Search results for: latin europe

Authors: Tatiana Rizova

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The migrant crisis, which peaked in 2015-2016, posed an unprecedented challenge to the European Union’s (EU) newest member states, including Bulgaria and Hungary. Their governments had to formulate sound migration policies with expediency and sensitivity to the needs of millions of people fleeing violent conflicts in the Middle East and failed states in North Africa. Political leaders in post-communist countries had to carefully coordinate with other EU member states on joint policies and solutions while minimizing the risk of alienating their increasingly anti-migrant domestic constituents. Post-communist member states’ governments chose distinct policy responses to the crisis, which were dictated by factors such as their governments’ partisan stances on migration, their views of the European Union, and the decision to frame the crisis as a security or a humanitarian issue. This paper explores how two Bulgarian governments (Boyko Borisov’s second and third government formed during the 43rd and 44th Bulgarian National Assembly, respectively) navigated the processes of EU migration policy making and managing the expectations of their electorates. Based on a comparative analysis of refugee policies in Bulgaria and Hungary during the height of the crisis (2015-2016) and a temporal analysis of refugee policies in Bulgaria (2015-2018), the paper advances the following conclusions. Drawing on insights of the Copenhagen school of security studies, the paper argues that cultural concerns dominated domestic debates in both Bulgaria and Hungary; both governments framed the issue predominantly as a matter of security rather than humanitarian disaster. Regardless of the similarities in issue framing, however, the two governments sought different paths of tackling the crisis. While the Bulgarian government demonstrated its willingness to comply with EU decisions (such as the proposal for mandatory quotas for refugee relocation), the Hungarian government defied EU directives and became a leading voice of dissent inside the EU. The current Bulgarian government (April 2017 - present) appears to be committed to complying with EU decisions and accepts the strategy of EU burden-sharing, while the Hungarian government has continually snubbed the EU’s appeals for cooperation despite the risk of hefty financial penalties. Hungary’s refugee policies have been influenced by the parliamentary representation of the far right-wing party Movement for a Better Hungary (Jobbik), which has encouraged the majority party (FIDESZ) to adopt harsher anti-migrant rhetoric and more hostile policies toward refugees. Bulgaria’s current government is a coalition of the center-right Citizens for a European Development of Bulgaria (GERB) and its far right-wing junior partners – the United Patriots (comprised of three nationalist political parties). The parliamentary presence of Jobbik in Hungary’s parliament has magnified the anti-migrant stance, rhetoric, and policies of Mr. Orbán’s Civic Alliance; we have yet to observe a substantial increase in the anti-migrant rhetoric and policies in Bulgaria’s case. Analyzing responses to the migrant/refugee crisis is a critical opportunity to understand how issues of cultural identity and belonging, inclusion and exclusion, regional integration and disintegration are debated and molded into policy in Europe’s youngest member states in the broader EU context.

Keywords: Copenhagen School, migrant crisis, refugees, security

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Authors: Batul Kagalwala

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The nervous system is made up of complex delicate structures such as the spinal cord, peripheral nerves and the brain. These are prone to various types of injury ranging from neurodegenerative diseases to trauma leading to diseases like Parkinson's, Alzheimer's, multiple sclerosis, amyotrophic lateral sclerosis (ALS), multiple system atrophy etc. Unfortunately, because of the complicated structure of nervous system, spontaneous regeneration, repair and healing is seldom seen due to which brain damage, peripheral nerve damage and paralysis from spinal cord injury are often permanent and incapacitating. Hence, innovative and standardized approach is required for advance treatment of neurological injury. Nigella sativa (N. sativa), an annual flowering plant native to regions of southern Europe and Asia; has been suggested to have neuroprotective and anti-seizures properties. Neuroregeneration is found to occur in damaged cells when treated using extract of N. sativa. Due to its proven health benefits, lots of experiments are being conducted to extract all the benefits from the plant. The flowers are delicate and are usually pale blue and white in color with small black seeds. These seeds are the source of active components such as 30–40% fixed oils, 0.5–1.5% essential oils, pharmacologically active components containing thymoquinone (TQ), ditimoquinone (DTQ) and nigellin. In traditional medicine, this herb was identified to have healing properties and was extensively used Middle East and Far East for treating diseases such as head ache, back pain, asthma, infections, dysentery, hypertension, obesity and gastrointestinal problems. Literature studies have confirmed the extract of N. sativa seeds and TQ have inhibitory effects on inducible nitric oxide synthase and production of nitric oxide as well as anti-inflammatory and anticancer activities. Experimental investigation will be conducted to understand which ingredient of N. sativa causes neuroregeneration and roots to its healing property. An aqueous/ alcoholic extract of N. sativa will be made. Seed oil is also found to have used by researchers to prepare such extracts. For the alcoholic extracts, the seeds need to be powdered and soaked in alcohol for a period of time and the alcohol must be evaporated using rotary evaporator. For aqueous extracts, the powder must be dissolved in distilled water to obtain a pure extract. The mobile phase will be the extract while the suitable stationary phase (substance that is a good adsorbent e.g. silica gels, alumina, cellulose etc.) will be selected. Different ingredients of N. sativa will be separated using High Performance Liquid Chromatography (HPLC) for treating damaged cells. Damaged brain cells will be treated individually and in different combinations of 2 or 3 compounds for different intervals of time. The most suitable compound or a combination of compounds for the regeneration of cells will be determined using DOE methodology. Later the gene will also be determined and using Polymerase Chain Reaction (PCR) it will be replicated in a plasmid vector. This plasmid vector shall be inserted in the brain of the organism used and replicated within. The gene insertion can also be done by the gene gun method. The gene in question can be coated on a micro bullet of tungsten and bombarded in the area of interest and gene replication and coding shall be studied. Investigation on whether the gene replicates in the organism or not will be examined.

Keywords: black cumin, brain cells, damage, extract, neuroregeneration, PCR, plasmids, vectors

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Authors: Delsy Salinas, Andreia Garcês, Augusto Silva, Paula Brilhante Simões

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Urinary tract infection (UTI) is a common disease affecting dogs and cats in both community and hospital environment. Bacteria is the most frequent agent isolated, fewer than 1% of infections are due to parasitic, fungal, or viral agents. Common symptoms and laboratory abnormalities includeabdominal pain, pyrexia, renomegaly, and neutrophilia with left shift. A rapid and precise identification of the bacterial agent is still a challenge in veterinarian laboratories. Therefore, this cross-sectional study aims to describe bacterial colony patterns of urine samples by using chromID™ CPS® EliteAgar (BioMérieux, France) from canine and feline specimens submitted to a veterinary laboratory in Portugal (INNO Veterinary Laboratory, Braga)from January to March2022. All urine samples were cultivated in CPS Elite Agar with calibrated 1 µL inoculating loop and incubated at 37ºC for 18-24h. Color,size, and shape (regular or irregular outline)were recorded for all samples. All colonies were classified as Gram-negative or Gram-positive bacteriausing Gram stain (PREVI® Color BioMérieux, France) and determined if they were pure colonies. Identification of bacteria species was performed using GP and GN cards inVitek 2® Compact(BioMérieux, France). A total of 256/1003 submitted urine samples presented bacterial growth, from which 172 isolates were included in this study. The sample’s population included 111 dogs (n=45 males and n=66 females) and 61 cats (n=35 males and n=26 females). The most frequent isolated bacteria wasEscherichia coli (44,7%), followed by Proteus mirabilis (13,4%). All Escherichia coli isolates presented red to burgundy colonies, a colony diameter between 2 to 6 mm, and regular or irregular outlines. Similarly, 100% of Proteus mirabilis isolates were dark yellow colonies with a diffuse pigment and the same size and shape as Escherichia coli. White and pink pale colonies where Staphylococcus species exclusively and S. pseudintermedius was the most frequent (8,2 %). Cian to blue colonies were mostly Enterococcusspp. (8,2%) and Streptococcus spp. (4,6%). Beige to brown colonies were Pseudomonas aeruginosa (2,9%) and Citrobacter spp. (1,2%).Klebsiella spp.,Serratia spp. and Enterobacter spp were green colonies. All Gram-positive isolates were 1 to 2 mm diameter long and had a regular outline, meanwhile, Gram-negative rods presented variable patterns. This results showed that theprevalence of E coli and P. mirabilis as uropathogenic agents follows the same trends in Europe as previously described in other studies. Both agents presented a particular color pattern in CPS Elite Agar to identify them without needing complementary tests. No other bacteria genus could be correlated strongly to a specific color pattern, and similar results have been observed instudies using human’s samples. Chromogenic media shows a great advantage for common urine bacteria isolation than traditional COS, McConkey, and CLEDAgar mediums in a routine context, especially when mixed fermentative Gram-negative agents grow simultaneously. In addition, CPS Elite Agar is versatile for Artificial Intelligent Reading Plates Systems. Routine veterinarian laboratories could use CPS Elite Agar for a rapid screening for bacteria identification,mainlyE coli and P.mirabilis, saving 6h to 10h of automatized identification.

Keywords: cats, CPS elite agar, dogs, urine pathogens

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Authors: Sarah Niklas, Lynne Chester, Mark Diesendorf

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Geopolitical tensions, climate change and recent movements favouring a transformative shift in institutional power structures have influenced the economics of conventional energy supply for decades. This study takes a multi-dimensional approach to illustrate the potential of renewable energy (RE) technology to provide a pathway to a low-carbon economy driven by ecologically sustainable, independent and socially just energy. This comparative analysis identifies economic, political and social drivers that shaped the adoption of RE policy in two significantly different economies, Germany and Australia, with strong and weak commitments to RE respectively. Two complementary political-economy theories frame the document-based analysis. Régulation Theory, inspired by Marxist ideas and strongly influenced by contemporary economic problems, provides the background to explore the social relationships contributing the adoption of RE within the macro-economy. Varieties of Capitalism theory, a more recently developed micro-economic approach, examines the nature of state-firm relationships. Together these approaches provide a comprehensive lens of analysis. Germany’s energy policy transformed substantially over the second half of the last century. The development is characterised by the coordination of societal, environmental and industrial demands throughout the advancement of capitalist regimes. In the Fordist regime, mass production based on coal drove Germany’s astounding economic recovery during the post-war period. Economic depression and the instability of institutional arrangements necessitated the impulsive seeking of national security and energy independence. During the postwar Flexi-Fordist period, quality-based production, innovation and technology-based competition schemes, particularly with regard to political power structures in and across Europe, favoured the adoption of RE. Innovation, knowledge and education were institutionalized, leading to the legislation of environmental concerns. Lastly the establishment of government-industry-based coordinative programs supported the phase out of nuclear power and the increased adoption of RE during the last decade. Australia’s energy policy is shaped by the country’s richness in mineral resources. Energy policy largely served coal mining, historically and currently one of the most capital-intense industry. Assisted by the macro-economic dimensions of institutional arrangements, social and financial capital is orientated towards the export-led and strongly demand-oriented economy. Here energy policy serves the maintenance of capital accumulation in the mining sector and the emerging Asian economies. The adoption of supportive renewable energy policy would challenge the distinct role of the mining industry within the (neo)-liberal market economy. The state’s protective role of the mining sector has resulted in weak commitment to RE policy and investment uncertainty in the energy sector. Recent developments, driven by strong public support for RE, emphasize the sense of community in urban and rural areas and the emergence of a bottom-up approach to adopt renewables. Thus, political economy frameworks on both the macro-economic (Regulation Theory) and micro-economic (Varieties of Capitalism theory) scales can together explain the strong commitment to RE in Germany vis-à-vis the weak commitment in Australia.

Keywords: political economy, regulation theory, renewable energy, social relationships, energy transitions

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Authors: Dean Sinković, Tea Golja, Morena Paulišić

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Upon the end of the vicious war in former Yugoslavia in 1995, international development community widely promoted microfinance as the key development framework to eradicate poverty, create jobs, increase income. Widespread claims were made that microfinance institutions would play vital role in creating a bedrock for sustainable ‘bottom-up’ economic development trajectory, thus, helping newly formed states to find proper way from economic post-war depression. This uplifting neoliberal narrative has no empirical support in the Republic of Croatia. Firstly, the type of enterprises created via microfinance sector are small, unskilled, labor intensive, no technology and with huge debt burden. This results in extremely high failure rates of microenterprises and poor individuals plunging into even deeper poverty, acute indebtedness and social marginalization. Secondly, evidence shows that microcredit is exact reflection of dangerous and destructive sub-prime lending model with ‘boom-to-bust’ scenarios in which benefits are solely extracted by the tiny financial and political elite working around the microfinance sector. We argue that microcredit providers are not proper financial structures through which developing countries should look way out of underdevelopment and poverty. In order to achieve sustainable long-term growth goals, public policy needs to focus on creating, supporting and facilitating the small and mid-size enterprises development. These enterprises should be technically sophisticated, capable of creating new capabilities and innovations, with managerial expertise (skills formation) and inter-connected with other organizations (i.e. clusters, networks, supply chains, etc.). Evidence from South-East Europe suggest that such structures are not created via microfinance model but can be fostered through various forms of social enterprises. Various legal entities may operate as social enterprises: limited liability private company, limited liability public company, cooperative, associations, foundations, institutions, Mutual Insurances and Credit union. Our main hypothesis is that cooperatives are potential agents of social and economic transformation and community development in the region. Financial cooperatives are structures that can foster more efficient allocation of financial resources involving deeper democratic arrangements and more socially just outcomes. In Croatia, pioneers of the first social enterprises were civil society organizations whilst forming a separated legal entity. (i.e. cooperatives, associations, commercial companies working on the principles of returning the investment to the founder). Ever since 1995 cooperatives in Croatia have not grown by pursuing their own internal growth but mostly by relying on external financial support. The greater part of today’s registered cooperatives tend to be agricultural (39%), followed by war veterans cooperatives (38%) and others. There are no financial cooperatives in Croatia. Due to the above mentioned we look at the historical developments and the prevailing social enterprises forms and discuss their advantages and disadvantages as potential agents for social and economic transformation and community development in the region. There is an evident lack of understanding of this business model and of its potential for social and economic development followed by an unfavorable institutional environment. Thus, we discuss the role of governance and management in the formation of social enterprises in Croatia, stressing the challenges for the governance of the country’s social enterprise movement.

Keywords: financial cooperatives, governance and management models, microfinance institutions, social enterprises

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Authors: Sopio Totibadze

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Although the legal framework of Georgia reflects the main principles of gender equality and is in line with the international situation (UNDP, 2018), Georgia remains a male-dominated society. This means that men prevail in many areas of social, economic, and political life, which frequently gives women a subordinate status in society and the family (UN women). According to the latest study, “violence against women and girls in Georgia is also recognized as a public problem, and it is necessary to focus on it” (UN women). Moreover, the Public Defender's report on the protection of human rights in Georgia (2019) reveals that “in the last five years, 151 women were killed in Georgia due to gender and family violence”. Sadly, these statistics have increased significantly since that time. The issue was acutely reflected in the document published by the Organization for Security and Cooperation in Europe, “Gender Hate Crime” (March 10, 2021). “Unfortunately, the rates of femicide ..... are still high in the country, and distrust of law enforcement agencies often makes such cases invisible, which requires special attention from the state.” More precisely, the cited document considers that there are frequent cases of crimes based on gender-based oppression in Georgia, which pose a threat not only to women but also to people of any gender whose desires and aspirations do not correspond to the gender norms and roles prevailing in society. According to the study, this type of crime has a “significant and lasting impact on the victim(s) and also undermines the safety and cohesion of society and gender equality”. It is well-known that language is often used as a tool for gender oppression (Rusieshvili-Cartledge and Dolidze, 2021; Totibadze, 2021). Therefore, feminist and gender studies in linguistics ultimately serve to represent the problem, reflect on it, and propose ways to solve it. Together with technical advancement in communication, a new form of discrimination has arisen- hate language against women in electronic media discourse. Due to the nature of social media and the internet, messages containing hate language can spread in seconds and reach millions of people. However, only a few know about the detrimental effects they may have on the addressee and society. This paper aims to analyse the hateful comments directed at women on various media platforms to determine (1) the linguistic strategies used while attacking women and (2) the reasons why women may fall victim to this type of hate language. The data have been collected over six months, and overall, 500 comments will be examined for the paper. Qualitative and quantitative analysis was chosen for the methodology of the study. The comments posted on various media platforms, including social media posts, articles, or pictures, have been selected manually due to several reasons, the most important being the problem of identifying hate speech as it can disguise itself in different ways- humour, memes, etc. The comments on the articles, posts, pictures, and videos selected for sociolinguistic analysis depict a woman, a taboo topic, or a scandalous event centred on a woman that triggered a lot of hatred and hate language towards the person to whom the post/article was dedicated. The study has revealed that a woman can become a victim of hatred directed at them if they do something considered to be a deviation from a societal norm, namely, get a divorce, be sexually active, be vocal about feministic values, and talk about taboos. Interestingly, people who utilize hate language are not only men trying to “normalize” the prejudiced patriarchal values but also women who are equally active in bringing down a "strong" woman. The paper also aims to raise awareness about the hate language directed at women, as being knowledgeable about the issue at hand is the first step to tackling it.

Keywords: femicide, hate language, media discourse, sociolinguistics

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Authors: Jonathan Adeyemi

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Context: This study focuses on El Anatsui and his global acclaim in the art world despite his origins from the global artworld’s margins. It addresses the disparities in the treatment between Western and non-Western artists and questions whether Anatsui’s consecration is a result of exoticism or the growing consensus on decolonization. Research Aim: The aim of this study is to investigate how El Anatsui achieved global acclaim from the margins of the art world and determine if his consecration represents a mark of decolonization or the typical Western desire for exoticism. Methodology: The study utilizes a case study approach, literature analysis, and in-depth interviews. The artist, the organizers of the Venice Biennale, the relevant curators at Tate Modern London, and the October Gallery in London, and other galleries in Nigeria, which represent the artist were interviewed for data collection. Findings: The study seeks to determine the authenticity of the growing consensus on decolonization, inclusion, and diversity in the global artistic field. Preliminary findings show that domestic socio-economic and political factors debilitated the mechanisms for local validation in Nigeria, weakening the domestic foundation for international engagement. However, alternative systems of exhibition, especially in London and the USA contributed critically to providing the initial international visibility, which formed the foundation for his global acclaim. Out of the 21 winners of the Golden Lion for Lifetime Achievement since its inception at the 47th Venice Biennale in 1997, American artists have dominated with 10 recipients, 8 recipients from Europe, 2 recipients from Africa (2007 and 2015) and 1 from Asia. This aligns with Bourdieu’s concept of cultural and economic capital, which prevented Africa countries from participation until recently. Moreover, while the average age of recipients is 76 years, Anatsui received the award at the age of 71, while Malick Sidibé (Mali) was awarded at 72. Thus, the Venice Biennale award for El Anatsui incline more towards a commitment to decolonisation than exoticism. Theoretical Importance: This study contributes to the field by examining the dynamics of the art world's monopoly of legitimation and the role of national, ethnicity and cultural differences in the promotion of artists. It aims to challenge the Westernized hierarchy of valorization and consecration in the art world. The research supports Bourdieu’s artistic field theory, which emphasises the importance of cultural, economic and social capital in determining agents’ position and access to the field resources (symbolic capital). Bourdieu also established that dominated agents can change their position in the field’s hierarchy either by establishing or navigating alternative systems. Data Collection and Analysis Procedures: The opacity of art world’s operations places the required information within the purview of the insiders (agents). Thus, the study collects data through in-depth interviews with relevant and purposively selected individuals and organizations. The data was/will be analyzed using qualitative methods, such as thematic analysis and content analysis. The interpretive analytical approach adopted facilitated the construction of meanings that may not be apparent in the data or responses. Questions Addressed: The study addresses how El Anatsui achieved global acclaim despite being from the margins, whether his consecration represents decolonization or exoticism, and the extent to which the global artistic field embraces decolonization, inclusion, and diversity. Conclusion: The study will contribute to knowledge by providing insights into the extent of commitment to decolonization, inclusion, and diversity in the global artistic field. It also shed light on the mechanisms behind El Anatsui's rise to global acclaim and challenge Western-dominated artistic hierarchies.

Keywords: decolonisation, exorticism, artistic field, culture game

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Authors: Hao Huang

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INTRODUCTION: The Association of American Colleges and Universities (AACU) recommends the development of ‘high-impact practices,’ in an effort to increase rates of student retention and student engagement at undergraduate institutions. To achieve these goals, the Scripps College Humanities Institute and HI Fellows Seminar not only featured distinguished academics presenting their scholarship about current immigration policy and its consequences in the USA and around the world but integrated socially significant community leaders and creative activists/artivists in public talks, student workshops and collaborative art events. Students participated in experiential learning that involved guest personal presentations and discussions, oral history interviews that applied standard oral history methodologies, detailed cultural documentation, collaborative artistic interventions, and weekly posts in Internet Digital Learning Environment Sakai collaborative course forums and regular responses to other students’ comments. Our teaching pedagogies addressed the four learning styles outlined in Kolb’s Learning Style Inventory. PROJECT DESCRIPTION: Over the academic year 2017-18, the Scripps College Humanities Institute and HI Fellows Seminar presented a Fall 2017 topic, ‘The World at Our Doorsteps: Immigration and Deportation in Los Angeles’. Our purpose was to address how current federal government anti-immigration measures have affected many students of color, some of whom are immigrants, many of whom are related to and are friends with people who are impacted by the attitudes as well as the practices of the U.S. Citizenship and Immigration Services. In Spring 2018, we followed with the topic, ‘Exclusive Nationalisms: Global Migration and Immigration’. This addresses the rise of white supremacists who have ascended to position of power worldwide, in America, Europe, Russia, and xenophobic nationalisms in China, Myanmar and the Philippines. Recent scholarship has suggested the existence of categories of refugees beyond the political or social, who fit into the more inclusive category of migrants. ASSESSMENT METHODOLOGIES: Assessment methodologies not only included qualitative student interviews and quantitative student evaluations in standard rubric format, but also Outcome Assessments, Formative Evaluations, and Outside Guest Teacher feedback. These indicated that the most effective educational practices involved collaborative inquiry in undergraduate research, community-based learning, and capstone projects. Assessments of E-portfolios, written and oral coursework, and final creative projects with associated 10-12 page analytic paper revealed that students developed their understanding of how government and social organizations work; they developed communication skills that enhanced working with others from different backgrounds; they developed their ability to thoughtfully evaluate their course performance by adopting reflective practices; they gained analytic and interpretive skills that encouraged self-confidence and self- initiative not only academically, but also with regards to independent projects. CONCLUSION: Most importantly, the Scripps Humanities Institute experiential learning project spurred on real-world actions by our students, such as a public symposium on how to cope with bigots, a student tutoring program for immigrant staff children, student negotiations with the administration to establish meaningful, sustainable diversity and inclusion programs on-campus. Activism is not only to be taught to and for our students– it has to be enacted by our students.

Keywords: immigration, migration, human rights, learning assessment

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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