Large-scale Transitions Research Articles

Pediatric Mental Healthcare Providers’ Perceptions of the Delivery of Partial Hospitalization and Outpatient Services via Telehealth during the COVID-19 Pandemic

ABSTRACT The COVID-19 pandemic has required healthcare providers to deliver services via telehealth. Unfortunately, many mental healthcare providers have not received direct training in telehealth delivery. Recent research suggests that this disconnect between the large-scale and rapid transition to telehealth service delivery required by the pandemic, combined with inadequate training or preparation time, may result in challenges to delivering quality clinical care. The current study presents results of an online questionnaire completed by 44 pediatric mental healthcare providers assessing provider perspectives of the experience of delivering services during the COVID-19 pandemic. Providers included psychiatrists, psychologists, social workers, licensed professional counselors, and direct-care staff. Services were delivered in three different partial hospitalization programs and in a general outpatient clinic at a children’s hospital associated with an academic medical center. Results showed moderate acceptability of telehealth, overall, and a clear preference for at least having a portion of visits be in-person as opposed to solely via telehealth. Provider satisfaction with telehealth delivery and perceptions of quality of clinical care appeared to differ among services. We discuss the implications of these data to inform healthcare settings delivering mental health services via telehealth.

Genomic characteristics of homologous recombination deficiency in prostate cancer.

e17004 Background: PARP inhibitors (PARPi) have been approved in the treatment of metastatic castration-resistant prostate cancer with deleterious or suspected deleterious alterations in homologous recombination repair (HRR) genes. Patients carrying alterations of different HRR genes showed diverse response to PARPi, while the underlying mechanism is unrevealed. Homologous recombination deficiency (HRD) score serves as a promising way to interpret the genomic instability by targeted next-generation sequencing (NGS). In this study, we analyzed HRD score and its relationship to genomic characteristics in a prostate cancer (PC) cohort. Methods: Tumor tissue and matched white blood cells from 295 PC patients were analyzed by NGS-based assays, which target over 10,000 single-nucleotide polymorphisms distributed across human genome to characterize genomic instability, as well as the whole coding region of 733 or 233 genes. HRD score was derived by the sum of three indexes, including loss-of-heterozygosity, telomeric allelic imbalance, and large-scale state transitions. Deleterious or suspected deleterious mutations were included for analysis. Tumor mutation burden (TMB) was calculated by the number of somatic single nucleotide variants and indels in examined coding regions, with driver mutations excluded. An ovarian and fallopian tube cancer cohort, carrying deleterious or suspected deleterious mutations in BRCA1/2, was also included. Results: In PC cohort, 25 patients (8.47%) had BRCA1/2 mutations, with additional 39 patients (13.2%) carrying mutations in HRR genes other than BRCA1/2. HRD score was similar among tumors with germline BRCA1/2 mutation (n = 9), somatic BRCA1/2 mutation (n = 14) or both (n = 2) (median HRD score 38.0, 32.5 and 49.5; P = 0.281). In BRCA1/2 mutation carriers, HRD score in PC cohort was lower than ovarian cancer (n = 222) and fallopian tube cancer (n = 8) (median HRD score 36, 54 and 67; P < 0.001). PC samples with CDK12 (n = 35), ATM (n = 13) and PALB2 (n = 2) mutations had lower HRD score compared with BRCA1/2 mutants (median HRD score 24, 14, 11 and 36; P < 0.001). In PC patients without HRR mutation, HRD score was higher in TP53 mutants compared with TP53 wildtype (median HRD score 25 and 14; P < 0.001), while tumors with ERG fusion had lower HRD score than ERG fusion absent tumors (median HRD score 8 and 18.5; P = 0.029). In four TP53 mutated PC patients treated with PARPi in our center, three patients achieved PSA response. Furthermore, no linear correlation was discovered between TMB and HRD score, while tumors with higher HRD score (HRD score ≥ 30) had a bit lower TMB (median TMB 3.07 vs 3.91, P = 0.002). Conclusions: HRD score was affected by alterations in different HRR genes, TP53 mutation and ERG fusion, which should be taken into consideration of the future clinical trials and research on intrinsic mechanisms. Patients carrying alterations other than HRR genes might benefit from PARPi. Further studies are needed.

Genomic characteristics of endometrial cancer in China.

e17569 Background: Molecular classification of endometrial cancer has been applied in patient stratification and treatment strategy. Although the Cancer Genome Atlas project and other genomic studies have established comprehensive molecular classification, its genomic characteristics in Chinese endometrial cancer remain unclear. Methods: Tumor tissue and matched white blood cells from 316 patients with endometrial cancer underwent next-generation sequencing (NGS), which targeted the whole coding region of 733 or 381 genes. Endometrial cancer was classified into four subtypes according to genomic characteristics: polymerase (POLE) ultramutated, microsatellite instability (MSI), TP53 wild type (TP53wt), and TP53 mutant (TP53mut). Tumor mutation burden (TMB) was calculated based on the number of somatic single nucleotide variants and indels in examined coding regions. Deleterious or suspected deleterious genes were included for analysis. Genomic instability was also evaluated with Homologous Recombination Deficiency (HRD) score by over 10, 000 single-nucleotide polymorphisms distributed across human genome. HRD algorithm combined loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST). Results: The 316 endometrial cancer patients were divided into four subtypes: POLE ultramutated (16, 5.06%), MSI tumors (70, 22.2%), TP53wt (131, 41.5%), and TP53mut (99, 31.3%). Median TMB was 26.5 mut/Mb in overall cohort and POLE ultramutated subtype possessed the highest TMB (181 mut/Mb), followed by MSI (54.1 mut/Mb), TP53mut (7.11 mut/Mb) and TP53wt (6.61 mut/Mb) subtypes. POLE, PTEN, LRP1B, BRCA2 and ATRX were the top frequently mutated genes in POLE ultramutated subtype, which mutation rate are more that 80%. The most frequent mutations were detected in ARID1A, PTEN, PIK3CA in MSI subtype, TP53, PIK3CA, PTEN in TP53mut subtype, and PTEN, PIK3CA, ARID1A in TP53wt subtype. HRD score was significantly higher in TP53mut subtype, followed by TP53wt, MSI and POLE ultramutated subtype (median HRD score, 21.7, 6.15, 3.65 and 0; P < 0.001). Conclusions: Our study revealed the heterogeneous genomic characteristics of four molecular subtypes in Chinese endometrial cancer. POLE ultramutated and MSI subtypes display higher TMB. TP53mut subtype showed genome features of HRD and would likely benefit from HRD-targeted therapy.

Efficacy of platinum-based chemotherapy in advanced triple-negative breast cancer in association with homologous recombination deficiency.

e13051 Background: Previous studies have identified that at least 50% of triple negative breast cancer (TNBC) harbor mutation characteristics of homologous recombination deficiency (HRD). Thus, more sophisticated research into comprehensive genomic profiling of HRD is urgently needed. Whereas BRCA1/2-deficient advanced TNBC patients are sensitive to treatment with platinum, it is not yet clear whether HRD status could predict platinum response. Methods: 3DMed-HRD algorithm was developed based on loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST) as previously described. HRD status was defined as HRD positive (deleterious mutation in BRCA1/2 or HRD score ≥30) or HRD negative (no deleterious mutation in BRCA1/2 and HRD score < 30). Tumor samples from 207 TNBC patients were analyzed by next-generation sequencing. Deleterious or suspected deleterious mutations were included for analysis. Among the overall cohort, 34 patients with advanced TNBC treated with chemotherapy were analyzed. Cox regression model was applied to evaluate the relationship between HRD status and clinical outcomes. Results: Deleterious BRCA1/2 mutations were detected in 22.2% (46/207) of TNBC patients as well as 54.6% (113/207) were defined as HRD positive. The most frequent mutations in HRD-positive patients were TP53 (93.5%), MYC (29.0%), PIK3R1 (22.6%), PTEN (22.6%) and MCL1 (19.4%), while TP53 (77.8%), MYC (29.6%), PIK3CA (18.5%), KMT2C (14.8%) and RIT1 (14.8%) enriched in HRD-negative patients. Mutations in DNA Damage Response (DDR), P53, Checkpoint and Receptor Tyrosine Kinase (RTK) pathways were most involved in HRD positive patients. In advanced TNBC cohort, 19 patients received platinum-based and 15 received platinum-free chemotherapy in the first-line treatment. The progression-free survival (PFS) of the platinum-based group was longer than that of the platinum-free group (media PFS 9.1 vs 2.2 months, HR 0.44, 95%CI, 0.20-0.94, P = 0.009). In HRD-positive patients, median PFS was significantly longer in platinum-based group (N = 6) than platinum-free group (N = 8) (media PFS 13.6 vs 1.9 months, HR 0.30, 95%CI, 0.09-0.95, P = 0.008). No significant difference in PFS between platinum-based and platinum-free group (p = 0.332) in patients with HRD-negative tumors. Patients with mutations in homologous recombination (HR) pathway had a worse PFS compared to wild-type in platinum-free group (1.4 vs 3.0 months, p = 0.050). Conclusions: Our findings illustrate the potential of HRD status as a marker to guide chemotherapy in advanced TNBC. In HRD positive patients, platinum-based chemotherapy might be a preferable regimen. Patients with mutations in HR pathway had a shorter PFS in platinum-free group. Prospective study with a larger sample-size is needed for further validation of our findings.

Accurately estimating the homologous recombination deficiency based on low-pass whole-genome sequencing and target sequencing.

e15077 Background: Homologous recombination deficiency (HRD) is a promising biomarker for poly ADP-ribose polymerase (PARP) inhibitors. In the past, the HRD status was mainly estimated by summing the loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transition (LST) based on target sequencing. However, the heterozygous loci coverage and probe number are closely correlated to B allele frequency and copy number variations (CNVs). Here we developed a novel method to combine the data from low-pass whole-genome sequencing (WGS) and target sequencing to accurately estimate the genome-wide CNVs and allelic imbalance. Methods: We first performed low-pass WGS and target sequencing on 30 healthy controls, formalin-fixed and paraffin-embedded (FFPE) samples, and matched blood cell samples for 29 patients with breast cancer or ovarian cancer. Two HRD positive samples were diluted to 40%, 30%, 20%, and 10% tumor purity with matched blood cell samples, respectively. Each diluted sample was sequenced 20 times. The baseline for CNVs was built based on the sequencing data of healthy donors. To eliminate the artifacts resulted from the sequencing platform, models for each candidate single nucleotide polymorphism (SNP) in target regions were trained using the data from healthy donors. The mutations of BRCA1/BRCA2 of 29 patients were used to define the threshold of the HRD score. The numbers of LOH, LST, and TAI were evaluated by CNVs and B allele frequency. Results: We defined a cutoff of 42 for the HRD status based on the low-pass WGS and target sequencing data of 29 patients. Specifically, the original HRD scores for two selected HRD positive samples were 68 and 89. The median HRD scores for 40%, 30%, 20%, and 10% tumor purity samples were 69 and 88, 66.5 and 90, 61 and 68, 52 and 34.5, respectively. Conclusions: We developed a novel method for robustly inferring the HRD status using low-pass WGS and target sequencing with a limit of detection of 20%.

Homologous recombination deficiency associated with response to poly (ADP-ribose) polymerase inhibitors in ovarian cancer patients: The first real-word data from China.

e17543 Background: Homologous recombination deficiency (HRD) is the first phenotypically defined predictive biomarker for Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. However, the proportion of HRD positive in real world and the relationship of HRD status with PARPi in Chinese ovarian cancer patients remains unknown. Methods: A total of sixty-four ovarian cancer patients underwent PARPi, both Olaparib and Niraparib, were enrolled from August 2018 to January 2021 in Jiangsu Institute of Cancer Hospital. HRD score which was the sum of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transitions (LST) events were calculated using tumor DNA-based next generation sequencing (NGS) assays. HRD-positive was defined by either BRCA1/2 pathogenic or likely pathogenic mutation or HRD score ≥42. Progression-free survival (PFS) was analyzed with a log-rank test using HRD status and summarized using Kaplan-Meier methodology. Univariate and multiple cox-regression analysis were conducted to investigate all possible clinical factors. Results: 71.9% (46/64) patients were HRD positive and the rest 28.1% (18/64) were HRD negative, which was higher than the HRD positive proportion reported in Western countries. The PFS among HRD positive patients was significantly longer than those HRD negative patients (medium PFS 8.9 m vs 3.6 m, hazard ratio [HR]: 0.22, p < 0.001). Among them, 23 patients who were BRCA wild type but HRD positive had longer PFS than those with BRCA wild type and HRD negative (medium PFS 9.2 m vs 3.6 m, HR: 0.20, p < 0.001). Univariate cox-regression analysis found that HRD status, previous treatment lines, secondary cytoreductive surgery (SCS) were significantly associated with PFS after PARPi treatment. After multiple regression correction, HRD status (HR: 0.39, 95% CI: [0.20-0.76], p = 0.006), ECOG score (HR: 2.53, 95% CI: [1.24-5.17], p = 0.011) and SCS (HR: 2.21, 95% CI: [1.09-4.48], p = 0.028) were the independent factors. Subgroup analysis in ECOG = 0 subgroup (N = 36), HRD positive patients had significant longer PFS than HRD negative patients (medium PFS 10.3 m vs 5.8 m, HR: 0.14, p < 0.001). Also in the subgroup of patients without SCS, PFS in patients with HRD was longer than patients without HRD (medium PFS 10.2 m vs 5.7 m, HR: 0.29, p = 0.003). Conclusions: This is the first real-world data of HRD status in ovarian cancer patients from China and demonstrate that HRD is a valid biomarker for PARP inhibitors in Chinese ovarian cancer patients.

Genomic profiling of biliary tract cancers to reveal clinically actionable genes and therapeutic biomarkers.

e16187 Background: Bile tract cancers are genetically and clinically heterogenous with a poor prognosis. Identifying novel biomarkers for targeted therapy is required to improve the clinical outcome of bile tract cancer patients. Methods: Tumor tissue samples of 482 Chinese biliary tract cancer (BTC) patients were genetically profiled using targeted next generation sequencing. Tumor mutation burden (TMB) was calculated by counting all nonsynonymous mutations per megabase of coding sequences. The R package ReactomePA was used in pathway enrichment analysis. Genomic instability was characterized by an in-house developed NGS-based Homologous Recombination Deficiency (HRD) panel and a HRD score was an unweighted sum of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST) scores. Results: The BTC cohort consisted of 135 gallbladder cancer (GBC), 73 intrahepatic cholangiocarcinoma (iCCA), 18 distal cholangiocarcinoma (dCCA), 14 perihilar cholangiocarcinoma (pCCA), while the remaining 242 BTC patients of no specific subtype information. Most frequently mutated genes included TP53 (56%), KRAS (25%), ARID1A (17%), SMAD4 (11%), and CDKN2A (10%) . A preliminary pathway analysis revealed that mutations of DNA damage repair (DDR) pathway genes were enriched in the cohort ( p< 1e-10), accounting for over 70% of the patients, particularly in homologous recombination repair (HRR), Fanconi anemia (FA), mismatch repair (MMR), and base excision repair (BER) genes. More specifically, approximately 50% of the cohort carried at least one mutation of the HRR genes (43%) or MMR genes (14%). Patients with impaired MMR had increased microsatellite instability status (MSI) comparing to those with wildtype MMR (33% vs. 3.1%, p< 0.0001), and patients harboring HRR mutations demonstrated elevated genomic instability than those without such mutations (median HRD: 18 vs.14, p < 0.05), indicative of potential response to poly (ADP-ribose) polymerase (PARP) inhibitors and other DNA-damage agents. Furthermore, high TMB was found to be highly correlated with DDR gene alterations ( p =0.004). In addition, we observed higher mutation frequencies of BRCA1/2 genes (including somatic and germline) in GBCs in contrast to other BTC subtypes. Conclusions: We herein reported the genomic features of 482 Chinese BTC samples and highlighted the role of DDR pathways including HRR and MMR. These findings could be useful to establish treatment and diagnostic strategies for BTC patients based on genetic information.

Synergistic optimization of renewable energy installations through evolution strategy

With large parts of the world moving toward renewable energies, there is an urgent need to organize this large-scale transition effectively. This paper presents a new methodology to guide the planning and siting of renewable electricity generation for countries or larger geographical regions. Its flexible approach accounts for the specific boundary conditions, constraints and available resources of the region of interest and enables solutions that optimize the interplay between the various types of generation. Evolution strategy permits a simultaneous optimization of the placement and the share of renewable electricity generation technologies that are to be added to a system, while most efficiently combining the new with the existing electricity generation and respecting the constraints of the electrical grid. Using Switzerland as case study, we demonstrate the method’s ability to devise national installation scenarios that are efficient, realistic with respect to land use and grid infrastructure and reduce significantly the need for seasonal storage. We show how the spatio-temporal variability of weather-driven electricity generation can be exploited to benefit the electrical system as a whole.

BRCA reversion mutations in a pan-cancer cohort to reveal BRCA-dependence in select noncanonical BRCA-mutant histologies.

3012 Background: Loss of BRCA1/2 function leads to homologous recombination deficiency (HRD) and can enhance platinum and PARP inhibitor sensitivity in breast, pancreas, prostate, and ovarian cancers. In BRCA-associated cancers, resistance can result from the development of BRCA1/2 reversion mutations, which restore BRCA1/2 function. By contrast, a BRCA mutation may be an incidental finding in other tumor histologies. Methods: To determine the distribution of reversion mutations in a pan-cancer cohort, the MSK-IMPACT clinical sequencing cohort was mined to identify patients who had both a germline BRCA1/2 mutation and a frameshift somatic reversion mutation that restored BRCA1/2 function. Whole exome resequencing was used to detect HRD signatures. Chart review enabled collection of data on treatment history in patients consented to germline testing. Results: Of the 33,277 patients with matched tumor and normal sequencing profiled in this study, 861 patients were found to have germline pathogenic BRCA1/2 alterations, including 347 (40%) in BRCA1 and 514 (60%) in BRCA2. Somatic BRCA1/2 driver alterations were also found in tumor tissue from an additional 447 patients, with 156 (35%) having BRCA1 mutations, and the remainder having alterations in BRCA2 (65%) . Among the 1,308 germline or somatic BRCA1/2 mutant tumors, we identified reversion mutations in 12 patients, all of whom were germline carriers of BRCA1/2, comprising 3 BRCA1 and 9 BRCA2 tumors. 7 patients consented to germline testing enabling review of clinical characteristics and treatment history, 5 of whom received PARP inhibitor or platinum-therapy prior to reversion detection. Ten of 12 tumors with reversion mutations were in canonical BRCA-associated cancers. Interestingly, reversion mutations were also found in patients with lung adenocarcinoma (n=1) and gastroesophageal junction adenocarcinoma (n=1). In both these non-canonical histologies, the reversion was detected following progression on platinum-based therapy. Whole exome resequencing of the lung tumor revealed the classic somatic molecular phenotypes of HRD that are characteristic of BRCA-dependent tumors, including in terms of large-scale transitions, HRD-loss of heterozygosity, signature 3, and the number of telomeric allelic imbalance score. Conclusions: Matched tumor and normal sequencing from a large cohort of patients with diverse cancer histologies reveals that reversion mutations are found across BRCA-associated cancer types. In rare cases, reversion mutations in BRCA1/2 following platinum-based therapy may be indicative of prior BRCA-dependence in select non-canonical tumor histologies.

THE APOLOGY OF THE WHOLE

At the level of the whole organism, an idea of the complexity of living things is formed as a combination of levels of organization (layers) of biological and virtual reality, which develops as a space for visualization (digitization) of living objects. New digital formats of living objects, coupled with the naturalistic ethics of obtaining them, create a trend towards a complete transition of biology to a quantitatively new level of obtaining biological information information about the state of living biological objects. The development of digital biology contributes to an increasingly large-scale transition to the creation and analysis of virtual images of living biological objects, and at the same time "removes" the biologist from the actual object of research: a biologist can work with a virtual image and not destroy his research object. Digital naturalism appears, and, consequently, a digital "experiment" must also be expected, which will undoubtedly continue the eternal confrontation between naturalists and naturalists or vitalists with mechanists in the new techno environment.

Cancer Whole-Genome Sequencing: The Quest for Comprehensive Genomic Profiling in Routine Oncology Care

One test to rule them all. This paraphrase of Tolkien concisely states the allure of clinically validated whole-genome sequencing (WGS) of tumors. This test has the potential to analyze nearly all clinically relevant genomic biomarkers with superior or at least equivalent accuracy compared to that of the bevy of separate diagnostic approaches currently used. WGS can be used to comprehensively assess single-nucleotide variants, small- to medium-sized indels, copy-number alterations, structural rearrangements, viral insertions, and the spectrum of established and emerging mutational signatures, including: microsatellite instability, tumor-mutation burden, loss of heterozygosity, large-scale transitions, telomeric allelic imbalance, and APOBEC.

Theory, Practice and Challenges of Agroecology in India

ABSTRACT With the Green Revolution in Asia, the gap in agricultural yield with the developed world has been closed, while the gap in farm labour productivity has greatly widened. This reveals a deepening agrarian and environmental crisis in India. The industrial mode of production has led to the massive use of costly industrial inputs to increase yields and offset economies of scale that are almost impossible to achieve in this densely populated country. Such a development path is a trap for millions Indian micro-farmers and their natural capital. We then unveil the promises of a type of agroecology called ‘natural farming' that has developed in Andhra Pradesh, a State in South India. Andhra’s natural farming has pioneered the adoption of technical and organizational innovations that could lead to the first large-scale agroecological transition in the world. But in 2019, these local innovations were accused of following a regressive path and endangering the country’s food security. This attack reveals the current omnipotence of the industrial sociotechnical regime over science, as well as a conception of science and progress antithetical to agroecology.

Coarse-Grained Modeling of Multiple Pathways in Conformational Transitions of Multi-Domain Proteins.

Large-scale conformational transitions in multi-domain proteins are often essential for their functions. To investigate the transitions, it is necessary to explore multiple potential pathways, which involve different intermediate structures. Here, we present a multi-basin (MB) coarse-grained (CG) structure-based Go̅ model for describing transitions in proteins with more than two moving domains. This model is an extension of our dual-basin Go̅ model in which system-dependent parameters are determined systematically using the multistate Bennett acceptance ratio method. In the MB Go̅ model for multi-domain proteins, we assume that intermediate structures may have partial inter-domain native contacts. This approach allows us to search multiple transition pathways that involve distinct intermediate structures using the CG molecular dynamics (MD) simulations. We apply this scheme to an enzyme, adenylate kinase (AdK), which has three major domains and can move along two different pathways. Using the optimized mixing parameters for each pathway, AdK shows frequent transitions between the Open, Closed, and the intermediate basins and samples a wide variety of conformations within each basin. The explored multiple transition pathways could be compared with experimental data and examined in more detail by atomistic MD simulations.

A fuzzy theory-based machine learning method for workdays and weekends short-term load forecasting

Countries around the globe have introduced renewable energies (RE) and minimized the dependency of fossil resources in power systems to address extensive environmental risks. However, such large-scale energy transitions pose a great challenge to power systems due to the volatility of RE. Meanwhile, power demand is increasing over time and it shows temporal characteristics, such as seasonal and peak-valley patterns. Whether the future power system with a larger proportion of RE can meet the surging but fluctuated electricity demand remains problematic. Previous studies on short-term load forecasting focused more on forecasting accuracy than stability. Further, there is a relative paucity of research into temporal patterns. In order to fill in these research gaps, this paper proposes a fuzzy theory-based machine learning model for workdays and weekends short-term load forecasting. Fuzzy time series (FTS) is applied for data mining and back propagation (BP) neural network is used as the main predictor for short-term load forecasting. To exploit the trade-offs between forecasting stability and accuracy, multi-objective optimization is applied to modify the parameters of BP. Moreover, an interval forecasting architecture with several statistical tests is constructed to address forecasting uncertainties. Short-term load data from Victoria in Australia is selected as a case study. Results demonstrate that the proposed method can significantly boost forecasting stability and accuracy, and help strategy making in the field of energy and electricity system management and planning.

Urgent Transition to Group Online Foreign Language Instruction: Problems and Solutions

The purpose of this work is to study how teachers and students react to the urgent large-scale transition to online education. The research was done via surveys conducted at the Center for Additional Educational Programs in the field of Russian as a Foreign Language at St. Petersburg State University. March 2020 transition to distance learning kept intact the lesson schedule, the duration of lessons, and the compliance with the approved programs. This case study was conducted as follows: (1) a questionnaire for teachers was distributed via e-mail; (2) teachers’ responses were collected and processed; (3) a questionnaire for students was created in Google Forms; (4) students’ responses were collected and processed; (5) the research results were described and analyzed; (6) teachers’ and students’ responses were compared. The study involved 45 teachers and 100 foreign students, mostly from China. The majority of teachers taught at Level A2 (48%); the majority of students studied at Level B1 (36%). The study shows that modern teachers (77.8%) have a high degree of adaptability, which allows them to switch to new teaching formats in two weeks. They use a variety of teaching aids: not only textbooks mandated by the curriculum (100%), but also other textbooks (91.1%), educational materials from the Internet (88.9%), authentic audio/video materials (51.1%), and self-developed educational materials (53.3%). According to students, the most effective are the authentic materials from the Internet (45%), and the textbook mandated by the program (41%). Both teachers and students noted difficulties in the online training of four language skills: speaking (35.6% of teachers and 32% of students), writing (17.8% and 32%, respectively), listening (15.6% and 40%), and reading (11.1% and 17%). Teachers lack personal communication with students (35.6%), specialized online tools for teaching Russian as a foreign language (13.3%), and effective means of monitoring the acquisition of educational material (31.1%). They strive to solve these problems through a variety of activities, creating an atmosphere conducive to authentic communication. Research data correspond with the conclusions of methodologists about the fundamentally new nature of the relationship between teachers and students in the virtual environment, which is manifested in a less hierarchic teacher-student relationship due to greater initiative, involvement, and independence of students in an online lesson. The article presents a way to study the perception of changes in the teaching mode by teachers and students. The research enriches the e-learning knowledge area with data on how the sudden mass transition to online foreign language learning was carried out.

Pluralising agency to understand behaviour change in sustainability transitions

In order to maintain a habitable planet, relatively fast and large-scale transitions towards sustainable societies are needed especially regarding the production and consumption of energy. The transitions require people to change the ways they conduct their daily lives as well as agency (capacity to act) in bringing about the needed changes at different levels of society. However, inadequate attention to human behaviour and agency is a recurring critique of the sustainability transition literature. In this article, we bring together insights from institutional, socio-psychological, practice theoretical and relational perspectives to highlight the diversity of understanding agency in sustainability transitions. The different approaches provide a nuanced view on the roles of people and the conduct of everyday lives in sustainability transitions. Building on the multi-level perspective (MLP), we argue that in order to acquire a more holistic understanding on the role of agency in sustainability transitions, attention should be paid to the links and interactions between different socio-technical systems, such as energy, transportation, waste and food as well as their internal dynamics, blurring the boundaries of micro-, meso- and macro-levels. Improved understanding of agency will bring to the fore everyday behaviour as an enabler of sustainability transitions. Furthermore, it will allow a more nuanced perception of the transition dynamics, which can significantly improve the overall understanding of the situated sustainability transitions mechanisms.

Energy citizenship in the Netherlands: The complexities of public engagement in a large-scale energy transition

The Netherlands aims to transition to a gas-free built environment by 2050, with meaningful public engagement considered central to success. We investigated how local government stakeholders – the primary facilitators of the transition – perceive the role of citizens and energy citizenship in achieving this transition at household level. Semi-structured interviews were conducted with officials from nine municipalities. Our data show mixed perceptions as to citizen interest and financial willingness and/or capacity to adopt gas-free alternatives. The cost of alternatives and practicalities of citizen engagement are considered the main barriers to the gas-free transition. Two alternatives are considered most appropriate in the municipalities that participated in our study: a collective heat network and an all-electric approach. We find that these alternatives do not offer equal opportunities to foster energy citizenship. A collective heat network, while socially inclusive, represents a passive form of citizen engagement due to its central and distant nature, though this can be mitigated by developing local heat cooperatives. In contrast, all-electric installations are more socially exclusive (due to high investment costs), but implementation requires active citizen engagement. Combining these two options could represent a viable option for a gas-free transition that represents a form of sustainable development.

Challenges and Approaches to Scaling the Global Commons

The re-emergence of commoning over the last decades is not incidental, but rather indicative of a large-scale transition to a more “generative” organization of society that is oriented toward the planet’s global carrying capacity. Digital commons governance frameworks are of particular importance for a new global paradigm of cooperation, one that can scale the organization of communities around common goals and resources to unprecedented levels of size, complexity and granularity. Distributed Ledger Technologies (DLTs) such as blockchain have lately given new impetus to the emergence of a new generation of authentic “sharing economy,” protected from capture by thorough distribution of power over infrastructure, that spans not only digital but also physical production of common value. The exploration of the frontiers of DLT-based commoning at the heart of this article considers three exemplary cases for this new generation of commons-oriented community frameworks: the Commons Stack, Holochain and the Commons Engine, and the Economic Space Agency. While these projects differ in their scope as well as in their relation to physical common-pool resources (CPRs), they all share the task of redefining markets so as to be more conducive to the production and sustainment of common value(s). After introducing each of them with regards to their specificities and commonalities, we analyze their capacity to foster commons-oriented economies and “money for the commons” that limit speculation, emphasize use-value over exchange-value, favor equity in human relations, and promote responsibility for the preservation of natural habitats. Our findings highlight the strengths of DLTs for a federated scaling of CPR governance frameworks that accommodates rather than obliterates cultural differences and creates webs of fractal belonging among nested communities.

The impacts of a reduction in British meat and dairy consumption on Northern Ireland’s agri-food sector

In 2020, the Committee on Climate Change (CCC) recommended that British consumers reduce their beef, lamb and dairy consumption by 20% for both environmental and health reasons. For a region like Northern Ireland, this presents a significant challenge. Northern Ireland, considered to be performing poorly local economy within the United Kingdom and Ireland, has an export-orientated agri-food sector with an extensive domestic supply chain. This study shows the likely trade-offs required for a small regional economy with a large, established cattle herd to sustainably transition from one agri-food system to another. In so doing, the study uses the most comprehensive agricultural data collections to rebalance Northern Irish input–output tables, to better account for the nature of NI intermediate consumption within an agri-food system. The results show that a large-scale transition from beef, lamb and dairy to fruit and vegetable production would create a more emission efficient agricultural sector. The worst economic effects could be offset within current NI policy parameters, although there would still likely be some economic costs.

Simulation of the hydrodynamics in polymerizers based on the CFD model for the synthesis of rubbers and plastics using the method of the solution polymerization

Mixing in a viscous medium, such as in polymerization processes, is worth noting. To control the polymerization process for improving the product quality, it is important to understand the mixing process. Also, it is essential to understand the flow behaviour in the stirred-tank reactor for the equipment design and from the point of view of the large-scale transition of the process. Local and general characteristics of mixing in the reactor are related to the design and selected speed of the agitator. 3D-modeling of the flow in the cylindrical reactor with the paddle stirrer was carried out using the potential of a supercomputer. Numerical results showed good consistency with experimental results and correlation developed by other researchers. To determine the best mode of introduction into the paddle space of the stirrer, two efficiency criteria were used: with respect to power and mixing time.