mortality and cardiovascular disease (CVD) among people with type 2 diabetes.Research Design and Methods: A MEDLINE search (January 1966-July 2007) was conducted to identify observational studies that examined the association between combination therapy of sulfonylureas and metformin on risk of CVD or all-cause mortality. From 299 relevant reports, 9 were included in the meta-analysis. In these studies, combination therapy of metformin and sulfonylurea was assessed, the risk of CVD and/or mortality was reported, and adjusted relative risk (RR) or equivalent (hazard ratio and odds ratio) and corresponding variance or equivalent was reported.Results: The pooled RRs (95% CIs) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88-1.62) for all-cause mortality, 1.29 (0.73-2.27) for CVD mortality, and 1.43 (1.10-1.85) for a composite end point of CVD hospitalizations or mortality (fatal or nonfatal events).Conclusions: The combination therapy of metformin and sulfonylurea significantly increased the RR of the composite end point of cardiovascular hospitalization or mortality (fatal and nonfatal events) irrespective of the reference group (diet therapy, metformin monotherapy, or sulfonylurea monotherapy); however, there were no significant effects of this combination therapy on either CVD mortality or all-cause mortality alone. [ABSTRACT FROM AUTHOR]

Encoding logical qubits in bosonic modes provides a potentially hardware-efficient implementation of fault-tolerant quantum information processing. Here, we demonstrate high-fidelity and deterministic preparation of highly nonclassical bosonic states in the mechanical motion of a trapped ion. Our approach implements error-suppressing pulses through optimized dynamical modulation of laser-driven spin-motion interactions to generate the target state in a single step. We demonstrate logical fidelities for the Gottesman-Kitaev-Preskill state as high as F[over ¯]=0.940(8), a distance-3 binomial state with an average fidelity of F=0.807(7), and a 12.91(5) dB squeezed vacuum state.

Background: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy., Methods: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed., Results: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria., Conclusions: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters., (© 2024 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Conical intersections are ubiquitous in chemistry and physics, often governing processes such as light harvesting, vision, photocatalysis and chemical reactivity. They act as funnels between electronic states of molecules, allowing rapid and efficient relaxation during chemical dynamics. In addition, when a reaction path encircles a conical intersection, the molecular wavefunction experiences a geometric phase, which can affect the outcome of the reaction through quantum-mechanical interference. Past experiments have measured indirect signatures of geometric phases in scattering patterns and spectroscopic observables, but there has been no direct observation of the underlying wavepacket interference. Here we experimentally observe geometric-phase interference in the dynamics of a wavepacket travelling around an engineered conical intersection in a programmable trapped-ion quantum simulator. To achieve this, we develop a technique to reconstruct the two-dimensional wavepacket densities of a trapped ion. Experiments agree with the theoretical model, demonstrating the ability of analogue quantum simulators-such as those realized using trapped ions-to accurately describe nuclear quantum effects., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Spectroscopy is one of the most accurate probes of the molecular world. However, predicting molecular spectra accurately is computationally difficult because of the presence of entanglement between electronic and nuclear degrees of freedom. Although quantum computers promise to reduce this computational cost, existing quantum approaches rely on combining signals from individual eigenstates, an approach whose cost grows exponentially with molecule size. Here, we introduce a method for scalable analog quantum simulation of molecular spectroscopy: by performing simulations in the time domain, the number of required measurements depends on the desired spectral range and resolution, not molecular size. Our approach can treat more complicated molecular models than previous ones, requires fewer approximations, and can be extended to open quantum systems with minimal overhead. We present a direct mapping of the underlying problem of time-domain simulation of molecular spectra to the degrees of freedom and control fields available in a trapped-ion quantum simulator. We experimentally demonstrate our algorithm on a trapped-ion device, exploiting both intrinsic electronic and motional degrees of freedom, showing excellent quantitative agreement for a single-mode vibronic photoelectron spectrum of SO 2 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Purpose of Review: The purpose of this review will be to shed light on novel techniques for assessment of bone tissue material properties., Recent Findings: Recently there has been an increase in modalities to investigate bone tissue material properties. Historically, clinicians treating patients with bone disorders have relied upon the use of bone mineral density (BMD) as assessed by dual-energy X-ray absorptiometry (DXA). Although DXA provides an ability to screen at a large-scale population level, it only explains about 60% of the fracture risk. Recent advances include the use of imaging modalities, responses to load, and novel infrared (IR) techniques., Summary: These newer techniques have not reached a point for population level screening; however, they may inform the science of bone biology further and help discern various bone disease states., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pencil beam scanning (PBS) proton therapy allows for far superior dose conformality compared with passive scattering techniques. However, one drawback of PBS is that the beam delivery time can be long, particularly when treating superficial disease. Minimizing beam delivery time is important for patient comfort and precision of treatment delivery. Mini-ridge filters (MRF) have been shown to reduce beam delivery time for synchrotron-based PBS. Given that cyclotron systems are widely used in proton therapy it is necessary to investigate the potential clinical benefit of mini-ridge filters in such systems., Purpose: To demonstrate the clinical benefit of using a MRF to reduce beam delivery time for patients with large target volumes and superficial disease in cyclotron-based PBS proton therapy., Methods: A MRF beam model was generated by simulating the effect of a MRF on our clinical beam data assuming a fixed snout position relative to the isocenter. The beam model was validated with a series of measurements. The model was used to optimize treatment plans in a water phantom and on six patient DICOM datasets to further study the effect of the MRF and for comparison with physician-approved clinical treatment plans. Beam delivery time was measured for six plans with and without the MRF to demonstrate the reduction achievable. Plans with and without MRF were reviewed to confirm clinical acceptability by a radiation oncologist. Patient-specific QA measurements were carried out with a two-dimensional ionization chamber array detector for one representative patient's plan optimized with the MRF beam model., Results: Results show good agreement between the simulated beam model and measurements with mean and maximum deviations of 0.06 mm (0.45%) and 0.61 mm (4.9%). The increase in Bragg peak width (FWHM) ranged from 2.7 mm at 226 MeV to 6.1 mm at 70 MeV. The mean and maximum reduction in beam delivery time observed per field was 29.1 s (32.2%) and 79.7 s (55.3%)., Conclusion: MRFs can be used to reduce treatment time in cyclotron-based PBS proton therapy without sacrificing plan quality. This is particularly beneficial for patients with large targets and superficial disease such as in breast cancer where treatment times are generally long, as well as patients treated with deep inspiration breath hold (DIBH)., (© 2023 American Association of Physicists in Medicine.)

Targeting metabolic vulnerabilities has been proposed as a therapeutic strategy in renal cell carcinoma (RCC). Here, we analyzed the metabolism of patient-derived xenografts (tumorgrafts) from diverse subtypes of RCC. Tumorgrafts from VHL -mutant clear cell RCC (ccRCC) retained metabolic features of human ccRCC and engaged in oxidative and reductive glutamine metabolism. Genetic silencing of isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 impaired reductive labeling of tricarboxylic acid (TCA) cycle intermediates in vivo and suppressed growth of tumors generated from tumorgraft-derived cells. Glutaminase inhibition reduced the contribution of glutamine to the TCA cycle and resulted in modest suppression of tumorgraft growth. Infusions with [amide- 15 N]glutamine revealed persistent amidotransferase activity during glutaminase inhibition, and blocking these activities with the amidotransferase inhibitor JHU-083 also reduced tumor growth in both immunocompromised and immunocompetent mice. We conclude that ccRCC tumorgrafts catabolize glutamine via multiple pathways, perhaps explaining why it has been challenging to achieve therapeutic responses in patients by inhibiting glutaminase.

Strategic plans provide a roadmap for value creation by outlining key priorities that, when executed successfully, enhance quality and efficiency. Nurses are uniquely positioned to inform strategic planning because of their understanding of clinical operations and consumer needs. This article describes a multiphase process for engaging nurses, at all levels, in developing, implementing, and revising a nursing strategic plan over a 5-year period., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The Bone Metastases Ensemble Trees for Survival Decision Support Platform (BMETS-DSP) provides patient-specific survival predictions and evidence-based recommendations to guide multidisciplinary management for symptomatic bone metastases. We assessed the clinical utility of the BMETS-DSP through a pilot prepost design in a simulated clinical environment., Methods: Ten Radiation Oncology physicians reviewed 55 patient cases at two time points: without and then with the use of BMETS-DSP. Assessment included 12-month survival estimate, confidence in and likelihood of sharing estimates with patients, and recommendations for open surgery, systemic therapy, hospice referral, and radiotherapy (RT) regimen. Paired statistics compared pre- versus post-DSP outcomes. Reported statistical significance is P < .05., Results: Pre- versus post-DSP, overestimation of true minus estimated survival time was significantly reduced (mean difference -2.1 [standard deviation 4.1] v -1 month [standard deviation 3.5]). Prediction accuracy was significantly improved at cut points of < 3 (72 v 79%), ≤ 6 (64 v 71%), and ≥ 12 months (70 v 81%). Median ratings of confidence in and likelihood of sharing prognosis significantly increased. Significantly greater concordance was seen in matching use of 1-fraction RT with the true survival < 3 months (70 v 76%) and < 10-fraction RT with the true survival < 12 months (55 v 62%) and appropriate use of open surgery (47% v 53%), without significant changes in selection of hospice referral or systemic therapy., Conclusion: This pilot study demonstrates that BMETS-DSP significantly improved physician survival estimation accuracy, prognostic confidence, likelihood of sharing prognosis, and use of prognosis-appropriate RT regimens in the care of symptomatic bone metastases, supporting future multi-institutional validation of the platform., Competing Interests: Sara R. AlcornEmployment: University of MinnesotaHonoraria: Allegheny Health NetworkResearch Funding: Radiation Oncology Institute (ROI), Pfizer-Prostate Cancer Foundation Jacob FikselEmployment: Janssen, VertexPatents, Royalties, Other Intellectual Property: I am listed on US patent No. 10,975,431, for cell-free DNA for assessing and/or treating cancer. I am not the main inventor and have not received any royalties Chen HuConsulting or Advisory Role: D1 Medical Technology Lawrence KleinbergConsulting or Advisory Role: NovocureResearch Funding: Novartis (Inst), Bristol Myers Squibb/Medarex (Inst), Incyte Adam LevinLeadership: Ensysce BiosciencesStock and Other Ownership Interests: Ensysce BiosciencesConsulting or Advisory Role: Ensysce BiosciencesPatents, Royalties, Other Intellectual Property: Patent Pending (Inst) Thomas SmithEmployment: UpToDateHonoraria: Athenex, Association of Community Cancer Centers (ACCC)Patents, Royalties, Other Intellectual Property: Royalties from Oxford Textbook of Cancer Communication, coeditorOpen Payments Link: https://openpaymentsdata.cms.gov/physician/202382/general-payments Zhi ChengEmployment: Siemens Healthineers (I)Research Funding: Toshiba (Inst)Patents, Royalties, Other Intellectual Property: Patents and royalties (Inst) Lindsey SloanEmployment: University of Minnesota (I)Consulting or Advisory Role: Sanofi/Regeneron (I)Research Funding: Arena Pharma (I) K. Ranh VoongHonoraria: Physicians' Education Resource LLCConsulting or Advisory Role: AstraZenecaTravel, Accommodations, Expenses: Prime Oncology Todd R. McNuttStock and Other Ownership Interests: Oncospace LLCResearch Funding: Canon Medical System (Inst), Oncospace LLC (Inst)Patents, Royalties, Other Intellectual Property: Radiation Dose Calculation Algorithm Michael R. BowersEmployment: Oncospace IncStock and Other Ownership Interests: Oncospace Inc Theodore L. DeWeeseStock and Other Ownership Interests: Digital HarmonicPatents, Royalties, Other Intellectual Property: Patent pending on the computer algorithm in radiation therapy planning Scott ZegerLeadership: Embold Health Jean L. WrightEmployment: Johns Hopkins HospitalHonoraria: American Society for Radiation OncologyResearch Funding: OncospacePatents, Royalties, Other Intellectual Property: Spouse receives royalties from Up To Date (I)Expert Testimony: Marshall DennehyNo other potential conflicts of interest were reported.

In mice and humans with cancer, intravenous 13 C-glucose infusion results in 13 C labeling of tumor tricarboxylic acid (TCA) cycle intermediates, indicating that pyruvate oxidation in the TCA cycle occurs in tumors. The TCA cycle is usually coupled to the electron transport chain (ETC) because NADH generated by the cycle is reoxidized to NAD + by the ETC. However, 13 C labeling does not directly report ETC activity, and other pathways can oxidize NADH, so the ETC's role in these labeling patterns is unverified. We examined the impact of the ETC complex I inhibitor IACS-010759 on tumor 13 C labeling. IACS-010759 suppresses TCA cycle labeling from glucose or lactate and increases labeling from glutamine. Cancer cells expressing yeast NADH dehydrogenase-1, which recycles NADH to NAD + independently of complex I, display normalized labeling when complex I is inhibited, indicating that cancer cell ETC activity regulates TCA cycle metabolism and 13 C labeling from multiple nutrients.

Purpose: Pancreatic cancer is the fourth leading cause of cancer-related death with a 10% 5-year overall survival rate (OS). Radiation therapy (RT) in addition to dose escalation improves the outcome by significantly increasing the OS at 2 and 3 years but is hindered by the toxicity of the duodenum. Our group showed that the insertion of hydrogel spacer reduces duodenal toxicity, but the complex anatomy and the demanding procedure make the benefits highly uncertain. Here, we investigated the feasibility of augmenting the workflow with intraoperative feedback to reduce the adverse effects of the uncertainties., Materials and Methods: We simulated three scenarios of the virtual spacer for four cadavers with two types of gross tumor volume (GTV) (small and large); first, the ideal injection; second, the nonideal injection that incorporates common spacer placement uncertainties; and third, the corrective injection that uses the simulation result from nonideal injection and is designed to compensate for the effect of uncertainties. We considered two common uncertainties: (1) "Narrowing" is defined as the injection of smaller spacer volume than planned. (2) "Missing part" is defined as failure to inject spacer in the ascending section of the duodenum. A total of 32 stereotactic body radiation therapy (SBRT) plans (33 Gy in 5 fractions) were designed, for four cadavers, two GTV sizes, and two types of uncertainties. The preinjection scenario for each case was compared with three scenarios of virtual spacer placement from the dosimetric and geometric points of view., Results: We found that the overlapping PTV space with the duodenum is an informative quantity for determining the effective location of the spacer. The ideal spacer distribution reduced the duodenal V33Gy for small and large GTV to less than 0.3 and 0.1cc, from an average of 3.3cc, and 1.2cc for the preinjection scenario. However, spacer placement uncertainties reduced the efficacy of the spacer in sparing the duodenum (duodenal V33Gy: 1.3 and 0.4cc). The separation between duodenum and GTV decreased by an average of 5.3 and 4.6 mm. The corrective feedback can effectively bring back the expected benefits from the ideal location of the spacer (averaged V33Gy of 0.4 and 0.1cc)., Conclusions: An informative feedback metric was introduced and used to mitigate the effect of spacer placement uncertainties and maximize the benefits of the EUS-guided procedure., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

A marginal sea in the north eastern Indian Ocean, the Andaman Sea, has been known for the presence of high-amplitude internal waves since the nineteenth century. In this study, we explored the interannual variations of the internal wave activity in this complex region. We found that the Dipole Mode Index, which represents the Indian Ocean Dipole (IOD), influences the circulation in the Andaman Sea, which in turn impacts its density stratification on interannual scales. Ocean Reanalysis System 5 data (1993-2018) is used to see an increasing trend in the sub-surface stratification, whereas it showed a decreasing trend in the near-surface waters. Numerical model simulations carried out from 2009 to 2018 have shown that the interannual variability in the generation of semidiurnal internal tides is governed by distinct parameters (tidal forcing and stratification) at different sites in different months. Enhanced upwelling (downwelling) is observed during positive (negative) IOD events. Sensitivity experiments conducted between extreme IOD events (2006 and 2016) revealed an increase in internal tide generation from positive IOD to negative IOD. Furthermore, a sharp decrease in local baroclinic dissipation is seen during negative IOD, increasing baroclinic flux into the Andaman Sea. An increase in the strength of positive IOD could lead to enhanced diapycnal mixing due to strong local dissipation, whereas an increase in the intensity of negative IOD could result in amplified propagation of internal waves., (© 2022. The Author(s).)

Despite being the leading cause of cancer deaths, metastasis remains a poorly understood process. To identify novel regulators of metastasis in melanoma, we performed a large-scale RNA sequencing screen of 48 samples from patient-derived xenograft (PDX) subcutaneous melanomas and their associated metastases. In comparison with primary tumors, expression of glycolytic genes was frequently decreased in metastases, whereas expression of some tricarboxylic acid (TCA) cycle genes was increased in metastases. Consistent with these transcriptional changes, melanoma metastases underwent a metabolic switch characterized by decreased levels of glycolytic metabolites and increased abundance of TCA cycle metabolites. A short isoform of glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) lacking the N-terminal domain suppressed metastasis and regulated this metabolic switch. GAPDHS was downregulated in metastatic nodules from PDX models as well as in human patients. Overexpression of GAPDHS was sufficient to block melanoma metastasis, whereas its inhibition promoted metastasis, decreased glycolysis, and increased levels of certain TCA cycle metabolites and their derivatives including citrate, fumarate, malate, and aspartate. Isotope tracing studies indicated that GAPDHS mediates this shift through changes in pyruvate carboxylase activity and aspartate synthesis, both metabolic pathways critical for cancer survival and metastasis. Together, these data identify a short isoform of GAPDHS that limits melanoma metastasis and regulates central carbon metabolism., Significance: This study characterizes metabolic changes during cancer metastasis and identifies GAPDHS as a novel regulator of these processes in melanoma cells., (©2022 American Association for Cancer Research.)

Background: Laparoscopic appendectomy (LA) is claimed to require less analgesic and allow for a faster return to work. This study examines whether these benefits hold true in Asian patient populations., Methods: A retrospective audit of emergency appendectomies over one year was conducted to study outcomes of postoperative pain, length of stay (LOS), duration of analgesia, and hospitalization leave (HL). A telephone questionnaire evaluated post-discharge analgesic intake, residual symptoms at follow-up, adequacy of HL and opinion on teleconsult reviews., Results: Of the 201 patients, 187 (93%) underwent LA. Presurgery symptoms were significantly longer in the open appendectomy (OA) group (mean: OA 3.79, LA 1.81 days; p  =   0.026) which also had a higher frequency of perforation (71.4%). LA patients reported less pain compared to OA (LA 3.60 vs. OA 4.14; p  =   0.068) but were prescribed the same 2 weeks of analgesics as OA. LOS was significantly less for LA (mean LA 3.09, OA 6.93 days; p  =   0.006). Mean HL for LA and OA were 17.9 and 21.8 days respectively ( p  =   0.05). Nearly 83% patients did not complete the prescribed course of analgesics and 47% patients felt that HL was more than adequate. Seventy-five percent of patients were asymptomatic at hospital follow-up and nearly 41% agreed to teleconsult reviews., Conclusion: Majority of LA patients do not need 2 weeks of analgesics and their HL can be shortened for faster return to work thereby realizing the true benefits of minimally invasive surgery. Selected cases can be offered postoperative teleconsultation., (© 2022 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Purpose: Pancreatic cancer is the fourth leading cause of cancer-related death, with a very low 5-year overall survival rate (OS). Radiation therapy (RT) together with dose escalation significantly increases the OS at 2 and 3 years. However, dose escalation is very limited due to the proximity of the duodenum. Hydrogel spacers are an effective way to reduce duodenal toxicity, but the complexity of the anatomy and the procedure makes the success and effectiveness of the spacer procedure highly uncertain. To provide a preoperative simulation of hydrogel spacers, we presented a patient-specific spacer simulator algorithm and used it to create a decision support system (DSS) to provide a preoperative optimal spacer location to maximize the spacer benefits., Materials and Methods: Our study was divided into three phases. In the validation phase, we evaluated the patient-specific spacer simulator algorithm (FEMOSSA) for the duodenal spacer using the dice similarity coefficient (DSC), overlap volume histogram (OVH), and radial nearest neighbor distance (RNND). For the simulation phase, we simulated four virtual spacer scenarios based on the location of the spacer in para-duodenal space. Next, stereotactic body radiation therapy (SBRT) plans were designed and dosimetrically analyzed. Finally, in the prediction phase, using the result of the simulation phase, we created a Bayesian DSS to predict the optimal spacer location and biological effective dose (BED)., Results: A realistic simulation of the spacer was achieved, reflected in a statistically significant increase in average target and duodenal DSC for the simulated spacer. Moreover, the small difference in average mean and 5th-percentile RNNDs (0.5 and 2.1 mm) and OVH thresholds (average of less than 0.75 mm) showed that the simulation attained similar separation as the real spacer. We found a spacer-location-independent decrease in duodenal V20Gy, a highly spacer-location-dependent change in V33Gy, and a strong correlation between L1cc and V33Gy. Finally, the Bayesian DSS predicted the change in BED with a root mean squared error of 3.6 Gys., Conclusions: A duodenal spacer simulator platform was developed and used to systematically study the dosimetric effect of spacer location. Further, L1cc is an informative anatomical feedback to guide the DSS to indicate the spacer efficacy, optimum location, and expected improvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hooshangnejad, Youssefian, Narang, Shin, Rao, Han-Oh, McNutt, Lee, Hu, Wong and Ding.)

Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately results in relapse. This residual disease is often characterized by non-genetic adaptive resistance, that in melanoma is characterised by altered metabolism. Here, we examine how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNA interference (RNAi) screen and global gene expression profiling. Using this systematic approach we demonstrate post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA processing kinase U2AF homology motif kinase 1 (UHMK1) associates with mRNAs encoding metabolism proteins and selectively controls their transport and translation during adaptation to BRAF-targeted therapy. UHMK1 inactivation induces cell death by disrupting therapy induced metabolic reprogramming, and importantly, delays resistance to BRAF and MEK combination therapy in multiple in vivo models. We propose selective mRNA processing and translation by UHMK1 constitutes a mechanism of non-genetic resistance to targeted therapy in melanoma by controlling metabolic plasticity induced by therapy., (© 2022. Crown.)

Background: Following mastectomy, immediate breast reconstruction often involves the use of temporary tissue expanders (TEs). TEs contain metallic ports (MPs), which complicate proton pencil-beam scanning (PBS) planning. A technique was implemented for delivering PBS post-mastectomy radiation (PMRT) to patients with TEs and MPs., Methods: A protocol utilizing a hybrid single- and multi-field optimization (SFO, MFO) technique was developed. Plans were robustly optimized using a Monte Carlo algorithm. A CTV&#95;eval structure including chest wall (CW) and regional nodal (RNI) targets and excluding the TE was evaluated. Organ at risk (OAR) dosimetry and acute toxicities were analyzed., Results: Twenty-nine women were treated with this technique. A 2-field SFO technique was used superior and inferior to the MP, with a 3 or 4-field MFO technique used at the level of the MP. Virtual blocks were utilized so that beams did not travel through the MP. A port-to-CW distance of 1 cm was required. Patients underwent daily image-guidance to ensure the port remained within a 0.5 cm internal planning volume (ITV). Median RT dose to CTV&#95;eval was 50.4 Gy (45.0-50.4). Median 95% CTV&#95;eval coverage was 99.5% (95-100). Optically stimulated luminescent dosimeter (OSLD) readings were available for 8 patients and correlated to the dose measurements in the treatment planning system (TPS); median OSLD ratio was 0.99 (range, 0.93-1.02)., Conclusions: Delivering PMRT with PBS for women with metal-containing TEs using a hybrid SFO/MFO technique is feasible, reproducible, and achieves excellent dose distributions. Specialized planning and image-guidance techniques are required to safely utilize this treatment in the clinic., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The USA has among the largest immigrant population of any country in the world, and over the past few decades, the proportion of Chinese immigrants in the USA has increased significantly. Immigrants may experience substantial acculturative stress as they learn to navigate their new environment, and this stress can contribute to depressive symptoms and poor mental health. Social support can help mitigate the effects of stress on depressive symptoms, but the protective effects of social support have been reported to differ between men and women. Thus, the present study examined associations of acculturative stress and depressive symptoms among Chinese immigrants and explored whether the effects of social support on depressive symptoms varied by gender. Participants included 620 foreign-born Chinese men and women who completed questionnaires on acculturative stress, social support, and depressive symptoms. In nested regression analyses, acculturative stress was positively associated with depressive symptoms among both men and women. However, the interaction of social support and acculturative stress on depressive symptoms was statistically significant among men (β = - 0.89, p < 0.001), but not women (β = - 0.43, p = 0.21). These findings suggest that social support moderates the association of acculturative stress with depressive symptoms, but only among Chinese immigrant men. Future research should explore factors that can enhance resilience and mitigate acculturative stress effects on psychological well-being among Chinese immigrant women., (© 2020. W. Montague Cobb-NMA Health Institute.)

Purpose: Early stage (stages I-II) classical Hodgkin lymphoma (cHL) is a highly curable disease typically diagnosed in adolescents and young adults (AYAs). Proton therapy can also reduce the late toxicity burden in this population, but data on its comparative efficacy with photon radiotherapy in this population are sparse. We assessed outcomes in AYAs with cHL in a multi-institution retrospective review., Materials and Methods: We identified 94 patients aged 15 to 40 years with stages I and II cHL treated with radiotherapy as part of their initial treatment between 2008 and 2017. We used Kaplan-Meier analyses and log-rank testing to evaluate survival differences between groups of patients., Results: A total of 91 patients were included in the analysis. The 2-year progression-free survival (PFS) rate was 89%. Of the 12 patients who experienced progression after radiotherapy, 4 occurred out-of-field, 2 occurred in-field, and 6 experienced both in- and out-of-field progression. There was no significant difference in 2-year PFS among AYA patients by radiotherapy dose received (≥ 30 Gy, 91%; < 30 Gy, 86%; P  = .82). Likewise, there was no difference in 2-year PFS among patients who received either proton or photon radiotherapy (proton, 94%; photon, 83%; P  = .07)., Conclusion: Our cohort of AYA patients had comparable outcomes regardless of radiotherapy dose or modality used. For patients with significant risk of radiation-induced late effects, proton therapy is a reasonable treatment modality., Competing Interests: Conflicts of Interest: Nancy P. Mendenhall, MD, and Bradford S. Hoppe, MD, MPH are Editor-in-Chief and Associate Editor of the International Journal of Particle Therapy, respectively. In the past 3 years, Raymond B. Mailhot Vega, MD, MPH, received an unrestricted educational grant from IBA. The other authors have no relevant conflicts of interest to disclose., (©Copyright 2021 The Author(s).)

Purpose/objective(s): With reports of CNS toxicity in patients treated with proton therapy at doses lower than would be expected based on photon data, it has been proposed that heavy monitor unit (MU) weighting of pencil beam scanning (PBS) proton therapy spots may potentially increase the risk of toxicity. We evaluated the impact of maximum MU weighting per spot (maxMU/spot) restrictions on PBS plan quality, prior to implementing clinic-wide maxMU/spot restrictions., Materials/methods: PBS plans of 11 patients, of which 3 plans included boosts, for a total of 14 PBS sample cases were included. Per sample case, a single dosimetrist created 4 test plans, gradually reducing the maxMU/spot in the plan. Test Plan 1, unrestricted in maxMU/spot, was the reference for all restricted plan comparisons (comparison sets 2 vs. 1; 3 vs. 1; and 4 vs. 1). The impact of MU/spot restrictions on plan quality metrics were analyzed with Wilcoxon signed rank test analyses. Treatment delivery time was modeled for a representative case., Results: A total of 14 PBS sample cases, 7 (50%) single-field optimized, 7 (50%) multi-field optimized, 9 (64%) delivering > 3500 cGy, 9 (64%) with 3 beams, and 7 (50%) without a range shifter were included. There were no differences in plan quality metrics of target coverage (V95% and V100% prescription), conformality and gradient indices, hot spot volume (V105% prescription), and dose to normal brain (V10%/30%/50%/70%/90%/100% prescription) with reductions of allowable maxMU/spot across all comparison sets (p > 0.05). Max MU/spot restrictions did not increase treatment delivery time when analyzed for a representative case., Conclusion: MaxMU/spot restrictions within the thresholds evaluated in this study did not degrade overall plan quality metrics. Future studies should evaluate spot weighting with linear energy transfer/relative biologic effectiveness-informed planning to determine if spot weighting manipulation impacts clinical outcomes and mitigates toxicity., (Copyright © 2021. Published by Elsevier B.V.)

The changes in the physical properties of the ocean on a diurnal scale primarily occur in the surface mixed layer and the pycnocline. Price-Weller-Pinkel model, which modifies the surface mixed layer, and the internal wave model based on Garrett-Munk spectra that calculates the vertical displacements due to internal waves are coupled to simulate the diurnal variability in temperature and salinity, and thereby density profiles. The coupled model is used to simulate the hourly variations in density at RAMA buoy (15° N, 90° E), in the central Bay of Bengal, and at BD12 (10.5° N, 94° E), in the Andaman Sea. The simulations are validated with the in-situ observations from December 2013 to November 2014. The primary advantage of this model is that it could simulate spatial variability as well. An integrated model is also tested and validated by using the output of the 3D model to initialize the coupled model during January, April, July, and October. The 3D model can be used to initialize the coupled model at any given location within the model domain to simulate the diurnal variability of density. The simulations showed promising results which could be further used in simulating the acoustic fields and propagation losses which are crucial for Navy operations.

Purpose: This multi-institutional retrospective study sought to examine the hematologic effects of craniospinal irradiation (CSI) in pediatric patients with medulloblastoma using proton or photon therapy., Methods and Materials: Clinical and treatment characteristics were recorded for 97 pediatric patients with medulloblastoma who received CSI without concurrent chemotherapy or with concurrent single-agent vincristine from 2000 to 2017. Groups of 60 and 37 patients underwent treatment with proton-based and photon-based therapy, respectively. Overall survival was determined by Kaplan-Meier curves with log-rank test. Comparisons of blood counts at each timepoint were conducted using multiple t tests with Bonferroni corrections. Univariate and multivariate analyses of time to grade ≥3 hematologic toxicity were performed with Cox regression analyses., Results: Median age of patients receiving proton and photon CSI was 7.5 years (range, 3.5-22.7 years) and 9.9 years (range, 3.6-19.5 years), respectively. Most patients had a diagnosis of standard risk medulloblastoma, with 86.7% and 89.2% for the proton and photon cohorts, respectively. Median total dose to involved field or whole posterior fossa was 54.0 Gy/Gy relative biological effectiveness (RBE) and median CSI dose was 23.4 Gy/Gy(RBE) (range, 18-36 Gy/Gy[RBE]) for both cohorts. Counts were significantly higher in the proton cohort compared with the photon cohort in weeks 3 to 6 of radiation therapy (RT). Although white blood cell counts did not differ between the 2 cohorts, patients receiving proton RT had significantly higher lymphocyte counts throughout the RT course. Similar results were observed when excluding patients who received vertebral body sparing proton RT or limiting to those receiving 23.4 Gy. Only photon therapy was associated with decreased time to grade ≥3 hematologic toxicity on univariate and multivariable analyses. No difference in overall survival was observed, and lymphopenia did not predict survival., Conclusions: Patients who receive CSI using proton therapy experience significantly decreased hematologic toxicity compared with those receiving photon therapy., (Published by Elsevier Inc.)

Research efforts in the twenty-first century have been paramount to the discovery and development of novel pharmacological treatments in a variety of diseases resulting in improved life expectancy. Yet, cardiac disease remains a leading cause of morbidity and mortality worldwide. Over time, there has been an expansion in conditions such as atrial fibrillation (AF) and heart failure (HF). Although past research has elucidated specific pathways that participate in the development of distinct cardiac pathologies, the exact mechanisms of action leading to disease remain to be fully characterized. Protein turnover and cellular bioenergetics are integral components of cardiac diseases, highlighting the importance of mitochondria and endoplasmic reticulum (ER) in driving cellular homeostasis. More specifically, the interactions between mitochondria and ER are crucial to calcium signaling, apoptosis induction, autophagy, and lipid biosynthesis. Here, we summarize mitochondrial and ER functions and physical interactions in healthy physiological states. We then transition to perturbations that occur in response to pathophysiological challenges and how this alters mitochondrial-ER and other intracellular organelle interactions. Finally, we discuss lifestyle interventions and innovative therapeutic targets that may be used to restore beneficial mitochondrial and ER interactions, thereby improving cardiac function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Kumar, Lackey, Snyder, Karhadkar, Rao, DiCarlo and Sato.)