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The study investigates sea-level measurements along the coastal area of Europe for the 60-year (1961–2020) time span. Linear and quadratic modeling of tide gauge measurements showed an almost positive rate of trend of sea-level rise (0.09 to 3.6 mm/yr) and low acceleration (−0.05 to 0.40 mm/yr2). A least-squares harmonic estimation tidal modeling was carried out to estimate frequency (cycles per day) for a certain period. The smaller and higher tidal frequencies of these stations indicate their stability in terms of their surface variation. We used the 1993–2020 satellite altimetry data from the nearest grid points of the tide gauge station. The correlation coefficient between observed and satellite altimetry (lowest 0.53 and highest 0.93) varies at each station. This happens because of many factors that can affect the large difference in the sea-level trend between the satellite-derived and tide gauge results. Finally, to implement a global reference system for physical heights, the offshore topographic slope direction and slope range with contour spacing from the sea to the associated coastline were analyzed using bathymetry data. The abrupt change in slope from the coastline toward the sea can be seen toward the east, west, and southeast on the European coast. This is also an important factor that affects the variation of sea level.

Active tectonics in an area includes ongoing or recent geologic events. This paper investigates the tectonic influence on the subsidence, uplift and tilt of western Saurashtra through morphotectonic analysis of ten watersheds along with characteristics of relief and drainage orientation. Watersheds 7–9 to the north (N) are tectonically active, which can be linked with the North Kathiawar Fault System (NKFS) and followed by watersheds 6, 10, 1, 4 and 5. Stream-length gradient index and sinuosity index indicate the effect of tectonic events along the master streams in watersheds 6–9. Higher R2 values of the linear curve fit for watershed 7 indicate its master stream is much more tectonically active than the others. The R2 curve fitting model and earthquake magnitude/depth analysis confirm the region to be active. The reactivation of the NKFS most likely led to the vertical movement of western Saurashtra.

In the 21st Century, students' critical thinking abilities are needed to utilize their knowledge in problem-solving. Also, these skills are very important for students in making decisions when faced with various choices. This study aimed to see the effectiveness of students' critical thinking variables in the learning process. This study used a Research and Development (RND) method with an instrument in the form of a questionnaire consisting of 2 constructs. This study was carried out by involving seven teachers from several schools. Data collection was carried out by filling out an online questionnaire. Data were then analyzed with the help of the SPSS program. The results of this study prove that the preparation and development of the evaluation instrument of critical thinking variables in student worksheet media for students in this study were carried out by testing two research constructs, namely accuracy and effectiveness variables. Furthermore, the results of testing the validity and reliability indicate that the data validity of the evaluation instrument meets the valid criteria. Also, the results of this study indicate that the instrument developed meets the requirements for use in the development of student worksheet media.

In the 21st Century, students' critical thinking abilities are fundamental to facing challenges and increasing societal obstacles, especially students. This study aimed to determine the level of critical thinking abilities in SMP/MTs students. This study's significance is obtaining test results related to SMP/MTs students' critical thinking abilities. This study used a survey method involving 75 SMP/MTs students who were selected randomly. The instrument used a questionnaire containing critical thinking questions distributed online via Google Forms. The data obtained were analyzed using SPSS. Based on the survey results, it is known that the average student's critical thinking abilities are 8.0 with a good category which details can be explained as follows: 1) Providing simple explanations (8.0); 2) Building basic skills (7,9); 3) Drawing a conclusion from the data (7.5); 4) Providing further explanations (8.0); and 5) Developing a follow-up strategy (7.5). The results of this study allow a conclusion that the constructs with the highest average scores are providing simple explanations and providing further explanations with an average score of 8.0. Thus, it is recommended that students improve their critical thinking abilities and that teachers continue to use the instruments they have used.

The Indian western coast is petroliferous and draws attention from academicians and industrial experts. In this work, geomorphic indices have been calculated to decode neotectonics of the Konkan onshore region on India's west coast. Earthquake and Bouguer anomaly data have been used along with the present-day stress data from the World Stress Map project. Gravity modeling was performed in order to gain seismotectonic insights. The b-values were determined using Z-MAP 7.1 (2021). Morphometric analysis at both linear and spatial scales were performed using the digital elevation model from the data derived from the Shuttle Radar Topography Mission, analyzed with ArcGIS 10.3 (2014) software. Maps depicting slopes, aspects, and reliefs were created. NW-SE trending lineaments in the Konkan plain guided the major stream courses. Two of the five watersheds, watersheds 4 and 5, reveal high tectonic activity, are landslide-prone and host hot springs. Interestingly, watersheds 4 and 5 show high b-values (except near the rivers' sources), low Bouguer anomalies, and higher Hypsometric integral values (0.18523 and 0.16698) than the other watersheds. A low b-value in watershed 3 indicates stress accumulation. Over a larger area, the gravity trend varies from ∼ −80 to 30 mGal. The lineaments diagram deduced from the first vertical derivative technique shows that the structural fabrics mostly trend ∼ NW-SE at the west of the Western Ghat Escarpment (WGE) while it is NE-SW at the east. The tilt derivative ratio technique reveals a major NE-SW trend to the west of the WGE and an E-W trend to the east. Structural interpretations based on drill-cores around Koyna combined with geophysical studies for deep crust will be required are required for a better understanding of the blind (active) structures in the region.

Benoîte Mery,1,2,* Christine Ménétrier-Caux,2,3,* Laure Montané,4 Pierre-Etienne Heudel,1 Isabelle Ray-Coquard,1 Thomas Bachelot,1 Olfa Derbel,5 Paule Augereau,6 Isabelle Treilleux,2,7 Justine Berthet,2,3 Axelle Nkodia,3 Christine Bardin-Dit-Courageot,3 Valery Attignon,8 Anthony Ferrari,9 Gwenaele Garin,4 David Perol,4 Christophe Caux,2,3 Bertrand Dubois,2,3,* Olivier Trédan1,2,* 1Department of Medical Oncology, Centre Léon Bérard, Lyon, France; 2Inserm U1052, CNRS 5286, Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, Lyon, France; 3Laboratory of Cancer Immunotherapy of LYON (LICL), Centre Léon Bérard, Lyon, France; 4Clinical Research Platform (DRCI), Centre Léon Bérard, Lyon, France; 5Department of Medical Oncology, Hôpital Privé Jean-Mermoz, Lyon, France; 6Department of Medical Oncology, Institut de Cancérologie de L’ouest- Paul Papin, Angers, France; 7Biopathology Department, Centre Léon Bérard, Lyon, France; 8Genomic of Cancer Platform, Centre Léon Bérard, Lyon, France; 9Gilles Thomas Bioinformatics Platform, Synergie Lyon Cancer Foundation, Centre Léon Bérard, Lyon, France*These authors contributed equally to this workCorrespondence: Benoîte Mery, Department of Medical Oncology, Centre Léon Bérard, 28 Rue Laennec, Lyon, 69008, France, Tel +33 4 78 78 26 44, Fax +33 4 78 78 27 15, Email Benoite.mery@lyon.unicancer.frPurpose: Metastatic endocrine-resistant breast cancer (MBC) is a disease with poor prognosis and few treatment options. Low lymphocyte count is associated with limited overall survival. In a prospective cohort of lymphopenic patients with HER-2 negative MBC, we assessed the clinical and biological impact of pembrolizumab combined with metronomic cyclophosphamide.Experimental Design: This multicenter Phase II study evaluated the safety and clinical activity of pembrolizumab (intravenous (IV), 200mg, every 3 weeks) combined with metronomic cyclophosphamide (50mg/day, per os) in lymphopenic adult patients with HER2-negative MBC previously treated by at least one line of chemotherapy in this setting according to a Simon’s minimax two-stage design. Blood and tumor samples were collected to assess the impact of the combined treatment on circulating immune cells and the tumor immune microenvironment through multiparametric flow cytometry and multiplex immunofluorescence analyses. Primary endpoint was the clinical benefit rate at 6 months of treatment (CBR-6M). Secondary endpoints were objective response rate (ORR), duration of response, progression free survival (PFS), and overall survival (OS).Results: Two out of the twenty treated patients presented clinical benefit (one Tumor Mutational Burden (TMB)-high patient with complete response (CR) and one patient with objective response (OR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) associated with a strong increase of cytokine-producing and proliferating CD4+ T cells and higher CD8+ T cells to macrophage ratios in the tumor. This impact on CD4+ and CD8+ T cell polyfunctionality was still observed more than one year for the patient with CR. A decreased in their absolute number of CD4+ and CD8+ memory T cells was observed in other patients.Conclusion: Pembrolizumab combined with metronomic cyclophosphamide was well tolerated, and displayed limited anti-tumoral activity in lymphopenic MBC. Correlative translational data of our trial advocates for additional studies with other chemotherapy combinations.Keywords: metastatic breast cancer, lymphopenia, immunotherapy, chemotherapy, immunomonitoring

Student Worksheets a media in the form of sheets containing tasks and activities that students must carry out, which are useful in supporting the learning process, one of which is in the material on the Structure and Function of Plant Tissues so that students can be active in the learning process. An assessment instrument is needed for the Student Worksheets. For this reason, this study aimed to measure the instrument's validity and reliability for using Student Worksheets as a learning media. This study used Research and Development (RND) methodology with an instrument in the form of a Student Worksheets measurement questionnaire consisting of three constructs: product design, material feasibility, and language feasibility. This research was carried out by involving seven teachers from several schools. Data were obtained by distributing the questionnaire via a Google form from September to October 2022 by obtaining prior consent from the respondents. The data obtained were quantitative, then analyzed using SPSS version 29 in the form of Alpha Cronbach analysis. The results of the test show that the validity of the instrument data meets the valid and reliable criteria with each Cronbach Alpha value per construct, namely Product Design (0.795), Material Feasibility (0.712), and Language Feasibility (0.712). Therefore, this study shows that the developed instrument meets the use requirements in developing Student Worksheets media students. Thus, stakeholders and teachers can use this instrument to develop media, particularly Student Worksheets, whereas further researchers can use this instrument to measure media before the study.

The Kutch Rift Basin (KRB) is of great attention for its possible hydrocarbon reserve. In this context, geomorphologic and structural geologic studies of the onland basin area are crucial. Application of geomorphic indicators viz., compactness coefficient (Cc), lemniscate coefficient (k), form ratio (Rf), basin shape index (Bs), basin asymmetry factor (AF), hypsometric integral (HI), elongation ratio (Re) and circularity ratio (Rc) have been utilized to calculate the Index of Active Tectonics (IAT) for a part of KRB. Watersheds 5 (the Bhuj area), 9, 10, 11, 17, 18 and 20 belong to class 1 as per the IAT. This indicates that these watersheds are very highly tectonically active at present. Calculated valley floor width height ratio (Vf) and mountain front sinuosity (Smf) quantify the active valley incision in the Quaternary that uplifted the Bhuj area. This uplift was accompanied by a high-degree of drainage rejuvenation due to neotectonics and formation of a canyon in the Khari river. Paleostress analyses revealed NNE and NW-oriented extensions around Bhuj that can correspond to NW and NNE-trending normal fault planes, respectively.

Perubahan kurikulum selalu terjadi menyesuaikan kebutuhan dan kondisi di lapangan. Mendikbud langsung meluncurkan program Merdeka belajar, hal ini disambut dengan kondisi dilapangan yang serba mengkhawatirkan karena adanya musibah yang melanda tidak hanya Indonesia tetapi juga dunia. Musibah tersebut yaitu berupa pandemic corona yang sangat mempengaruhi sendi-sendi kehidupan termasuk ekonomi, pendidikan. Tentu program ini sangat terkait dengan adanya penggunaan dan pemanfaat tekhnologi informasi dalam proses pembelajaran di sekolah. Untuk mendukung program merdeka belajar maka pengabdi ingin melakukan pelatihan dan bimbingan teknis pemanfaatan tekhnologi informasi dalam pembelajaran. Dalam pengabdian ini akan melibatkan para guru di Pelalawan. Pelatihan ini memberikan implikasi bagi guru SD untuk memanfaatkan TIK dalam pembelajaran daring.

Abstract This study describes the initial ability of teachers in carrying out online learning activities. This research was conducted through survey research involving 154 elementary school teachers in Pelalawan and Rengat Regencies, Riau Provinces as the research samples were taken by purposive sampling. Research data were obtained through a survey using google forms and distributed via WhatsApp. Data analysis was carried out descriptively and inferentially using SPSS version 26. Based on the data analysis, it was identified that 97 teachers (63%) choose a combination learning model between offline and online as the most frequently learning model used during the covid-19 pandemic. In carrying out the learning process, 93 teachers (60.4%) chose schools as teaching locations. Regarding the quality of the internet in schools, 110 teachers (71.4%) assessed that the quality of the internet in schools was good and could support learning activities. Furthermore, teachers also apply various ways of teaching online learning, for example, 50 teachers (32.5%) choose to provide interactive material through online media and 45 teachers (29.2%) ask students to learn to use textbooks and give assignments to students in the form of assignments on worksheets, projects, books, etc. The main obstacle for teachers during online learning is that they find it difficult to observe student progress and have difficulty communicating with parents. The efforts made by teachers to adapt online learning is by providing materials/tasks and establishing basic competencies according to student needs.

Knowledge is an ability that students must possess in solving various problems and applying them in everyday life. This study aimed to determine how far the Effectiveness of knowledge variables for students in the learning process. This study uses the ADDIE development model. with the instrument in the form of a questionnaire consisting of 2 constructs. The survey study was carried out by involving ten teachers from various schools. Data collection techniques were carried out by filling out online questionnaires, which were then analyzed with the help of the SPSS program. The results of the research prove that: 1) the preparation and development of the evaluation of the problem variable instrument in the media for students in this study was carried out by testing two research constructs, namely 1) the accuracy of the variable and 2) the Effectiveness of the variable. As well as the results of testing the validity and reliability indicate that the data validity of the evaluation instrument meets the valid criteria. This research shows that the developed instrument meets the requirements for use in media development in the form of an e-module.

Andean lupin (Lupinus mutabilis) oil is rich in monounsaturated (54.2%) and polyunsaturated (28.5%) fatty acids but has a ω-3:ω-6 ratio (1:9.2) above the recommended values for human health. Sacha inchi (Plukenetia volubilis) oil presents a high polyunsaturated fatty acid content (linolenic 47.2% and linoleic 34.7%), along a ω-3:ω-6 ratio (1:0.74) good for human consumption. The objective of this research was to study the physico-chemical properties and oxidative stability of tarwi and sacha inchi oil blends (1:4, 1:3, 1:1, 3:1 and 4:1 w:w) with suitable ω-3:ω-6 ratios. All blends showed ω-3:ω-6 ratios between 1:0.8 and 1:1.9, acceptable from a nutritional point of view, and high total tocopherols’ content (1834–688 mg/kg), thanks to sacha inchi. The oxidative stability index (OSI) of the mixtures by the Rancimat method at 120 °C ranged from 0.46 to 8.80 h. The shelf-life of 1:1 tarwi/sacha inchi oil blend was 1.26 years; its entropy (−17.43 J/mol), enthalpy (107.04 kJ/mol), activation energy (110.24 kJ/mol) and Gibbs energy (113.76 kJ/mol) suggest low oxidation reaction rates and good stability. Hence, balanced blends of tarwi/sacha inchi oils can achieve optimal nutritional properties and enhanced shelf-life.