Waterfall Plots Research Articles

Concrete Pile Defect Identification: Insights from Cross-Hole Sonic Logging and High Strain Dynamic Pile Test

This paper aims to identify the types of defects, location of defects, size of defects, and capacity of five concrete piles using a High strain dynamic pile test and Cross-hole sonic logging test. In this study, Cross-Hole Sonic Logging method (CSL) is a potent quality-control tool that exclusively detects much smaller flaws with high accuracy with utilizing velocity and first arrival time (FAT) from ultrasonic waves to find out the integrity of the drill shaft. From CSL test, the bearing capacity needs to be calculated manually using a waterfall diagram and soil profile. Moreover, the high strain dynamic pile test is used to identify integrity and bearing capacity of concrete pile via resistance analysis down to the pile and split of the base to shaft resistance when only pile head measurements are taken then using Case Method and CAPWAP analysis. Through this analysis, the bearing capacity can be interpreted; the Belta (damage factor) is applied to estimate location and size of the defect in the concrete pile. Based on the result of CLS test for three concrete piles, P01, P04, and P10, indicated that P01 and P04 are “Good” pile integrity with the bearing capacity of 4583kN and 6600kN, while P10 showed as “Potential defect at depth 9.25m to 10.25m” of pile integrity with bearing capacity of 6600kN. Furthermore, High strain dynamic pile test of two concrete piles, P2E and P2P, showed that the integrity category is “Ok” with bearing capacity 9896kN.

극/슬롯 조합에 따른 영구자석 동기전동기의 전자기 및 NVH 특성 비교 분석

In this paper, electromagnetic noise sources of permanent magnet synchronous motors with 8-pole 9-slot and 12-slot fractional slot concentrated windings were analyzed through finite element analysis, and the radiated noise/vibration levels were compared through structural-acoustic analysis. Electromagnetic noise sources are classified into cogging torque, torque ripple, magnetic pull force, and unbalanced magnetic force, and the main values of electromagnetic excitation forces are different according to the pole/slot combination. In particular, the effect of electromagnetic noise sources on vibration/noise was analyzed in the frequency domain through the electromagnetic-mechanical coupling analysis. The noise level according to the speed was compared with the noise characteristics for each frequency using the waterfall diagram.

The Influence of Rotor Adjustment Parameters on the Dynamic Balance of a Scale-Model Rigid Variable Speed Rotor

In this paper, the dynamic balance of a rigid variable speed rotor is tested and analyzed. The vibration acceleration is measured by vibration analyzer instrumentations. The rotor adjustment parameters of counterweight, pitch, and trailing-edge flap are considered. The amplitude and phase of the 1 Ω vibration acceleration are analyzed through an all-phase fast Fourier transform. The experiments are conducted using two rigid rotors with the same geometry. The accelerations of the fuselage in the x, y, and z directions are measured. Through a waterfall diagram of the auto-power spectrum, it is found that the imbalance of counterweight, pitch, and trailing-edge flap causes an obvious increase in 1 Ω and 2 Ω acceleration. The hub counterweight mainly causes the lateral and longitudinal vibration in the disc plane, and the aerodynamic factors such as pitch and trailing-edge flap mainly affect the vertical vibration. In order to achieve dynamic balance for variable speed rotors, the counterweight adjustment should be given the highest priority for the vibration in the disc plane, and the pitch and trailing-edge flap adjustment should be given the highest priority for the vertical vibration. The results obtained from this experiment may be helpful toward reasonable designs of variable speed rotor helicopters.

Therapeutic effectiveness and safety of sequential ICIs with radiotherapy for symptomatic brain and bone metastases in NSCLC patients.

In advanced non-small cell lung cancer (NSCLC), the brain and bones are common metastatic sites, and the disease seriously affects the survival time and quality of life. For metastatic lesions with symptoms, local treatment often precedes systemic treatment. However, in clinical trials, patients with symptomatic brain or bone metastases are often excluded. Therefore, limited data are available on the efficacy of immune checkpoint inhibitors (ICIs) in those patients. We aimed to evaluate the effectiveness and safety of local radiotherapy followed by ICIs in driver gene-negative NSCLC patients with symptomatic local metastasis in the brain and bone. This is a 29-month 2 centered retrospective cohort study performed in China between March 2019 and August 2021. A total of 22 patients with advanced NSCLC were included. All patients received radiotherapy in the brain or bone before the administration of ICIs. For all patients, the overall response rate was 59.09%, the median progression-free survival (PFS) was 7.5 months, the PFS rate at 6 months was 72.73%, and the PFS rate at 1 year was 13.64%. Waterfall plots showed that tumor size was mostly reduced compared with baseline. The spider map showed that the tumor continued to shrink. In terms of symptom improvement, 100% pain control and 83.33% improvement were observed in epilepsy and neurological function. Sequential ICIs with local radiotherapy is effective for the treatment of patients with symptomatic brain and bone metastases of driver gene-negative NSCLC, which will benefit patients and improve their symptoms.

Improvement in Individual Symptoms and Total Symptom Score (TSS) and Matching-Adjusted Indirect Comparison (MAIC) Analysis to Compare TSS As a Continuous Endpoint in Patients with Myelofibrosis Treated with Pelabresib in Combination with Ruxolitinib Versus Janus Kinase Inhibitor Monotherapy

Background: Pelabresib (CPI-0610; PELA) is a bromodomain and extraterminal domain (BET) inhibitor in development for the treatment of myelofibrosis (MF). PELA combined with ruxolitinib (RUX) has shown a 56% response rate for ≥50% reduction in total symptom score (TSS) at Wk 24 from baseline (BL; TSS50) in Janus kinase inhibitor (JAKi) treatment-naïve patients (pts) with intermediate or high-risk MF in Arm 3 of the open-label Phase 2 MANIFEST study (NCT02158858). TSS50 is a standard measure of symptom improvement; however, the 50% response threshold does not capture clinical benefit in pts with TSS reduction <50% or pts who achieve TSS50 but could benefit from further symptom improvement (Dueck A, et al. European Hematology Association 2017. Poster E1331). Here, we present percentage change in TSS and subdomains as a continuous endpoint from Arm 3 of MANIFEST and indirect comparisons with historical double-blind JAKi trials in MF. Aims: To assess clinically meaningful changes in TSS with PELA in combination with RUX. TSS subdomains were analyzed to assess the underlying impact of PELA + RUX on symptom scores. In the absence of head-to-head studies of PELA + RUX vs JAKi monotherapy, naïve and matching-adjusted indirect comparison (MAIC) analysis (correcting for potential imbalances in baseline characteristics) were used to investigate improvement in TSS as a continuous endpoint in pts treated with PELA + RUX in Arm 3 of the MANIFEST study with historical double-blind Phase 3 JAKi trials: COMFORT-I (RUX), SIMPLIFY-1 (RUX, momelotinib [MOM]) and JAKARTA (fedratinib [FED]). Methods: In MANIFEST, percentage change in TSS and subdomains (fatigue, night sweats, itching, abdominal discomfort, pain under ribs, feeling of fullness and bone pain) from BL at Week (Wk) 12, 24, 36 and 48 were calculated. Pts with BL score = 0 were excluded. For the MAIC analysis, individual pt level data were available for MANIFEST Arm 3, and study-level data were extracted from published waterfall plots using WebPlotDigitizer (Rohatgia A. https://automeris.io/) for COMFORT-I, SIMPLIFY-1 and JAKARTA (FED 400 mg arm). Unanchored MAIC was conducted, whereby pts were reweighted to adjust for imbalances in key prognostic BL characteristics: gender, MF subtype, International Prognostic Scoring System risk status (IPSS), previous hydroxyurea use, platelet count, hemoglobin levels, spleen volume and JAK2V617F status; as a result, bias due to potential unmeasured differences is unlikely. The weights were used to calculate the effective sample size. Pts with IPSS intermediate-1 were excluded from the analysis. Weighted and unweighted treatment effects in terms of difference in least square (LS) means with their 95% confidence intervals using robust sandwich estimators for variance are presented. Studies used different TSS questionnaire versions; however, variations are subtle, and so comparisons across versions are valid (Dueck A, et al.Blood 2017;130:2168). Results: Comparable mean BL TSS scores were observed: 16.1 in MANIFEST Arm 3 and 17.5-19.4 across comparator Phase 3 studies. In MANIFEST Arm 3, a median reduction from BL of >50% was observed for TSS and all subdomains, and this reduction remained consistent across Wk 12 to Wk 48. TSS distribution in MANIFEST at Wk 24 showed greater median and mean reductions from BL vs JAKi monotherapy studies (Figure 1 shows comparison with RUX in SIMPLIFY-1). Complete summary level balance was achieved in the weighted distributions of the prognostic factors in MANIFEST Arm 3 versus comparators. After adjusting for imbalances, >20% greater reduction in LS mean percentage change in TSS from BL at Wk 24 was observed for all comparisons of MANIFEST Arm 3 vs historical studies, as shown in Figure 2. P values for all MAIC analyses were statistically significant. Conclusions: Analyzing TSS as a continuous endpoint in addition to responder analysis overcomes limitations of using TSS50 alone. TSS50 rates in MANIFEST Arm 3 were higher than all comparator MF studies, and clinically relevant improvements in TSS and its subdomains were observed as early as Wk 12 and were durable over time. When indirectly comparing Arm 3 of the Phase 2 MANIFEST study with historical Phase 3 MF studies using MAIC analysis, improved estimates of changes in TSS with PELA + RUX vs RUX, MOM or FED monotherapy were observed. A randomized Phase 3 MANIFEST-2 study of PELA + RUX vs RUX monotherapy in JAKi-naïve pts is ongoing (NCT04603495). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Urine-derived exosomal PSMA is a promising diagnostic biomarker for the detection of prostate cancer on initial biopsy.

It is well-established that the lack of accurate diagnostic modalities for prostate cancer (PCa) leads to overdiagnosis and overtreatments. Accordingly, this study aimed to assess the value of urine-derived exosomal prostate-specific membrane antigen (PSMA) as a biomarker for the diagnosis of PCa and clinically significant prostate cancer (csPCa). A total of 284 urine samples were collected from patients after the digital rectal examination (DRE). Urinary exosomes were extracted using commercial kits, and urine-derived exosomal PSMA was determined via enzyme-linked immunosorbent assay (ELISA). Evaluation of diagnostic accuracy of PSMA was performed via receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and waterfall plots. We found that urine-derived exosomal PSMA was significantly higher in PCa and csPCa than in benign prostatic hyperplasia (BPH) and BPH + non-aggressive prostate cancer (naPCa) groups (P < 0.001). Furthermore, the urine-derived exosome PSMA yielded area under the ROC curve (AUC) values of 0.876 and 0.826 for detecting PCa and csPCa, respectively, suggesting better performance than traditional clinical biomarkers. Besides, when the cutoff value used corresponded to a sensitivity of 95%, urine-derived exosomal PSMA could avoid unnecessary biopsies in 41.2% of cases and missed only 0.7% of csPCa cases. Urine-derived exosomal PSMA exhibits a good diagnostic yield for detecting PCa and csPCa. Findings of the present study provide the foothold for future studies on cancer management and research in this patient population.

Efficacy and safety of combination therapy with chemotherapy, programmed death-1 inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma

Objective: To investigate the efficacy and safety of the combination therapy with chemotherapy, programmed death-1 (PD-1) inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma (DDLPS). Methods: The clinical data of patients with dedifferentiated liposarcoma who received chemotherapy combined with PD-1 inhibitor and anlotinib in the Department of Medical Oncology, Zhongshan Hospital Affiliated to Fudan University from January 1, 2020 to November 30, 2021 were retrospectively analyzed. A total of 24 patients were included in this study, including 12 males and 12 females, with a median age of onset of 56 years (range, 31-69 years). Efficacy and safety in those patients were assessed. Results: All patients had unresectable or metastatic dedifferentiated liposarcoma with G2 (moderate differentiation) or G3 (differential differentiation) in a concise three-grade grading scheme of tumor pathology. Twelve patients received the regimen as the first-line treatment, while the other 7 taken the regimen as second-line treatment and 5 as third-line or above. The median follow-up time for overall survival (OS) was 7.7 months. The overall response rate (ORR) was 20.8% (5/24) and disease control rate (DCR) was 83.3% (20/24) with 5 partial response (PR), 15 stable disease (SD) and 4 progressive disease (PD). Overall, the median progression-free survival (PFS) was 4.9 months (95%CI: 3.4-16.2 months). The ORR of anthracycline-based, eribulin-based or gemcitabine-based regimens was 1/12, 2/6 and 2/6, respectively; and the median PFS was 7.7, 7.3 and 4.4 months, respectively. Waterfall plots showed notable tumor shrinkage of any degree in eribulin and gemcitabine-based regimens(3/6 and 2/6, respectively), while there were more patients presented with SD in anthracycline-based group(9/12). Common adverse reactions included myelosuppression, fatigue, anorexia, rash, pruritus, palpitate, hypothyroidism and hypertension. Conclusions: The combination regimen with chemotherapy, PD-1 inhibitor and anlotinib in the treatment of advanced DDLPS is effective and well tolerable. There are more responders in eribulin or gemcitabine-based regimens.

Analysis of fault coupling vibration and transmission characteristics of multistage gear transmission system

In multi-stage gear transmission system, the accident is often not caused by a single fault, but by coupling fault. The decoupling and identification of coupling faults has always been a hot topic. Through the analysis of frequency characteristics and transmission characteristics, this paper explored the correlation of coupling faults in multistage gear transmission system, and analyzed the coupling mechanism of faults. According to the fault test-bed, a 3D model was built to analyze the contact force and vibration characteristics of gears at all stages. STFT and waterfall diagram were used to analyze the coupling correlation characteristics of experimental signals under two single faults and coupling faults: fixed-axis gear crack and planetary gear wear. The contact force transfer function of all stages of gears to the box was built by using the system identification theory. The source of the fault characteristic frequency component was found through the transfer function, and the transmission characteristic of the fault was revealed. It can be seen from the results that the fault coupling is not the superposition of frequency characteristics. In the coupled signal, the frequency characteristic with the largest amplitude increase is not the fault gear itself, but the intermediate gear connected with them and affected by them. This phenomenon is often misled and misjudged in the analysis.

Experimental investigation of dynamic behavior of rotor system with a novel double layers flexible support tilting pad bearing

Among all kinds of journal bearings, the tilting pad bearing has the characteristics of high stability. In order to further reduce the vibration and improve the stability of rotor-bearing systems, a novel double layers flexible support tilting pad bearing (DL-FSTPB) is presented in this paper. The bearing utilizes two layers of springs, which have different functions. The offset springs control the swing angle of the tilting pad to ensure the formation of a convergent oil film, and the symmetrical springs are used to change the bearing stiffness coefficient, increase the bearing elasticity, and improve the ability to accommodate misalignment. Experiments were carried out to study the vibration characteristics of the rotor system. The results were analyzed using wavelet analysis of acceleration and displacement, waterfall plots, a wavelet analysis, a run-up process and shaft center orbits areas. The results show that the DL-FSTPB exhibits excellent vibration attenuation characteristics, which can effectively reduce the amplitude and the system vibration level.

Activity of combination trametinib/navitoclax in patients with RAS-mutated gynecologic (GYN) cancers in a Phase 1/2 study (LBA 12)

<b>Objectives:</b> Preclinical data suggest that concurrent MEK and BCLxL inhibition can be synergistic. Mechanistically, inhibition of RAS signaling upregulates BIM, "priming" cells for apoptosis with BCLxL inhibition. A Phase 1 trial of the MEK inhibitor trametinib with the BCLxL inhibitor navitoclax was conducted to establish the recommended phase 2 dose (RP2D) and activity in select <i>RAS</i>-mutated tumors. We report the activity of this combination in patients (pts) with <i>RAS</i>-mutated GYN cancers. <b>Methods:</b> Pts with <i>RAS</i>-mutated GYN cancers were enrolled at the Dana-Farber Cancer Institute and Massachusetts General Hospital. Pts had RECIST 1.1 measurable disease and had progressed after at least one prior line of systemic chemotherapy. Eligible pts had cancers with activating mutations affecting codons 12, 13, 61, or 146 in <i>KRAS</i> or <i>NRAS</i>. Pts received combination trametinib and navitoclax either in dose escalation (7 pts) or in a dose expansion (24 pts) at the RP2D of navitoclax 250mg days 1-28 and trametinib 2mg days 1-14, following a lead-in cycle of navitoclax 150mg days 1-7 and 250mg days 8-28 with trametinib 2mg days 1-14 in 28-day cycles. <b>Results:</b> Between 1-22-2015 and 9-21-2021, 31 pts with GYN cancers (15 ovarian, 10 endometrial, 5 cervical, 1 mullerian) were enrolled. Data cutoff was 11-1-2021. Median follow-up is 4.9 mos. The median number of prior lines was 3 (range 1-7). Overall, 6 pts (19.4%; CI 7.5-37.5%) had a confirmed response. These included 3 ovarian cancers (1 low grade serous, 1 mucinous, 1 endometrioid), 1 endometrial (adenocarcinoma NOS), 1 cervical (mixed adenocarcinoma and neuroendocrine tumor), and 1 mullerian cancer (endometrioid). 9 pts stopped treatment before their disease was re-evaluated, and 1 pt's post baseline scan was deemed nonevaluable. Among 21 pts with at least one evaluable restaging scan, the response rate was 28.6% (95% CI 11.3-52.2%). Figure 1 shows the waterfall plot of best responses in these 21 pts. Median PFS time was 3.9 mos (95% CI 3.7-13.4) and 6-mo PFS was 37.7% (95% CI 17.5-57.9). In the 6 pts with response, the median duration for response was 9.5 mos (range 3.9-27.6). The most frequently observed adverse events included LFT changes, thrombocytopenia, diarrhea, nausea, and rash. <b>Conclusions:</b> Combined MEK and BCLxL inhibition with trametinib and navitoclax had clinical activity in pts with <i>RAS</i>-mutated GYN cancers, with a response rate in all pts of 19.4%. Among pts with at least one evaluable reassessment, the response rate was 28.6%. Further studies of combined MEK and BCLxL inhibition in pts with RAS-activated GYN cancers are warranted.Fig. 1

A Phase Ib Dose-finding Study of Panobinostat and Ruxolitinib in Myelofibrosis.

A Phase Ib Dose-finding Study of Panobinostat and Ruxolitinib in Myelofibrosis.

Lateral Decubitus Position Enables Further Advancement of the Bronchoscope into the Lung Periphery.

Lateral Decubitus Position Enables Further Advancement of the Bronchoscope into the Lung Periphery.

Nonlinear dynamics of the rotor system with a floating raft isolation structure under the coupled motion of ship heaving and rolling

A floating raft isolation structure is adopted to reduce the vibration of the marine rotor-bearing system, however, the system on the moving hull will be affected by the ship implicate motion, and its vibration will be difficult to predict. In this study, a dynamic model of the system under heaving and rolling coupled motion is established after considering the nonlinear oil film reaction force, unbalance inertia force, restoring force of the structure and inertia force of the ship motion. A numerical method is introduced to present the responses of the system, such as the amplitude and rotating speed curve, waterfall diagrams, and the rotor orbit and its Poincaré maps, etc. Moreover, the effects of rotating speed, amplitudes and frequencies of the coupled motion on the dynamic behaviours of the system are studied. The results indicate that the unstable region of rotating speed of the system increases under the coupled motion, the vibration of the system is greatly affected by the parameters of coupled motion, and the vibration amplitudes of rotor and raft can be effectively limited due to the displacement restrictor.

New technique for determining a pulsar period: Waterfall principal component analysis

Aims. This paper describes a new technique for determining the optimal period of a pulsar and consequently its light curve. Methods. The implemented technique makes use of the principal component analysis (PCA) applied to the so-called waterfall diagram, which is a bidimensional representation of the acquired data of the pulsar. In this context, we have developed the python package pywpf to easily retrieve the period with the presented method. Results. We applied this technique to sets of data of the brightest pulsars in visible light that we obtained with the fast photon counter Iqueye. Our results are compared with those obtained by different and more classical analyses (e.g., epoch folding), showing that the periods so determined agree within the errors, and that the errors associated with the waterfall-PCA folding technique are slightly smaller than those obtained by the x2 epoch-folding technique. We also simulated extremely noisy situations, showing that by means of a new merit function associated with the waterfall-PCA folding, it is possible to become more confident about the determined period with respect to the x2 epoch-folding technique.

Abstract 327: Antitumor efficacy of trastuzumab deruxtecan in combination with adavosertib in HER2-expressing Cyclin E amplified gastroesophageal cancers

Abstract Purpose: Trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody-drug conjugate approved for patients with HER2-positive gastric/gastroesophageal junction (GEJ) cancers. Amplification of CCNE1, which encodes cyclin E, has been proposed as a mechanism of resistance to HER2-targeted therapies. The Wee1 kinase inhibitor adavosertib (AZD1775) has demonstrated enhanced antitumor activity in the setting of cyclin E overexpression. We investigated the efficacy of T-DXd in combination with adavosertib in HER2-expressing cancers with and without co-amplification of CCNE1. Methods: Frequency of CCNE1 amplification was determined among patients with ERBB2 amplification in a clinical genomic database at the MD Anderson Cancer Center (MDACC) and within The Cancer Genome Atlas (TCGA). Sulforhodamine B assay, western blotting, and Annexin V staining were used to determine the effects of T-DXd and DXd in combination with adavosertib in vitro. Four HER2-expressing gastric/GEJ patient-derived xenograft (PDX) models with or without co-amplification of CCNE1 were tested with T-DXd in combination with adavosertib in vivo. Tumor volume and body weights were measured twice weekly and treatment responses were assessed by the relative treatment-to-control ratio, waterfall plots, and event-free survival (event defined as the day which tumors doubled in size from baseline). Results: Of 515 patients identified at MDACC with ERBB2 amplification, 60 (11.6%) had co-amplification of CCNE1. Of the 405 patients identified within the TCGA with ERBB2 amplification, 43 (10.6%) had co-amplification of CCNE1. Tumor types with the highest frequency of ERBB2/CCNE1 co-amplification were gastric/GEJ (38.1% MDACC, 31.0% TCGA), endometrial (25.0% MDACC, 29.6% TCGA), and ovarian (15.4% MDACC, 15.4% TCGA). Adavosertib was synergistic in combination with DXd in four cell lines with ERBB2 amplification, CCNE1 amplification, or ERBB2/CCNE1 co-amplification. Both DXd and T-DXd upregulated cyclin E and γH2AX protein expression at 24 and 96 hours, and the combination of DXd or T-DXd with adavosertib enhanced apoptosis. T-DXd induced durable tumor regression in two HER2 amplified and HER2 overexpressing gastroesophageal PDX cancer models with HER2 amplification/3+ overexpression and concomitant cyclin E amplification/expression. Adavosertib enhanced the antitumor activity of T-DXd in two HER2 low, cyclin E amplified gastroesophageal cancer PDX models (one with an ERBB2 G778A mutation). Conclusions: ERBB2 and CCNE1 are frequently co-amplified. Our findings provide supporting rationale for combining T-DXd with adavosertib in HER2-expressing cancers with CCNE1 co-amplification. Further study is needed to determine if therapeutic induction of cyclin E with DXd may sensitize to Wee1 kinase inhibition in patients without cyclin E amplification as well. Citation Format: Timothy P. DiPeri, Kurt W. Evans, Gabriela Raso, Yasmeen Q. Rizvi, Xiaofeng Zheng, Bryce Kirby, Kathleen Kong, Khandan Keyomarsi, Jaffer A. Ajani, Timothy A. Yap, Funda Meric-Bernstam. Antitumor efficacy of trastuzumab deruxtecan in combination with adavosertib in HER2-expressing Cyclin E amplified gastroesophageal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 327.

OD PĘCZKA KOMÓREK SŁUCHOWYCH DO BŁONY BĘBENKOWEJ

BackgroundAn earlier oscillator model for the generation of spontaneous otoacoustic emissions (SOAEs) from the lizard ear is extended with a connection of the oscillators to the basilar papilla, to make it possible that these SOAEs can be transported to the tympanic membrane, to be emitted.Material and methodsThe generators of spontaneous otoacoustic emissions are modelled as a one-dimensional array of Hopf-resonators. The resonators (or oscillators) are coupled to their neighbours, and to the basilar papilla. The papilla is modelled as a rigid structure, that is flexibly connected to its surroundings.ResultsFrequency spectra are given for different sets of coupling parameters, both for nearest neighbour coupling of the oscillators, and for coupling to the papilla, and also after the introduction of irregularities in the damping of the oscillators. Waterfall and density plots show clustering of the oscillators in frequency plateaus, and entrainment of a cluster of oscillators by an externally applied sinusoidal force. All these model outcomes correspond with characteristics of SOAEs emitted by real lizard ears.ConclusionsThe present model is a useful extension of an earlier model. Because its characteristics differ from that of a model that is used to describe the generation of SOAEs by mammalian ears, it revives the discussion whether different models are needed for SOAE generation in different animal species.

Long-term efficacy and safety of anlotinib in advanced sarcomas.

e23564 Background: Treatment of sarcomas has advanced in recent years partly because of the application of multitarget tyrosine kinase inhibitor (TKI) drugs. Anlotinib is an oral TKI with the dual effects of antiproliferation and antiangiogenesis, and it has a therapeutic effect with good tolerance and low side effects. In theory, physicians can gain long-term tumor control with anlotinib in certain advanced sarcomas. Methods: We conducted a retrospective analysis of patients with advanced sarcomas with measurable target lesions who had been treated in our ward since 2018. There were 22 patients who had taken anlotinib regularly for more than 12 months. Their general information, clinical efficacy, and toxicities were statistically analyzed. We used a swimmer plot to observe the efficacy and duration of the drugs and a waterfall plot to express the best treatment effect. Results: There were 14 male and 8 female patients, ranging in age from 14 to 75 (44.77 on average) years. The primary sarcomas were ASPS in five cases; synovial sarcoma (SS) in four cases; LMS in three cases; epithelioid sarcoma (ES) and UPS in two cases each; and clear cell sarcoma, RMS, angiosarcoma (AS), fibrosarcoma (FS), pleomorphic liposarcoma (LS), and osteosarcoma (OS) in one case each. The sites of metastasis were the lung in 15 cases, lymph nodes in 4 cases, and multiple sites in 3 cases. Therapies were as follows: first-line therapy (6 cases), second-line therapy (9 cases), third-line therapy (5 cases), and more than third-line therapy (2 cases). The current therapy protocols were nine cases with oral anlotinib alone, nine cases with combination chemotherapy, and four cases with combination immunotherapy (anti-PD1). The best clinical efficacy of this group was complete response (CR) in four cases (18.18%), partial response (PR) in five cases (22.73%), and stable disease in 13 cases (59.09%), with an overall response rate of 40.91% and the longest lasting time of 26, 16, 38 months in different response groups. The mean of progression-free survival (PFS) was 23.32 months. The main adverse effects included myelosuppression in seven cases (31.82%), hypertension in three cases (13.64%), and hand-foot syndrome and weakness in two cases (9.10%). Severe adverse effects included hypothyroidism with weakness in one case and wound ulceration with pneumothorax formation in another case. Conclusions: Anlotinib monotherapy or combination therapy can be an effective and safe choice for some advanced sarcomas with a longer maintenance time and acceptable side effects. Besides, anlotinib combined with anti-PD1 therapy has better therapeutic efficacy for specific diseases such as ASPS and ES. Anlotinib combined with chemotherapy has therapeutic efficacy for SS, LMS, FS, and RMS. Clinical efficacy such as CR and PR may be a prediction of long-term PFS in some advanced sarcomas.

Long-Term Efficacy and Safety of Anlotinib as a Monotherapy and Combined Therapy for Advanced Sarcoma.

ObjectiveTo analyze the effectiveness of the long-term (> 12 months) administration of anlotinib as a monotherapy or combined therapy in patients with advanced sarcomas.MethodsA retrospective analysis was conducted of patients with advanced sarcomas with measurable target lesions since 2018. Twenty-two of the patients had taken anlotinib regularly for > 12 months. The patients’ general information and the drug’s clinical efficacy and toxicity data were collected and statistically analyzed using RECIST 1.1 to measure the target lesions and tumor PFS time as the main endpoints. We used a swimmer plot to observe the drug’s efficacy and duration, and employed a waterfall plot to express the best treatment effect.ResultsThe study included 14 male and 8 female patients, ranging in age from 14 to 75 (mean: 44.82) years. The primary diseases included alveolar soft part sarcoma, synovial sarcoma, leiomyosarcoma, and others. The metastasis sites were the lungs in fifteen cases, lymph nodes in four cases, and multiple sites in three cases. Fourteen patients had previously undergone chemotherapy. The current therapy protocol was oral anlotinib alone for nine cases, combination chemotherapy for nine cases, and combination immunotherapy (anti-PD-1) for four cases. The highest clinical efficacy was complete remission (CR) in four (18.18%) cases, partial response (PR) in five (22.73%) cases, and stable disease in 13 (59.09%) cases, with an odds ratio of response of 40.91%. The mean PFS for the CR, PR, and stable disease groups was 16.50, 14.50, and 29.31 months, respectively (p < 0.05). The main adverse effects included hand-foot syndrome, hypertension, and leukopenia.ConclusionAnlotinib monotherapy or combination therapy can be more effective and safer for certain advanced sarcomas, with more extended maintenance and acceptable side effects. Clinical efficacy at the CR and PR levels might predict the long-term PFS in certain advanced sarcomas.

Experimental Investigation of Low-Frequency Distributed Acoustic Strain-Rate Responses to Propagating Fractures

Summary Low-frequency distributed acoustic sensing (LF-DAS) responds to strain changes due to far-field fracture propagation. To better understand the LF-DAS response to fracture propagation, we performed laboratory-scale hydraulic fracture experiments with embedded optical strain sensors. The objectives of this research are to generate hydraulic fractures of known geometry, measure the strain response along the embedded fiber-optic cable comparable to LF-DAS measurements, and use the results to inform the interpretation of field-derived LF-DAS data. The experiments were conducted in unconfined transparent cubic blocks with a dimension of 8 in. on each side. The block was made of transparent epoxy to visualize the fracture propagation. Fiber-optic sensing cables were embedded in the block at different distances to the source of injection. We injected dyed water through an injection tubing to generate a transverse, radial fracture along an initial flaw. An optical interrogator recorded the response of offset fiber Bragg grating (FBG) strain sensors normal to the plane of the fracture. The strain data were visualized on a waterfall plot, akin to visualizations of field-derived LF-DAS data. Dimensional analysis was used to scale the laboratory results to field conditions. We compared the evolution of the strain response at the fiber-optic cable, injection pressure, and rate with known fracture geometry. The measured strains were compared with Sneddon’s (1946) linear elastic solution for a penny-shaped crack and found to follow this behavior. The generated radial fractures in transparent media can be modeled with Sneddon’s linear elastic radial fracture model and a Mode I critical stress intensity factor. The LF-DAS characteristic response of a narrowing region of extension surrounded by compression was exhibited as a fracture that approached and intersected the fiber-optic cable. The experimentally derived strain and strain-rate waterfall plots with known fracture geometry, injection rate, and pressure response provide insight in understanding LF-DAS responses in the field. Furthermore, we developed a method to estimate fracture geometry evolution from the fiber-optic strain data and validated the method against the experimental data.

Clinical and molecular characteristics of acute myeloid leukemia with MPL mutation

ABSTRACT Objectives The current study aimed to explore the incidence of MPL mutations and the clinical and molecular characteristics of AML with MPL mutation. Methods In total, 1509 patients with newly diagnosed AML were retrospectively analyzed between January 2017 and December 2020. MPL mutations were detected via next-generation sequencing. During the same period, we also enrolled 30 patients with other myeloid neoplasms (MNs) with MPL mutation, which included myelodysplastic syndrome (n = 15), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) (n = 6), and MPN (n = 9). The clinical characteristics of MPL-mutated AML and other types of MNs or MPL-wide type (MPL-wt) AML were compared, and the spectrum of co-mutations and MPL mutation profiles in MPL-mutated AML were analyzed. Results MPL mutations were identified in 19 (1.26%) of 1509 patients with AML. The waterfall diagram showed that the co-mutations were mainly epigenetic modifications (TET2, IDH1, and EZH2), spliceosomes (SRSF2), and transcription factors (RUNX1). The platelet count of the AML group was significantly lower than that of the MPN group (p = 0.001). MPL mutations were commonly observed in the intracellular region in AML but the transmembrane region in MPN (p = 0.013). The MPL-mutated AML group had a lower white blood cell count and a lower rate of complete remission than the MPL wild-type AML group (p = 0.037). Conclusion MPL mutations are clinically relevant in patients with AML, and they may be a novel subtype characterized by lower white blood cell counts and poor complete remission rates. However, further studies must be conducted to identify its correlated mechanism.