PD Measurements Research Articles

Periodontal disease indicators in adults with and without physical activity: a comparative analysis

Introduction: The intriguing link between periodontal disease severity and physical activity remains largely understudied, particularly in the Saudi Arabian population. Thus, the current research was intended to ascertain the effect of physical activity on the prevalence and indicators of periodontal diseases. Materials: The cross-sectional approach with convenience sampling was applied to the recruitment of 160 adult subjects attending gymnasiums, sports clubs, malls, primary health centres, and community dental health programs. Based on IPAQ scores, the participants were split into two distinct groups: a physically active group and a physically inactive group. The two study groups were compared with one another in terms of recorded parameters. The gathered data subsequently underwent statistical processing using SPSS 20.0. Results: Of the 160 subjects, 66.87% (n = 107) had gingivitis and 33.12% (n = 53) periodontitis. A lower mean PI (1.62±0.31) was observed in the physically active group compared to the physically inactive group (6.91±1.12). The physically active group had a mean BI of 19.01±4.53 and the inactive group 69.98±9.29. For physically active and inactive groups, mean PD measurements were 2.49±0.33 mm and 4.61±0.07 mm, respectively.Physically active individuals had a significantly lower mean CAL (2.98±0.88 mm) compared to the inactive group (5.37±1.02 mm). Parametric variances between groups are statistically significant (p<0.001). Conclusion: Insufficient engagement in physical activity has undeniably been identified as a risk factor for the development and severity of periodontal disease, marked by escalated indicators of gingivitis and periodontitis. The study findings unequivocally endorse the adoption of a consistent physical activity regimen as strategic initiatives to proactively address the incidence of inflammatory periodontal diseases. Many patients with different psychophysical characteristics seek periodontal therapy at dental clinics. This study alerts clinicians to the impact of physical inactivity in a wide-spectrum population and helps identify periodontal risk in sedentary patients. It also aids in treatment planning for these periodontally risky, physically inactive people. Bangladesh Journal of Medical Science Vol.23 (Special Issue) 2024 p.S20-S25

The long-term effects of topical latanoprost 0.005% treatment on pupillary functions: A 2-year longitudinal study.

To investigate the long-term effects of topical latanoprost 0.005% treatment on pupillary functions in early-stage primary open-angle glaucoma (POAG) eyes using automated pupillometry. This prospective study involved 20 eyes of 20 treatment-naive subjects with early-stage POAG. After comprehensive ophthalmic examination, static and dynamic pupillometry measurements were performedbefore treatment, at the 1st follow-up visit (1.10 ± 0.30 months) and the 2nd follow-up visit (25.85 ± 10.26 months) after treatment initiation. Dynamic parameters included resting diameter (mm), amplitude (mm), latency (ms), duration (ms), and velocity (mm/s) of pupil contraction and dilation. Static pupillometry parameters were pupil diameter (PD, mm) in high-photopic, low-photopic, mesopic and scotopic conditions. The velocity of pupil dilation significantly decreased during the 1st visit (p = 0.008) and the 2nd visit (p = 0.0003) of treatment compared to the pre-treatment visit. The resting PD was also significantly higher after the 1st visit (p = 0.003) and the 2nd visit (p = 0.001) compared to the pre-treatment visit. However, the difference in resting PD measured between the 1st and 2nd visits did not reach statistical significance (p = 0.065). There were no significant changes in other dynamic parameters (p > 0.05 for all). Additionally, a mild, but not significant, mydriatic effect was observed in PD measurements under scotopic, mesopic and low photopic lighting conditions after follow-up. None of the static and dynamic parameters correlate with age, changes in intraocular pressure (IOP) or mean deviation (MD) values of visual field tests. The long-term topical latanoprost 0.005% treatment in early-stage POAG has a slight mydriatic effect on the pupil. Further longitudinal clinical studies with larger patient cohorts are necessary to better understand the effects of latanoprost on pupillary functions.

Experimental analysis of ageing of a dry transformer: comparison of two methods for PD measurements

Experimental analysis of ageing of a dry transformer: comparison of two methods for PD measurements

Evaluation Study on Wavelet Denoising of Antenna-based PD Measurements in Strong Interference Environments considering a New Reliability Score of Pulse Detection

Evaluation Study on Wavelet Denoising of Antenna-based PD Measurements in Strong Interference Environments considering a New Reliability Score of Pulse Detection

Abstract B159: A first-in-human study of CDK9 inhibitor KB-0742 demonstrates evidence of tolerability and clinical activity

Abstract Background: Cyclin-dependent kinase 9 (CDK9) is a transcriptional regulator that mediates expression and downstream activity of oncogenic transcription factors (TFs) including MYC and chimeric TFs. Inhibiting CDK9 presents a promising approach to treat transcriptionally addicted cancers. KB-0742 is a potent, selective, orally bioavailable inhibitor of CDK9 that is currently being studied in a phase 1/2 dose escalation in solid tumors and NHL and cohort expansion for patients with transcription-dependent tumors (NCT04718675). Methods: KB-0742 is administered orally once daily for 3 consecutive days with 4 days off, weekly, in 28-day cycles until toxicity or disease progression. Eligibility criteria include age > 18 years, relapsed or refractory solid tumors or NHL, acceptable organ function and ECOG PS < 2. Study objectives include evaluation of safety, tolerability, PK, PD, and identification of KB-0742 MTD and RP2D using a modified Continuous Reassessment Method (mCRM). PK was measured from patient plasma and PD was assessed in peripheral blood mononuclear cells (PBMCs). PD measurements included analysis of phosphorylation of the CDK9 substrate serine 2 of the RNA Polymerase II C-terminal domain (pSER2), and changes in gene expression of prospectively defined CDK9 responsive genes. Results: As of 1 June 2023, 28 patients enrolled in dose escalation up to 60 mg. Patients had received a median of 4 (2-11) prior lines of therapy and remained on KB-0742 for a median of 86 days (10-311+). Twelve of 28 patients received at least 4 cycles of KB-0742. The most common tumor types enrolled were colorectal (5), chordoma (4), sarcoma (4), and breast (3). Treatment-emergent adverse events (TEAEs) occurring in >20% of patients included nausea, vomiting, anemia, fatigue, nervous system disorders, and peripheral edema. The most common reasons for treatment discontinuation were progressive disease, TEAEs, and withdrawal of consent. Across 4 dose levels, AUC and Cmax of KB-0742 increased linearly with a terminal half-life of 24 hours. At 60 mg, evidence of target engagement was observed by pSER2 reduction and proportional changes to CDK9 responsive genes. In the escalation phase 60 mg cohort, three patients, (2 colorectal and 1 PTCL) had MYC over-expressing tumors and achieved SD. Of the two patients with myxoid liposarcoma, both exhibited radiographic regression of their target lesions. One patient achieved 26% reduction in the sum of partial diameters lasting > 5 mos. The second patient achieved a RECIST 1.1 partial response and remains on treatment at > 12 mos. Consistent with the therapeutic hypothesis, both patients had TF fusions. Conclusions: KB-0742 treatment was well tolerated with manageable toxicity and no evidence of neutropenia. CDK9 inhibition was observed at the 60 mg dose level, and expansion cohorts in tumor types with a high prevalence of MYC amplification or overexpression and other transcriptionally addicted tumors are accruing. The MTD has not been reached and further dose escalation is continuing. Citation Format: Miguel Villalona-Calero, Monica Mita, Alain Mita, Noah Federman, Drew Rasco, David Spigel, Jia Luo, Glenn J Hanna, Gregory M Cote, Richard E Cutler, Pavan Kumar, Crystal MacKenzie, Charles Lin, Jorge F DiMartino, Elizabeth A Olek, Brian Van Tine. A first-in-human study of CDK9 inhibitor KB-0742 demonstrates evidence of tolerability and clinical activity [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B159.

Abstract 13963: Redefining the Assessment of “Therapeutic” Platelet Response to Acetylsalicylic Acid

Background: Despite extensive investigations, the optimal assessment of the “therapeutic response” to acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between serum thromboxane (Tx)B 2 ; arachidonic acid (AA)-induced platelet aggregation (PA) by light transmittance aggregometry (LTA); aspirin reaction units (ARU) by VerifyNow aspirin test (VN), and pharmacokinetics (PK). Methods: Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy volunteers. ASA response was defined as >95% inhibition of serum TxB 2, <550 ARU by VN test and ≤20% AA-induced PA. Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. Results: ASA Response measured by VN, and AA-induced PA was achieved within 30 minutes of ASA administration. A good correlation was observed between VN ARU and 1 mM AA-induced maximum PA (r=0.80, p<0.001), serum TxB 2 (r=0.76, p<0.001), and inhibition of serum TxB 2 (r=0.87, p<0.001). The relation between platelet aggregation and TxB 2 inhibition appears to be dichotomous, with only modest inhibition of TxB 2 (~50% inhibition) associated with marked inhibition of platelet aggregation. ROC curve analyses indicated that ≤558 ARU and ≤7% AA-induced PA were associated with >95% inhibition of TxB 2 . A plasma ASA 686 ng/mL cut-off was associated with >95% inhibition of serum TxB 2 , ≤7% 1 mM AA-induced PA by LTA, and ≤585 ARU. Conclusion: Our study demonstrated an important relationship between PD and PK parameters measured immediately following oral ASA and cutoff values for VN assay and LTA that is associated with >95% inhibition of serum TxB 2 . We demonstrated that ~50% inhibition of TxB 2 is required to reach high levels of platelet function inhibition.

The effect of virtual simulation technology applied to undergraduate teaching of periodontal probing.

The rise of virtual simulation technology and dental simulators has created a new pedagogical approach for undergraduate medical education. The purpose of this study is to evaluate the effect of virtual simulation (VS) technology on improving the students' comprehensive abilities in periodontal probing teaching in pre-practicum periodontology, such as increasing the accuracy of probing, tactile perception and performance on force control. Twenty students were randomly selected among the fourth-year students and equally divided into VS technology teaching group (VS group) and traditional teaching group (TT group) by drawing half lots. One day later, students were required to probe the periodontal pathology model. The consistency rate between PD measurements and PD reference values, time consumption and final exam scores were recorded and statistically analysed using an unpaired Student's t test and p < .05 was considered statistical significance. Finally, questionnaires relating to teaching methods evaluation and the fidelity of the digital VS training system were distributed to students and teachers. VS group had a significantly higher consistency rate (72.976 ± 6.811%) than TT group (64.107 ± 4.988%, p = .004). To specify, the difference of consistency rates between the two groups in posterior teeth was larger than anterior teeth. Similarly, a larger difference was also found in proximal surfaces compared with buccal-lingual surfaces. As the pocket depth increased, the difference between the two groups increased too. These results indicated that VS is more efficient in complicated parts of periodontal probing teaching. In addition, students in VS group spent less time and gained a higher score than TT group (p < .05). The overall satisfaction rating in VS group was significantly higher than TT group. Lastly, teachers gave significant lower scores than students concerning the fidelity of VS system. Although there are much to improve, VS technology has obvious advantages in periodontal probing teaching in pre-practicum periodontology.

Partial Discharge Measurement of GIS With Damped AC (DAC) Voltage: Case Study for the Particle on Insulator

Off-line PD measurement is important for GIS. Interference signal generated by frequency-tuned resonant test set has a huge impact on PD measurement. Damped alternating current (DAC) voltage has been widely used in field testing of power cable and has no power interference. Whether the DAC can be used for PD testing of GIS still needs to be studied. The particle on insulator can greatly reduce the dielectric strength compared to clean condition, which is a very destructive defect. In this paper, the PDIV of AC and DAC were measured, the number of discharges per cycle was counted, and the PRPD pattern was obtained. For the defect model we set up, test results show that PDIV is independent of waveform and frequency; PD distribution area and the number of PDs per cycle increase with frequency. This is because SF <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sub> gap needs to recover its dielectric strength after discharge. When the recovery time and discharge interval are on the same order, it's possible to excite PD at a lower voltage, thereby increasing the number of PDs in each cycle. DAC is effective for detecting the defect of particle on insulator in GIS, and the PD activity of DAC is more obvious.

Abstract 855: Model-informed drug design (MIDD) exploration of a theoretical CD47xTAA bispecific antibody using available data from magrolimab, an anti-CD47 monoclonal antibody

Abstract Purpose: The goal of this study is to outline the process and utility of using fit-for-purpose, semi-mechanistic PK/PD modeling to inform the design of a theoretical CD47 bispecific antibody targeted to a generic tumor-associated antigen (CD47xTAA bsAb) with improved efficacy, tolerability, and PK compared to single target anti-CD47 therapies. Approach: To help guide the CD47xTAA bsAb design, a 3-compartment human model was built to include a target-mediated drug disposition (TMDD) component from CD47 expressed on red blood cells (RBC), white blood cells (WBC), and cells in the peripheral compartment. The model was parameterized using available literature data and calibrated against magrolimab human PK data that exhibited potential TMDD. The magrolimab model was used to identify key CD47 receptor occupancy (RO) thresholds associated with tolerability (the priming dose threshold) and efficacy (the recommended Phase 2 dose/RP2D threshold). Next, assumed drug properties and TAA expression levels for a CD47xTAA bsAb were implemented in a similar human model and drug PK and doses required to match key CD47 RO thresholds were explored across a range of single-arm binding affinities. Results: The calibrated magrolimab model projected target engagement levels on RBCs and WBCs and showed rapid antibody-induced CD47 pruning on RBCs that is consistent with clinical PD measurements. At TAA binding affinities that produce sufficient binding to tumor antigen, the model predicts that lowering the CD47 binding affinity allows for a higher starting dose that matches the priming threshold, while lowering the dose required to match the RP2D threshold. The model also shows that lowering the binding affinity to CD47 may improve PK exposure in the tumor compartment by reducing systemic CD47 TMDD. Conclusions: This modeling exercise demonstrates how semi-mechanistic PK/PD models can be used in model-informed drug design (MIDD) by leveraging the targeting advantage of avid bispecific antibody therapies and by using publicly available preclinical and clinical data. Furthermore, these model projections can help inform future studies with bispecific CD47 drug candidates. Citation Format: Emily A. Pace, Bjorn L. Millard. Model-informed drug design (MIDD) exploration of a theoretical CD47xTAA bispecific antibody using available data from magrolimab, an anti-CD47 monoclonal antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 855.

Multivariate Vocal Data Analysis with Deep Learning Applied for Parkinson Disease Detection

Different decision-making skills are used differently in the advancement of ML and DL techniques. In particular, it will probably be necessary to use ML and DL approaches for disease detection. The proposed effort uses acoustic-based DL approaches' ability to detect PD symptoms. This investigation also examines a number of motor metrics such as nonmotor PD measurements in this regard. Many DL approaches, including deep knowledge generation networks and recurrent networks, can be employed to identify this disease. Different decision-making capabilities are used differentially in the deployment of ML and DL methods. In particular, it will soon be necessary to use Machine learning and Deep Learning techniques for disease detection. The proposed effort uses acoustic-based DL approaches' ability to detect PD symptoms. This investigation also examines a number of motor metrics such as nonmotor PD measurements in this regard. Many DL approaches, including deep knowledge generation networks and recurrent networks, can be employed to identify this disease.

Machine Learning for Pharmacokinetic/Pharmacodynamic Modeling

A variety of new recurrent neural networks (RNNs) including the ODE-LSTM, Phased LSTM, CTGRU and GRU-D, were evaluated on modeling irregularly sampled PK/PD data with 6 or 12 time points/day and predicting PD data of unseen dosing regimens and dosing levels. The one-compartment absorption PK model and the Indirect PK/PD model I was used to simulate the PK/PD with inter-individual variabilities in volume of distribution and residual errors in PD measurement. The four RNNs were able to successfully model daily dose (QD) PK/PD and extrapolate to twice daily (BID) dose PD based on BID PK. The RNNs not only captured the additional fluctuations in the BID regimen but also the return phase to the baseline PD. However, extrapolating to unseen dose levels outside of the dose range for training proved to be challenging for all the RNNs tested. Only the GRUD demonstrated reasonable prediction results when extrapolating to unseen doses that were 3 or 10-fold outside the training doses. Overall, these new RNNs were able to overcome some limitations of previous RNNs evaluated and showed promise of integrating neural networks in PK/PD.

Partial Discharge Activity in Rotating Machine Type II Insulation Systems as a Function of Temperature and AC Supply Frequency

The main purpose of this study was to investigate if the application of very low frequencies for PD measurements in type II generator bar insulation is relevant when compared to applying power line frequency at different test temperatures. Laboratory experiments were performed on two stator bar types rated 6.4 kV and 7.4 kV, labeled as Group A and Group B. The stator bars were taken from service and spare part storage (pristine). The samples were preconditioned at the maximum test voltage of 1.5 <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">U</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> before sweeping the AC high voltage supply from 0.1 Hz and 50 Hz. The test temperature was varied between 20 °C and 155 °C. Investigation of cross sections of the generator bars was done to qualitatively describe the voids. The main results showed that the partial discharge inception voltage (PDIV) for Group A was temperature independent at 50 Hz and decreased by 40 % at 0.1 Hz with increased temperatures, whereas the PDIV for Group B was frequency independent and increased by 70 % with temperature. Similarly, the PD magnitude and total apparent charge decreased by 90 % for Group B with increased temperature, whereas it more than doubled for Group A with temperature. The tested bars from Group A showed significantly larger voids, located close to the copper conductors, compared to Group B, where voids were mainly located within the mainwall insulation. Results indicated that tests performed at 0.1 Hz cannot directly represent results obtained at 50 Hz. Using a wide range of frequencies and test temperatures broadens the understanding of the behavior of the voids inside the mainwall insulation.

Clinical evaluation of Laser-Assisted New Attachment Procedure® (LANAP®) surgical treatment of chronic periodontitis: a retrospective case series of 1-year results in 22 consecutive patients.

Treatment for periodontitis has evolved over the years as new technologies have become available. Currently, lasers seem attractive as a treatment modality, but their effectiveness needs to be verified. The purpose of this project was to evaluate Laser Assisted New Attachment Procedure® (LANAP®) surgery as a single treatment modality. As part of a mandatory training program for periodontists and other dentists, 22 consecutive patients diagnosed with moderate to severe periodontitis (probing depth [PD] up to 11 mm) were treated with the LANAP® surgical approach using a 1064-nm Nd:YAG laser as part of a multi-step protocol. Following single-session active therapy, they were entered into a maintenance program. Their clinical status was re-evaluated at 12-18 months following surgery. All 22 patients completed the 12- to 18-month follow-up. PD, clinical attachment level, and furcation (FURC) showed substantial improvement. Recession was minimal (mean, 0.1 mm), while 93.5% of PD measurements were 3 mm or less at re-evaluation. Furthermore, 40% of grade 2 FURC closed clinically. Within the limits of this case series, LANAP® was found to be an effective, minimally invasive, laser surgical therapy for moderate to advanced periodontitis.

Electrochemical corrosion behavior of tantalum coated 316L stainless steel by D.C. Magnetron sputtering for orthopedic applications

The austenitic stainless steel type 316L was engineered with a thin multilayer of tantalum with a thickness of 1.504µm, 3.893 µm and 6.083µm and a duration of 15, 30 and 60 minutes, respectively, by the DC Magnetron Sputtering. Electrochemical behaviors of all three samples were investigated by potentiodynamic and electrochemical impedance spectroscopy techniques. Simulated body fluid was used as the corrosive medium for the electrochemical measurement. The highest corrosion resistance was obtained for the sample subjected to 60 minutes of Ta deposited on 316L S.S. according to EIS measurements, and the lowest corrosion rate of 0.0047 mm/year was obtained for the same sample according to the PD measurements. All the measurements were carried out after the determination of open circuit potential (OCP) at 37˚C with 1 ±°C. All the samples were then characterized by scanning electron microscopy (SEM) to observe the morphology of coating after corrosion. The number of corrosion pits observed from the SEM micrograph was much less on the three coated samples compared to the bare sample. X-ray Photoelectron Spectroscopy (XPS) was used to identify the chemical states of coated and bare 316L SS. Ta4f is present as oxidation states in Ta coated stainless steel 316L, whereas Ta4f is the main species examined along with other elements (C1s, N1s, O1s, Cr2p, Fe2p, Ni2p, and Mo3d). It was also observed that there was strong adhesion between substrate and Ta-coating. After the potentiodynamic studies, results show a significant improvement in corrosion resistance attributed to the strong, stable oxide layer formation.

Breast cancer risk coordinators: Artificial intelligence-based density measurement and Mullerian-inhibiting substance.

Due to its increasing prevalence, breast cancer has become a serious public health problem. In addition to the models used to identify individuals at risk, the search for fast and accurate tools has continued for years. In our study, we aimed to examine the correlation of mammographic density measurement and serum Mullerian-inhibiting substance (MIS) levels with an effective model such as Gail. Of the women whose serum MIS levels were measured in the last 1year, 214 participants who applied for routine breast examination were included in the study. The age range was between 40 and 60. Exclusion criteria were determined as pathological mammographic findings, active breast symptom, and thoracic radiotherapy history. Mammographic density measurement (PD) was performed with the artificial intelligence-based Deep-LIBRA software. The relationship of these two parameters with the lifetime risk of developing breast cancer was examined. The correlation between PD and GRP was remarkable (p < 0.01cc:0.35). A positive correlation was observed between serum MIS levels and increased breast cancer, but it was not possible to prove this statistically (p = 0.056). It was thought that this situation was caused by perimenopausal patients. Because when the menopause group was excluded, the correlation between MIS levels and GRP decreased (p = 0.12cc:0.17). PD measurement can be considered as a promising method for the determination of individuals at risk for breast cancer in a large group of patients, but we think that serum MIS levels are not suitable for risk assessment in perimenopausal patients.

Medium and Low Voltage Cable Measurements - TD, PD, LIRA

Elmont d.o.o. Krško – We have spread our main scope of the services from electrical maintenance, modifications implementations and quality control to cable testing area. The main reason for expanding our scope was to support Nuclear Power Plant Krško Cable Aging Management program and the world trend of LTE (Life Time Extension) in power plants. Scope of work – We are identifying potential downgraded conditions for safety and operational important cables in special areas (heat, water, radiation). Our main scope is visual control, and testing with analysis. For low voltage cables the main testing method is Line Resonance Analysis (LIRA). LIRA technology is based on the transmission line theory, through the estimation and analysis of the complex line impedance as a function of the applied signal frequency. We can monitor the global, progressive degradation of the cable insulation due to harsh environment conditions (high temperature, humidity, radiation) and detect local degradation of the insulation material due to mechanical impacts or local abnormal environmental conditions. For medium voltage cables we are using new methods with a power generator that uses Very Low Frequency – 0,1Hz (VLF). The main reason for this is that the measurement unit needs 500 times less energy than the unit which uses 50Hz frequency (50/0,1=500). With this power source we are performing dielectric loss measurements – Tan delta (TD) and Partial discharge measurements (PD). TD measurements show the severity of Water treeing in the measured cable. Water trees mainly come from moisture and are therefore present in cables that lie in manholes filled with water or they submerged in any other way. PD measurements show the severity of voids or other types of defects in cable insulation. These defects can arise during the manufacturing of the cable or they can arise during the installation of the cable or from an accident with the cable during the operational time.

CaboMain: A phase 2 study of cabozantinib as a maintenance agent in patients with ultra-high risk pediatric solid tumors.

TPS10060 Background: Patients with relapsed or refractory pediatric solid tumors have one-year progression-free survival (PFS) &lt;25% even if a remission is achieved [1-9]. Maintenance treatments may extend survival for these patients but have not been tested. Many tyrosine kinase inhibitors (TKIs) target oncogenic pathways active in pediatric cancers and are being evaluated in children with cancer. The multitargeted TKI cabozantinib inhibits MET, VEGFR, AXL, RET, ROS1, KIT, TRKB, FLT3, and TIE2. Preclinical studies and clinical use suggest that cabozantinib may be active against childhood cancers [10-20]. A pediatric Phase 1 study defined a dose of 40 mg/m2/day[21], currently used in an ongoing pediatric Phase 2 study for measurable relapsed/refractory solid tumors, NCT02867592. However, cabozantinib has not been tested as a maintenance agent against cancers in children. We hypothesize that cabozantinib, in patients with ultra-high-risk pediatric solid tumors with minimal disease burden, can prevent recurrent tumor formation or induce a durable remission. Methods: Trial Design: Single arm, open-label, multisite investigator-initiated Phase 2 trial for patients with a “best response,” defined as no progression at least 28 days after end of prior therapy. Primary objective: Evaluate the effect of cabozantinib administered for up to 12 months on 1-year PFS. Statistical design and measure: Bayesian time-to-event optimal phase 2 design with a single interim analysis designed to detect 20% increase in PFS at 1 year with 80% power. Secondary objectives include 2- and 5-year PFS; 1-, 2-, and 5- year OS, duration of response, and safety and tolerability. Exploratory objectives include patient-reported outcomes, predictive biomarkers, PK and PD measurements. Treatment: Patients will take cabozantinib tablets on a continuous dosing schedule, partitioned into 28-day cycles, at an initial dose of 40 mg/m2/day (per dosing nomogram), for up to 365 days. Assessments are defined; radiographic assessment every 3 cycles. Dose modifications will be based on toxicities per protocol. Patients will continue on therapy until progression, toxicities not relieved by dose reduction, or end of planned therapy. Major eligibility criteria: Three strata: Neuroblastoma with residual disease at end of upfront therapy (“Best Response 1”, BR1) or after any relapse, n=36. Pediatric CNS tumors, defined in the protocol, n=30. Other pediatric solid tumors, as defined in the protocol, n=36. Patients must be ≥ 18 months and ≤40 years of age at enrollment, have completed prior therapy ≥ 4 weeks and ≤ 12 weeks prior to enrollment and demonstrate radiographic BR at time of enrollment. Measurable or evaluable disease is not required. Enrollment: Protocol is open to enrollment as of February 12, 2022. At time of abstract submission, we have not yet enrolled the first patient. Clinical trial information: NCT05135975.

Determination of the sub-picomolar concentration of dissolved palladium in open ocean seawater

Palladium, which is used in various fields, including automobile catalysis, is a precious metal with an extremely low content (0.4 μg/kg) in the earth's crust. Previous studies have suggested its release from anthropogenic sources into a wide range of environments, including aquatic environments. However, reliable analytical methods by which it can be quantified have not yet been established owing to its extremely low concentration in aquatic environments and the vulnerability of its measurements to interfering elements. Therefore, the aim of this study was to establish a highly sensitive and accurate analytical method for its quantification in open ocean seawater using isotope dilution-inductively coupled plasma mass spectrometry (ICP-MS) and thereafter, clarify its vertical distribution. To establish the analytical method, the effects of the concentrations and compositions of the cleaning solution and eluent used during the column pre-concentration process on the analysis were examined. Further, we applied the ammonia dynamic reaction cell (NH3 DRC) during ICP-MS measurements and also optimized the NH3 gas flow rate as well as rejection parameter, q (Rpq). The open ocean seawater samples were acidified to obtain 0.5 M HCl concentration followed by the addition of 105Pd isotope enriched spike solution. Thereafter, the samples were allowed to stand for 24 h before analysis. Solid-phase extraction of Pd in seawater was performed using an anion exchange resin (AG1-X8). To remove interfering elements, a cleaning method was employed. Specifically, cadmium, with the most significant effect on Pd measurements, was removed using HNO3 (> 0.5 M), while other interfering species, including strontium and zirconium were removed using either HCl or HNO3. The flow rate of the cleaning solution and the eluate were also optimized. Thus, a pre-concentration method with a Pd recovery rate of 89–95% was established. Furthermore, the isobaric interference caused by 90Zr16O+, which increased the procedural blank value of our analytical method and could not be completely removed during pre-concentration, was eliminated by employing NH3 DRC in the ICP-MS process, while that caused by 88Sr14N1H3+ was suppressed by setting the NH3 gas flow rate above 1.8 mL/min and the Rpq at 0.81. Thus, when 470 mL of open ocean seawater samples were analyzed under these conditions, the detection limit and blank value obtained were 0.060 and 0.050 pmol/L, respectively (both of which are lower than previously reported values). Additionally, an investigation of the vertical distribution of Pd in the North Pacific using the established methods revealed that Pd concentrations showed a tendency to decreased from 0.32 pmol/L at depth of 50 m to 0.10 pmol/L at a depth of 1500 m, and at depths below 2000 m, the concentrations varied in the range 0.10–0.13 pmol/L. Therefore, our established method showed sufficient suitability for the determination of the sub-picomolar concentration of Pd in open ocean seawater.

Measurements and Analysis of Partial Discharges at HVDC Voltage with AC Components

This paper presents the methodology for phase-resolved partial discharge measurements in HVDC systems with a DC voltage containing trace AC harmonics or a DC voltage ripple. The measurement result of partial discharges is an indicator of the current condition of the high-voltage power devices’ insulation system. The voltage waveforms in HVDC systems are not ideal DC, because different disturbances occurring naturally in these systems can affect the DC voltage. The AC harmonics related to the AC source voltage, and the voltage ripples provided by the power converter topology, can be found in the HVDC voltage. This paper proposes a novel approach to partial discharge measurement in DC networks. The synchronization to the particular AC harmonics appearing in DC voltage was applied to the PD measurements. The analyses were performed on the model sample containing a void inclusion, which was placed between electrodes fed by the DC voltages with the imposed chosen AC harmonics. Two scenarios were analyzed at a constant DC level: one with a variable AC magnitude and the second with a variable frequency of an AC source adjusted to the harmonics: 50, 150, 300, and 350 Hz. It was observed that the superimposed AC voltage component resulted in an intensification of PDs.

A Study of Cognitive Radio Sensing Techniques for Optimum Spectrum Utilization

Background: The spectrum scarcity plays a vital role in wireless communications. We are in the situation to use it through an efficient methodology. Objective: To identify the holes in the spectrum through an efficient spectrum sensing and to allocate the bands to the unlicensed users (Secondary Users- SU). Methods: It has been proposed to make a comparative study among the existing spectrum sensing methods based on the following parameters such as Probability detection (Pd) measurement, Algorithm, Decision fusion method, Network model. Results: Comparative study has been made to find the pros and cons of the existing techniques with their limitations and the field of application. CSS (Cooperative Spectrum Sensing) technique significantly consumes less energy and reporting time to FC (Fusion Centre) since it utilizes LLR (Log Likelihood Ratio) Method to find the Probability of detection using Chair-varshney rule in local sensing with parallel report approach in the cluster based network. Conclusion: Through the study and the comparison of parameters in literature, it is found that CSS provide better detection. Therefore, this technique can be considered as an efficient technique to find the holes and to share the frequency with SU’s.