Premature Depletion Research Articles

Cassandra speaks: a case series of unanticipated subcutaneous ICD premature battery depletion in a single-centre experience

Abstract Background Subcutaneous ICDs (S-ICD) are a valuable option in sudden cardiac death prevention. The main advantage over conventional transvenous ICDs is the absence of intravascular hardware for patients without the need for cardiac stimulation, resynchronization therapy or anti-tachycardia pacing. The claim of reduced lead-related complications has on the contrary been challenged by recent warnings of unexpected lead fracture. Moreover, concerns related to premature battery depletion (PBD) leading to unanticipated device replacement are increasing. Purpose To evaluate retrospectively the incidence of unanticipated S-ICD premature battery depletion in a single-centre experience. Method 168 consecutive patients implanted with S-ICD from February 2015 to November 2022 in our tertiary cardiology centre were included in this study. 4 patients moved to other sites and were thus lost to follow-up, leaving a total of 164 patients. PBD was defined as the occurrence of battery depletion requiring generator replacement earlier than 60 months post-implantation in the absence of therapy being delivered, or as a result of manufacturer recommendations. Results Most patients were implanted for primary prevention (101 patients, 60%). The main aetiology was hypertrophic cardiomyopathy (47 patients, 28%), followed by arrhythmogenic (35, 21%) and dilated idiopathic cardiomyopathy (24, 14%). Mean age and left ventricular ejection fraction at baseline were 46±18yrs and 51±16%, respectively. Over a total follow up period of 44±25 months, at 58±17 months following implantation 19 (11,6%) patients needed early replacement due to PBD, while 2 (1.2%) patients had lead fracture after respectively 41 and 26 months, for a total of 12,8% of patients with system-related complications. In addition to those patients requiring early replacement due to PBD or lead fracture, two underwent S-ICD extraction due to infection. Analysis of freedom from unanticipated PBD per year of implantation showed higher rates in years 2016 and 2017, with 67% and 27% of all implanted patients, respectively (Figure 1). Conclusions In this study, the incidence of PBDs appear to be higher than reported in literature though confined to a limited device series. However, if on the contrary the trend should remain remarkably high, that would not only endanger patients health due to repeated replacements, but also pose a huge economic burden to health systems.

Real world battery longevity of the subcutaneous implantable cardioverter-defibrillator (S-ICD)

Abstract Background Subcutaneous implantable cardiac defibrillators (S-ICDs) protect against sudden cardiac death and avoid transvenous ICD lead complications. Objective To investigate S-ICD real-world battery longevity estimates and the impact of device parameters and advisory status. Methods Second and third generation S-ICD device longevity labeling is 7.3 years (yr) under normal use (e.g remote monitoring, pre-arrhythmia EGM storage, etc.). De-identified data from S-ICD devices implanted ≥3 months, with recent uploads from the patient devices to the LATITUDE system, were obtained in Nov 2022. For early to mid-life devices (15-100% battery life), longevity estimates were derived from storage time, implant time, and number of high voltage charges (HVC). For late-life devices, longevity estimates were calculated more accurately from battery voltage. Monte Carlo simulations estimated future HVCs. Multivariable maximum likelihood parameter models were used to analyze battery longevity determinants for the overall cohort and for patients who received >1 shock, assuming 1 shock due to conversion testing at implant. Variables were considered clinically significant if univariable difference and multivariable estimate’s magnitude were both ≥0.2 yr. Results are reported in median and interquartile range. Results The 32,678 EMBLEM devices had a 2.5 yr [1.2,4.1] device dwell-time with 8.7 yr [8.3,8.9] longevity estimate. Of these patients, 28,544 (87.3%) received ≥1 shocks and 11,480 (35.1%) received >2 shocks, including shocks delivered during conversion testing. Late life devices (n=3091, 9.5%) had a 5.2 yr [4.6,5.9] dwell time. For devices under the battery depletion advisory (n=13,900), the Monte Carlo model does not account for premature battery depletion (PBD), which is projected to impact 11.5% of advisory devices at 5 yrs. Longevity for PBD is 6.6 yr (Q4 2022 product performance report). While all variables except AF trend, AF episodes/yr, and post shock pacing statistically impact device longevity, only advisory status and number of device charges per yr impacted longevity by ≥0.2 yr (Figure, panel A). Patients who received >1 shock have 8.5 yr [8.0,8.8] longevity estimates, vs 8.8 [8.4,8.9] for patients with 0 or 1 shock. For patients with >1 shock, (Figure, panel B), only advisory status had a ≥0.2 yr impact on longevity in multivariable and univariable analyses. Dwell time, shocks delivered per yr, and system impedance software upgrade impacted longevity by only 0.1 yr in univariable analysis. Conclusion Median EMBLEM S-ICD longevity estimate is 8.7 years, which is longer than device labeling. Longevity is reduced by 0.26 years for each device charge. AF monitoring and post shock pacing did not impact device longevity significantly. Low and high voltage impedance as well as remote monitoring transmission impacted longevity by less than 0.1 years. These data are important to consider during shared decision-making.Device Longevity Predictors

Cystic endometrial hyperplasia-pyometra syndrome impairs the preantral follicle reserve in domestic bitches (Canis familiaris)

Cystic endometrial hyperplasia (CEH)-pyometra syndrome is the most common uterine pathological condition reported in breeding bitches, however, their described effects on fertility are limited to uterine disorders and conception rates. As the preantral follicle population represents the available reserve of gametes recruited during the lifespan, the aim of this study was to evaluate the effects of CEH-pyometra syndrome on the: (i) preantral follicle morphology, (ii) developing follicle rates, and (iii) preantral follicle and stromal cell densities. Ovarian fragments from bitches subjected to elective or therapeutic ovariohysterectomy were allocated according to uterine diagnosis as follows: control (n = 7, clinically healthy), CEH-mucometra (n = 8, uterine lumen filled with a sterile mucus), and pyometra (n = 17, presence of a purulent mucus) groups. Overall, the control group had 3.4 and 4.1-fold higher probability (P < 0.0001) of the presence of normal preantral follicles compared with CEH-mucometra and pyometra groups, respectively. Moreover, ovarian fragments from the pyometra group showed an increase in the percentage of developing follicles (P < 0.05) compared to the control. Both CEH-mucometra and pyometra groups showed lower (P < 0.05) preantral follicle and stromal cell densities (P < 0.05) compared to the control. In summary, the CEH-pyometra syndrome decreased the percentage of morphologically normal follicles and enhanced the developing follicle rates. Additionally, a reduction of preantral follicle and stromal cell densities suggests that the inappropriate uterine environment induced by CEH-pyometra syndrome can lead to premature depletion of ovarian reserve.

Impact of Radiotherapy on Malfunctions and Battery Life of Cardiac Implantable Electronic Devices in Cancer Patients.

This study analyses a large number of cancer patients with CIEDs for device malfunction and premature battery depletion by device interrogation after each radiotherapy fraction and compares different guidelines in regard to patient safety. From 2007 to 2022, a cohort of 255 patients was analyzed for CIED malfunctions via immediate device interrogation after every RT fraction. Out of 324 series of radiotherapy treatments, with a total number of 5742 CIED interrogations, nine device malfunctions (2.8%) occurred. Switching into back-up/safety mode and software errors occurred four times each. Once, automatic read-out could not be performed. The median prescribed cumulative dose at planning target volume (PTV) associated with CIED malfunction was 45.0 Gy (IQR 36.0-64.0 Gy), with a median dose per fraction of 2.31 Gy (IQR 2.0-3.0 Gy). The median maximum dose at the CIED at time of malfunction was 0.3 Gy (IQR 0.0-1.3 Gy). No correlation between CIED malfunction and maximum photon energy (p = 0.07), maximum dose at the CIED (p = 0.59) nor treatment localization (p = 0.41) could be detected. After excluding the nine malfunctions, premature battery depletion was only observed three times (1.2%). Depending on the national guidelines, 1-9 CIED malfunctions in this study would have been detected on the day of occurrence and in none of the cases would patient safety have been compromised. Radiation-induced malfunctions of CIEDs and premature battery depletion are rare. If recommendations of national safety guidelines are followed, only a portion of the malfunctions would be detected directly after occurrence. Nevertheless, patient safety would not be compromised.

A QoS-Aware Energy-Efficient Chimp Optimization Routing Protocol with Efficient Sensor Node Deployment Strategy in Underwater Acoustic Sensor Network

As an extension of wireless sensor networks in the underwater environment, Underwater Acoustic Sensor Networks (UASNs) have led to a broad consideration of academicians. One of the problems that lower UWSN effectiveness in terms of network lifespan is premature energy depletion. It might be caused by the network nodes using different amounts of energy. In UASNs, the effectiveness and dependability of data transfer remain so adverse because of the intricate underwater environment in diverse ocean applications like surveilling atypical submarine oil pipelines. Inspired by the significance of UASNs’ quality of service in several implementations, this study proffers a metaheuristic optimization algorithm (AG) called Chimp Optimization-based Routing Protocol (CH-ORP) for UASNs obtaining intricate features of underwater (UW) medium into concern like 3D changing topology, high propagation delay, node mobility, and density, and, also, cluster head nodes’ rotation mechanism. Initially, the entire network (NW) paradigm has been considered as a three-dimensional cube out of a grid point of view, and the three-dimensional cube has been split into several little cubes by employing Delaunay Triangulation. The optimization has been carried out for lessening node failure rate and NW energy consumption rate by ideally placing the sensor nodes in UW acoustic communication. The NW topology’s steadiness has been assured by the AG, and this optimizes the node redeployment scheme by computing the fitness function for all nodes. The proffered AG’s simulation substantiations have been performed for exhibiting the CH-ORP’s efficiency that executes finer when compared to the advanced methodologies concerning energy efficiency, reliability, and end-to-end delay. It has been found that the proposed Ch-ORP achieves 698 packets received with 28% of energy consumption, 156-sec Network delay, 257 packet loss, 97.23% of PDR, and 1256 Mbps of Network throughput.

Modeling early human cortical development and evaluating neurotoxicity with a forebrain organoid system

The complexity and subtlety of brain development renders it challenging to examine effects of environmental toxicants on human fetal brain development. Advances in pluripotent cell-derived organoid systems open up novel avenues for human development, disease and toxicity modeling. Here, we have established a forebrain organoid system and recapitulated early human cortical development spatiotemporally including neuroepithelium induction, apical-basal axis formation, neural progenitor proliferation and maintenance, neuronal differentiation and layer/region patterning. To explore whether this forebrain organoid system is suitable for neurotoxicity modeling, we subjected the organoids to bisphenol A (BPA), a common environmental toxicant of global presence and high epidemic significance. BPA exposure caused substantial abnormalities in key cortical developmental events, inhibited progenitor cell proliferation and promoted precocious neuronal differentiation, leading premature progenitor cell depletion and aberrant cortical layer patterning and structural organization. Consistent with an antagonistic mechanism between thyroid hormone and BPA, T3 supplementation attenuated BPA-mediated cortical developmental abnormalities. Altogether, our in vitro recapitulation of cortical development with forebrain organoids provides a paradigm for efficient neural development and toxicity modeling and related remedy testing/screening.

MicroRNA-144-3p protects against chemotherapy-induced apoptosis of ovarian granulosa cells and activation of primordial follicles by targeting MAP3K9

Premature ovarian failure (POF) is defined by amenorrhea, ovarian atrophy, hypoestrogenism, elevated gonadotropin level, and infertility under the age of 40. POF is frequently induced by chemotherapeutic agents. However, the underlying mechanisms regarding chemotherapy-mediated damage to ovarian function are unclear. In this study, enhanced apoptosis of granulosa cells (GCs) and aberrant activation of primordial follicles were observed in a POF mouse model induced by cisplatin. We subsequently observed significant downregulation of miR-144-3p and upregulation of mitogen-activated protein kinase kinase kinase 9 (MAP3K9) in primary ovarian GCs from POF mice, as revealed by microarrays. Furthermore, MAP3K9 expression was higher in human ovarian granulosa cells (COV434) treated with cisplatin and was identified as a novel target of miR-144-3p. Functional analysis revealed that miR-144-3p attenuated cisplatin induced apoptosis of GCs via silencing MAP3K9 expression, which suppressed the activity of the downstream p38 mitogen activated protein kinase (MAPK) pathway. Meanwhile, miR-144-3p prevented premature primordial follicle depletion in cisplatin-induced POF mice through targeting Map3k9, which led to a decline in the phosphorylation and activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase b (AKT) pathway. Taken together, this study revealed the protective effects of miR-144-3p on ovarian function and shed light on the epigenetic regulatory mechanism in the development of POF, which might provide new biomarkers for the ovarian reserve.

Subcutaneous implantable cardioverter-defibrillator generator removal: a multicenter analysis

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): University Hospital Cologne Introduction The subcutaneous implantable cardioverter-defibrillator (S-ICD) was a significant recent advance in sudden cardiac death prevention. Device-related complications, including infection or lead fracture, or changes in the medical status, such as necessity for cardiac pacing, may necessitate device removal. (1) Real-world multicenter data on S-ICD removal are sparse. Purpose This multicenter analysis sought to assess the incidence and indications for S-ICD generator removal. Methods Retrospective data and the most recent follow-up data on S-ICD devices implanted at 14 participating centers in Europe, the US and Canada, and information on subsequent device removal was submitted to an online database (2). Limited baseline patient information and the incidence of and reasons for S-ICD generator removal or failure were reported. Premature device removal was defined as device removal for any reason other than regular battery depletion (&amp;gt;5 years of longevity). Results Data from 1106 devices was analyzed. Devices were implanted between 15.10.2009 and 16.04.2021 at the participating centers. The first-generation model 1010 generator was implanted in 55 (5%), the newer models A209 or A219 were implanted in 457 (41.3%) and 594 (53.7%) respectively. Patients were aged 46.7±16.1 years and the indication for ICD therapy was primary prevention in 616 (55.7%) and secondary prevention in 484 (43.8%). During the follow-up period, 37 (3%) patients deceased, and 96 patients were excluded from the analysis due to lack of follow-up (&amp;lt;4 weeks). Premature device removal was performed in 103 (9.3%) during the follow-up period of 31.3±19.5 months. The most common reasons for removal were battery depletion (52%), of which premature, defined as &amp;lt;5 years longevity, depletion accounted for 57%, upgrade to transvenous ICD or CRT (17%) and infection (11%). Other indications for removal included heart transplantation (4%) or ventricular assist device implantation (1.5%), noise detection or inappropriate shocks (6.5%), and patient discomfort (0.7%). (see figure 1) Regular battery depletion occurred in 34 devices after 69.2±5.3 months. There was no difference in device longevity between the different generator models (1010, A209, and A219). There were no significant differences between the different generator models with respect to indications for explanation. Conclusions In this real-world retrospective multicenter analysis, premature S-ICD generator removal was necessary in 9.3% of patients. Premature battery depletion, infections, and the need for pacing were the most common indications for unplanned generator removal.

Adverse events associated with AveirTM VR leadless pacemaker: A Food and Drug Administration MAUDE database study.

Leadless pacemaker (LP) offers an innovative approach for treating bradyarrhythmia, thus avoiding pacemaker pocket and lead-related complications. The Food and Drug Administration (FDA) has recently approved the Aveir™ leadless pacing system (screw-in type LP). We queried the FDA MAUDE database to study the safety profile and assess the types of complications with this relatively novel device technology. A MAUDE database search was conducted on January 20, 2023, for reports received post-FDA approval to capture all adverse events. A total of 98 medical device report were reported for Aveir™ LP. After excluding duplicate, programmer-related, or introducer-sheath-related entries (n = 34), 64 entries were included. The most commonly encountered problem was high threshold/noncapture (28.1%, 18 events), followed by stretched helix (17.2%, 11 events) and device dislodgement (15.6%, ten events-5 intraprocedural, while 5 in the postoperative Day 1). Other reported events included high impedance (14.1%, nine events), sensing issues (12.5%, eight events), bent/broken helix (7.8%, five events), premature separation (4.7%, three events), interrogation problem (3.1%, two events), low impedance (3.1%, two events), premature battery depletion (1.6%, one event) and inadvertent MRI mode switch (1.6%, one event) and miscellaneous (15.6%, n = 10). There were eight serious patient injury events-pericardial effusion requiring pericardiocentesis (7.8%, five events) due to cardiac perforation that resulted in two deaths (3.1%) followed by sustained ventricular arrhythmias (4.6%, n = 3). In our study assessing the real-world safety profile of the Aveir™ LP, serious adverse events have been reported-life-threatening ventricular arrhythmias, pericardial effusion, device explantation/reimplantation, and death.

Study on depletion of ovarian function and late-life chronic diseases in India.

The current study aims to understand premature and early menopausal age in association with chronic conditions. The present cross-sectional study analyzed nationally representative data from LASI (Longitudinal Aging Study in India) from 2017 to 2018. Bivariate analysis including cross-tabulation and χ2 tests were performed. Further multiple regression analysis was performed, using the generalized linear model of logit link. Approximately 2533 (8%) older women reported that they had experienced premature menopause (before age 40), while 3889 (12.4%) reported having early menopause (age 40-44). The likelihood of a woman with premature menopause developing cardiovascular diseases (CVDs) is 15% higher (adjusted odds ratio [AOR], 1.15; P < 0.05) than those who do not experience premature menopause, while women with early menopause have a 13% higher risk (AOR, 1.13; P < 0.05). For women who experienced premature menopause and were also smokers, the probability of developing CVDs was higher. Other chronic diseases such as bone or joint problems, diabetes, and eye vision problems were also shown to be significant health problems among women who had premature ovarian failure. Our results show significant association between women with premature or early depletion of ovarian function and chronic health conditions such as cardiovascular diseases, bone or joint problems, vision problems, and neurological or psychiatric disorders at their later life ages. Comprehensive strategies in the form of lifestyle changes may regulate hormonal levels and allow the body to reach menopause at the appropriate age.

Antagonism between DDX6 and PI3K-AKT signaling is an oocyte-intrinsic mechanism controlling primordial follicle growth†.

Oocyte maturation and subsequent ovulation during the reproductive lifespan ensure long-term reproduction in mammalian females. This is achieved by tight regulation for the maintenance and growth of primordial follicles. However, the underlying mechanisms remain unsolved. We herein report that posttranscriptional gene regulation mediated by an RNA helicase, DEAD-box helicase 6 (DDX6), and phosphoinositide-3-kinase (PI3K)-AKT signaling exhibits an antagonistic interaction in mouse primordial follicles. DDX6 forms P-body-like cytoplasmic foci in oocytes, which colocalize to a P-body component, DCP1A. Interestingly, the P-body-like granules predominantly assemble in primordial follicles, but disperse once follicle growth is initiated, suggesting that they play a role in the maintenance of primordial follicles. Oocyte-specific knockout of Ddx6 using Gdf9-iCre revealed that Ddx6-deficient oocytes are defective in foci assembly and are abnormally enlarged, resulting in premature depletion of primordial follicles. These results indicate that DDX6 is required to maintain primordial follicles. The abnormal oocyte enlargement is because of enhanced PI3K-AKT signaling, a pivotal signaling pathway in the growth of primordial follicles. Conversely, the forced activation of PI3K-AKT signaling by knocking out Pten disassembles P-body-like granules in primordial follicles. These data suggest that DDX6 and PI3K-AKT signaling mutually antagonize the assembly of P-body-like granules and the growth of primordial follicles. We propose this mutual antagonism as an oocyte-intrinsic mechanism controlling the maintenance and growth of primordial follicles, ensuring the longevity of female reproduction.

Third-generation subcutaneous implantable cardioverter defibrillator and intermuscular two-incision implantation technique in patients with Arrhythmogenic cardiomyopathy: 3-year follow-up

BackgroundLong-term data on the potential advantages of combining the third-generation subcutaneous implantable cardioverter defibrillator (S-ICD) with modern software upgrade including the “SMART Pass”, modern programming strategies and the intermuscular (IM) two-incision implantation technique in arrhythmogenic cardiomyopathy (ACM) with different phenotypic variants are lacking. In this study we evaluated the long-term outcome of patients with ACM who underwent third-generation S-ICD (Emblem, Boston Scientific) and IM two-incision technique. MethodsThe study population included 23 consecutive patients [70% male, median age 31 (24–46) years] diagnosed with ACM with different phenotypic variants who received third-generation S-ICD implantation with the IM two-incision technique. ResultsDuring a median follow-up of 45.5 months [16–65], 4 patients (17.4%) received a at least one inappropriate shock (IS), with median annual event rate of 4.5%. Extra-cardiac oversensing (myopotential) during effort represented the only cause of IS. No IS due to T-wave oversensing (TWOS) were recorded. Only one patient (4.3%) experienced device-related complication consisting of premature cell battery depletion requiring device replacement. No device explantation because of need for anti-tachycardia pacing or ineffective therapy occurred. There was no significant difference between patients who did and did not experienced IS with regard to baseline clinical, ECG and technical characteristics. Five patients (21.7%) received appropriate shocks on ventricular arrythmias. ConclusionsAccording to our findings, although the third-generation S-ICD implanted with the IM two-incision technique appears to be associated with a low risk of complications and IS due to cardiac oversensing, the risk of IS due to myopotential mainly during effort should be considered.

Incidence of premature battery depletion in subcutaneous cardioverter-defibrillator patients: insights from a multicenter registry.

The subcutaneous ICD established its role in the prevention of sudden cardiac death in recent years. The occurrence of premature battery depletion in a large subset of potentially affected devices has been a cause of concern. The incidence of premature battery depletion has not been studied systematically beyond manufacturer-reported data. Retrospective data and the most recent follow-up data on S-ICD devices from fourteen centers in Europe, the US, and Canada was studied. The incidence of generator removal or failure was reported to investigate the incidence of premature S-ICD battery depletion, defined as battery failure within 60 months or less. Data from 1054 devices was analyzed. Premature battery depletion occurred in 3.5% of potentially affected devices over an observation period of 49 months. The incidence of premature battery depletion of S-ICD potentially affected by a battery advisory was around 3.5% after 4 years in this study. Premature depletion occurred exclusively in devices under advisory. This is in line with the most recently published reports from the manufacturer. ClinicalTrials.gov Identifier: NCT04767516 .

Bearing Fault Prognosis Method Based on Priori Knowledge-Enhanced Particle Filter

A priori knowledge-enhanced particle filter (PKE-PF) method is proposed to solve the problem of particle impoverishment in bearing fault prognosis with incomplete data. Based on the existing bearing life degradation data and the parameter transfer method in the transfer learning theory, particle initialization optimization, which is very important in the PF method, is carried out to effectively improve particle effectiveness and avoid the problem of premature particle exhaustion. Based on the whole-life degradation experiment of rolling bearings, the validation results show that the traditional PF method and its improved method are prone to particle exhaustion, which seriously affects the fault prediction results. The PKE-PF method proposed in this paper can effectively avoid the problem of premature particle depletion and obtain a more ideal fault prognosis results.

Potentials of direct air capture and storage in a greenhouse gas-neutral European energy system

Negative emission technologies will likely be needed to achieve the European Commission's goal of greenhouse gas neutrality by 2050. This article investigates the potential of reducing greenhouse gases in the atmosphere via the DACCS pathway, i.e., to capture CO2 from the ambient air and permanently store it in geological formations. Since the capture of CO2 from ambient air is energy-intensive, this study particularly models the integration of DACCS plants into a greenhouse gas-neutral European energy system. The model results show that DACCS in Europe 2050 could cost between 160 €/tCO2 and 270 €/tCO2 with very conservative techno-economic assumptions and between 60 €/tCO2 and 140 €/tCO2 using more progressive parameters. Annually capturing 5% of Europe's 1990 emissions with a fully electric DACCS system would increase the capacities of onshore wind by 80–119 GWel and PV by 85–126 GWel. In the model results, Sweden, the Iberian Peninsula, Norway, and Finland incorporate the essential characteristics for a successful deployment of capturing and storing CO2 from ambient air: Sufficiently large geological CO2 storage capacities and relatively low-cost, vacant renewable power generation potentials. The low DACCS costs could minimize the cost of combating climate change and prevent the implementation of more expensive mitigation strategies. On the other hand, a DACCS-based climate protection strategy is fraught with the risks of CO2 storage leaks, acceptance problems for the additional required expansion of renewable energies, and premature depletion of global CO2 storage potentials.

External cardioversion of atrial fibrillation and flutter in patients with cardiac implantable electrical devices.

Atrial fibrillation and flutter are often treated with external electrical cardioversion (ECV) in patients with potentially electrically sensitive cardiovascular implantable electronic devices (CIED). Long-term follow-up data on contemporary CIED undergoing ECV is sparse. The aim is to investigate shock-related complications and impact on CIEDs. All ECV procedures from 2010 to 2020 in patients with CIED performed at a tertiary university hospital were identified in the Danish National Patient Registry. Changes in device measurements after ECV were retrospectively studied and procedure-related complications were identified by review of medical records. We analyzed 763 ECV procedures in 372 patients, median device implant time 1.9years. The mean age of patients was 69.9±9.9years of which 73.4% were men. We identified two cases of device programming changes and four cases of premature battery depletion (≤3years after device implant). Minor changes in device measurements were found for impedances, sensing, and pacing thresholds. No patients died due to ECV-related device dysfunctions within the first 12 months after cardioversions. External cardioversion in patients with contemporary pacemakers and implantable cardioverter-defibrillators seems safe in the majority of patients. Clinically important changes in device function following cardioversion were rarely observed but may be critical for device function. In an observational study, causality between cardioversion and device dysfunction cannot be established. For patient safety, we suggest that routine device interrogation after cardioversion still should be part of standard care.

Hydro Economic Asymmetries and Common‐Pool Overdraft in Transboundary Aquifers

AbstractThe common‐pool nature of groundwater resources creates incentives to over pump that contribute to their rapid global depletion. In transboundary aquifers, users are separated by a territorial border and might face substantially different economic and hydrogeologic conditions that can alternatively dampen or amplify incentives to over pump. We develop a theoretical model that couples principles of game theory and groundwater flow to capture the combined effect of well locations and user asymmetries on pumping incentives. We find that heterogeneities across users (here referred to as asymmetries) in terms of either energy cost, groundwater profitability or aquifer response tend to dampen incentives to over pump. However, combinations of two or more types of asymmetry can substantially amplify common‐pool overdraft, particularly when the same user simultaneously faces comparatively higher costs (or aquifer response) and profitability. We use this theoretical insight to interpret the emergence of the Disi agreement between Saudi Arabia and Jordan in association with the Disi‐Amman water pipeline. By using bounded non‐dimensional parameters to encode user asymmetries and groundwater connectivity, the theory provides a tractable generalized framework to understand the premature depletion of shared aquifers, whether transboundary or not.

Methods for Evaluating Li/CFx Primary Cell Performance and Depth-of-Discharge

Primary batteries have been used in past deep space exploration missions, providing power for periods of several hours to several days of mission operations [1,2]. Future missions planned by the National Aeronautics and Space Administration (NASA) will require more advanced primary batteries to provide power to missions for up to 60 days [3].The Li/CFx primary battery chemistry has a high specific energy, low self-discharge rate, and a relatively wide operating temperature range which makes it a suitable power source for extended mission durations in deep space, particularly for applications involving low to moderate discharge rates [4]. Li/CFx batteries have not been used in any NASA missions to date, and are now being developed for the Europa Lander mission concept [5]. An extensive evaluation of EaglePicher’s D-sized Li/CFx cells is underway, to benchmark the calendar life performance, radiation tolerance, and performance under different temperatures and currents.One of the unique characteristics of the Li/CFx chemistry is the extremely flat voltage plateau during cell discharge (Figure 1) [6, 7]. As the cell approaches end of life, its voltage quickly drops prior to reaching the 1.5V recommended discharge limit. While the cell’s stable voltage is a key component to the high specific energy of this chemistry, it also makes it challenging to accurately predict the battery’s remaining capacity. Premature battery depletion is a risk to mission success, and improved methods for determining depth-of-discharge (DOD) in this unique cell chemistry are of great interest.A pulse-discharge test method is developed and implemented to investigate the change in cell direct current internal resistance (DCIR) during discharge. Varied responses based on the discharge rate are observed and will be discussed. The resulting data are analyzed for possible correlation with DOD, along with changes in the cell voltage over various segments of the discharge curve. This talk discusses the test method and results achieved using the pulse-discharge test method.

Effect of proton radiation therapy on cardiovascular implantable electronic devices [CIED

Abstract Background The number of cancer patients with CIED receiving radiotherapy has increased dramatically with improving life expectancy in both patients with cardiovascular disease and cancer. The advent of proton therapy adds new concern for potential malfunction in CIED devices, both due to significant neutron scatter and its use of strong magnets to focus radiation beams. Therefore, we aimed to assess the incidence of CIED malfunction secondary to proton therapy in this patient cohort. Methods We retrospectively analyzed patients with CIED undergoing proton therapy at our institute between 2011–2021. Each device was programmed pre-treatment and monitored post-treatment according to a special protocol developed in our centre. Treatments were prescribed to doses up to 70 Gy (RBE) and delivered using either passive-scattering or pencil beam techniques. Distances between the CIED and treated volumes ranged from 10–50 cm. We analyzed baseline patient demographics, CIED demographics, CIED outcomes pre-proton therapy as well as post-proton therapy including device reset and requirement for replacement, analyzing up to most recent check. Results Fifty-one patients with CIED underwent proton therapy during the study period. Estimated neutron dose ranged from 0.05–2.0 mSv/GyRBE for this patient cohort. Baseline demographics outlines in table 1. Of note 26/51 patients underwent proton therapy for ophthalmic malignancies, 6/51 for brain/skull malignancies. CIED comprised of 39 pacemakers and 12 implantable cardioverter defibrillators. Fourteen patients were pacemaker-dependent. Using 95% Confidence Interval, ventricular threshold, impedance, and amplitude, as well as atrial threshold and amplitude were unchanged, whereas atrial impedance measurements had a change pre- and post-proton therapy (Table 2). No patients had a device reset. One patient had a premature battery depletion three months post-radiotherapy for pancreatic cancer. Conclusions Our findings suggest that proton therapy does not significantly impact CIED function. Whilst caution remains as further data is accrued, close monitoring, particularly with the advent of remote monitoring, of these patients should be recommended. Funding Acknowledgement Type of funding sources: None.

The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells.

Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that MuSC mitochondria rapidly fragment upon an activation stimulus, via systemic HGF/mTOR, to drive the exit from deep quiescence. Deletion of the mitochondrial fusion protein OPA1 and mitochondrial fragmentation transitions MuSCs into G-alert quiescence, causing premature activation and depletion upon a stimulus. OPA1 loss activates a glutathione (GSH)-redox signaling pathway promoting cell-cycle progression, myogenic gene expression, and commitment. MuSCs with chronic OPA1 loss, leading to mitochondrial dysfunction, continue to reside in G-alert but acquire severe cell-cycle defects. Additionally, we provide evidence that OPA1 decline and impaired mitochondrial dynamics contribute to age-related MuSC dysfunction. These findings reveal a fundamental role for OPA1 and mitochondrial dynamics in establishing the quiescent state and activation potential of adult stem cells.