International Research Institutions Research Articles

The Analysis of Intelligent Functions Required for Inland Ships

Sorting out the requirements for intelligent functions is the prerequisite and foundation of the top-level design for the development of intelligent ships. In light of the development of inland intelligent ships for 2030, 2035, and 2050, based on the analysis of the division of intelligent ship functional modules by international representative classification societies and relevant research institutions, eight necessary functional modules have been proposed: intelligent navigation, intelligent hull, intelligent engine room, intelligent energy efficiency management, intelligent cargo management, intelligent integration platform, remote control, and autonomous operation. Taking the technical realization of each functional module as the goal, this paper analyzes the status quo and development trend of related intelligent technologies and their feasibility and applicability when applied to each functional module. At the same time, it clarifies the composition of specific functional elements of each functional module, puts forward the stage goals of China’s inland intelligent ship development and the specific functional requirements of different modules under each stage, and provides reference for the Chinese government to subsequently formulate the top-level design development planning and implementation path of inland waterway intelligent ships.

Seismic Discrimination Between Nuclear Explosions and Natural Earthquakes using Multi-Machine Learning Techniques

AbstractIn the field of seismic signal analysis, it is of utmost importance to accurately differentiate between earthquakes and underground nuclear explosions. As a contribution for the verification regime of the Comprehensive Nuclear Test Ban Treaty (CTBT), Various methods have been employed for this purpose, including Complexity, Spectral ratio, mb—Ms (body wave and surface wave magnitudes), and corner frequency of P and S waves. These discrimination techniques have been examined to manually identify natural seismic events from nuclear explosions across different regions worldwide, such as China, India, Pakistan, North Korea, and the United States. To gather the necessary data, a comprehensive dataset comprising nuclear explosions and earthquakes of the same magnitude range (4 ≤ mb ≤ 6.5) of 35 seismic events from 1945 to 2017 has been compiled from the International Research Institute for Seismology (IRIS) using broadband and long period seismic stations. The objective of this study is to employ a range of linear and nonlinear Machine Learning (ML) models with the aim of automatically distinguishing between underground nuclear explosions and large earthquakes to enhance the accuracy of manual feature extraction. For this purpose, time domain waveforms and different classifier techniques focused on feature extraction have been used. The ML models employed include logistic regression, K-nearest neighbours classifier, decision tree classifier, random forest classifier, voting classifier, and Naive Bayes. The outcomes of the ROC and AUC analyses were employed to validate the validity of our proposed discrimination algorithm. The results show that the Random Forest Classifier is the most effective model, obtaining 100% accuracy in the case of feature extraction, while the best model for the time domain waveform classifier that achieved 75.5% accuracy is the voting classifier.

Application of Good Corporate Governance (GCG) Principles in Cirebon Publications According to Islamic Economics

Recent developments show that it is not enough for management to ensure that the leadership management process is effective. In order for management to run well, a new tool is needed, namely Good Corporate Governance (GCG). This concept emphasizes two things, first, the importance of shareholders' rights to obtain accurate and timely information, and second, the company's obligation to publish all information regarding company performance accurately, timely and transparently. property and interested parties. The study aims to evaluate the extent to which the principles of good corporate governance (GCG) have been implemented in the Indonesian banking sector, both in conventional and Islamic banks. In this study, the type of research used is a type of qualitative descriptive research. The results of various national and international independent research institutions show that Indonesian business people do not understand the importance and strategic implementation of GCG principles. In addition, organizational culture also influences the implementation of GCG in Indonesia.

Development and Application of Robotics for Decommissioning of Fukushima Daiichi NPS by IRID

The most challenging task in the decommissioning of the Fukushima Daiichi Nuclear Power Station is to retrieve molten and solidified fuel debris, including in reactor internals. The International Research Institute for Nuclear Decommissioning (IRID) has developed various robots that can investigate the interior of a primary containment vessel (PCV) to clarify where fuel debris has accumulated and how it has formed. The scenarios of each unit caused by the accident are different; therefore, IRID has developed robots to satisfy the requirements of each unit. The robots can be categorized into three types: non-submersible robots driving through air, submersible robots swimming underwater, and investigation robots with arms that can extend to enter the PCV. This review focuses on the technological development of robots based on their functionality. Most of the robotic technology is acquired and utilized based on the results of subsidy projects for countermeasures for decommissioning and contaminated water granted by the Japanese government.

Pressure Data from Neonatalie Live Manikin to Determine Appropriate Ventilation During Simulation Training of Undergraduate Students in Neonatal Resuscitation

Background: Neonatalie Live (NL) was developed as a part of the Safer Births project with collaboration between Laerdal Global Health and Tanzanian, Norwegian, and international research institutions. Its features allow instructors to determine the time of starting ventilation, the percentage of valid ventilations, etc. NL generated real-time data during the assessment. Aim: To evaluate whether undergraduate students trained on Neonatalie and NL manikins had equivalent ventilation skills on NL. Study design: Randomized Control Trial. Methods: Final-year MBBS students were randomly assigned to Neonatalie (72 students) or NL (71 students) groups after providing written and informed consent and assessed on NL. Live data generated by NL was analyzed. Outcome: To assess the success rate at bag and mask ventilation (BMV), as evidenced by objective data from NL. Results: A total of 142 students (assessed only on NL) participated in the study before and after four months. Total time from initiation of BMV to spontaneous breathing did not differ significantly between the Neonatalie and NL [127.6 sec (57.4) vs. 115.1 sec (48.3), p = .16]. “Try to ventilate the baby continuously without pauses” was the most common feedback to all students 70 (49.2%), but no statistical significance between the Neonatalie and NL groups [34 (47.2%) vs. 36 (51.43%)] was found. Conclusion: Undergraduate students trained on either manikin had similar success at BMV, as evidenced by independent objective data generated from within the manikin.

China: as an Emerging Superpower

The research paper aims to answer the main research question whether China can really becomethe next superpower towards the middle of 21st century through its economic performance, energypolicy, population, nuclear capacity and ideology. The hypothesis of the research paper is that in 21stcentury international system will become a bipolar with hegemony of the United States and China.With regard to the research methods, the following methods have been used: Case Study and ContentAnalysis. Case Studies are perhabs the most widely used research approach in internationalrelations (IR).In addition, to assert the main research question the Content Analysis is used. That method involvesanalyzing large amounts of text-based data. During research it was exercised books, analytical articles,and different research papers of international research institutes: like Carnegie Center, CenterStrategic and International Studies (CSIS), Belfer Center of International Affairs Harvard KennedySchool etc.Other method is the statistical method, related to the presenting the concrete statistics, for instance,concerning GDP of China, statistics of foreign trade, energy import etc.Theoretical context in this research is theory of international relations Realism. Particularly HansMorgenthau’s Realist Theory (6 principle) second principle – National Interest defined in terms ofNational Power. According to this principle nations always define and act for securing their nationalinterests by means of power. History tells us that nations have always acted on the basis of power.

The Application of Artificial Intelligence Models for Food Security: A Review

Emerging technologies associated with Artificial Intelligence (AI) have enabled improvements in global food security situations. However, there is a limited understanding regarding the extent to which stakeholders are involved in AI modelling research for food security purposes. This study systematically reviews the existing literature to bridge the knowledge gap in AI and food security, focusing on software modelling perspectives. The study found the application of AI models to examine various indicators of food security across six continents, with most studies conducted in sub-Saharan Africa. While research organisations conducting AI modelling were predominantly based in Europe or the Americas, their study communities were in the Global South. External funders also supported AI modelling research on food security through international universities and research institutes, although some collaborations with local organisations and external partners were identified. The analysis revealed three patterns in the application of AI models for food security research: (1) the exclusive utilisation of AI models to assess food security situations, (2) stakeholder involvement in some aspects of the AI modelling process, and (3) stakeholder involvement in AI modelling for food security through an iterative process. Overall, studies on AI models for food security were primarily experimental and lacked real-life implementation of the results with stakeholders. Consequently, this study concluded that research on AI, which incorporates feedback and/or the implementation of research outcomes for stakeholders, can contribute to learning and enhance the validity of the models in addressing food security challenges.

Nursing Educators’ Experiences and Expectations of Research Production at a Faculty of Health Sciences: A Qualitative Study

Research production remains one of the most important tools to predict the likely number of future outputs for a set of researchers. Nursing educators have expectations when they enter an academic institution; however, if these expectations are not matched with their experiences, then their research production will be hampered. The purpose of this study was to explore nursing educators’ expectations and experiences regarding research production at the Faculty of Health Sciences at a national university in Namibia. The study used the qualitative approach with an explorative, descriptive and contextual design. Eighteen nursing educators from the School of Nursing and Public Health participated in the study. Participants were chosen by using a convenience sampling method. Data were collected through semi-structured interviews between June and September 2022 and were analysed using thematic analysis for recurring themes. The following themes emerged from the data analysis: individual research output and role expectations; institutional factors affecting research production; and corrective measures to improve research production. These findings demonstrate that there is a significant need to support the production of quality research of nursing educators by addressing the requirements of the academic and research staff so as to maximise the impact of their research and establish the University of Namibia as a renowned international research institution. This can be achieved through creating an opportunity for hosting research seminars, and by providing adequate financial support to academics and research staff to maximise the impact of their research. The findings of this study can be used to develop baseline data, which can enable a “point-in-time” snapshot of individual activity. This will enable consolidation of metrics on research activity up to faculty, school and institutional performance that is geared towards improving research production among academics, as well as the development of policies that support such production.

Health and well-being of serving and ex-serving UK Armed Forces personnel: protocol for the fourth phase of a longitudinal cohort study

IntroductionThis is the fourth phase of a longitudinal cohort study (2022–2023) to investigate the health and well-being of UK serving (Regulars and Reservists) and ex-serving personnel (veterans) who served during...

Vaccination against highly pathogenic avian influenza (HPAI): From opposition to acceptance. Proceeding of The First International Avian Influenza Summit, University of Arkansas- October 16-17, 2023”

The emergence of Highly Pathogenic Avian Influenza (HPAI) strains poses a significant threat to both avian populations and human health. Vaccination has been identified as a critical tool in mitigating the spread of HPAI. However, the acceptance and implementation of avian influenza vaccination programs have been met with opposition from various stakeholders, including poultry producers, public health authorities, and consumers. This abstract provides a comprehensive overview of the evolving landscape of HPAI vaccination strategies, tracing the trajectory from initial resistance to widespread acceptance. Initially, concerns surrounding vaccine efficacy, potential adverse effects, and the economic burden associated with large-scale vaccination campaigns led to hesitancy among poultry producers and industry stakeholders. Additionally, public health authorities grappled with challenges related to regulatory approval, vaccine strain selection, and the development of robust surveillance systems. Over time, advancements in vaccine technology and extensive research demonstrating the safety and effectiveness of HPAI vaccines have gradually shifted perceptions. Adopting innovative vaccination strategies, such as vector-based vaccines and recombinant technologies, has addressed previous limitations and bolstered confidence in immunization as a viable control measure. Moreover, collaborative efforts between international organizations, governments, and research institutions have played a pivotal role in establishing standardized vaccine development, distribution, and administration protocols. These endeavors have facilitated harmonizing global strategies and enhanced the preparedness and response mechanisms for potential HPAI outbreaks. Consumer attitudes have also evolved, driven by increased awareness of the public health implications of avian influenza and a growing demand for sustainable and ethically produced poultry products. This shift in consumer sentiment has incentivized industry stakeholders to embrace vaccination as a proactive measure to safeguard both avian welfare and human health. In conclusion, this abstract highlights the transformative journey of HPAI vaccination programs, underscoring the pivotal role of scientific innovation, collaborative partnerships, and evolving consumer perspectives in overcoming initial resistance. As the global community continues to confront emerging infectious diseases, the successful trajectory of HPAI vaccination provides valuable insights into the dynamic interplay between science, policy, and public perception in the face of evolving health challenges.

Analysis of Hotspots and Trends in Soil Moisture Research since the 21st Century

Soil moisture is a key factor in ecosystems that profoundly affects carbon, nitrogen, and water cycles on land surfaces, vegetation growth, and climate change. Consequently, numerous scholars have researched and authored scientific literature on soil moisture and related topics. Using the Web of Science database, we conducted a bibliometric analysis of 60,581 papers published in the field of soil moisture between 2000 and 2022. The findings revealed the following trends. (1) The number of publications on soil moisture has consistently increased in the 21st century at an increasing rate. For instance, although the annual increase was only 94 publications in 2005, it surged to 321 publications in 2020. (2) The United States (US), China, and developed European countries emerged as primary research institutions and authors. The US occupies a leading position in soil moisture research, boasting the highest number of publications and total citations in the field, whereas China ranks second in both publications and total citations. (3) Regarding international collaboration, the US has established close partnerships with numerous international research institutions. However, China’s international cooperation in this field requires improvement. (4) The Journal of Hydrology holds the top position in terms of both the total number of published articles and citations. Research on water resources ranked first in terms of its H-index. (5) Keyword analysis highlighted several current research hotspots, including the coupled covariance effect of soil moisture and land surface environmental factors in the context of climate change, soil moisture utilization rate, crop yield, influence mechanism of soil moisture on soil ecosystem structure, and development of high-precision soil moisture data products. In conclusion, this study provides a systematic review of the research hotspots and trends in soil moisture studies in the 21st century. The objective is to offer a comprehensive reference to aid in understanding the evolutionary patterns of soil moisture research in multiple dimensions.

Framework to Assess the Impact of International Research Experiences in Civil Engineering on Graduate Students

With globalization, the demand for competent engineering graduates with international acumen increases. In order to respond to this rising demand, the National Science Foundation (NSF) funded the International Research Experiences in Civil, Construction, and Environmental Engineering (IRECCEE) program to understand the impact of international research experiences on students through a multidisciplinary lens. The program provides Ph.D. students in civil engineering disciplines the opportunity to gain valuable international research experience and establish long-lasting collaborations with international researchers. The program funds students to travel and perform research work at an international research institution. For every student, such research experience becomes the intervention. This paper discusses the program and the corresponding research framework with the aim that the research community can leverage such framework. The mixed-method research framework was designed to comprehensively capture the immediate and sustained impact of the program on the students’ competencies. With a multidisciplinary approach, the framework captures impacts on students’ intercultural competence, professional development, intellectual growth, personal development, and academic development. The data collection includes survey designs and interviews. In order to capture immediate and sustained impacts, data is collected before and multiple times after the intervention.

Towards a bottom-up approach for collaboration in cultural heritage: the case of the Council for British Research in the Levant (CBRL) Amman Institute and the JEA's Urban Heritage Preservation Committee

Since the 19th century, Jordan, with its diverse and rich heritage, has been a thriving hub for international scholars and researchers. To further this pursuit, several international research institutes have been established in the country. This article showcases the partnership between the Council for British Research in the Levant (CBRL) Amman Institute, an international institute whose research topics include archaeology and heritage, and the Jordan Engineers Association’s Urban Heritage Preservation Committee. Their collaboration aimed to attract architects and increase their interest and knowledge of Jordan’s heritage, in theory and practice, by designing a comprehensive programme of activities. These activities included a training course, webinars, a heritage award, heritage walks and heritage days. By considering the specific interests of the audience, and leveraging the knowledge and experience of both partners, they were able to collaborate with over 18 organizations in 9 events. The success and expansion of this partnership can be attributed to several factors, such as a wide range of activities, inclusive topics, bilingualism and efficient communication tools.

A probabilistic framework for forecasting maize yield response to agricultural inputs with sub-seasonal climate predictions

Crop yield results from the complex interaction between genotype, management, and environment. While farmers have control over what genotype to plant and how to manage it, their decisions are often sub-optimal due to climate variability. Sub-seasonal climate predictions embrace the great potential to improve risk analysis and decision-making. However, adequate frameworks integrating future weather uncertainty to predict crop outcomes are lacking. Maize (Zea mays L.) yields are highly sensitive to weather anomalies, and very responsive to plant density (plants m−2). Thus, economic optimal plat density is conditional to the seasonal weather conditions and can be anticipated with seasonal prospects. The aims of this study were to (i) design a model that describes the yield-to-plant density relationship (herein termed as yield–density) as a function of weather variables, and provides probabilistic forecasts for the economic optimum plant density (EOPD), and (ii) analyze the model predictive performance and sources of uncertainty. We present a novel approach to enable decision-making in agriculture using sub-seasonal climate predictions and Bayesian modeling. This model may inform crop management recommendations and accounts for various sources of uncertainty. A Bayesian hierarchical shrinkage model was fitted to the response of maize yield–density trials performed during the 2010–2019 period across seven states in the United States, identifying the relative importance of key weather, crop, and soil variables. Tercile forecasts of precipitation and temperature from the International Research Institute were used to forecast EOPD before the start of the season. The variables with the greatest influence on the yield–density relationship were weather anomalies, especially those variables indicating months with above-normal temperatures. Improvements on climate forecasting may also improve forecasts on yield responses to management, as we found reduced bias and error (by a factor >10), and greater precision (e.g. R2 increased from 0.26 to 0.32) for cases where weather forecasts matched observations. This study may contribute to the development of decision-support tools that can trigger discussions between farmers and consultants about management strategies and their associated risks.

Berlin statement on legacy and emerging contaminants in polar regions

Polar regions should be given greater consideration with respect to the monitoring, risk assessment, and management of potentially harmful chemicals, consistent with requirements of the precautionary principle. Protecting the vulnerable polar environments requires (i) raising political and public awareness and (ii) restricting and preventing global emissions of harmful chemicals at their sources. The Berlin Statement is the outcome of an international workshop with representatives of the European Commission, the Arctic Council, the Antarctic Treaty Consultative Meeting, the Stockholm Convention on Persistent Organic Pollutants (POPs), environmental specimen banks, and data centers, as well as scientists from various international research institutions. The statement addresses urgent chemical pollution issues in the polar regions and provides recommendations for improving screening, monitoring, risk assessment, research cooperation, and open data sharing to provide environmental policy makers and chemicals management decision-makers with relevant and reliable contaminant data to better protect the polar environments. The consensus reached at the workshop can be summarized in just two words: “Act now!”Specifically, “Act now!” to reduce the presence and impact of anthropogenic chemical pollution in polar regions by.•Establishing participatory co-development frameworks in a permanent multi-disciplinary platform for Arctic-Antarctic collaborations and establishing exchanges between the Arctic Monitoring and Assessment Program (AMAP) of the Arctic Council and the Antarctic Monitoring and Assessment Program (AnMAP) of the Scientific Committee on Antarctic Research (SCAR) to increase the visibility and exchange of contaminant data and to support the development of harmonized monitoring programs.•Integrating environmental specimen banking, innovative screening approaches and archiving systems, to provide opportunities for improved assessment of contaminants to protect polar regions.

The Japanese Neolithic: The Sea at the Origins of the Jōmon Culture and the Iriae Archaeological Excavations on Tsushima Island

Archaeology & Anthropology:Open Access The Japanese Neolithic: The Sea at the Origins of the Jōmon Culture and the Iriae Archaeological Excavations on Tsushima Island Daniele Petrella* International Research Institute for Archaeology and Ethnology, Italy *Corresponding author: Daniele Petrella, International Research Institute for Archaeology and Ethnology, Via Mezzocannone 109, Naples, Italy Submission: March 06, 2023Published: March 28, 2023 DOI: 10.31031/AAOA.2023.04.000612 ISSN: 2577-1949 Volume4 Issue4

Evolution trend and hot topic measurement of climate migration research under the influence of climate change

IntroductionGlobal climate change, which is characterized by climate warming, has become one of the most prominent risk problems in society at present. Climate migration brings many accompanying problems to the environment, economy, politics, society, and culture. It is of great theoretical and practical significance to study the internal relationship between climate change and population migration.MethodsThe data were extracted from the Web of Science core collection database (WOS) and China Knowledge Network database (CNKI). A total of 785 documents and 157 documents in the field of climate migration from 2008 to 2021 were selected as analysis samples. Word frequency analysis, clustering analysis, sudden word detection analysis, and other methods were extensively used to build the evolution trend map of climate migration using CiteSpace visual bibliometric software.ResultsIt is concluded that climate migration research has experienced three stages of development: initial exploration stage (2008-2011), development enrichment stage (2012-2017), and system deepening stage (2018).The hot topics of climate migration include: (1) different types of climate migration research; (2) Quantitative model research on climate migration; (3) Climate justice research. Different types of climate migration include 7 main types: (1) migration caused by sea level rise; (2) Resettlement caused by flood disaster; (3) Migration due to worsening drought; (4) Migration caused by extreme climate events; (5) Voluntary migration due to climate change discomfort; (6) Project resettlement caused by climate change response engineering measures; (7) Migrants whose livelihoods are broken due to climate change.DiscussionThe study points out that climate migration research is an interdisciplinary research field, which needs joint research by scholars from different academic backgrounds. In the future climate migration research, 1) strengthen the prediction ability of climate change population migration model; 2) Make use of China’s beneficial exploration in the migration fields such as engineering resettlement, ecological resettlement and poverty alleviation resettlement to formulate climate migration policies, regulations and strategic planning; 3) Establish a database cloud platform related to climate change and population migration; 4) Strengthen the exchange and cooperation between Chinese researchers in the field of climate migration and international scientific research institutions.

Proceedings of the ANSO-PAS-MAAP Conference on Epidemic and Pandemic Preparedness

An EPIDEMIC is a disease that affects many people within a community, population, or region. ENDEMIC is something that belongs to a particular people or country. A PANDEMIC is an epidemic that’s spread over multiple countries or continents. Epidemics and pandemics are some of the leading threats to global health security. They not only affect people’s health and well-being, but they can also have a massive impact on livelihoods and entire societies too. Pandemics can cause sudden, widespread morbidity and mortality as well as social, political, and economic disruption. The world has endured several notable pandemics, including the Black Death, Spanish flu, and human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Most new pandemics have originated through the “zoonotic” transmission of pathogens from animals to humans, and the next pandemic is likely to be a zoonosis as well. Zoonoses enter human populations from both domesticated animals (such as farmed swine or poultry) and wildlife. Many historically significant zoonoses were introduced through increased human-animal interaction following domestication, and potentially high-risk zoonoses (including avian influenzas) continue to emerge from livestock production systems. Some pathogens (including Ebola) have emerged from wildlife reservoirs and entered human populations through the hunting and consumption of wild species (such as bushmeat), the wild animal trade, and other contacts with wildlife. Spending and costs specifically associated with pandemic preparedness and response efforts are poorly tracked. There is no widely accepted, consistent methodology for estimating the economic impacts of pandemics.
 To highlight strategies to combat pandemics, a three-day ANSO-PAS-MAAP Conference on Epidemic and Pandemic Preparedness was jointly organized by the Pakistan Academy of Sciences (PAS), Alliance of International Science Organization (ANSO), and MonbukagakushoMEXT Alumni Association of Pakistan (MAAP) organized a three-day ANSO-PAS-MAAP Conference on “Epidemic and Pandemic Preparedness” from December 5 - 7, 2022 in the Pakistan Academy of Sciences, Islamabad. In total, 31 lectures were delivered at the ANSOPAS-MAAP Conference by leading experts in five technical sessions focused on the surveillance and preparedness against global Pandemics and epidemics. Of these, seven (07) lectures were presented by international speakers and twenty-six (26) lectures were presented by Pakistani speakers. The resource persons were leading foreign experts from different countries i.e., China, New Zealand, Italy, USA, and Pakistan. While 32 posters were presented on various themes of pandemics and epidemics in the Poster competition, in which young scientists from across the country participated. Over 400 academicians, scientists, researchers, and postgraduate students from Pakistan and abroad have registered to participate in the deliberations of the conference through physical and/or virtual (online) presence. In addition to the technical sessions, four group works were conducted to formulate recommendations. Recommendations of the conference will be shared with national and international bodies and research institutions dealing with the development of vaccines for the control of potential epidemic and pandemic-related issues worldwide.

Theoretical description of marketing system of automotive enterprises

The article examines the issues of using benchmarking to increase the competitiveness of auto industry enterprises. In the present conditions, the interaction concept in the marketing activities of auto industry enterprises consists of relations (communication) between buyers and the participants of the buying and selling process; scientific proposals and recommendations are given to increase the importance of effective communication of marketing interaction. At the same time, it is important to effectively influence the marketing system of auto industry enterprises by implementing the results of marketing research of international research institutes in forming directions for increasing the effectiveness of the marketing activities of auto industry enterprises, and as a result, to increase the investment potential and competitiveness of auto industry enterprises. Studying the theoretical foundations of the formation of marketing strategies in the automotive industry and approaches to classifying the types of marketing strategies allow to determine the peculiarities of their use in the automotive industry of Uzbekistan and to develop appropriate measures. The analysis of the characteristics of the main methodological approaches to the development of marketing strategies of automobile industry enterprises in foreign countries practically substantiates the fact that the flexibility to the processes related to market development is important, not the relationships that arise during the development of the marketing strategy and its implementation.

Trifluridine–tipiracil plus bevacizumab versus capecitabine plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer ineligible for intensive therapy (SOLSTICE): a randomised, open-label phase 3 study

Trifluridine-tipiracil plus bevacizumab has shown efficacy in previous phase 2 studies including patients with unresectable metastatic colorectal cancer. We aimed to investigate first-line trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab in patients with unresectable metastatic colorectal cancer ineligible for intensive treatment. In this open-label, randomised, phase 3 study, we enrolled patients aged 18 years and older with histologically confirmed metastatic colorectal cancer, ineligible for full-dose doublet or triplet chemotherapy and curative resection across 25 countries and regions. Participants were randomly allocated (1:1) to trifluridine-tipiracil plus bevacizumab or capecitabine plus bevacizumab until disease progression or unacceptable toxicity using an interactive web response system, stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), primary tumour location (right vs left colon), and the main reason for not being a candidate for intensive therapy (clinical condition vs non-clinical condition). The primary endpoint was investigator-assessed progression-free survival, defined as the time from randomisation to radiological progression or death from any cause, in the intention-to-treat population. Safety was assessed in all patients having taken at least one dose of the study drug. The trial is ongoing, findings presented here are those of the primary analysis of progression-free survival, conducted after 629 events had occurred. This study is registered with ClinicalTrials.gov, NCT03869892. Between March 21, 2019, and Sept 14, 2020, 856 patients (54% male, 46% female) were randomly assigned to trifluridine-tipiracil plus bevacizumab (n=426) or capecitabine plus bevacizumab (n=430). After a median follow-up of 16·6 months (95% CI 16·5-17·1), the hazard ratio for progression-free survival for trifluridine-tipiracil plus bevacizumab versus capecitabine plus bevacizumab was 0·87 (0·75-1·02; p=0·0464; protocol-defined significance level of p=0·021 not met). Investigator-assessed median progression-free survival was 9·4 months (95% CI 9·1-10·9) with trifluridine-tipiracil plus bevacizumab versus 9·3 months (8·9-9·8) with capecitabine plus bevacizumab. The most common grade 3 and higher treatment-emergent adverse events were neutropenia (220 [52%] of 423 patients in the trifluridine-tipiracil plus bevacizumab group vs six [1%] of 427 in the capecitabine plus bevacizumab group), decreased neutrophil count (78 [18%] vs four [<1%]), anaemia (60 [14%] vs 16 [4%]), and hand-foot syndrome (none vs 61 [15%]). Nine deaths (five in the trifluridine-tipiracil plus bevacizumab group and four in the capecitabine plus bevacizumab group) were treatment related. First-line trifluridine-tipiracil plus bevacizumab was not superior to capecitabine plus bevacizumab in this population. As expected, the safety profile differed between the two treatments, but there were no new safety concerns. Trifluridine-tipiracil plus bevacizumab represents a feasible alternative to capecitabine plus bevacizumab in this population. Servier International Research Institute, Suresnes, France.