Search results for: bone fracture risk
Commenced in January 2007
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Edition: International
Paper Count: 7201

Search results for: bone fracture risk

5851 Fear of Falling and Subjective Cognitive Decline Are Predictors of Fall Risk in Community-dwelling Older Adults Living in Low-income Settings

Authors: Ladda Thiamwong, Renata Komalasari

Abstract:

Falls are the leading cause of disability and hospitalization in low-income older adults. Fear of falling is present in 20% to 85 % of older adults and has been identified as an independent risk factor of fall risk, activity restriction, and loss of independence. About 12% of American older adults have subjective cognitive decline. Cognitive impairment is also an established factor of fall risk. However, it is unclear whether measures of fear of falling and subjective cognitive decline have the greatest association with fall risk in low-income older adults. The aim of this study was to evaluate the association between fear of falling, subjective cognitive decline-functional performance (SCD-FP), and fall risk using simple screening tools. In this cross-section study, we collected data from community-dwelling older adults 60 years or older in low-income settings in Central Florida, and 86 participants were included in the data analysis. Fear of falling was assessed by the Short Fall Efficacy Scale- International (Short FES-I) with seven items. Subjective cognitive decline-functional performance (SCD-FP) was assessed by a self-reported experience of worsening or more frequent confusion or memory loss in the past 12 months and its functional implications. Fall risk was evaluated by the Centers for Disease Control and Prevention (CDC)'s Stay Independent checklist with 12 items. The majority of participants were female, and more than half of the participants were African American. More than half of the participants had a higher school degree or higher, and less than 20% had no financial problems. Less than 30% of the participants perceived their general health as very good- excellent. More than half of the participants lived alone, and less than 15% lived with a partner or spouse. About 60% of the participants had hypertension, 40% had diabetes, 16% had cancer, and 50% had arthritis. About 30% of the participants had difficulty walking up ten steps without resting, more than 40% felt unsteady when walking, and 30% had been advised to use a cane or walker to get around safely. Regression analysis showed that fall risk was associated with fear of falling ( = .524, p <.001) and subjective cognitive decline-functional performance ( = .465, p =.027). The structure coefficient showed that fear of falling (rs2 = .922) was a stronger predictor of fall risk than subjective cognitive decline-functional performance (rs2= .200). Fear of falling and subjective cognitive decline-functional performance are growing public health issues, and addressing those issues is a public priority. Proactive screening for fear of falling and subjective cognitive decline-functional performance is critical in fall prevention. A combination of all three self-reported tools (Short FES-I, SCD-FP, and CDC's Stay Independent checklist) takes less than 5 minutes to complete. Primary care providers or public health professionals should consider including these tools to screen fear of falling and subjective cognitive decline-functional performance as part of fall risk assessment, especially in low-income settings. Thus, encouraging older adults and healthcare professionals to discuss fear of falling, subjective cognitive decline, and fall risk during routine medical office visits.

Keywords: falls, fall risk, fear of falling, cognition, subjective cognitive decline, low-income, older adults, community, screening, nursing, primary care

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5850 Identifying Children at Risk for Specific Language Impairment Using a Wordless Picture Narrative: A Study on Hindi, an Indian Language

Authors: Yozna Gurung

Abstract:

This paper presents preliminary findings from an on-going study on the use of Internal State Terms (IST) in the production of narratives of Hindi-English bilinguals in an attempt to identify children at risk for Specific Language Impairment. Narratives were examined for macrostructure (story structure and story complexity) and internal state terms or mental state terms (IST/MST). 31 students generated stories based on six pictures that were matched for content and story structure in L1 (Hindi) and L2 (English) using a wordless picture narrative. From 30 sample population, 2 students are at risk of Specific Language Impairment, according to this study i.e 6.45%. They showed least development in story grammar as well as IST in both their languages.

Keywords: internal state terms, macrostructure, specific language impairment, wordless picture narrative

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5849 Earthquakes' Magnitude and Density Controls by Mechanical Stratigraphy in the Zagros, Iran

Authors: Asaad Pireh

Abstract:

The Zagros fold and thrust belt is one of the most active seismic zones of Iran where hosts many people and considerable oil and gas resources. The Zagros fold and thrust belt, based on its stratigraphy has been divided into three provinces. Mechanical stratigraphy of these provinces is different together. Statistical analyses all of earthquakes which has happened in the Zagros fold and thrust belt from 1964 up to December 2014, shows that strong earthquakes have occurred within the southeastern part of these subdivisions which has a smaller ratio of incompetent to competent thickness and in the northwestern part of these subdivisions which has a greater ratio of incompetent to competent thickness has occurred the weakest earthquakes. The southeastern part of the Zagros has a higher seismic risk and northwestern part of these fold belt have a lower seismic risk.

Keywords: earthquake, mechanical stratigraphy, seismic risk, Zagros

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5848 Prevalence of Life Style Diseases and Physical Activities among Older in India

Authors: Vaishali Chaurasia

Abstract:

Ageing is the universal phenomenon that is associated with deteriorating health status. As the human becomes old, certain changes take place in an organism leading to morbidities, disabilities, and event death. Furthermore, older people are more vulnerable for the various kinds of diseases and health problem. Due to the some unhealthy conventions like smoking, drinking and unhealthy foods is the genesis of the lifestyle diseases. These diseases associated with the way a person or group of people lives. The main purpose of the study is to determine the prevalence of lifestyle diseases and its association with physical activity as well as the risk factors associated with it among the adult population in India. Longitudinal Aging Study in India and Study on Global Aging and Adult Health in India were used in the study. We will take population aged 50 and older, began in 1935, and regularly refreshed at younger ages with new birth cohorts. Life style diseases are more prominent in 65+ age group. The study finds an association between prevalence of life style diseases and life style risk factors. The lifestyle disease prevalence is more among higher age group people, female, richest quintile, and doing lesser physical activity. A higher prevalence of lifestyle diseases associated with the multiple risk factors. The occurrence of three and four risk factors was more prevalent in India. The frequency of different type of life style disease is higher among those who hardly or never do any physical activity as compare to those who do physical activity every day. The pattern remains the same in Moderate as well as vigorous physical activity. Those who are regularly doing physical activities have lesser percentage of having any disease and those who hardly ever or never do any physical activities and equally involve with some risk factors have higher percentage of having all type of diseases.

Keywords: lifestyle disease, morbidity, disability, physical activity

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5847 Virtual Reality Technology for Employee Training in High-Risk Industries: Benefits and Advancements

Authors: Yeganeh Jabbari, Sepideh Khalatabad

Abstract:

This study explores the development of virtual reality (VR) technology for training applications, specifically its the potential benefits of VR technology for employee training and its ability to simulate real-world scenarios in a safe and controlled environment are highlighted, along with the associated cost and time savings. The adoption of VR technology in high-risk industrial organizations such as the oil and gas industry is discussed, with a focus on its ability to improve worker performance. Additionally, the use of VR technology in activities such as simulation and data visualization in the oil and gas industry is explored, leading to enhanced safety measures and collaboration between teams. The integration of advanced technologies such as robotics is mentioned as a way to further promote efficiency and sustainability. Also, the study mentions that the digital transformation of the oil and gas industry is revolutionizing operations and promoting safety, efficiency, and sustainability through the use of VR technology.

Keywords: virtual reality training, virtual reality benefits, high-risk industries, digital transformation

Procedia PDF Downloads 88
5846 Secure Mobile E-Business Applications

Authors: Hala A. Alrumaih

Abstract:

It is widely believed that mobile device is a promising technology for lending the opportunity for the third wave of electronic commerce. Mobile devices have changed the way companies do business. Many applications are under development or being incorporated into business processes. In this day, mobile applications are a vital component of any industry strategy. One of the greatest benefits of selling merchandise and providing services on a mobile application is that it widens a company’s customer base significantly. Mobile applications are accessible to interested customers across regional and international borders in different electronic business (e-business) area. But there is a dark side to this success story. The security risks associated with mobile devices and applications are very significant. This paper introduces a broad risk analysis for the various threats, vulnerabilities, and risks in mobile e-business applications and presents some important risk mitigation approaches. It reviews and compares two different frameworks for security assurance in mobile e-business applications. Based on the comparison, the paper suggests some recommendations for applications developers and business owners in mobile e-business application development process.

Keywords: e-business, mobile applications, risk mitigations, security assurance

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5845 The Coexistence of Dual Form of Malnutrition among Portuguese Institutionalized Elderly People

Authors: C. Caçador, M. J. Reis Lima, J. Oliveira, M. J. Veiga, M. Teixeira Veríssimo, F. Ramos, M. C. Castilho, E. Teixeira-Lemos

Abstract:

In the present study we evaluated the nutritional status of 214 institutionalized elderly residents of both genders, aged 65 years and older of 11 care homes located in the district of Viseu (center of Portugal). The evaluation was based on anthropometric measurements and the Mini Nutritional Assessment (MNA) score. The mean age of the subjects was 82.3 ± 6.1 years-old. Most of the elderly residents were female (72.0%). The majority had 4 years of formal education (51.9%) and was widowed (74.3%) or married (14.0%). Men presented a mean age of 81.2±8.5 years-old, weight 69.3±14.5 kg and BMI 25.33±6.5 kg/m2. In women, the mean age was 84.5±8.2 years-old, weight 61.2±14.7 kg and BMI 27.43±5.6 kg/m2. The evaluation of the nutritional status using the MNA score showed that 24.0% of the residents show a risk of undernutrition and 76.0% of them were well nourished. There was a high prevalence of obese (24.8%) and overweight residents (33.2%) according to the BMI. 7.5% were considered underweight. We also found that according to their waist circumference measurements 88.3% of the residents were at risk for cardiovascular disease (CVD) and 64.0% of them presented very high risk for CVD (WC≥88 cm for women and WC ≥102 cm for men). The present study revealed the coexistence of a dual form of malnutrition (undernourished and overweight) among the institutionalized Portuguese concomitantly with an excess of abdominal adiposity. The high prevalence of residents at high risk for CVD should not be overlooked. Given the vulnerability of the group of institutionalized elderly, our study highlights the importance of the classification of nutritional status based on both instruments: the BMI and the MNA.

Keywords: nutritional satus, MNA, BMI, elderly

Procedia PDF Downloads 324
5844 Hydroxyapatite Based Porous Scaffold for Tooth Tissue Engineering

Authors: Pakize Neslihan Taslı, Alev Cumbul, Gul Merve Yalcın, Fikrettin Sahin

Abstract:

A key experimental trial in the regeneration of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. A different approach combining the gel-casting method with Hydroxy Apatite HA-based scaffold and different cell lineages as a hybrid system leads to successively mimic the early stage of tooth development, in vitro. HA is widely accepted as a bioactive material for guided bone and tooth regeneration. In this study, it was reported that, HA porous scaffold preparation, characterization and evaluation of structural and chemical properties. HA is the main factor that exists in tooth and it is in harmony with structural, biological, and mechanical characteristics. Here, this study shows mimicking immature tooth at the late bell stage design and construction of HA scaffolds for cell transplantation of human Adipose Stem Cells (hASCs), human Bone Marrow Stem Cells (hBMSCs) and Gingival Epitelial cells for the formation of human tooth dentin-pulp-enamel complexes in vitro. Scaffold characterization was demonstrated by SEM, FTIR and pore size and density measurements. The biological contraction of dental tissues against each other was demonstrated by mRNA gene expressions, histopatologic observations and protein release profile by ELISA tecnique. The tooth shaped constructs with a pore size ranging from 150 to 300 µm arranged by gathering right amounts of materials provide interconnected macro-porous structure. The newly formed tissue like structures that grow and integrate within the HA designed constructs forming tooth cementum like tissue, pulp and bone structures. These findings are important as they emphasize the potential biological effect of the hybrid scaffold system. In conclusion, this in vitro study clearly demonstrates that designed 3D scaffolds shaped as a immature tooth at the late bell stage were essential to form enamel-dentin-pulp interfaces with an appropriate cell and biodegradable material combination. The biomimetic architecture achieved here is providing a promising platform for dental tissue engineering.

Keywords: tooth regeneration, tissue engineering, adipose stem cells, hydroxyapatite tooth engineering, porous scaffold

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5843 Financial Risk Tolerance and Its Impact on Terrorism-Tourism Relation in Pakistan

Authors: Sania Sana, Afnan Nasim, Usman Malik, Maroof Tahir

Abstract:

The aim of this research is to scrutinize the interdependent relationship between terrorism and behavioral changes in the tourism activities in Pakistan with the moderating impact of a unique variable titled 'Financial Risk Tolerance'. The article looks at the inter-reliant relationship with the alleged political and economic aspects and behavioral changes in the tourists and the consumers by these variables over time. The researchers used many underlying theories like the catastrophe theory by (Svyantek, Deshon and Siler 1991), information integration theory (Anderson 1981, 1982) and prospect theory (Kahneman and Tversky 1979) to shape the study’s framework as per tourist decision making model. A sample of around 110 locals was used for this purpose and the data was gathered by convenience sampling. The responses were analyzed using regression analysis. The results exhibited how terrorism along with the influence of financial risk tolerance had inclined a behavioral shift in the travelling patterns and vacation destination choice of the local tourists. Lastly, the paper proposes a number of suggestive measures for the tourism industry and the legislative bodies to ensure the safety of travelers and to boost the tourist activities in the vacation industry of Pakistan.

Keywords: terrorism, tourism, financial risk tolerance, tourist decision-making, destination choice

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5842 Conjugated Linoleic Acid (CLA) Health Benefits and Sources

Authors: Hilal Ahmad Punoo

Abstract:

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid with two conjugated double bonds. Of more than a dozen isomers of CLA found naturally in dairy and meat products from ruminants, c-9, t-11 and t-10, c-12 are the two isomers with known physiological importance, including anticarcinogenic, antidiabetic, antilipogenic, and antiatherosclerotic effects. Conjugated linoleic acids (CLA) may influence the onset and severity of several chronic diseases, including various cancers, atherosclerosis, obesity, bone density loss, and diabetes. These findings are of special interest to the agriculture community, because dietary sources of CLA are almost exclusively beef and dairy products. Thus, a better understanding of the specific isomers and mechanisms responsible for these positive effects of CLA on human health would be both prudent and economically beneficial. To date, research related to the advantages of CLA consumption on human health has been conducted using experimental laboratory animals and cell culture systems. These data consistently show that relatively low levels of CLA can influence risk of cancer. Further, very recent investigations suggest that the predominate CLA isoform (cis-9, trans-11 CLA or rumenic acid) found in beef and milk fat possesses anticarcinogenic effects but does not alter body composition; the trans-10, cis-12 CLA has been shown to inhibit lipogenesis. Clearly, further work, especially using human subjects, will be required to characterize the potential benefits of CLA consumption on human health. Moreover, we suggest that foods naturally containing high amounts of CLA (e.g., beef and dairy products) be considered as meeting the definition of functional foods.

Keywords: conjugated linoleic acid, potential health benefits, fats, animals, humans

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5841 Risk Assessment of Heavy Metals in River Sediments and Suspended Matter in Small Tributaries of Abandoned Mercury Mines in Wanshan, Guizhou

Authors: Guo-Hui Lu, Jing-Yi Cai, Ke-Yan Tan, Xiao-Cai Yin, Yu Zheng, Peng-Wei Shao, Yong-Liang Yang

Abstract:

Soil erosion around abandoned mines is one of the important geological agents for pollutant diffuses to the lower reaches of the local river basin system. River loading of pollutants is an important parameter for remediation of abandoned mines. In order to obtain information on pollutant transport and diffusion downstream in mining area, the small tributary system of the Xiaxi River in Wanshan District of Guizhou Province was selected as the research area. Sediment and suspended matter samples were collected and determined for Pb, As, Hg, Zn, Co, Cd, Cu, Ni, Cr, and Mn by inductively coupled plasma mass spectrometry (ICP-MS) and atomic fluorescence spectrometry (AFS) with the pretreatment of wet digestion. Discussions are made for pollution status and spatial distribution characteristics. The total Hg content in the sediments ranged from 0.45 to 16.0 g/g (dry weight) with an average of 5.79 g/g, which was ten times higher than the limit of Class II soil for mercury by the National Soil Environmental Quality Standard. The maximum occurred at the intersection of the Jin River and the Xiaxi River. The potential ecological hazard index (RI) was used to evaluate the ecological risk of heavy metals in the sediments. The average RI value for the whole study area suggests the high potential ecological risk level. High Cd potential ecological risk was found at individual sites.

Keywords: heavy metal, risk assessment, sediment, suspended matter, Wanshan mercury mine, small tributary system

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5840 Juvenile Justice in Maryland: The Evidence Based Approach to Youth with History of Victimization and Trauma

Authors: Gabriela Wasileski, Debra L. Stanley

Abstract:

Maryland efforts to decrease the juvenile criminality and recidivism shifts towards evidence based sentencing. While in theory the evidence based sentencing has an impact on the reduction of juvenile delinquency and drug abuse; the assessment of juveniles’ risk and needs usually lacks crucial information about juvenile’s prior victimization. The Maryland Comprehensive Assessment and Service Planning (MCASP) Initiative is the primary tool for developing and delivering a treatment service plan for juveniles at risk. Even though it consists of evidence-based screening and assessment instruments very little is currently known regarding the effectiveness and the impact of the assessment in general. In keeping with Maryland’s priority to develop successful evidence-based recidivism reduction programs, this study examined results of assessments based on MCASP using a representative sample of the juveniles at risk and their assessment results. Specifically, it examined: (1) the results of the assessments in an electronic database (2) areas of need that are more frequent among delinquent youth in a system/agency, (3) the overall progress of youth in an agency’s care (4) the impact of child victimization and trauma experiences reported in the assessment. The project will identify challenges regarding the use of MCASP in Maryland, and will provide a knowledge base to support future research and practices.

Keywords: Juvenile Justice, assessment of risk and need, victimization and crime, recidivism

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5839 A Novel Treatment of the Arthritic Hip: A Prospective, Cross-Sectional Study on Changes Following Bone Marrow Concentrate Injection and Arthroscopic Debridement

Authors: A. Drapeaux, S. Aviles, E. Garfoot

Abstract:

Stem cell injections are a promising alternative treatment for hip osteoarthritis. Current literature has focused on short-term outcomes for both knee and hip osteoarthritis; however, there is a significant gap for longitudinal benefits for hip OA and limited firm conclusions due to small sample sizes. The purpose of this prospective study was to determine longitudinal changes in pain, function, and radiographs following bone marrow concentrate injection (BMAC) into the osteoarthritic hip joint. Methods: A prospective, cross-sectional study was conducted over the course of 12 months at an orthopedic practice. The study recruited 15 osteoarthritic pre-surgical hips with mild to moderate osteoarthritic severity who were scheduled to undergo hip arthroscopy. Data was collected at both pre-operative and post-operative time frames. Data collected included: hip radiographs, i-HOT-33 questionnaire data, BMAC autologous volume, and demographics. Questionnaire data was captured using Qualtrics XM software, and participants were sent an anonymous link at the following time frames: pre-operative, 2 weeks, 6 weeks, 12 weeks, 6 months, 12 months, and 24 months. Radiographic changes and BMAC volume were collected and reviewed by an orthopedic surgeon and sent to the primary investigator. Data was exported and analyzed in IBM-SPSS. Results: A total of 15 hips from 15 participants (mean age: 49, gender: 50% males, 50% females, BMI: 29.7) were used in the final analysis. Summative i-HOT 33 mean scores significantly changed between pre-operative status and 2-6 weeks post-operative status (p <.001) and pre-operative status and 3-6 months post-operative status (p <.001). There were no significant changes between other post-operative phases or between pre-operative status and 12 months post-operative. Significant improvements were found between summative i-HOT 33 mean (p<.001), daily pain (p<.001), daily sitting (p=.02), daily distance walked (p =.003), and daily limp (p=0.03) and post-operative status (2-6 weeks). No significant differences between demographic variables (gender, age, tobacco use, or diabetes) and i-HOT 33 summative mean scores. Discussion/Implications: The purpose of this study was to determine longitudinal changes in pain and function following a hip joint bone marrow concentrate injection. Results indicate that participants experience a significant improvement in pain and function between pre-operative and 2-6 weeks and 3-6 months post-injection. Participants also self-reported a significant change in average daily pain with sitting and walking between pre-operation and 2-6 weeks post-operative. This study includes a larger sample size of hip osteoarthritis cases; however, future research is warranted to include random controlled trials with a larger sample size.

Keywords: adult stem cell, orthopedics, osteoarthritis (hip), patient outcome assessment

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5838 Portfolio Risk Management Using Quantum Annealing

Authors: Thomas Doutre, Emmanuel De Meric De Bellefon

Abstract:

This paper describes the application of local-search metaheuristic quantum annealing to portfolio opti- mization. Heuristic technics are particularly handy when Markowitz’ classical Mean-Variance problem is enriched with additional realistic constraints. Once tailored to the problem, computational experiments on real collected data have shown the superiority of quantum annealing over simulated annealing for this constrained optimization problem, taking advantages of quantum effects such as tunnelling.

Keywords: optimization, portfolio risk management, quantum annealing, metaheuristic

Procedia PDF Downloads 383
5837 The Prodomain-Bound Form of Bone Morphogenetic Protein 10 is Biologically Active on Endothelial Cells

Authors: Austin Jiang, Richard M. Salmon, Nicholas W. Morrell, Wei Li

Abstract:

BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

Keywords: bone morphogenetic protein 10 (BMP10), endothelial cell, signal transduction, transforming growth factor beta (TGF-B)

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5836 Transparency Obligations under the AI Act Proposal: A Critical Legal Analysis

Authors: Michael Lognoul

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In April 2021, the European Commission released its AI Act Proposal, which is the first policy proposal at the European Union level to target AI systems comprehensively, in a horizontal manner. This Proposal notably aims to achieve an ecosystem of trust in the European Union, based on the respect of fundamental rights, regarding AI. Among many other requirements, the AI Act Proposal aims to impose several generic transparency obligationson all AI systems to the benefit of natural persons facing those systems (e.g. information on the AI nature of systems, in case of an interaction with a human). The Proposal also provides for more stringent transparency obligations, specific to AI systems that qualify as high-risk, to the benefit of their users, notably on the characteristics, capabilities, and limitations of the AI systems they use. Against that background, this research firstly presents all such transparency requirements in turn, as well as related obligations, such asthe proposed obligations on record keeping. Secondly, it focuses on a legal analysis of their scope of application, of the content of the obligations, and on their practical implications. On the scope of transparency obligations tailored for high-risk AI systems, the research notably notes that it seems relatively narrow, given the proposed legal definition of the notion of users of AI systems. Hence, where end-users do not qualify as users, they may only receive very limited information. This element might potentially raise concern regarding the objective of the Proposal. On the content of the transparency obligations, the research highlights that the information that should benefit users of high-risk AI systems is both very broad and specific, from a technical perspective. Therefore, the information required under those obligations seems to create, prima facie, an adequate framework to ensure trust for users of high-risk AI systems. However, on the practical implications of these transparency obligations, the research notes that concern arises due to potential illiteracy of high-risk AI systems users. They might not benefit from sufficient technical expertise to fully understand the information provided to them, despite the wording of the Proposal, which requires that information should be comprehensible to its recipients (i.e. users).On this matter, the research points that there could be, more broadly, an important divergence between the level of detail of the information required by the Proposal and the level of expertise of users of high-risk AI systems. As a conclusion, the research provides policy recommendations to tackle (part of) the issues highlighted. It notably recommends to broaden the scope of transparency requirements for high-risk AI systems to encompass end-users. It also suggests that principles of explanation, as they were put forward in the Guidelines for Trustworthy AI of the High Level Expert Group, should be included in the Proposal in addition to transparency obligations.

Keywords: aI act proposal, explainability of aI, high-risk aI systems, transparency requirements

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5835 Spatially Random Sampling for Retail Food Risk Factors Study

Authors: Guilan Huang

Abstract:

In 2013 and 2014, the U.S. Food and Drug Administration (FDA) collected data from selected fast food restaurants and full service restaurants for tracking changes in the occurrence of foodborne illness risk factors. This paper discussed how we customized spatial random sampling method by considering financial position and availability of FDA resources, and how we enriched restaurants data with location. Location information of restaurants provides opportunity for quantitatively determining random sampling within non-government units (e.g.: 240 kilometers around each data-collector). Spatial analysis also could optimize data-collectors’ work plans and resource allocation. Spatial analytic and processing platform helped us handling the spatial random sampling challenges. Our method fits in FDA’s ability to pinpoint features of foodservice establishments, and reduced both time and expense on data collection.

Keywords: geospatial technology, restaurant, retail food risk factor study, spatially random sampling

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5834 Risk Assessment of Contamination by Heavy Metals in Sarcheshmeh Copper Complex of Iran Using Topsis Method

Authors: Hossein Hassani, Ali Rezaei

Abstract:

In recent years, the study of soil contamination problems surrounding mines and smelting plants has attracted some serious attention of the environmental experts. These elements due to the non- chemical disintegration and nature are counted as environmental stable and durable contaminants. Variability of these contaminants in the soil and the time and financial limitation for the favorable environmental application, in order to reduce the risk of their irreparable negative consequences on environment, caused to apply the favorable grading of these contaminant for the further success of the risk management processes. In this study, we use the contaminants factor risk indices, average concentration, enrichment factor and geoaccumulation indices for evaluating the metal contaminant of including Pb, Ni, Se, Mo and Zn in the soil of Sarcheshmeh copper mine area. For this purpose, 120 surface soil samples up to the depth of 30 cm have been provided from the study area. And the metals have been analyzed using ICP-MS method. Comparison of the heavy and potentially toxic elements concentration in the soil samples with the world average value of the uncontaminated soil and shale average indicates that the value of Zn, Pb, Ni, Se and Mo is higher than the world average value and only the Ni element shows the lower value than the shale average. Expert opinions on the relative importance of each indicators were used to assign a final weighting of the metals and the heavy metals were ranked using the TOPSIS approach. This allows us to carry out efficient environmental proceedings, leading to the reduction of environmental ricks form the contaminants. According to the results, Ni, Pb, Mo, Zn, and Se have the highest rate of risk contamination in the soil samples of the study area.

Keywords: contamination coefficient, geoaccumulation factor, TOPSIS techniques, Sarcheshmeh copper complex

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5833 Integrating Deterministic and Probabilistic Safety Assessment to Decrease Risk & Energy Consumption in a Typical PWR

Authors: Ebrahim Ghanbari, Mohammad Reza Nematollahi

Abstract:

Integrating deterministic and probabilistic safety assessment (IDPSA) is one of the most commonly used issues in the field of safety analysis of power plant accident. It has also been recognized today that the role of human error in creating these accidents is not less than systemic errors, so the human interference and system errors in fault and event sequences are necessary. The integration of these analytical topics will be reflected in the frequency of core damage and also the study of the use of water resources in an accident such as the loss of all electrical power of the plant. In this regard, the SBO accident was simulated for the pressurized water reactor in the deterministic analysis issue, and by analyzing the operator's behavior in controlling the accident, the results of the combination of deterministic and probabilistic assessment were identified. The results showed that the best performance of the plant operator would reduce the risk of an accident by 10%, as well as a decrease of 6.82 liters/second of the water sources of the plant.

Keywords: IDPSA, human error, SBO, risk

Procedia PDF Downloads 129
5832 Health Risk Assessment of Exposing to Benzene in Office Building around a Chemical Industry Based on Numerical Simulation

Authors: Majid Bayatian, Mohammadreza Ashouri

Abstract:

Releasing hazardous chemicals is one of the major problems for office buildings in the chemical industry and, therefore, environmental risks are inherent to these environments. The adverse health effects of the airborne concentration of benzene have been a matter of significant concern, especially in oil refineries. The chronic and acute adverse health effects caused by benzene exposure have attracted wide attention. Acute exposure to benzene through inhalation could cause headaches, dizziness, drowsiness, and irritation of the skin. Chronic exposures have reported causing aplastic anemia and leukemia at the occupational settings. Association between chronic occupational exposure to benzene and the development of aplastic anemia and leukemia were documented by several epidemiological studies. Numerous research works have investigated benzene emissions and determined benzene concentration at different locations of the refinery plant and stated considerable health risks. The high cost of industrial control measures requires justification through lifetime health risk assessment of exposed workers and the public. In the present study, a Computational Fluid Dynamics (CFD) model has been proposed to assess the exposure risk of office building around a refinery due to its release of benzene. For simulation, GAMBIT, FLUENT, and CFD Post software were used as pre-processor, processor, and post-processor, and the model was validated based on comparison with experimental results of benzene concentration and wind speed. Model validation results showed that the model is highly validated, and this model can be used for health risk assessment. The simulation and risk assessment results showed that benzene could be dispersion to an office building nearby, and the exposure risk has been unacceptable. According to the results of this study, a validated CFD model, could be very useful for decision-makers for control measures and possibly support them for emergency planning of probable accidents. Also, this model can be used to assess exposure to various types of accidents as well as other pollutants such as toluene, xylene, and ethylbenzene in different atmospheric conditions.

Keywords: health risk assessment, office building, Benzene, numerical simulation, CFD

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5831 Closed Incision Negative Pressure Therapy Dressing as an Approach to Manage Closed Sternal Incisions in High-Risk Cardiac Patients: A Multi-Centre Study in the UK

Authors: Rona Lee Suelo-Calanao, Mahmoud Loubani

Abstract:

Objective: Sternal wound infection (SWI) following cardiac operation has a significant impact on patient morbidity and mortality. It also contributes to longer hospital stays and increased treatment costs. SWI management is mainly focused on treatment rather than prevention. This study looks at the effect of closed incision negative pressure therapy (ciNPT) dressing to help reduce the incidence of superficial SWI in high-risk patients after cardiac surgery. The ciNPT dressing was evaluated at 3 cardiac hospitals in the United Kingdom". Methods: All patients who had cardiac surgery from 2013 to 2021 were included in the study. The patients were classed as high risk if they have two or more of the recognised risk factors: obesity, age above 80 years old, diabetes, and chronic obstructive pulmonary disease. Patients receiving standard dressing (SD) and patients using ciNPT were propensity matched, and the Fisher’s exact test (two-tailed) and unpaired T-test were used to analyse categorical and continuous data, respectively. Results: There were 766 matched cases in each group. Total SWI incidences are lower in the ciNPT group compared to the SD group (43 (5.6%) vs 119 (15.5%), P=0.0001). There are fewer deep sternal wound infections (14(1.8%) vs. 31(4.04%), p=0.0149) and fewer superficial infections (29(3.7%) vs. 88 (11.4%), p=0.0001) in the ciNPT group compared to the SD group. However, the ciNPT group showed a longer average length of stay (11.23 ± 13 days versus 9.66 ± 10 days; p=0.0083) and higher mean logistic EuroSCORE (11.143 ± 13 versus 8.094 ± 11; p=0.0001). Conclusion: Utilization of ciNPT as an approach to help reduce the incidence of superficial and deep SWI may be effective in high-risk patients requiring cardiac surgery.

Keywords: closed incision negative pressure therapy, surgical wound infection, cardiac surgery complication, high risk cardiac patients

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5830 Modeling and Mapping of Soil Erosion Risk Using Geographic Information Systems, Remote Sensing, and Deep Learning Algorithms: Case of the Oued Mikkes Watershed, Morocco

Authors: My Hachem Aouragh, Hind Ragragui, Abdellah El-Hmaidi, Ali Essahlaoui, Abdelhadi El Ouali

Abstract:

This study investigates soil erosion susceptibility in the Oued Mikkes watershed, located in the Meknes-Fez region of northern Morocco, utilizing advanced techniques such as deep learning algorithms and remote sensing integrated within Geographic Information Systems (GIS). Spanning approximately 1,920 km², the watershed is characterized by a semi-arid Mediterranean climate with irregular rainfall and limited water resources. The waterways within the watershed, especially the Oued Mikkes, are vital for agricultural irrigation and potable water supply. The research assesses the extent of erosion risk upstream of the Sidi Chahed dam while developing a spatial model of soil loss. Several important factors, including topography, land use/land cover, and climate, were analyzed, with data on slope, NDVI, and rainfall erosivity processed using deep learning models (DLNN, CNN, RNN). The results demonstrated excellent predictive performance, with AUC values of 0.92, 0.90, and 0.88 for DLNN, CNN, and RNN, respectively. The resulting susceptibility maps provide critical insights for soil management and conservation strategies, identifying regions at high risk for erosion across 24% of the study area. The most high-risk areas are concentrated on steep slopes, particularly near the Ifrane district and the surrounding mountains, while low-risk areas are located in flatter regions with less rugged topography. The combined use of remote sensing and deep learning offers a powerful tool for accurate erosion risk assessment and resource management in the Mikkes watershed, highlighting the implications of soil erosion on dam siltation and operational efficiency.

Keywords: soil erosion, GIS, remote sensing, deep learning, Mikkes Watershed, Morocco

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5829 The Exploration of Psychosocial Risk and the Handling of Unsafe Acts and Misconduct

Authors: Jacquelene Swanepoel, J. C. Visagie, H. M. Linde

Abstract:

Purpose: The aim of this article is to investigate the psychosocial risk environment influencing employee behaviour, and subsequently the trust relationship between employer and employee. Design/methodology/approach: The unique nature and commonness of negative acts, such as unsafe behaviour, human errors, poor performance and negligence, also referred to as unsafe practice, are explored. A literature review is formulated to investigate the nature of negative acts or unsafe behaviour. The findings of this study are used to draw comparisons between unsafe behaviour/misconduct and accidents in the workplace and finally conclude how it should be addressed from a labour relations point of view. Findings: The results indicate comparisons between unsafe practice/misconduct and occupational injuries and accidents, as a result of system flaws, human error or psychosocial risk.

Keywords: occupational risks, unsafe practice, misconduct, organisational safety culture, ergonomics, management commitment and leadership, labour relations

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5828 Development of a Geomechanical Risk Assessment Model for Underground Openings

Authors: Ali Mortazavi

Abstract:

The main objective of this research project is to delve into a multitude of geomechanical risks associated with various mining methods employed within the underground mining industry. Controlling geotechnical design parameters and operational factors affecting the selection of suitable mining techniques for a given underground mining condition will be considered from a risk assessment point of view. Important geomechanical challenges will be investigated as appropriate and relevant to the commonly used underground mining methods. Given the complicated nature of rock mass in-situ and complicated boundary conditions and operational complexities associated with various underground mining methods, the selection of a safe and economic mining operation is of paramount significance. Rock failure at varying scales within the underground mining openings is always a threat to mining operations and causes human and capital losses worldwide. Geotechnical design is a major design component of all underground mines and basically dominates the safety of an underground mine. With regard to uncertainties that exist in rock characterization prior to mine development, there are always risks associated with inappropriate design as a function of mining conditions and the selected mining method. Uncertainty often results from the inherent variability of rock masse, which in turn is a function of both geological materials and rock mass in-situ conditions. The focus of this research is on developing a methodology which enables a geomechanical risk assessment of given underground mining conditions. The outcome of this research is a geotechnical risk analysis algorithm, which can be used as an aid in selecting the appropriate mining method as a function of mine design parameters (e.g., rock in-situ properties, design method, governing boundary conditions such as in-situ stress and groundwater, etc.).

Keywords: geomechanical risk assessment, rock mechanics, underground mining, rock engineering

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5827 Risk Assessment on New Bio-Composite Materials Made from Water Resource Recovery

Authors: Arianna Nativio, Zoran Kapelan, Jan Peter van der Hoek

Abstract:

Bio-composite materials are becoming increasingly popular in various applications, such as the automotive industry. Usually, bio-composite materials are made from natural resources recovered from plants, now, a new type of bio-composite material has begun to be produced in the Netherlands. This material is made from resources recovered from drinking water treatments (calcite), wastewater treatment (cellulose), and material from surface water management (aquatic plants). Surface water, raw drinking water, and wastewater can be contaminated with pathogens and chemical compounds. Therefore, it would be valuable to develop a framework to assess, monitor, and control the potential risks. Indeed, the goal is to define the major risks in terms of human health, quality of materials, and environment associated with the production and application of these new materials. This study describes the general risk assessment framework, starting with a qualitative risk assessment. The qualitative risk analysis was carried out by using the HAZOP methodology for the hazard identification phase. The HAZOP methodology is logical and structured and able to identify the hazards in the first stage of the design when hazards and associated risks are not well known. The identified hazards were analyzed to define the potential associated risks, and then these were evaluated by using the qualitative Event Tree Analysis. ETA is a logical methodology used to define the consequences for a specific hazardous incidents, evaluating the failure modes of safety barriers and dangerous intermediate events that lead to the final scenario (risk). This paper shows the effectiveness of combining of HAZOP and qualitative ETA methodologies for hazard identification and risk mapping. Then, key risks were identified, and a quantitative framework was developed based on the type of risks identified, such as QMRA and QCRA. These two models were applied to assess human health risks due to the presence of pathogens and chemical compounds such as heavy metals into the bio-composite materials. Thus, due to these contaminations, the bio-composite product, during its application, might release toxic substances into the environment leading to a negative environmental impact. Therefore, leaching tests are going to be planned to simulate the application of these materials into the environment and evaluate the potential leaching of inorganic substances, assessing environmental risk.

Keywords: bio-composite, risk assessment, water reuse, resource recovery

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5826 Prognostic Implication of Nras Gene Mutations in Egyptian Adult Acute Myeloid Leukemia

Authors: Doaa M. Elghannam, Nashwa Khayrat Abousamra, Doaa A. Shahin, Enas F. Goda, Hanan Azzam, Emad Azmy, Manal Salah El-Din

Abstract:

Background: The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. Point mutations of the NRAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). Aim: The present work was conducted to study the frequency and prognostic significance of NRAS gene mutations (NRASmut) in de novo Egyptian adult AML. Material and methods: Bone marrow specimens from 150 patients with de novo acute myeloid leukemia and controls were analyzed by genomic PCR-SSCP at codons 12, 13 (exon 1), and 61 (exon 2) for NRAS mutations. Results: NRAS gene mutations was found in 19/150 (12.7%) AML cases, represented more frequently in the FAB subtype M4eo (P = 0.028), and at codon 12, 13 (14of 19; 73.7%). Patients with NRASmut had a significant lower peripheral marrow blasts (P = 0.004, P=0.03) and non significant improved clinical outcome than patients without the mutation. Complete remission rate was (63.2% vs 56.5%; p=0.46), resistant disease (15.8% vs 23.6%; p=0.51), three years overall survival (44% vs 42%; P = 0.85) and disease free survival (42.1% vs 38.9%, P = 0.74). Multivariate analysis showed that age was the strongest unfavorable factor for overall survival (relative risk [RR], 1.9; P = .002), followed by cytogenetics (P = .004). FAB types, NRAS mutation, and leukocytosis were less important. Conclusions: NRAS gene mutation frequency and spectrum differ between biologically distinct subtypes of AML but do not significantly influence prognosis and clinical outcome.

Keywords: NRAS Gene, egyptian adult, acute myeloid leukemia, cytogenetics

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5825 Cost Based Analysis of Risk Stratification Tool for Prediction and Management of High Risk Choledocholithiasis Patients

Authors: Shreya Saxena

Abstract:

Background: Choledocholithiasis is a common complication of gallstone disease. Risk scoring systems exist to guide the need for further imaging or endoscopy in managing choledocholithiasis. We completed an audit to review the American Society for Gastrointestinal Endoscopy (ASGE) scoring system for prediction and management of choledocholithiasis against the current practice at a tertiary hospital to assess its utility in resource optimisation. We have now conducted a cost focused sub-analysis on patients categorized high-risk for choledocholithiasis according to the guidelines to determine any associated cost benefits. Method: Data collection from our prior audit was used to retrospectively identify thirteen patients considered high-risk for choledocholithiasis. Their ongoing management was mapped against the guidelines. Individual costs for the key investigations were obtained from our hospital financial data. Total cost for the different management pathways identified in clinical practice were calculated and compared against predicted costs associated with recommendations in the guidelines. We excluded the cost of laparoscopic cholecystectomy and considered a set figure for per day hospital admission related expenses. Results: Based on our previous audit data, we identified a77% positive predictive value for the ASGE risk stratification tool to determine patients at high-risk of choledocholithiasis. 47% (6/13) had an magnetic resonance cholangiopancreatography (MRCP) prior to endoscopic retrograde cholangiopancreatography (ERCP), whilst 53% (7/13) went straight for ERCP. The average length of stay in the hospital was 7 days, with an additional day and cost of £328.00 (£117 for ERCP) for patients awaiting an MRCP prior to ERCP. Per day hospital admission was valued at £838.69. When calculating total cost, we assumed all patients had admission bloods and ultrasound done as the gold standard. In doing an MRCP prior to ERCP, there was a 130% increase in cost incurred (£580.04 vs £252.04) per patient. When also considering hospital admission and the average length of stay, it was an additional £1166.69 per patient. We then calculated the exact costs incurred by the department, over a three-month period, for all patients, for key investigations or procedures done in the management of choledocholithiasis. This was compared to an estimate cost derived from the recommended pathways in the ASGE guidelines. Overall, 81% (£2048.45) saving was associated with following the guidelines compared to clinical practice. Conclusion: MRCP is the most expensive test associated with the diagnosis and management of choledocholithiasis. The ASGE guidelines recommend endoscopy without an MRCP in patients stratified as high-risk for choledocholithiasis. Our audit that focused on assessing the utility of the ASGE risk scoring system showed it to be relatively reliable for identifying high-risk patients. Our cost analysis has shown significant cost savings per patient and when considering the average length of stay associated with direct endoscopy rather than an additional MRCP. Part of this is also because of an increased average length of stay associated with waiting for an MRCP. The above data supports the ASGE guidelines for the management of high-risk for choledocholithiasis patients from a cost perspective. The only caveat is our small data set that may impact the validity of our average length of hospital stay figures and hence total cost calculations.

Keywords: cost-analysis, choledocholithiasis, risk stratification tool, general surgery

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5824 Corporate Governance and Firm Performance in the UAE

Authors: Bakr Ali Al-Gamrh, Ku Nor Izah B. Ku Ismail

Abstract:

We investigate the relationship between corporate governance, leverage, risk, and firm performance. We use a firm level panel that spans the period 2008 to 2012 of all listed firms on Abu Dhabi Stock Exchange and Dubai Financial Market. After constructing an index of corporate governance strength, we find a negative effect of corporate governance on firm performance. We, however, discover that corporate governance strength indirectly improves the negative influence of leverage on firm performance in normal times. On the contrary, the results completely reversed when there is a black swan event. Corporate governance strength plays a significantly negative role in moderating the relationship between leverage and firm performance during the financial crisis. We also reveal that corporate governance strength increases firms’ risk and deteriorates performance during crisis. Results provide evidence that corporate governance indirectly plays a completely different role in different time periods.

Keywords: corporate governance, firm performance, risk, leverage, the UAE

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5823 Treatment of Type 2 Diabetes Mellitus: Physicians’ Adherence to the American Diabetes Association Guideline in Central Region, Saudi Arabia

Authors: Ibrahim Mohammed

Abstract:

Background: Diabetes mellitus is a chronic disease that can cause devastating secondary complications, reducing the quality and length of life as well as increasing medical costs for the patient and society. The guidelines recommend both clinical and preventive strategies for diabetes management and are regularly updated. The aim of the study is to assess the level of adherence of physicians to American Diabetes Association Guidelines. Method: Observational multicenter retrospective study will be conducted among different hospitals in the central region. Patient data will be collected from the records of the last three years (2017- 2020). Records will be selected randomly after a complete randomized design. The study focuses on the management of type 2 according to ADA not changed in the last three updating; those standards; all patients should be taking Metformin 1500 to 2000 mg/day as recommended dose and should be received a high dose of statin if the high risk to ASCVD or moderate statin if not at risk, patients with hypertension and diabetes should taking ACE or ARBS. Result: The study aimed to evaluate the commitment of physicians in the central region to the ADA. Out of the 153 selected patients, only 17 % were able to control their diabetes with an average A1c below 7. ADA stated that to reach the minimum benefit of using Metformin, the daily dose should be between 1500 and 2000 mg. Results showed that 110 patients were on Metformin, where 68% of them were on the recommended dose. ADA recommended the intake of high statin for diabetic patients with ASCVD risk, while diabetic patients without ASCVD risk should be on a moderate statin. Results showed that 61.5% of patients with ASCVD risk were at high statin while only 36% of patients without ASCVD risk were at moderate statin. Results showed that 89 patients have hypertension, and 80% of them are getting ACE/ARBs as recommended by the ADA. Recommendation: It is necessary to implement periodic training courses for some physicians to enhance and update their knowledge.

Keywords: American Diabetic Association, diabetes mellitus, atherosclerotic cardiovascular disease, ACE inhibitors

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5822 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients

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

Abstract:

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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