Treatment of primary cardiac diffuse large B-cell lymphoma involving the coronary sinus with R-EPOCH: a case report and literature review.

Primary cardiac lymphomas (PCLs) are a rare clinical entity, in which treatment guidelines remain to be established. Rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) has been proposed, given that it involves a continuous infusion of anthracycline, reducing the risk of a cardiotoxicity and therefore the theoretical risk of perforation. However, the literature on this method of treatment is scarce. Herein, we present a unique case of a 75-year-old male, diagnosed with primary cardiac diffuse large B-cell lymphoma (DLBCL) with relatively unusual involvement of the coronary sinus, treated first with one cycle of R-EPOCH, followed by three cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) to reduce said risk. To our knowledge, this is one of two cases, in which a patient with PCL was treated this way.

Venetoclax plus dose-adjusted R-EPOCH (VR-DA-EPOCH) or G-EPOCH bridging to subsequent cellular therapy for the patients with transformed lymphoma a single center clinical experience.

Indolent lymphoma, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL), can undergo histological transformation into an aggressive subtype, typically diffuse large B-cell lymphoma (DLBCL). The prognosis of transformed lymphoma is poor. In this study, we reported the efficacy and toxicity of a combination of venetoclax, dose-adjusted rituximab or obinutuzumab, etoposide, prednisone, vincristine, doxorubicin, and cyclophosphamide (VR-DA-EPOCH or VG-DA-EPOCH) in 11 patients with biopsy-proven histology transformation into DLBCL, including 8 patients with RT and 3 with transformed FL (tFL). The study was conducted between October 2019 and March 2023 at our single center. The median age of participants at enrolment was 53 years. Six patients (85.7%, 6/7) achieved complete remission (CR) at the end of treatment. The best overall response rate (ORR) and CR rate were both 72.7%, respectively. Two patients received autologous hemopoietic stem cell transplant (ASCT) while two patients received ASCT concurrently with CAR-T therapy for consolidation. With a median follow-up of 13.5 (range, 2.4-29.8) months after enrollment, the median event-free survival, progression-free survival, and overall survival were 9.4, 11.5, and 17.5 months, respectively. Hematologic toxicities of grade ≥3 consisted of neutropenia (90.9%, 10/11), thrombocytopenia (63.6%, 7/11), and febrile neutropenia (54.5%, 6/11). In conclusion, VR-DA-EPOCH or VG-DA-EPOCH was a promising strategy to achieve an early remission, bridging to cellular therapy within this population.

Isolated central nervous system relapse in two adolescents with primary mediastinal large B-cell lymphoma after treatment with R-DA-EPOCH.

The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.

Machine learning-empowered sleep staging classification using multi-modality signals.

The goal is to enhance an automated sleep staging system's performance by leveraging the diverse signals captured through multi-modal polysomnography recordings. Three modalities of PSG signals, namely electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG), were considered to obtain the optimal fusions of the PSG signals, where 63 features were extracted. These include frequency-based, time-based, statistical-based, entropy-based, and non-linear-based features. We adopted the ReliefF (ReF) feature selection algorithms to find the suitable parts for each signal and superposition of PSG signals. Twelve top features were selected while correlated with the extracted feature sets' sleep stages. The selected features were fed into the AdaBoost with Random Forest (ADB + RF) classifier to validate the chosen segments and classify the sleep stages. This study's experiments were investigated by obtaining two testing schemes: epoch-wise testing and subject-wise testing. The suggested research was conducted using three publicly available datasets: ISRUC-Sleep subgroup1 (ISRUC-SG1), sleep-EDF(S-EDF), Physio bank CAP sleep database (PB-CAPSDB), and S-EDF-78 respectively. This work demonstrated that the proposed fusion strategy overestimates the common individual usage of PSG signals.

Optimizing Epoch Length and Activity Count Threshold Parameters in Accelerometry: Enhancing Upper Extremity Use Quantification in Cerebral Palsy.

Various accelerometry protocols have been used to quantify upper extremity (UE) activity, encompassing diverse epoch lengths and thresholding methods. However, there is no consensus on the most effective approach. The aim of this study was to delineate the optimal parameters for analyzing accelerometry data to quantify UE use in individuals with unilateral cerebral palsy (CP). METHODS: A group of adults with CP (n = 15) participated in six activities of daily living, while a group of children with CP (n = 14) underwent the Assisting Hand Assessment. Both groups performed the activities while wearing ActiGraph GT9X-BT devices on each wrist, with concurrent video recording. Use ratio (UR) derived from accelerometry and video analysis and accelerometer data were compared for different epoch lengths (1, 1.5, and 2 s) and activity count (AC) thresholds (between 2 and 150). RESULTS: In adults, results are comparable across epoch lengths, with the best AC thresholds being ≥ 100. In children, results are similar across epoch lengths of 1 and 1.5 (optimal AC threshold = 50), while the optimal threshold is higher with an epoch length of 2 (AC = 75). CONCLUSIONS: The combination of epoch length and AC thresholds should be chosen carefully as both influence the validity of the quantification of UE use.

LSTM-Based GNSS Localization Using Satellite Measurement Features Jointly with Pseudorange Residuals.

In the Global Navigation Satellite System (GNSS) context, the growing number of available satellites has led to many challenges when it comes to choosing the most-accurate pseudorange contributions, given the strong impact of biased measurements on positioning accuracy, particularly in single-epoch scenarios. This work leverages the potential of machine learning in predicting linkwise measurement quality factors and, hence, optimize measurement weighting. For this purpose, we used a customized matrix composed of heterogeneous features such as conditional pseudorange residuals and per-link satellite metrics (e.g., carrier-to-noise-power-density ratio and its empirical statistics, satellite elevation, carrier phase lock time). This matrix is then fed as an input to a long short-term memory (LSTM) deep neural network capable of exploiting the hidden correlations between these features relevant to positioning, leading to the predictions of efficient measurement weights. Our extensive experimental results on real data, obtained from extensive field measurements, demonstrate the high potential of our proposed solution, which is able to outperform traditional measurement weighting and selection strategies from the state-of-the-art. In addition, we included detailed illustrations based on representative sessions to provide a concrete understanding of the significant gains of our approach, particularly in strongly GNSS-challenged operating conditions.

Periodical Cicada Emergences Affect Masting Behavior of Oaks.

AbstractOaks (Quercus spp.) are masting species exhibiting highly variable and synchronized acorn production. We investigated the hypothesis that periodical cicadas (Magicada spp.), well known to have strong effects on the ecosystems in which they occur, affect acorn production of oaks through their xylem feeding habits as nymphs, the oviposition damage they inflict as adults during emergences, or the nutrient pulse resulting from the decomposition of their bodies following breeding. We found negative effects on acorn production during emergence years and the year following emergences and enhanced acorn production 2 years after emergence. We also found evidence indicating a significant effect of cicada emergences on spatial synchrony of acorn production by trees growing within the range of the same cicada brood compared with different broods. These results demonstrate that periodical cicadas act as a trophic environmental "veto" depressing acorn production during and immediately following emergences, after which the nutrient pulse associated with the cicada's demise enhances oak reproduction.

Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem).

PURPOSE: Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) is a regimen used for the treatment of high-risk diffuse large B-cell lymphoma (DLBCL) designed to overcome resistance to standard R-CHOP by combining prolonged exposure of lymphoma cells to cytotoxic agents and dose-adjustment based on toxicity. Data on outcomes of older patients are scarce. PATIENTS AND METHODS: We collected data on patients with newly diagnosed high-risk DLBCL older than 60 years treated with DA-EPOCH-R. High-risk patients were defined by the age-adjusted international prognostic index score 2 or 3. RESULTS: A total of 120 patients were included. Median age was 69 years (range 60-82). Response rate was 74%; with 59% complete responses. Dose of DA-EPOCH-R was escalated in 50 patients (42%). Three-year progression-free survival (PFS) and overall survival (OS) was 53% and 58%, respectively, with treatment-related mortality (TRM) of 13%. In univariate analysis, favorable prognostic factors were performance status (PS) (0-2 vs. 3-4), age (<70 vs. ≥70 years), and center. In multivariate analysis, PS and center retained prognostic significance. Patients with PS 0-2 had 3-year PFS and OS of 58% and 64%, respectively, with TRM of 6%. CONCLUSION: DA-EPOCH-R is efficacious in sufficiently fit older high-risk DLBCL patients. Patients with poor PS have unacceptable toxicity and require less intensive therapy.

Hyper-CVAD versus dose-adjusted EPOCH as initial treatment for adults with acute lymphoblastic leukemia.

OBJECTIVES: We recently performed a single-arm phase II trial of DA-EPOCH in adults with acute lymphoblastic leukemia (ALL). We sought to compare these results to those with standard Hyper-CVAD. METHODS: We created a retrospective matched cohort of patients who received Hyper-CVAD (n = 69) at our center and otherwise met eligibility criteria for the DA-EPOCH trial (n = 53). RESULTS: Our outcomes support the use of Hyper-CVAD over DA-EPOCH in Ph- disease for both overall survival (OS; HR 0.18, p = .004) and event-free survival (EFS; HR 0.51, p = .06). In contrast, outcomes were similar in Ph+ disease (OS HR 0.97, p = .96; EFS HR 0.65, p = .21). Rates of morphologic remission and measurable residual-disease negativity were similar between the regimens. Hyper-CVAD was associated with significantly more febrile neutropenia (OR 1.9, p = .03) and a greater incidence of Grade 4 or 5 adverse events (20% vs. 6%). Average transfusions per cycle of both red blood cells (p < .001) and platelets (p < .001) were five-fold higher with Hyper-CVAD. CONCLUSIONS: Our findings support continued use of Hyper-CVAD for Ph- ALL but suggest that DA-EPOCH may be a reasonable alternative for Ph+ ALL. These data also highlight a potential role for DA-EPOCH in resource-limited settings or when more intense therapy is not feasible.

Reliability of the P3 component in a 3-stimulus concealed information test with known and unknown stimuli.

The parietal P3 amplitude of the event-related potential (ERP) has been highlighted to signal stimulus salience in concealed information tests (CITs) with known and unknown stimuli. To extend previous validity investigations in deception research, the reliability of the early parietal P3 amplitude in a 3-stimulus CIT including known and unknown stimuli has been investigated in a sample of N = 68 participants. Variations of Cronbach's Alpha and split-half reliability (odd-even, 1st vs. 2nd half) of the early parietal P3 amplitude were considered for ERP quantification method (peak-to-peak, mean, baseline-to-peak), epoch selection strategies (chronological vs. random) and number of epochs (10-40) in three stimulus types (probe, target, irrelevant). Excellent reliability coefficients have been summarized for number of epochs, P3 quantifications, and epoch selection strategies. Moreover, the best-practice recommendations highlight mandatory combinations of epoch selection strategy, number of epochs and P3 quantifications to ensure robust and excellent reliabilities of the early parietal P3 amplitude in a 3-stimulus CIT with known (probe, target) and unknown (irrelevant) stimuli. The robustness of mandatory excellent reliability coefficients for the early parietal P3 has been discussed for two data tracks in single-case analyses.

FedDdrl: Federated Double Deep Reinforcement Learning for Heterogeneous IoT with Adaptive Early Client Termination and Local Epoch Adjustment.

Federated learning (FL) is a technique that allows multiple clients to collaboratively train a global model without sharing their sensitive and bandwidth-hungry data. This paper presents a joint early client termination and local epoch adjustment for FL. We consider the challenges of heterogeneous Internet of Things (IoT) environments including non-independent and identically distributed (non-IID) data as well as diverse computing and communication capabilities. The goal is to strike the best tradeoff among three conflicting objectives, namely global model accuracy, training latency and communication cost. We first leverage the balanced-MixUp technique to mitigate the influence of non-IID data on the FL convergence rate. A weighted sum optimization problem is then formulated and solved via our proposed FL double deep reinforcement learning (FedDdrl) framework, which outputs a dual action. The former indicates whether a participating FL client is dropped, whereas the latter specifies how long each remaining client needs to complete its local training task. Simulation results show that FedDdrl outperforms the existing FL scheme in terms of overall tradeoff. Specifically, FedDdrl achieves higher model accuracy by about 4% while incurring 30% less latency and communication costs.

[Plasmablastic lymphoma presenting clinical symptoms similar to plasmablastic myeloma].

A 75-year-old man developed multiple head masses as well as a compression fracture. His blood test revealed elevated immunoglobulin G (IgG) protein levels, and immunofixation electrophoresis revealed the presence of monoclonal IgGκ. Furthermore, positron emission tomography/computed tomography revealed multiple bone lesions, although bone marrow examination revealed only 1.2% of plasma cells. Biopsy of a head mass led to the diagnosis of plasmablastic lymphoma (PBL), an aggressive B-cell lymphoma with plasma cell phenotypes but no B-cell antigen expression. Because the tumor cells have plasmablastic morphologies, it is difficult to distinguish PBL from plasmablastic myeloma, which is a subtype of multiple myeloma. Both diseases have similar immunophenotypes and clinical courses. In this case, PBL was finally diagnosed based on Epstein-Barr virus positivity, and the patient made a complete recovery after treatment with DA-EPOCH.

Evaluating the incidence of chemotherapy-induced nausea and vomiting in patients with B-cell lymphoma receiving dose-adjusted EPOCH and rituximab.

BACKGROUND: Studies evaluating antiemetic prophylaxis have primarily focused on the solid tumor setting and single-day regimens. This study evaluates antiemetic prophylaxis and chemotherapy induced nausea and vomiting (CINV) in patients with lymphoma receiving a multiday doxorubicin-cyclophosphamide containing regimen. METHODS: This was a retrospective, single center, cohort study evaluating patients with aggressive non-Hodgkin B-cell lymphoma receiving dose-adjusted R-EPOCH in the hospital. Data was collected from the electronic medical record from April 2016 to September 2019. Complete response over 120 hours was the primary outcome. Secondary outcomes included complete response during the acute and delayed phases as well as complete control. RESULTS: A total of 73 patients who received dose adjusted R-EPOCH were identified. Most patients (n = 39, 53%) were male with a the median age was 63 years (range: 21-81). Most patients received ondansetron 16 mg once daily (n = 48, 66%) on days 1-5 as antiemetic prophylaxis with a minority receiving either dexamethasone (n = 8) or an NK1 antagonist (n = 13) in addition to ondansetron. Complete response rate was 32% and the complete response in the acute and delayed phase was also 32%. CONCLUSION: Control of CINV in patients with lymphoma hospitalized to receive dose-adjusted R-EPOCH was suboptimal, with only 32% of patients achieving complete response. Nearly three-quarters of patients received only a 5HT3 receptor antagonist as scheduled antiemetic therapy without an NK1 receptor antagonist. This data supports the importance of improving awareness of regarding multiday CINV guidelines and ensuring timely update and implementation of these evidence-based guidelines.

Scorepochs: A Computer-Aided Scoring Tool for Resting-State M/EEG Epochs.

M/EEG resting-state analysis often requires the definition of the epoch length and the criteria in order to select which epochs to include in the subsequent steps. However, the effects of epoch selection remain scarcely investigated and the procedure used to (visually) inspect, label, and remove bad epochs is often not documented, thereby hindering the reproducibility of the reported results. In this study, we present Scorepochs, a simple and freely available tool for the automatic scoring of resting-state M/EEG epochs that aims to provide an objective method to aid M/EEG experts during the epoch selection procedure. We tested our approach on a freely available EEG dataset containing recordings from 109 subjects using the BCI2000 64 channel system.

[Long-term complete remission of HIV-negative primary testicular plasmablastic lymphoma treated with bortezomib in combination with EPOCH].

Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B-cell lymphoma that is frequently associated with HIV infection or other immunodeficiencies. We present a case of HIV-negative primary testicular PBL with long-term complete remission (CR) and successful treatment with bortezomib in combination with EPOCH (V-EPOCH). Because of rapidly increasing right testicular swelling, an 86-year-old man without immunodeficiencies was admitted to our hospital. Following that, a right high orchiectomy was performed. Histopathological and immunohistochemical analyses revealed diffuse infiltration of plasmablastic lymphocytes, which were positive for CD38, CD138, CD56, MUM1, lambda, EBER, and MYC respectively, but negative for CD20. The MIB-1 index was 90%. FDG abnormal uptake was discovered on PET/CT at systemic lymph nodes. There was no abnormal cell infiltration in either the bone marrow or cerebral spinal fluid. He was diagnosed with PBL, clinical-stage IIIE-A, IPI high-intermediate risk. He achieved durable CR more than 30 months after the diagnosis after six courses of V-EPOCH, followed by intrathecal prophylaxis (IT) and adjuvant radiation therapy (total 30 Gy). Although PBL shows an aggressive clinical course and poor prognosis, adequate therapeutic approaches for PBL have not been established due to the rarity of this disease. According to our findings, V-EPOCH combined with IT and adjuvant radiotherapy appeared to be feasible and effective as a frontline treatment for elderly patients with primary testicular PBL.

Treatment of posttransplant lymphoproliferative disorder with poor prognostic features in children and young adults: Short-course EPOCH regimens are safe and effective.

No guidelines exist for which intensive chemotherapy regimen is best in pediatric or young adult patients with high-risk posttransplant lymphoproliferative disorder (PTLD). We retrospectively reviewed patients with PTLD who received interval-compressed short-course etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (SC-EPOCH) regimens at our institution. Eight patients were included with median age of 12 years. All patients achieved a complete response with a manageable toxicity profile. Two patients developed second, clonally unrelated, EBV-positive PTLD and one patient had recurrence at 6 months off therapy. No graft rejection occurred during therapy. All eight patients are alive with median follow-up of 29 months.

Low-frequency technology for a lunar interferometer.

This work sketches a possible design architecture of a low-frequency radio interferometer located on the lunar surface. The design has evolved from single antenna experiments aimed at the global signal detection of the epoch of reionization (EoR) to the square kilometre array (SKA) which, when complete, will be capable of imaging the highly red-shifted H1-signal from the cosmic dawn through to the EoR. However, due to the opacity of the ionosphere below 10 MHz and the anthropogenic radio-frequency interference, these terrestrial facilities are incapable of detecting pre-ionization signals and the moon becomes an attractive location to build a low-frequency radio interferometer capable of detecting such cosmological signals. Even though there are enormous engineering challenges to overcome, having this scientific facility on the lunar surface also opens up several new exciting possibilities for low-frequency radio astronomy. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades'.

Safety and financial analysis of outpatient dose-adjusted EPOCH for B-cell lymphoma at a tertiary comprehensive cancer center.

INTRODUCTION: Dose-adjusted (DA-) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) is a front-line treatment option for aggressive B-cell lymphomas. Due to regimen complexity, inpatient administration of DA-EPOCH has been historically required. Moffitt Cancer Center (MCC) developed an Inpatient/Outpatient (IPOP) program to facilitate administration of complicated regimens in the outpatient setting. We hypothesized that outpatient administration of DA-EPOCH at a comprehensive cancer center is both safe and cost-effective. METHODS: We conducted a single-center, retrospective chart review including B-cell lymphoma patients who were 18 years or older and who had received DA-EPOCH at MCC from April 26, 2017 through August 10, 2019. The primary endpoint was hospital admissions during outpatient chemotherapy administration. Additional safety endpoints included hospitalizations between cycles, infectious complications, extravasations, drug spills, pump-malfunctions, and drug-related adverse events. Financial analysis included drug cost, resource utilization, and impact of hospital bed backfill. RESULTS: 56 patients received 219 cycles of DA-EPOCH with 193 cycles administered outpatient. Zero patients required hospitalization during outpatient administration of DA-EPOCH, resulting in 965 saved hospital days. 23 patients (41%) were hospitalized between cycles, most commonly due to neutropenic fever (52%). No extravasations were documented throughout the study period. There were few incidences of drug spills or pump malfunctions. Based on current regimen utilization, the annual transition of 84 cycles of DA-EPOCH to the outpatient setting has a positive impact on margin of $1,444,548. CONCLUSIONS: Routine outpatient administration of DA-EPOCH is both safe and feasible with a positive annual impact on margin of $1,444,548 at a comprehensive cancer center.

Antiemetic medication efficacy during EPOCH and R-EPOCH treatment.

INTRODUCTION: This study aims to determine the adequacy of current institutional standard practice for CINV prophylaxis for EPOCH and R-EPOCH at The Ohio State University James Cancer Hospital. METHODS: Single-center, retrospective analysis was performed including all patients receiving EPOCH or R-EPOCH chemotherapy for Non-Hodgkin's lymphomas from 1/1/2012 to 6/30/2017. The primary endpoint was rate of CINV events, which included usage of more than 50 percent of available doses of breakthrough antiemetics while inpatient, hospitalization due to CINV or related complications, or adjustments made to the CINV prophylactic or breakthrough regimen during current or subsequent cycles. Secondary endpoints included determining prescriber adherence to institutional standard CINV prophylaxis, characterization of adjustments to the antiemetic regimen following the incidence of CINV, and identification of high-risk patients that may benefit from additional CINV prophylaxis. RESULTS: Of 111 patients, 54 (48.6%) experienced CINV events with any cycle of EPOCH or R-EPOCH chemotherapy. Of those patients, 17 (31.5%) received institutional standard CINV prophylaxis at baseline, 8 (14.8%) received additional scheduled antiemetics, and 26 (48.1%) were prescribed additional breakthrough antiemetics with their first cycle of EPOCH or R-EPOCH. Younger age, diagnosis of anxiety, and previous susceptibility to nausea were significantly associated with CINV events. CONCLUSION: This study illustrates the inadequacy of current institutional standard for CINV prophylaxis for patients receiving EPOCH and R-EPOCH, highly emetogenic chemotherapy regimens. With nearly half of included patients experiencing CINV events, and most initially receiving more than our standard prophylaxis, changes to our standard antiemetics used with this chemotherapy regimen are needed.

Do epoch lengths of hypnotic depth indicators affect estimated of blood-brain equilibration rate constants of propofol?

This study aimed to investigate the effect of epoch length of hypnotic depth indicators on the blood-brain equilibration rate constant (ke0) estimates of propofol. Propofol was administered by zero-order infusion (1.5, 3.0, 6, and 12 mg·kg-1·h-1) for one hour in 63 healthy volunteers. The ke0 of propofol was estimated using an effect-compartment model linking pharmacokinetics and pharmacodynamics, in which response variables were electroencephalographic approximate entropy (ApEn) or bispectral index (BIS) (n = 32 each for propofol infusion rates of 6 and 12 mg·kg-1·h-1). Epoch lengths of ApEn were 2, 10, 30, and 60 seconds (s). The correlations between plasma propofol concentrations (Cp) and BIS and ApEn 2, 10, 30, and 60 s were determined, as was the Ce associated with 50% probability of unconsciousness (Ce50,LOC). The pharmacokinetics of propofol were well described by a three-compartment model. The correlation coefficient between Cp and ApEn 2, 10, 30, and 60 s were -0.64, -0.54, -0.39, and -0.26, respectively, whereas correlation coefficient between Cp and BIS was -0.74. The blood-brain equilibration half-life based on the ke0 estimates for ApEn at 2, 10, 30, 60 s and BIS were 4.31, 3.96, 5.78. 6.54, 5.09 min, respectively, whereas the Ce50,LOC for ApEn at 2, 10, 30, 60 s and BIS were 1.55, 1.47, 1.28, 1.04, and 1.55 µg·ml-1, respectively. Since ke0, which determines the onset of drug action, varies according to the epoch length, it is necessary to consider the epoch length together when estimating ke0.