Search results for: Sanjay Sinha
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 228

Search results for: Sanjay Sinha

18 Re-Entrant Direct Hexagonal Phases in a Lyotropic System Induced by Ionic Liquids

Authors: Saheli Mitra, Ramesh Karri, Praveen K. Mylapalli, Arka. B. Dey, Gourav Bhattacharya, Gouriprasanna Roy, Syed M. Kamil, Surajit Dhara, Sunil K. Sinha, Sajal K. Ghosh

Abstract:

The most well-known structures of lyotropic liquid crystalline systems are the two dimensional hexagonal phase of cylindrical micelles with a positive interfacial curvature and the lamellar phase of flat bilayers with zero interfacial curvature. In aqueous solution of surfactants, the concentration dependent phase transitions have been investigated extensively. However, instead of changing the surfactant concentrations, the local curvature of an aggregate can be altered by tuning the electrostatic interactions among the constituent molecules. Intermediate phases with non-uniform interfacial curvature are still unexplored steps to understand the route of phase transition from hexagonal to lamellar. Understanding such structural evolution in lyotropic liquid crystalline systems is important as it decides the complex rheological behavior of the system, which is one of the main interests of the soft matter industry. Sodium dodecyl sulfate (SDS) is an anionic surfactant and can be considered as a unique system to tune the electrostatics by cationic additives. In present study, imidazolium-based ionic liquids (ILs) with different number of carbon atoms in their single hydrocarbon chain were used as the additive in the aqueous solution of SDS. At a fixed concentration of total non-aqueous components (SDS and IL), the molar ratio of these components was changed, which effectively altered the electrostatic interactions between the SDS molecules. As a result, the local curvature is observed to modify, and correspondingly, the structure of the hexagonal liquid crystalline phases are transformed into other phases. Polarizing optical microscopy of SDS and imidazole-based-IL systems have exhibited different textures of the liquid crystalline phases as a function of increasing concentration of the ILs. The small angle synchrotron x-ray diffraction (SAXD) study has indicated the hexagonal phase of direct cylindrical micelles to transform to a rectangular phase at the presence of short (two hydrocarbons) chain IL. However, the hexagonal phase is transformed to a lamellar phase at the presence of long (ten hydrocarbons) chain IL. Interestingly, at the presence of a medium (four hydrocarbons) chain IL, the hexagonal phase is transformed to another hexagonal phase of direct cylindrical micelles through the lamellar phase. To the best of our knowledge, such a phase sequence has not been reported earlier. Even though the small angle x-ray diffraction study has revealed the lattice parameters of these phases to be similar to each other, their rheological behavior has been distinctly different. These rheological studies have shed lights on how these phases differ in their viscoelastic behavior. Finally, the packing parameters, calculated for these phases based on the geometry of the aggregates, have explained the formation of the self-assembled aggregates.

Keywords: lyotropic liquid crystals, polarizing optical microscopy, rheology, surfactants, small angle x-ray diffraction

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17 Effect of Perioperative Multimodal Analgesia on Postoperative Opioid Consumption and Complications in Elderly Traumatic Hip Fracture Patients: A Systematic Review of Randomised Controlled Trials

Authors: Raheel Shakoor Siddiqui, Shahbaz Malik, Manikandar Srinivas Cheruvu, Sanjay Narayana Murthy, Livio DiMascio

Abstract:

Background: elderly traumatic hip fracture patients frequently present to trauma services globally. Rising low energy falls amongst an osteoporotic aging population is the commonest cause for injury. Hip fractures in this population are a major cause for severe pain, morbidity and mortality. The term hip fracture is interchangeable with neck of femur fracture, fractured neck of femur or proximal femur fracture. Hip fracture pain management protocols and guidelines suggest conventional analgesia, nerve block and opioid based treatment as rescue analgesia. There is a current global opioid crisis with overuse, abuse and dependence. Adverse opioid related complications in vulnerable elderly patients further adds to morbidity and mortality. Systematic reviews in literature have evidenced superiority of multimodal analgesia in osteoarthritic primary joint replacements compared to opioids however, this has not yet been conducted for elderly traumatic hip fracture patients. Aims: The primary aim of this systematic review is to provide standardised evidence following Cochrane and PRISMA guidance in determining advantages of perioperative multimodal analgesia over conventional opioid based treatments in elderly traumatic hip fractures. Methods: 5 databases were searched from January 2000-2023 which identified 8 randomised controlled trials and 446 total participants. These trials met defined PICOS eligibility criteria of patient mean age ≥ 65 years presenting with a unilateral traumatic fractured neck of femur for operative intervention. Analgesic intervention with perioperative multimodal analgesia has been compared to conventional opioid based analgesia. Outcomes of interest include, primarily, the change in postoperative opioid consumption within a 0-30 postoperative period and secondarily, the change in postoperative adverse events and complications. A qualitative synthesis has been performed due to clinical heterogenicity and variance amongst trials. Results: GRADE evidence of moderate quality supports perioperative multimodal analgesia leads to a reduction in postoperative opioid consumption however, low quality evidence supports a reduction of adverse effects and complications. Conclusion: Perioperative multimodal analgesia whether used preoperative, intraoperative and/or postoperative leads to a reduction in postoperative opioid consumption for elderly traumatic hip fracture patients. This review recommends the use of perioperative multimodal analgesia as part of hip fracture pain protocols however, caution and clinical judgement should be used as the risk of adverse effects may not be lower.

Keywords: trauma, orthopaedics, hip, fracture, neck of femur fracture, analgesia, multimodal analgesia, opioid

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16 Tracking Patient Pathway for Assessing Public Health and Financial Burden to Community for Pulmonary Tuberculosis: Pointer from Central India

Authors: Ashish Sinha, Pushpend Agrawal

Abstract:

Background: Patients with undiagnosed pulmonary TB predominantly act as reservoirs for its transmission through 10-15 secondary infections in the next 1-5 Yrs. Delays in the diagnosis and treatment may worsen the disease with increase the risk of death. Factors responsible for such delays by tracking patient pathways to treatment may help in planning better interventions. The provision of ‘free diagnosis and treatment’ forms the cornerstone of the National Tuberculosis Elimination Programme (NTEP). OOPE is defined as the money spent by the patient during TB care other than public health facilities. Free TB care at all health facilities could reduce out-of-pocket expenses to the minimum possible levels. Material and Methods: This cross-sectional study was conducted among randomly selected 252 TB patients from Nov – Oct 2022 by taking in-depth interviews following informed verbal consent. We documented their journey from initial symptoms until they reached the public health facility, along with their ‘out-of-pocket expenditure’ (OOPE) pertaining to TB care. Results: Total treatment delay was 91±72 days on average (median: 77days, IQR: 45-104 days), while the isolated patient delay was 31±45 days (median: 15 days, IQR: 0 days to 43 days); diagnostic delay; 57±60 days (median: 42days, IQR 14-78 days), treatment delay 19 ± 18 days (median: 15days, IQR: 11-19 days). A patient delay (> 30 days) was significantly associated with ignorance about classic symptoms of pulmonary TB, adoption of self-medication, illiteracy, and middle and lower social class. Diagnostic delay was significantly higher among those who contacted private health facilities, were unaware of signs and symptoms, had >2 consultations, and not getting an appropriate referral for TB care. Most (97%) of the study participants interviewed claimed to have incurred some expenditure.Median total expenses were 6155(IQR: 2625-15175) rupees. More than half 141 (56%) of the study participants had expenses >5000 rupees. Median transport expenses were 525(IQR: 200-1012) rupees; Median consultation expenses were 700(IQR: 200-1600) rupees; Median investigation expenses were 1000(IQR: 0-3025) rupees and the Median medicine expenses were 3350(IQR: 1300-7525).OOPE for consultation, investigation, and medicine was observed to be significantly higher among patients who ignored classical signs& symptoms of TB, repeated visits to private health facilities, and due to self-medication practices. Transport expenses and delays in seeking care at facilities were observed to have an upward trend with OOP Expenses (r =1). Conclusion: Delay in TB care due to low awareness about signs and symptoms of TB and poor seeking care, lack of proper consultation, and appropriate referrals reported by the study subjects indicate the areas which need proper attention by the program managers. Despite a centrally sponsored programme, the financial burden on TB patients is still in the unacceptable range. OOPE could be reduced as low as possible by addressing the responsible factors linked to it.

Keywords: patient pathway, delay, pulmonary tuberculosis, out of pocket expenses

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15 A Fermatean Fuzzy MAIRCA Approach for Maintenance Strategy Selection of Process Plant Gearbox Using Sustainability Criteria

Authors: Soumava Boral, Sanjay K. Chaturvedi, Ian Howard, Kristoffer McKee, V. N. A. Naikan

Abstract:

Due to strict regulations from government to enhance the possibilities of sustainability practices in industries, and noting the advances in sustainable manufacturing practices, it is necessary that the associated processes are also sustainable. Maintenance of large scale and complex machines is a pivotal task to maintain the uninterrupted flow of manufacturing processes. Appropriate maintenance practices can prolong the lifetime of machines, and prevent associated breakdowns, which subsequently reduces different cost heads. Selection of the best maintenance strategies for such machines are considered as a burdensome task, as they require the consideration of multiple technical criteria, complex mathematical calculations, previous fault data, maintenance records, etc. In the era of the fourth industrial revolution, organizations are rapidly changing their way of business, and they are giving their utmost importance to sensor technologies, artificial intelligence, data analytics, automations, etc. In this work, the effectiveness of several maintenance strategies (e.g., preventive, failure-based, reliability centered, condition based, total productive maintenance, etc.) related to a large scale and complex gearbox, operating in a steel processing plant is evaluated in terms of economic, social, environmental and technical criteria. As it is not possible to obtain/describe some criteria by exact numerical values, these criteria are evaluated linguistically by cross-functional experts. Fuzzy sets are potential soft-computing technique, which has been useful to deal with linguistic data and to provide inferences in many complex situations. To prioritize different maintenance practices based on the identified sustainable criteria, multi-criteria decision making (MCDM) approaches can be considered as potential tools. Multi-Attributive Ideal Real Comparative Analysis (MAIRCA) is a recent addition in the MCDM family and has proven its superiority over some well-known MCDM approaches, like TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) and ELECTRE (ELimination Et Choix Traduisant la REalité). It has a simple but robust mathematical approach, which is easy to comprehend. On the other side, due to some inherent drawbacks of Intuitionistic Fuzzy Sets (IFS) and Pythagorean Fuzzy Sets (PFS), recently, the use of Fermatean Fuzzy Sets (FFSs) has been proposed. In this work, we propose the novel concept of FF-MAIRCA. We obtain the weights of the criteria by experts’ evaluation and use them to prioritize the different maintenance practices according to their suitability by FF-MAIRCA approach. Finally, a sensitivity analysis is carried out to highlight the robustness of the approach.

Keywords: Fermatean fuzzy sets, Fermatean fuzzy MAIRCA, maintenance strategy selection, sustainable manufacturing, MCDM

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14 Insulin Resistance in Early Postmenopausal Women Can Be Attenuated by Regular Practice of 12 Weeks of Yoga Therapy

Authors: Praveena Sinha

Abstract:

Context: Diabetes is a global public health burden, particularly affecting postmenopausal women. Insulin resistance (IR) is prevalent in this population, and it is associated with an increased risk of developing type 2 diabetes. Yoga therapy is gaining attention as a complementary intervention for diabetes due to its potential to address stress psychophysiology. This study focuses on the efficacy of a 12-week yoga practice in attenuating insulin resistance in early postmenopausal women. Research Aim: The aim of this research is to investigate the effect of a 3-month long yoga practice on insulin resistance in early postmenopausal women. Methodology: The study conducted a prospective longitudinal design with 67 women within five years of menopause. Participants were divided into two groups based on their willingness to join yoga. The Yoga group (n = 37) received routine gynecological management along with an integrated yoga module, while the Non-Yoga group (n = 30) received only routine management. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR) method before and after the intervention. Statistical analysis was performed using GraphPad Prism Version 5 software, with statistical significance set at P < 0.05. Findings: The results indicate a significant decrease in serum fasting insulin levels and HOMA-IR measurements in the Yoga group, although the decrease did not reach statistical significance. In contrast, the Non-Yoga group showed a significant rise in serum fasting insulin levels and HOMA-IR measurements after 3 months, suggesting a detrimental effect on insulin resistance in these postmenopausal women. Theoretical Importance: This study provides evidence that a 12-week yoga practice can attenuate the increase in insulin resistance in early postmenopausal women. It highlights the potential of yoga as a preventive measure against the early onset of insulin resistance and the development of type 2 diabetes mellitus. Regular yoga practice can be a valuable tool in addressing hormonal imbalances associated with early postmenopause, leading to a decrease in morbidity and mortality related to insulin resistance and type 2 diabetes mellitus in this population. Data Collection and Analysis Procedures: Data collection involved measuring serum fasting insulin levels and calculating HOMA-IR. Statistical analysis was performed using GraphPad Prism Version 5 software, and mean values with standard error of the mean were reported. The significance level was set at P < 0.05. Question Addressed: The study aimed to address whether a 3-month long yoga practice could attenuate insulin resistance in early postmenopausal women. Conclusion: The research findings support the efficacy of a 12-week yoga practice in attenuating insulin resistance in early postmenopausal women. Regular yoga practice has the potential to prevent the early onset of insulin resistance and the development of type 2 diabetes mellitus in this population. By addressing the hormonal imbalances associated with early post menopause, yoga could significantly decrease morbidity and mortality related to insulin resistance and type 2 diabetes mellitus in these subjects.

Keywords: post menopause, insulin resistance, HOMA-IR, yoga, type 2 diabetes mellitus

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13 The Structural Alteration of DNA Native Structure of Staphylococcus aureus Bacteria by Designed Quinoxaline Small Molecules Result in Their Antibacterial Properties

Authors: Jeet Chakraborty, Sanjay Dutta

Abstract:

Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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12 Cinema Reception in a Digital World: A Study of Cinema Audiences in India

Authors: Sanjay Ranade

Abstract:

Traditional film theory assumes the cinema audience in a darkened room where cinema is projected on to a white screen, and the audience suspends their sense of reality. Shifts in audiences due to changes in cultural tastes or trends have been studied for decades. In the past two decades, however, the audience, especially the youth, has shifted to digital media for the consumption of cinema. As a result, not only are audiences watching cinema on different devices, they are also consuming cinema in places and ways never imagined before. Public transport often crowded to the brim with a lot of ambient content, and a variety of workplaces have become sites for cinema viewing. Cinema is watched piecemeal and at different times of the day. Audiences use devices such as mobile phones and tablets to watch cinema. The cinema viewing experience is getting redesigned by the user. The emerging design allows the spectator to not only consume images and narratives but also produce, reproduce, and manipulate existing images and narratives, thereby participating in the process and influencing it. Spectatorship studies stress on the importance of subjectivity when dealing with the structure of the film text and the cultural and psychological implications in the engagement between the spectator and the film text. Indian cinema has been booming and contributing to global movie production significantly. In 2005 film production was 1000 films a year and doubled to 2000 by 2016. Digital technology helped push this growth in 2012. Film studies in India have had a decided Euro-American bias. The studies have chiefly analysed the content for ideological leanings or myth or as reflections of society, societal changes, or articulation of identity or presented retrospectives of directors, actors, music directors, etc. The one factor relegated to the background has been the spectator. If they have been addressed, they are treated as a collective of class or gender. India has a performative tradition going back several centuries. How Indians receive cinema is an important aspect to study with respect to film studies. This exploratory and descriptive study looked at 162 young media students studying cinema at the undergraduate and postgraduate levels. The students, speaking as many as 20 languages amongst them, were drawn from across the country’s media schools. The study looked at nine film societies registered with the Federation of Film Societies of India. A structured questionnaire was made and distributed online through media teachers for the students. The film societies were approached through the regional office of the FFSI in Mumbai. Lastly, group discussions were held in Mumbai with students and teachers of media. A group consisted of between five and twelve student participants, along with one or two teachers. All the respondents looked at themselves as spectators and shared their experiences of spectators of cinema, providing a very rich insight into Indian conditions of viewing cinema and challenges for cinema ahead.

Keywords: audience, digital, film studies, reception, reception spectatorship

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11 Capability of a Single Antigen to Induce Both Protective and Disease Enhancing Antibody: An Obstacle in the Creation of Vaccines and Passive Immunotherapies

Authors: Parul Kulshreshtha, Subrata Sinha, Rakesh Bhatnagar

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This study was conducted by taking B. anthracis as a model pathogen. On infecting a host, B. anthracis secretes three proteins, namely, protective antigen (PA, 83kDa), edema factor (EF, 89 kDa) and lethal factor (LF, 90 kDa). These three proteins are the components of two anthrax toxins. PA binds to the cell surface receptors, namely, tumor endothelial marker (TEM) 8 and capillary morphogenesis protein (CMG) 2. TEM8 and CMG2 interact with LDL-receptor related protein (LRP) 6 for endocytosis of EF and LF. On entering the cell, EF acts as a calmodulin-dependent adenylate cyclase that causes a prolonged increase of cytosolic cyclic adenosine monophosphate (cAMP). LF is a metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MAPKK/MEK) close to their N-terminus. By secreting these two toxins, B.anthracis ascertains death of the host. Once the systemic levels of the toxins rise, antibiotics alone cannot save the host. Therefore, toxin-specific inhibitors have to be developed. In this wake, monoclonal antibodies have been developed for the neutralization of toxic effects of anthrax toxins. We created hybridomas by using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor of B. anthracis) to obtain anti-toxin antibodies. Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immunized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies from all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H8 and H10) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). The protective efficacy of H7, H8, H10 and H11 was investigated. H7, H8 and H10 were found to be protective. H11 was found to have disease enhancing characteristics in-vitro and in mouse model of challenge with B. anthracis. In this study the disease enhancing character of H11 monoclonal antibody and anti-rLFn polyclonal sera was investigated. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature both in-vitro and in-vivo. But combination of H11 with LETscFv (an scFv with VH and VL identical to H10 but lacking Fc region) could not abrogate the disease-enhancing character of H11 mAb. Therefore it was concluded that for suppression of disease enhancement, Fc portion was absolutely essential for interaction of H10 with H11. Our study indicates that the protective potential of an antibody depends equally on its idiotype/ antigen specificity and its isotype. A number of monoclonal and engineered antibodies are being explored as immunotherapeutics but it is absolutely essential to characterize each one for their individual and combined protective potential. Although new in the sphere of toxin-based diseases, it is extremely important to characterize the disease-enhancing nature of polyclonal as well as monoclonal antibodies. This is because several anti-viral therapeutics and vaccines have failed in the face of this phenomenon. The passive –immunotherapy thus needs to be well formulated to avoid any contraindications.

Keywords: immunotherapy, polyclonal, monoclonal, antibody-dependent disease enhancement

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10 Optimizing Data Transfer and Processing in Multi-Cloud Environments for Big Data Workloads

Authors: Gaurav Kumar Sinha

Abstract:

In an era defined by the proliferation of data and the utilization of cloud computing environments, the efficient transfer and processing of big data workloads across multi-cloud platforms have emerged as critical challenges. This research paper embarks on a comprehensive exploration of the complexities associated with managing and optimizing big data in a multi-cloud ecosystem.The foundation of this study is rooted in the recognition that modern enterprises increasingly rely on multiple cloud providers to meet diverse business needs, enhance redundancy, and reduce vendor lock-in. As a consequence, managing data across these heterogeneous cloud environments has become intricate, necessitating innovative approaches to ensure data integrity, security, and performance.The primary objective of this research is to investigate strategies and techniques for enhancing the efficiency of data transfer and processing in multi-cloud scenarios. It recognizes that big data workloads are characterized by their sheer volume, variety, velocity, and complexity, making traditional data management solutions insufficient for harnessing the full potential of multi-cloud architectures.The study commences by elucidating the challenges posed by multi-cloud environments in the context of big data. These challenges encompass data fragmentation, latency, security concerns, and cost optimization. To address these challenges, the research explores a range of methodologies and solutions. One of the key areas of focus is data transfer optimization. The paper delves into techniques for minimizing data movement latency, optimizing bandwidth utilization, and ensuring secure data transmission between different cloud providers. It evaluates the applicability of dedicated data transfer protocols, intelligent data routing algorithms, and edge computing approaches in reducing transfer times.Furthermore, the study examines strategies for efficient data processing across multi-cloud environments. It acknowledges that big data processing requires distributed and parallel computing capabilities that span across cloud boundaries. The research investigates containerization and orchestration technologies, serverless computing models, and interoperability standards that facilitate seamless data processing workflows.Security and data governance are paramount concerns in multi-cloud environments. The paper explores methods for ensuring data security, access control, and compliance with regulatory frameworks. It considers encryption techniques, identity and access management, and auditing mechanisms as essential components of a robust multi-cloud data security strategy.The research also evaluates cost optimization strategies, recognizing that the dynamic nature of multi-cloud pricing models can impact the overall cost of data transfer and processing. It examines approaches for workload placement, resource allocation, and predictive cost modeling to minimize operational expenses while maximizing performance.Moreover, this study provides insights into real-world case studies and best practices adopted by organizations that have successfully navigated the challenges of multi-cloud big data management. It presents a comparative analysis of various multi-cloud management platforms and tools available in the market.

Keywords: multi-cloud environments, big data workloads, data transfer optimization, data processing strategies

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9 Indoor Air Pollution and Reduced Lung Function in Biomass Exposed Women: A Cross Sectional Study in Pune District, India

Authors: Rasmila Kawan, Sanjay Juvekar, Sandeep Salvi, Gufran Beig, Rainer Sauerborn

Abstract:

Background: Indoor air pollution especially from the use of biomass fuels, remains a potentially large global health threat. The inefficient use of such fuels in poorly ventilated conditions results in high levels of indoor air pollution, most seriously affecting women and young children. Objectives: The main aim of this study was to measure and compare the lung function of the women exposed in the biomass fuels and LPG fuels and relate it to the indoor emission measured using a structured questionnaire, spirometer and filter based low volume samplers respectively. Methodology: This cross-sectional comparative study was conducted among the women (aged > 18 years) living in rural villages of Pune district who were not diagnosed of chronic pulmonary diseases or any other respiratory diseases and using biomass fuels or LPG for cooking for a minimum period of 5 years or more. Data collection was done from April to June 2017 in dry season. Spirometer was performed using the portable, battery-operated ultrasound Easy One spirometer (Spiro bank II, NDD Medical Technologies, Zurich, Switzerland) to determine the lung function over Forced expiratory volume. The primary outcome variable was forced expiratory volume in 1 second (FEV1). Secondary outcome was chronic obstruction pulmonary disease (post bronchodilator FEV1/ Forced Vital Capacity (FVC) < 70%) as defined by the Global Initiative for Obstructive Lung Disease. Potential confounders such as age, height, weight, smoking history, occupation, educational status were considered. Results: Preliminary results showed that the lung function of the women using Biomass fuels (FEV1/FVC = 85% ± 5.13) had comparatively reduced lung function than the LPG users (FEV1/FVC = 86.40% ± 5.32). The mean PM 2.5 mass concentration in the biomass user’s kitchen was 274.34 ± 314.90 and 85.04 ± 97.82 in the LPG user’s kitchen. Black carbon amount was found higher in the biomass users (black carbon = 46.71 ± 46.59 µg/m³) than LPG users (black carbon=11.08 ± 22.97 µg/m³). Most of the houses used separate kitchen. Almost all the houses that used the clean fuel like LPG had minimum amount of the particulate matter 2.5 which might be due to the background pollution and cross ventilation from the houses using biomass fuels. Conclusions: Therefore, there is an urgent need to adopt various strategies to improve indoor air quality. There is a lacking of current state of climate active pollutants emission from different stove designs and identify major deficiencies that need to be tackled. Moreover, the advancement in research tools, measuring technique in particular, is critical for researchers in developing countries to improve their capability to study the emissions for addressing the growing climate change and public health concerns.

Keywords: black carbon, biomass fuels, indoor air pollution, lung function, particulate matter

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8 Effect of Dietary Inclusion of Moringa oleifera Leaf Meal on Blood Biochemical Changes and Lipid Profile of Vanaraja Chicken in Tropics

Authors: Kaushalendra Kumar, Abhishek Kumar, Chandra Moni, Sanjay Kumar, P. K. Singh, Ajeet Kumar

Abstract:

Present study investigated the dietary inclusion of Moringa oleifera leaf meal (MOLM) on production efficiency, hemato-biochemical profile and economy of Vanaraja birds under tropical condition. Experiment was conducted for a period of 56 days on 300 Vanaraja birds randomly divided in to five different experimental groups including control of 60 birds each group replicated with 20 chicks in each replicate. T1, T2, T3, T4, and T5 were offered with 0, 5, 10, 15, and 20% Moringa oleifera leaf meal along with basal ration. All the standard managemental practices were followed during experimental period including vaccination schedule. Locally available Moringa oleifera leaves were harvested at mature stage and allowed to dry under shady and aerated conditions. Thereafter, dried leaves were milled to make a leaf meal and stored in the airtight nylon bags to avoid any possible contamination from foreign material and use for experiment. Production parameters were calculated based on the amount of feed consumed and weight gain every weeks. The body weight gain of T2 group was significantly (P < 0.05) higher side whereas T3 group was comparable with control. The feed conversion ratio for T2 group was found to be significantly (P < 0.05) lower than all other treatment groups, while none of the group was comparable with each other. At the end of the experiment blood samples were collected from birds for haematology study while serum biochemistry performed using spectrophotometer following statndard protocols. The haematological attributes were significantly (P > 0.05) not differed among the groups. However, serum biochemistry showed significant reduction (P < 0.05) of blood urea nitrogen, uric acid and creatinine level with higher level of MOLM diet, indicates better utilization of protein supplemented through MOLM. The total cholesterol and triglyceride level was declined significantly (P < 0.05) as compare to control group with increased level of MOLM in basal diet, decreasing trend of serum cholesterol noted. However, value of HDL for T3 group was highest and for T1 group was lowest but no significant difference (P < 0.05) found among the groups. It might be due to presence of β-sitosterol a bioactive compound present in MOLM which causes lowering of plasma concentration of LDL. During experiment total, LDL and VLDL level was found to be decreased significantly (P < 0.05) as compare to control group. It was observed that the production efficiency of birds significantly improved with 5% followed by 10% Moringa oleifera leaf meal among the treatment groups. However, the maximum profit per kg live weight was noted in 10 % level and least profit observed in 20% MOLM fed group. It was concluded that the dietary inclusion of MOLM improved overall performances without affecting metabolic status and effective in reducing cholesterol level reflects healthy chicken production for human consumption.

Keywords: hemato biochemistry, Moringa oleifera leaf meal, performance, Vanaraja birds

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7 Growth Mechanism and Sensing Behaviour of Sn Doped ZnO Nanoprisms Prepared by Thermal Evaporation Technique

Authors: Sudip Kumar Sinha, Saptarshi Ghosh

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While there’s a perpetual buzz around zinc oxide (ZnO) superstructures for their unique optical features, the versatile material has been constantly utilized to manifest tailored electronic properties through rendition of distinct morphologies. And yet, the unorthodox approach of implementing the novel 1D nanostructures of ZnO (pristine or doped) for volatile sensing applications has ample scope to accommodate new unconventional morphologies. In the last two decades, solid-state sensors have attracted much curiosity for their relevance in identifying pollutant, toxic and other industrial gases. In particular gas sensors based on metal oxide semiconducting (wide Eg) nanomaterials have recently attracted intensive attention owing to their high sensitivity and fast response and recovery time. These materials when exposed to air, the atmospheric O2 dissociates and get absorb on the surface of the sensors by trapping the outermost shell electrons. Finally a depleted zone on the surface of the sensors is formed, that enhances the potential barrier height at grain boundary . Once a target gas is exposed to the sensor, the chemical interaction between the chemisorbed oxygen and the specific gas liberates the trapped electrons. Therefore altering the amount of adsorbate is a considerable approach to improve the sensitivity of any target gas/vapour molecule. Likewise, this study presents a spontaneous but self catalytic creation of Sn-doped ZnO hexagonal nanoprisms on Si (100) substrates through thermal evaporation-condensation method, and their subsequent deployment for volatile sensing. In particular, the sensors were utilized to detect molecules of ethanol, acetone and ammonia below their permissible exposure limits which returned sensitivities of around 85%, 80% and 50% respectively. The influence of Sn concentration on the growth, microstructural and optical properties of the nanoprisms along with its role in augmenting the sensing parameters has been detailed. The single-crystalline nanostructures have a typical diameter ranging from 300 to 500 nm and a length that extends up to few micrometers. HRTEM images confirmed the hexagonal crystallography for the nanoprisms, while SAED pattern asserted the single crystalline nature. The growth habit is along the low index <0001>directions. It has been seen that the growth mechanism of the as-deposited nanostructures are directly influenced by varying supersaturation ratio, fairly high substrate temperatures, and specified surface defects in certain crystallographic planes, all acting cooperatively decide the final product morphology. Room temperature photoluminescence (PL) spectra of this rod like structures exhibits a weak ultraviolet (UV) emission peak at around 380 nm and a broad green emission peak in the 505 nm regime. An estimate of the sensing parameters against dispensed target molecules highlighted the potential for the nanoprisms as an effective volatile sensing material. The Sn-doped ZnO nanostructures with unique prismatic morphology may find important applications in various chemical sensors as well as other potential nanodevices.

Keywords: gas sensor, HRTEM, photoluminescence, ultraviolet, zinc oxide

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6 OpenFOAM Based Simulation of High Reynolds Number Separated Flows Using Bridging Method of Turbulence

Authors: Sagar Saroha, Sawan S. Sinha, Sunil Lakshmipathy

Abstract:

Reynolds averaged Navier-Stokes (RANS) model is the popular computational tool for prediction of turbulent flows. Being computationally less expensive as compared to direct numerical simulation (DNS), RANS has received wide acceptance in industry and research community as well. However, for high Reynolds number flows, the traditional RANS approach based on the Boussinesq hypothesis is incapacitated to capture all the essential flow characteristics, and thus, its performance is restricted in high Reynolds number flows of practical interest. RANS performance turns out to be inadequate in regimes like flow over curved surfaces, flows with rapid changes in the mean strain rate, duct flows involving secondary streamlines and three-dimensional separated flows. In the recent decade, partially averaged Navier-Stokes (PANS) methodology has gained acceptability among seamless bridging methods of turbulence- placed between DNS and RANS. PANS methodology, being a scale resolving bridging method, is inherently more suitable than RANS for simulating turbulent flows. The superior ability of PANS method has been demonstrated for some cases like swirling flows, high-speed mixing environment, and high Reynolds number turbulent flows. In our work, we intend to evaluate PANS in case of separated turbulent flows past bluff bodies -which is of broad aerodynamic research and industrial application. PANS equations, being derived from base RANS, continue to inherit the inadequacies from the parent RANS model based on linear eddy-viscosity model (LEVM) closure. To enhance PANS’ capabilities for simulating separated flows, the shortcomings of the LEVM closure need to be addressed. Inabilities of the LEVMs have inspired the development of non-linear eddy viscosity models (NLEVM). To explore the potential improvement in PANS performance, in our study we evaluate the PANS behavior in conjugation with NLEVM. Our work can be categorized into three significant steps: (i) Extraction of PANS version of NLEVM from RANS model, (ii) testing the model in the homogeneous turbulence environment and (iii) application and evaluation of the model in the canonical case of separated non-homogeneous flow field (flow past prismatic bodies and bodies of revolution at high Reynolds number). PANS version of NLEVM shall be derived and implemented in OpenFOAM -an open source solver. Homogeneous flows evaluation will comprise the study of the influence of the PANS’ filter-width control parameter on the turbulent stresses; the homogeneous analysis performed over typical velocity fields and asymptotic analysis of Reynolds stress tensor. Non-homogeneous flow case will include the study of mean integrated quantities and various instantaneous flow field features including wake structures. Performance of PANS + NLEVM shall be compared against the LEVM based PANS and LEVM based RANS. This assessment will contribute to significant improvement of the predictive ability of the computational fluid dynamics (CFD) tools in massively separated turbulent flows past bluff bodies.

Keywords: bridging methods of turbulence, high Re-CFD, non-linear PANS, separated turbulent flows

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5 Development & Standardization of a Literacy Free Cognitive Rehabilitation Program for Patients Post Traumatic Brain Injury

Authors: Sakshi Chopra, Ashima Nehra, Sumit Sinha, Harsimarpreet Kaur, Ravindra Mohan Pandey

Abstract:

Background: Cognitive rehabilitation aims to retrain brain injured individuals with cognitive deficits to restore or compensate lost functions. As illiterates or people with low literacy levels represent a significant proportion of the world, specific rehabilitation modules for such populations are indispensable. Literacy is significantly associated with all neuropsychological measures and retraining programs widely use written or spoken techniques which essentially require the patient to read or write. So, the aim of the study was to develop and standardize a literacy free neuropsychological rehabilitation program for improving cognitive functioning in patients with mild and moderate Traumatic Brain Injury (TBI). Several studies have pointed out to the impairments seen in memory, executive functioning, and attention and concentration post-TBI, so the rehabilitation program focussed on these domains. Visual item memorization, stick constructions, symbol cancellations, and colouring techniques were used to construct the retraining program. Methodology: The development of the program consisted of planning, preparing, analyzing, and revising the different modules. The construction focussed on areas of retraining immediate and delayed visual memory, planning ability, focused and divided attention, concentration, and response inhibition (to control irritability and aggression). A total of 98 home based retraining modules were prepared in the 4 domains (42 for memory, 42 for executive functioning, 7 for attention and concentration, and 7 for response inhibition). The standardization was done on 20 healthy controls to review, select and edit items. For each module, the time, errors made and errors per second were noted down, to establish the difficulty level of each module and were arranged in increasing level of difficulty over a period of 6 weeks. The retraining tasks were then administered on 11 brain injured individuals (5 after Mild TBI and 6 after Moderate TBI). These patients were referred from the Trauma Centre to Clinical Neuropsychology OPD, All India Institute of Medical Sciences, New Delhi, India. Results: The time was taken, errors made and errors per second were analysed for all domains. Education levels were divided into illiterates, up to 10 years, 10 years to graduation and graduation and above. Mean and standard deviations were calculated. Between group and within group analysis was done using the t-test. The performance of 20 healthy controls was analyzed and only a significant difference was observed on the time taken for the attention tasks and all other domains had non-significant differences in performance between different education levels. Comparing the errors, time taken between patient and control group, there was a significant difference in all the domains at the 0.01 level except the errors made on executive functioning, indicating that the tool can successfully differentiate between healthy controls and patient groups. Conclusions: Apart from the time taken for symbol cancellations, the entire cognitive rehabilitation program is literacy free. As it taps the major areas of impairment post-TBI, it could be a useful tool to rehabilitate the patient population with low literacy levels across the world. The next step is already underway to test its efficacy in improving cognitive functioning in a randomized clinical controlled trial.

Keywords: cognitive rehabilitation, illiterates, India, traumatic brain injury

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4 Cognitive Decline in People Living with HIV in India and Correlation with Neurometabolites Using 3T Magnetic Resonance Spectroscopy (MRS): A Cross-Sectional Study

Authors: Kartik Gupta, Virendra Kumar, Sanjeev Sinha, N. Jagannathan

Abstract:

Introduction: A significant number of patients having human immunodeficiency virus (HIV) infection show a neurocognitive decline (NCD) ranging from minor cognitive impairment to severe dementia. The possible causes of NCD in HIV-infected patients include brain injury by HIV before cART, neurotoxic viral proteins and metabolic abnormalities. In the present study, we compared the level of NCD in asymptomatic HIV-infected patients with changes in brain metabolites measured by using magnetic resonance spectroscopy (MRS). Methods: 43 HIV-positive patients (30 males and 13 females) coming to ART center of the hospital and HIV-seronegative healthy subjects were recruited for the study. All the participants completed MRI and MRS examination, detailed clinical assessments and a battery of neuropsychological tests. All the MR investigations were carried out at 3.0T MRI scanner (Ingenia/Achieva, Philips, Netherlands). MRI examination protocol included the acquisition of T2-weighted imaging in axial, coronal and sagittal planes, T1-weighted, FLAIR, and DWI images in the axial plane. Patients who showed any apparent lesion on MRI were excluded from the study. T2-weighted images in three orthogonal planes were used to localize the voxel in left frontal lobe white matter (FWM) and left basal ganglia (BG) for single voxel MRS. Single voxel MRS spectra were acquired with a point resolved spectroscopy (PRESS) localization pulse sequence at an echo time (TE) of 35 ms and a repetition time (TR) of 2000 ms with 64 or 128 scans. Automated preprocessing and determination of absolute concentrations of metabolites were estimated using LCModel by water scaling method and the Cramer-Rao lower bounds for all metabolites analyzed in the study were below 15\%. Levels of total N-acetyl aspartate (tNAA), total choline (tCho), glutamate + glutamine (Glx), total creatine (tCr), were measured. Cognition was tested using a battery of tests validated for Indian population. The cognitive domains tested were the memory, attention-information processing, abstraction-executive, simple and complex perceptual motor skills. Z-scores normalized according to age, sex and education standard were used to calculate dysfunction in these individual domains. The NCD was defined as dysfunction with Z-score ≤ 2 in at least two domains. One-way ANOVA was used to compare the difference in brain metabolites between the patients and healthy subjects. Results: NCD was found in 23 (53%) patients. There was no significant difference in age, CD4 count and viral load between the two groups. Maximum impairment was found in the domains of memory and simple motor skills i.e., 19/43 (44%). The prevalence of deficit in attention-information processing, complex perceptual motor skills and abstraction-executive function was 37%, 35%, 33% respectively. Subjects with NCD had a higher level of Glutamate in the Frontal region (8.03 ± 2.30 v/s. 10.26 ± 5.24, p-value 0.001). Conclusion: Among newly diagnosed, ART-naïve retroviral disease patients from India, cognitive decline was found in 53\% patients using tests validated for this population. Those with neurocognitive decline had a significantly higher level of Glutamate in the left frontal region. There was no significant difference in age, CD4 count and viral load at initiation of ART between the two groups.

Keywords: HIV, neurocognitive decline, neurometabolites, magnetic resonance spectroscopy

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3 Structural Characteristics of HPDSP Concrete on Beam Column Joints

Authors: Hari Krishan Sharma, Sanjay Kumar Sharma, Sushil Kumar Swar

Abstract:

Inadequate transverse reinforcement is considered as the main reason for the beam column joint shear failure observed during recent earthquakes. DSP matrix consists of cement and high content of micro-silica with low water to cement ratio while the aggregates are graded quartz sand. The use of reinforcing fibres leads not only to the increase of tensile/bending strength and specific fracture energy, but also to reduction of brittleness and, consequently, to production of non-explosive ruptures. Besides, fibre-reinforced materials are more homogeneous and less sensitive to small defects and flaws. Recent works on the freeze-thaw durability (also in the presence of de-icing salts) of fibre-reinforced DSP confirm the excellent behaviour in the expected long term service life.DSP materials, including fibre-reinforced DSP and CRC (Compact Reinforced Composites) are obtained by using high quantities of super plasticizers and high volumes of micro-silica. Steel fibres with high tensile yield strength of smaller diameter and short length in different fibre volume percentage and aspect ratio tilized to improve the performance by reducing the brittleness of matrix material. In the case of High Performance Densified Small Particle Concrete (HPDSPC), concrete is dense at the micro-structure level, tensile strain would be much higher than that of the conventional SFRC, SIFCON & SIMCON. Beam-column sub-assemblages used as moment resisting constructed using HPDSPC in the joint region with varying quantities of steel fibres, fibre aspect ratio and fibre orientation in the critical section. These HPDSPC in the joint region sub-assemblages tested under cyclic/earthquake loading. Besides loading measurements, frame displacements, diagonal joint strain and rebar strain adjacent to the joint will also be measured to investigate stress-strain behaviour, load deformation characteristics, joint shear strength, failure mechanism, ductility associated parameters, stiffness and energy dissipated parameters of the beam column sub-assemblages also evaluated. Finally a design procedure for the optimum design of HPDSPC corresponding to moment, shear forces and axial forces for the reinforced concrete beam-column joint sub-assemblage proposed. The fact that the implementation of material brittleness measure in the design of RC structures can improve structural reliability by providing uniform safety margins over a wide range of structural sizes and material compositions well recognized in the structural design and research. This lead to the development of high performance concrete for the optimized combination of various structural ratios in concrete for the optimized combination of various structural properties. The structural applications of HPDSPC, because of extremely high strength, will reduce dead load significantly as compared to normal weight concrete thereby offering substantial cost saving and by providing improved seismic response, longer spans, and thinner sections, less reinforcing steel and lower foundation cost. These cost effective parameters will make this material more versatile for use in various structural applications like beam-column joints in industries, airports, parking areas, docks, harbours, and also containers for hazardous material, safety boxes and mould & tools for polymer composites and metals.

Keywords: high performance densified small particle concrete (HPDSPC), steel fibre reinforced concrete (SFRC), slurry infiltrated concrete (SIFCON), Slurry infiltrated mat concrete (SIMCON)

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2 Critical Factors for Successful Adoption of Land Value Capture Mechanisms – An Exploratory Study Applied to Indian Metro Rail Context

Authors: Anjula Negi, Sanjay Gupta

Abstract:

Paradigms studied inform inadequacies of financial resources, be it to finance metro rails for construction or to meet operational revenues or to derive profits in the long term. Funding sustainability is far and wide for much-needed public transport modes, like urban rail or metro rails, to be successfully operated. India embarks upon a sustainable transport journey and has proposed metro rail systems countrywide. As an emerging economic leader, its fiscal constraints are paramount, and the land value capture (LVC) mechanism provides necessary support and innovation toward development. India’s metro rail policy promotes multiple methods of financing, including private-sector investments and public-private-partnership. The critical question that remains to be addressed is what factors can make such mechanisms work. Globally, urban rail is a revolution noted by many researchers as future mobility. Researchers in this study deep dive by way of literature review and empirical assessments into factors that can lead to the adoption of LVC mechanisms. It is understood that the adoption of LVC methods is in the nascent stages in India. Research posits numerous challenges being faced by metro rail agencies in raising funding and for incremental value capture. A few issues pertaining to land-based financing, inter alia: are long-term financing, inter-institutional coordination, economic/ market suitability, dedicated metro funds, land ownership issues, piecemeal approach to real estate development, property development legal frameworks, etc. The question under probe is what are the parameters that can lead to success in the adoption of land value capture (LVC) as a financing mechanism. This research provides insights into key parameters crucial to the adoption of LVC in the context of Indian metro rails. Researchers have studied current forms of LVC mechanisms at various metro rails of the country. This study is significant as little research is available on the adoption of LVC, which is applicable to the Indian context. Transit agencies, State Government, Urban Local Bodies, Policy makers and think tanks, Academia, Developers, Funders, Researchers and Multi-lateral agencies may benefit from this research to take ahead LVC mechanisms in practice. The study deems it imperative to explore and understand key parameters that impact the adoption of LVC. Extensive literature review and ratification by experts working in the metro rails arena were undertaken to arrive at parameters for the study. Stakeholder consultations in the exploratory factor analysis (EFA) process were undertaken for principal component extraction. 43 seasoned and specialized experts participated in a semi-structured questionnaire to scale the maximum likelihood on each parameter, represented by various types of stakeholders. Empirical data was collected on chosen eighteen parameters, and significant correlation was extracted for output descriptives and inferential statistics. Study findings reveal these principal components as institutional governance framework, spatial planning features, legal frameworks, funding sustainability features and fiscal policy measures. In particular, funding sustainability features highlight sub-variables of beneficiaries to pay and use of multiple revenue options towards success in LVC adoption. Researchers recommend incorporation of these variables during early stage in design and project structuring for success in adoption of LVC. In turn leading to improvements in revenue sustainability of a public transport asset and help in undertaking informed transport policy decisions.

Keywords: Exploratory factor analysis, land value capture mechanism, financing metro rails, revenue sustainability, transport policy

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1 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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