Search

Parental attitudes towards children are one of the key categories of parenting. With the aim to investigate the attitude of mothers who have schizophrenia towards their children we used psychosemiotic approach and the procedure of biclustering. We hypothesized that there are statistically significant differences in semantic operational parameters between mothers suffering from schizophrenia or schizoaffective disorder, and a control group. 30 participants of the clinical group ― mothers of children 0–18 y.o (Age (years): M=39.3, SD=7.54; Duration of psychiatric observation (years): M=10.45, SD=7.84) suffering from schizophrenia and schizoaffective disorder were recruited from patients of the women’s ward of Moscow psychiatric hospital. 30 mothers of the control group were recruited according to the age of their children, similar to the age of the children’s age in the clinical group (Age: M=35.06, SD=4.97). Psychosemiotic analysis was applied to the texts of the semi-structured parental essay in the incomplete-sentence form (test “Рarental composition”). Statistical analysis confirmed the relevance of psychosemiotic parameters. The psychosemiotic analysis of the text with the procedure of biclustering showed that three of the lists of binary parameters: Opposition, Quality/Situation, Present/Future show regular combinations that differ in healthy and ill mothers, and the probability of accidental coincidences can be excluded. Combination “the absence of opposition, situatedness, the future time” was detected only in the texts of mothers of the clinical group. To our mind, it describes a weak parent who cannot withstand ambivalence and sees his child in the perspective of an abstract future.

The accumulators utilized in electric transport differ from those of other applications. Their main features are high capacity, minimum size and weight, and reasonable price. There is extensive research worldwide to improve the battery technology. The aim of the research is to create a mathematical model of an electric vehicle that can capture the vehicle speed curve as a data input to generate the consumed and recovered battery current, which can allow the battery parameters to be analysed and conclude whether the vehicle can perform the trip around the city route with the selected battery parameters. This model serves as a tool to simplify and speed up the necessary calculations and to examine individual sections of the route and their impact on the battery. To complete this task, a simplified electric transport mathematical model gives an opportunity to check if the selected battery can be used in the electrical public transport of the city. The input parameters of the model are the parameters of electrical transport. Simulation of the most popular types of batteries has been performed for two routes of buses in Jelgava in order to determine whether the chosen batteries can provide the necessary bus movement. The mathematical model has been developed in the MATLAB/Simulink software. A GPS mobile application SpeedTracker has been used for data logging.

Introduction: Our research is funded by RFBR and Moscow city Government according to the research project # 18-013-00921 A. According the results of our previous research, among 2592 patients under long-term follow-up observation only 62 had children 0-18 y.o. 80,7% of them lived with their children and were assessed by local psychiatrists as «good enough parents with assistance of family» (Kostjuk G., 2018). Objectives: To study parenting of persons under long-term followup psychiatrical observation. Methods: Analysis of medical records; clinical interview; semistructured interview, comprised of 75 open-ended questions regarding child's development and parent-child relationship; semi-structured interview, devoted to social risk factors. Results: In a sample, added by 4 cases (N=66), local psychiatrists assesses parenting competency of their patients as «high» in 39,4%, «good enough with assistance of family» in 31,8%, «not good» in 28,8%. On the base of the analysis of medical records 7 groups of parents were detected: ever were dangerous for their child (N=8, in 6 cases parental rights were restricted by the court); ever neglected their child (N=5); with formal attitude towards child (N=8); with inappropriate methods of upbringing (N=6); with difficulties in upbringing (N=4); «good» and «good enough» parents (N=26); no information available (N=9). The results of interviewing were compared between groups. «Bad» and «not good-enough» parenting was relevant to clinical factors: psychotic state, content of delusional ideas, non-compliance, deficit symptoms. «Goodenough parenting» was relevant to social support (corrected 2 = 6,33; p = 0,012). Conclusions: The results should be used in elaboration of preventive services and social support of such families and principals of legal assessment of parenting competency on the basis of adequate social support. Disclosure: The reported study was funded by RFBR and Moscow city Government according to the research project 18-013-00921. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated efficacy and safety of cabozantinib plus atezolizumab or cabozantinib alone in advanced NSCLC previously treated with an immune checkpoint inhibitor (ICI)., Methods: COSMIC-021 (NCT03170960) is a phase 1b, multicenter study in advanced solid tumors. This analysis included patients with stage IV non-squamous NSCLC without actionable genomic aberrations in EGFR, ALK, ROS1 , or BRAF - V600E who progressed on one prior ICI and less than or equal to two prior lines of systemic anticancer therapy. Patients received cabozantinib 40 mg orally/day plus atezolizumab 1200 mg intravenously every three weeks (combination cohort) or cabozantinib 60 mg orally/day (single-agent cabozantinib cohort). Primary end point of the combination cohort was objective response rate per Response Evaluation Criteria in Solid Tumors v1.1 by investigator. Outcomes in the single-agent cabozantinib cohort were exploratory., Results: Eighty-one patients assigned to combination therapy and 31 assigned to single-agent cabozantinib received greater than or equal to one dose of study treatment. Median (range) follow-up was 26.1 months (12.1-44.2) and 22.4 months (1.5-29.0), respectively. Objective response rate was 20% (95% confidence interval: 11.7%-30.1%) in combination cohort and 6% (95% confidence interval: 0.8%-21.4%) in single-agent cabozantinib cohort. Treatment-related adverse events (TRAEs) occurred in 86% of patients in the combination cohort and 90% in the single-agent cabozantinib cohort; grade 3/4 TRAEs were 44% and 48%, respectively. There were two grade 5 TRAEs: pneumonitis (n = 1, combination) and gastric ulcer hemorrhage (n = 1, single-agent). Neither PD-L1 expression in tumor cells nor tumor mutation burden correlated with outcomes., Conclusions: Cabozantinib plus atezolizumab demonstrated modest clinical activity and manageable toxicity in advanced NSCLC after progression on prior ICI., Competing Interests: Dr. Neal reported receiving honoraria from Biomedical Learning Institute CME, Clinical Care Options, CME Matter, Medscape CME, MJH Life Sciences CME, MLI Peerview CME, Prime Oncology CME, Projects in Knowledge CME, Research to Practice CME, Rockpointe CME, Medical Educator Consortium, HMP Education, a consulting or advisory role with AstraZeneca, Blueprint Pharmaceuticals, Calithera Biosciences, D2G Oncology, Exelixis, Genentech, Roche, Jounce Therapeutics, Eli Lilly and Company, Natera, Regeneron, Sanofi, Surface Oncology, Takeda Pharmaceuticals, Turning Point Therapeutics, and receiving institutional research funding from 10.13039/100006483AbbVie, Adaptimmune, Boehringer Ingelheim, 10.13039/100010544Exelixis, 10.13039/100004328Genentech, 10.13039/100004337Roche, GSK, 10.13039/100005565Janssen, 10.13039/100004334Merck, Nektar Therapeutics, 10.13039/100004336Novartis, Takeda Pharmaceuticals. Dr. Armando Santoro reported having a consulting or advisory role with Sanofi, Incyte, receiving honoraria from AbbVie, Amgen, ArQule, AstraZeneca, Bayer, BMS, Celgene, Eisai, Gilead Sciences, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Servier, Takeda, and participating in a data safety or advisory board with BMS, Servier, Gilead, Pfizer, Eisai, Bayer, MSD. Dr. Maria Gonzalez-Cao reported receiving grants or contracts from Roche, AstraZeneca, and Novartis, honoraria from Bristol Myers Squibb, MSD, AstraZeneca, Novartis, and Pierre Fabre, support for travel, accommodations, and expenses from MSD, AstraZeneca, and Pierre Fabre, and having a leadership or fiduciary role with the Spanish Melanoma Group. Dr. Ryan D. Gentzler reported receiving honoraria from Targeted Oncology, OncLive, Clinical Care Options, Society for Immunotherapy of Cancer, American Society of Clinical Oncology, MedStar Health, Aptitude Health, support for attending meetings from International Association for the Study of Lung Cancer, American Society of Clinical Oncology, Dava Oncology, Tempus, having a consulting or advisory role with AstraZeneca, Daiichi Sankyo, Gilead, Janssen, Jazz Pharmaceuticals, Mirati Therapeutics, OncoCyte, Sanofi, Takeda, Merus, Regeneron, receiving institutional research funding from 10.13039/100002429Amgen, Alliance Foundation, 10.13039/100004325AstraZeneca, Big Ten Research Consortium, 10.13039/100002491Bristol Myers Squibb, 10.13039/100010795Chugai, 10.13039/501100022274Daiichi Sankyo, 10.13039/100008130Helsinn Therapeutics, Hoosier Cancer Research Network, 10.13039/100005565Janssen, 10.13039/100016765Jounce Therapeutics, Merck, 10.13039/100016957Mirati Therapeutics, 10.13039/100004319Pfizer, 10.13039/100008199RTI International, Takeda, Dizal, Puma, and having leadership or committee roles with Hoosier Cancer Research Network, ASCO, Journal of Clinical Oncology, NCI Investigational Drug Steering Committee, and International Association for the Study of Lung Cancer. Dr. Jerome Goldschmidt reported receiving honoraria from G1 Therapeutics, and support for travel, accommodations, and expenses from Sara Cannon Research Institute. Dr. Claudia Proto reports receiving honoraria from AstraZeneca, Bristol Myers Squibb, MSD, Roche, Sanofi, having a consulting or advisory role with AstraZeneca, MSD and Roche, institutional research funding from MSD, Lilly, Pfizer, support for travel, accommodations, expenses from AstraZeneca, MSD, and Roche, and is the principal investigator in clinical trials for Janssen, Pfizer, Lilly, Spectrum Pharmaceuticals, Roche, MSD, BMS, and AstraZeneca. Dr. Shiven Patel reported receiving a consulting or advisory role with AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, Regeneron, Sanofi, TerSera Therapeutics LLC, Total Health Conferencing, Natera, Takeda, Merck, BMS, and receiving institutional research funding from AstraZeneca, Janssen, Merck, and Takeda. Dr. Sonam Puri reported having an institutional consulting or advisory role with Jazz Pharma, receiving consulting fees from G1 Therapeutics, Pfizer, Bristol-Myers Squibb, receiving honoraria from Aptitude Health, and support for travel, accommodations, and expenses from Dava Oncology. Dr. Stephen V. Liu reported having a consulting or advisory role with AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech, Roche, Gilead Sciences, Guardant Health, Janssen Oncology, Jazz Pharmaceuticals, Merck, Merus, Mirati, Novartis, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics, receiving institutional research funding from AbbVie, 10.13039/100018529Alkermes, Elevation Oncology, Ellipses, Genentech, Roche, 10.13039/100005564Gilead Sciences, Merck, Merus, Nuvalent, Inc., RAPT Therapeutics, and Turning Point Therapeutics, and participation in a data safety monitoring board or advisory board with Candel Therapeutics. Dr. Erminia Massarelli reported receiving honoraria from AstraZeneca, Merck, Eli Lilly and Company, Takeda Pharmaceuticals, Mirati, and having a consulting or advisory role with Bristol Myers Squibb, Daiichi Sankyo Co., Fusion Therapeutics, Janssen, Eli Lilly and Company, Sanofi, AbbVie, Iovance Therapeutics, and Mirati. Ms. Denise Williamson, Drs. Martin Schwickart, Christian Scheffold, and Svetlana Adrianova are employees of and reported having stock with Exelixis. In addition, Dr. Christian Scheffold reported a patent: Combinations of Cabozantinib and Atezolizumab to Treat Cancer; patent number 11198731. Dr. Enriqueta Felip reported having a consulting or advisory role with AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GlaxoSmithKline, Janssen, Merck Serono, MSD, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, Daiichi Sankyo, honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Peervoice, Pfizer, Sanofi, Takeda, Touch Oncology, and receiving support for travel, accommodations, and expenses from AstraZeneca, Janssen, Roche. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Background: Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for unresectable or metastatic HCC untreated with prior systemic therapy. We evaluated efficacy and safety of cabozantinib plus atezolizumab in aHCC previously untreated with systemic anticancer therapy or previously treated GC/GEJ., Methods: COSMIC-021 (ClinicalTrials.gov, NCT03170960) is an open-label, phase 1b study in solid tumours with a dose-escalation stage followed by tumour-specific expansion cohorts, including aHCC (cohort 14) and GC/GEJ (cohort 15). Eligible patients were aged ≥18 years with measurable locally advanced, metastatic, or recurrent disease per RECIST version 1.1. Patients received oral cabozantinib 40 mg daily and intravenous atezolizumab 1200 mg once every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate per RECIST version 1.1., Findings: Patients were screened between February 14, 2019, and May 7, 2020, and 61 (30 aHCC, 31 GC/GEJ) were enrolled and received at least one dose of study treatment. Median duration of follow-up was 31.2 months (IQR 28.5-32.7) for aHCC and 30.4 months (28.7-31.9) for GC/GEJ. Objective response rate was 13% (4/30, 95% CI 4-31) for aHCC and 0% (95% CI 0-11) for GC/GEJ. Six (20%) aHCC patients and three (10%) GC/GEJ patients had treatment-related adverse events resulting in discontinuation of either study drug., Interpretation: Cabozantinib plus atezolizumab had clinical activity with a manageable safety profile in aHCC previously untreated with systemic anticancer therapy. Clinical activity of cabozantinib plus atezolizumab was minimal in previously treated GC/GEJ., Funding: Exelixis, Inc., Alameda, CA, USA., Competing Interests: Daneng Li: Advisory/Consultancy: Adagene, AstraZeneca, Delcath, Eisai, Exelixis, Genentech, Ipsen, Merck, QED, TerSera Therapeutics; Honoraria: Coherus, Eisai, Exelixis, Ipsen, Servier, TerSera Therapeutics; Research Grant/Funding (institution): AstraZeneca, Brooklyn Immunotherapeutics; Travel Accommodations/Expenses: Genentech. Yohann Loriot: Honoraria: Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Gilead, Janssen, Merck KGaA, MSD (Merck Sharp & Dohme), Pfizer; Travel Accommodation/Expenses: Astellas Pharma, Bristol Myers Squibb, Janssen, Merck KGaA, MSD (Merck Sharp & Dohme), Pfizer, Roche. Adam Burgoyne: Advisory/Consultancy: Deciphera, Kuur Therapeutics; Research Funding (institution): AstraZeneca, Deciphera, Exelixis, Genentech, Hengrui, Merck, Natera; Speaker Bureau/Expert Testimony: AstraZeneca, Deciphera; Participation on Advisory Boards: Deciphera, Eisai, Exelixis, Genentech. James M Cleary: Honoraria: Syros Pharmaceuticals, Incyte, Blueprint Medicines; Research Grant/Funding (institution): Merus, Roche, Bristol Myers Squibb; Research Grant/Funding (self): Merck, AstraZeneca, Esperas Pharma, Bayer, Tesaro, Arcus Biosciences, Apexigen; Travel Accommodation/Expenses: Incyte. Armando Santoro: Advisory/Consultancy: Sanofi, Incyte; Honoraria: Takeda, BMS (Bristol-Myers-Squibb), Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Eli Lilly, Sandoz, Eisai, Novartis, Bayer, MSD (Merck Sharp & Dohme); Participation on a Data Safety Monitoring Board or Advisory Board: BMS (Bristol-Myers-Squibb), Servier, Gilead, Pfizer, Eisai, Bayer, MSD (Merck Sharp & Dohme). Daniel Lin: Advisory/Consultancy: Exelixis; Stock Ownership: Bionano Genomics. Santiago Ponce Aix: Honoraria: AstraZeneca; Patents, Royalties, or Other Intellectual Property: Pharmamar. Ignacio Garrido-Laguna: Advisory/Consultancy: Kanaph, Jazz Pharmaceuticals, OncoXerna; Participation on Data Safety Monitoring Board: SOTIO. Ramu Sudhagoni: employed by and have stock ownership in Exelixis. Svetlana Andrianova: Employment: Exelixis; Spouse Employment: InhibRx; Stock Ownership: Exelixis; Stock Ownership (spouse): InhibRx. Xiang Guo: employed by Exelixis; Patents Filed: Methods for determining responsiveness to TYK2 inhibitor; Stock Ownership: AbbVie, AstraZeneca, Exelixis, Pfizer. Scott Paulson: Advisory/Consultancy: Aadi, Advanced Accelerator Applications, Amgen, Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Eisai, Eli Lilly, EMD Serono, Exelixis, Hutchinson MediPharma, Incyte, Ipsen, Mirati Therapeutics, Pfizer, QED Therapeutics, Servier, Stromatis Pharma; Honoraria: Cardinal Health; Research Grant/Funding (institution): AstraZeneca, Bayer, BioNTech SE, Bristol Myers Squibb, Camurus, Deciphera, Exelixis, Eli Lilly, G1 Therapeutics, Gilead Sciences, Gritstone Bio, Hutchinson MediPharma, Incyte, Innovative Cellular Therapeutics Co, Ipsen, Merck, Nucana, Regenxbio, Relay Therapeutics, Seagen, Sotio, Taiho Pharmaceutical, Tempus, Zentalis; Stock or Stock Options: Actinium Pharmaceuticals, Aptose Biosciences, Alexion Pharmaceuticals, Lynx Health, Stromatis Pharma; Travel Accommodations/Expenses: Camurus, Pfizer., (© 2023 The Author(s).)

Experimental data on the pharmacokinetics, toxicity, antitumor activity of the antitumor drug diiodo-benzo-TEPA are reported.