Search results for: expression recognition
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3496

Search results for: expression recognition

16 An Analytic Cross-Sectional Study on the Association between Social Determinants of Health, Maternal and Child Health-Related Knowledge and Attitudes, and Utilization of Maternal, Newborn, Child Health and Nutrition Strategy-Prescribed Services for M

Authors: Rafael Carlos C. Aniceto, Bryce Abraham M. Anos, Don Christian A. Cornel, Marjerie Brianna S. Go, Samantha Nicole U. Roque, Earl Christian C. Te

Abstract:

Indigenous peoples (IPs) in the Philippines are a vulnerable, marginalized group in terms of health and overall well-being due to social inequities and cultural differences. National standards regarding maternal healthcare are geared towards facility-based delivery with modern medicine, health services, and skilled birth attendants. Standards and procedures of care for pregnant mothers do not take into account cultural differences between indigenous people and the majority of the population. There do exist, however, numerous other factors that cause relatively poorer health outcomes among indigenous peoples (IPs). This analytic cross-sectional study sought to determine the association between social determinants of health (SDH), focusing on status as indigenous peoples, and maternal health-related knowledge and attitudes (KA), and health behavior of the Dumagat-Agta indigenous people of Barangay Catablingan and Barangay San Marcelino, General Nakar, Quezon Province, and their utilization of health facilities for antenatal care, facility-based delivery and postpartum care, which would affect their health outcomes (that were not within the scope of this study). To quantitatively measure the primary/secondary exposures and outcomes, a total of 90 face-to-face interviews with IP and non-IP mothers were done. For qualitative information, participant observation among 6 communities (5 IP and 1 non-IP), 11 key informant interviews (traditional and modern health providers) and 4 focused group discussions among IP mothers were conducted. Primary quantitative analyses included chi-squared, T-test and binary logistic regression, while secondary qualitative analyses involved thematic analysis and triangulation. The researchers spent a total of 15 days in the community to learn the culture and participate in the practices of the Dumagat-Agta more intensively and deeply. Overall, utilization of all MNCHN services measured in the study was lower for IP mothers compared to their non-IP counterparts. After controlling for confounders measured in the study, IP status (primary exposure) was found to be significantly correlated with utilization of and adherence to two MNCHN-prescribed services: number of antenatal care check-ups and place of delivery (secondary outcomes). Findings show that being an indigenous mother leads to unfavorable social determinants of health, and if compounded by a difference in knowledge and attitudes, would then lead to poor levels of utilization of MNCHN-prescribed services. Key themes from qualitative analyses show that factors that affected utilization were: culture, land alienation, social discrimination, socioeconomic status, and relations between IPs and non-IPs, specifically with non-IP healthcare providers. The findings of this study aim to be used to help and guide in policy-making, to provide healthcare that is not only adequate and of quality, but more importantly, that addresses inequities stemming from various social determinants, and which is socio-culturally acceptable to indigenous communities. To address the root causes of health problems of IPs, there must be full recognition and exercise of their collective rights to communal assets, specifically land, and self-determination. This would improve maternal and child health outcomes to one of the most vulnerable and neglected sectors in society today.

Keywords: child health, indigenous people, knowledge-attitudes-practices, maternal health, social determinants of health

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15 Sinhala Sign Language to Grammatically Correct Sentences using NLP

Authors: Anjalika Fernando, Banuka Athuraliya

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This paper presents a comprehensive approach for converting Sinhala Sign Language (SSL) into grammatically correct sentences using Natural Language Processing (NLP) techniques in real-time. While previous studies have explored various aspects of SSL translation, the research gap lies in the absence of grammar checking for SSL. This work aims to bridge this gap by proposing a two-stage methodology that leverages deep learning models to detect signs and translate them into coherent sentences, ensuring grammatical accuracy. The first stage of the approach involves the utilization of a Long Short-Term Memory (LSTM) deep learning model to recognize and interpret SSL signs. By training the LSTM model on a dataset of SSL gestures, it learns to accurately classify and translate these signs into textual representations. The LSTM model achieves a commendable accuracy rate of 94%, demonstrating its effectiveness in accurately recognizing and translating SSL gestures. Building upon the successful recognition and translation of SSL signs, the second stage of the methodology focuses on improving the grammatical correctness of the translated sentences. The project employs a Neural Machine Translation (NMT) architecture, consisting of an encoder and decoder with LSTM components, to enhance the syntactical structure of the generated sentences. By training the NMT model on a parallel corpus of Sinhala wrong sentences and their corresponding grammatically correct translations, it learns to generate coherent and grammatically accurate sentences. The NMT model achieves an impressive accuracy rate of 98%, affirming its capability to produce linguistically sound translations. The proposed approach offers significant contributions to the field of SSL translation and grammar correction. Addressing the critical issue of grammar checking, it enhances the usability and reliability of SSL translation systems, facilitating effective communication between hearing-impaired and non-sign language users. Furthermore, the integration of deep learning techniques, such as LSTM and NMT, ensures the accuracy and robustness of the translation process. This research holds great potential for practical applications, including educational platforms, accessibility tools, and communication aids for the hearing-impaired. Furthermore, it lays the foundation for future advancements in SSL translation systems, fostering inclusive and equal opportunities for the deaf community. Future work includes expanding the existing datasets to further improve the accuracy and generalization of the SSL translation system. Additionally, the development of a dedicated mobile application would enhance the accessibility and convenience of SSL translation on handheld devices. Furthermore, efforts will be made to enhance the current application for educational purposes, enabling individuals to learn and practice SSL more effectively. Another area of future exploration involves enabling two-way communication, allowing seamless interaction between sign-language users and non-sign-language users.In conclusion, this paper presents a novel approach for converting Sinhala Sign Language gestures into grammatically correct sentences using NLP techniques in real time. The two-stage methodology, comprising an LSTM model for sign detection and translation and an NMT model for grammar correction, achieves high accuracy rates of 94% and 98%, respectively. By addressing the lack of grammar checking in existing SSL translation research, this work contributes significantly to the development of more accurate and reliable SSL translation systems, thereby fostering effective communication and inclusivity for the hearing-impaired community

Keywords: Sinhala sign language, sign Language, NLP, LSTM, NMT

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14 Nigeria Rural Water Supply Management: Participatory Process as the Best Option

Authors: E. O. Aluta, C. A. Booth, D. G. Proverbs, T. Appleby

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Challenges in the effective management of potable water have attracted global attention in recent years and remain many world regions’ major priorities. Scarcity and unavailability of potable water may potentially escalate poverty, obviate democratic expression of views and militate against inter-sectoral development. These challenges contra-indicate the inherent potentials of the resource. Thus, while creation of poverty may be regarded as a broad-based problem, it is capable of reflecting life-span reduction diseases, the friction of interests manifesting in threats and warfare, the relegation of democratic principles for authoritarian definitions and Human Rights abuse. The challenges may be identified as manifestations of ineffective management of potable water resource and therefore, regarded as major problems in environmental protection. In reaction, some nations have re-examined their laws and policies, while others have developed innovative projects, which seek to ameliorate difficulties of providing sustainable potable water. The problems resonate in Nigeria, where the legal framework supporting the supply and management of potable water has been criticized as ineffective. This has impacted more on rural community members, often regarded as ‘voiceless’. At that level, the participation of non-state actors has been identified as an effective strategy, which can improve water supply. However, there are indications that there is no pragmatic application of this, resulting in over-centralization and top-down management. Thus, this study focuses on how the participatory process may enable the development of participatory water governance framework, for use in Nigeria rural communities. The Rural Advisory Board (RAB) is proposed as a governing body to promote proximal relationships, institute democratisation borne out of participation, while enabling effective accountability and information. The RAB establishes mechanisms for effectiveness, taking into consideration Transparency, Accountability and Participation (TAP), advocated as guiding principles of decision-makers. Other tools, which may be explored in achieving these are, Laws and Policies supporting the water sector, under the direction of the Ministries and Law Courts, which ensure non-violation of laws. Community norms and values, consisting of Nigerian traditional belief system, perceptions, attitude and reality (often undermined in favour of legislations), are relied on to pave the way for enforcement. While the Task Forces consist of community members with specific designation of duties, which ensure compliance and enforceability, a cross-section of community members are assigned duties. Thus, the principle of participation is pragmatically reflected. A review of the literature provided information on the potentials of the participatory process, in potable water governance. Qualitative methodology was explored by using the semi-structured interview as strategy for inquiry. The purposive sampling strategy, consisting of homogeneous, heterogeneous and criterion techniques was applied to enable sampling. The samples, sourced from diverse positions of life, were from the study area of Delta State of Nigeria, involving three local governments of Oshimili South, Uvwie and Warri South. From the findings, there are indications that the application of the participatory process is inhered with empowerment of the rural community members to make legitimate demands for TAP. This includes the obviation of mono-decision making for the supply and management of potable water. This is capable of restructuring the top-down management to a top-down/bottom-up system.

Keywords: participation, participatory process, participatory water governance, rural advisory board

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13 Cardiac Hypertrophy in Diabetes; The Role of Factor Forkhead Box Class O-Regulation by O-GlcNAcylation

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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12 Towards Better Integration: Qualitative Study on Perceptions of Russian-Speaking Immigrants in Australia

Authors: Oleg Shovkovyy

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This research conducted in response to one of the most pressing questions on the agenda of many public administration offices around the world: “What could be done for better integration and assimilation of immigrants into hosting communities?” In author’s view, the answer could be suggested by immigrants themselves. They, often ‘bogged down in the past,’ snared by own idols and demons, perceive things differently, which, in turn, may result in their inability to integrate smoothly into hosting communities. Brief literature review suggests that perceptions of immigrants are completely neglected or something unsought in the current research on migrants, which, often, based on opinion polls by members of hosting communities themselves or superficial research data by various research organizations. Even those specimens that include voices of immigrants, unlikely to shed any additional light onto the problem simply because certain things are not made to speak out loud, especially to those in whose hands immigrants’ fate is (authorities). In this regard, this qualitative study, conducted by an insider to a few Russian-speaking communities, represents a unique opportunity for all stakeholders to look at the question of integration through the eyes of immigrants, from a different perspective and thus, makes research findings especially valuable for better understanding of the problem. Case study research employed ethnographic methods of gathering data where, approximately 200 Russian-speaking immigrants of first and second generations were closely observed by the Russian-speaking researcher in their usual setting, for eight months, and at different venues. The number of informal interviews with 27 key informants, with whom the researcher managed to establish a good rapport and who were keen enough to share their experiences voluntarily, were conducted. The field notes were taken at 14 locations (study sites) within the Brisbane region of Queensland, Australia. Moreover, all this time, researcher lived in dwelling of one of the immigrants and was an active participant in the social life (worship, picnics, dinners, weekend schools, concerts, cultural events, social gathering, etc.) of observed communities, whose members, to a large extent, belong to various religious lines of the Russian and Protestant Church. It was found that the majority of immigrants had experienced some discrimination in matters of hiring, employment, recognition of educational qualifications from home countries, and simply felt a sort of dislike from society in various everyday situations. Many noted complete absences or very limited state assistance in terms of employment, training, education, and housing. For instance, the Australian Government Department of Human Services not only does not stimulate job search but, on the contrary, encourages to refuse short-term works and employment. On the other hand, offered free courses on adaptation, and the English language proved to be ineffective and unpopular amongst immigrants. Many interviewees have reported overstated requirements for English proficiency and local work experience, whereas it was not critical for the given task or job. Based on the result of long-term monitoring, the researcher also had the courage to assert the negative and decelerating roles of immigrants’ communities, particularly religious communities, on processes of integration and assimilation. The findings suggest that governments should either change current immigration policies in the direction of their toughening or to take more proactive and responsible role in dealing with immigrant-related issues; for instance, increasing assistance and support to all immigrants and probably, paying more attention to and taking stake in managing and organizing lives of immigrants’ communities rather, simply leaving it all to chance.

Keywords: Australia, immigration, integration, perceptions

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11 Microfluidic Plasmonic Device for the Sensitive Dual LSPR-Thermal Detection of the Cardiac Troponin Biomarker in Laminal Flow

Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

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Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

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10 White-Rot Fungi Phellinus as a Source of Antioxidant and Antitumor Agents

Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

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9 Translating the Australian National Health and Medical Research Council Obesity Guidelines into Practice into a Rural/Regional Setting in Tasmania, Australia

Authors: Giuliana Murfet, Heidi Behrens

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Chronic disease is Australia’s biggest health concern and obesity the leading risk factor for many. Obesity and chronic disease have a higher representation in rural Tasmania, where levels of socio-disadvantage are also higher. People living outside major cities have less access to health services and poorer health outcomes. To help primary healthcare professionals manage obesity, the Australian NHMRC evidence-based clinical practice guidelines for management of overweight and obesity in adults were developed. They include recommendations for practice and models for obesity management. To our knowledge there has been no research conducted that investigates translation of these guidelines into practice in rural-regional areas; where implementation can be complicated by limited financial and staffing resources. Also, the systematic review that informed the guidelines revealed a lack of evidence for chronic disease models of obesity care. The aim was to establish and evaluate a multidisciplinary model for obesity management in a group of adult people with type 2 diabetes in a dispersed rural population in Australia. Extensive stakeholder engagement was undertaken to both garner support for an obesity clinic and develop a sustainable model of care. A comprehensive nurse practitioner-led outpatient model for obesity care was designed. Multidisciplinary obesity clinics for adults with type 2 diabetes including a dietitian, psychologist, physiotherapist and nurse practitioner were set up in the north-west of Tasmania at two geographically-rural towns. Implementation was underpinned by the NHMRC guidelines and recommendations focused on: assessment approaches; promotion of health benefits of weight loss; identification of relevant programs for individualising care; medication and bariatric surgery options for obesity management; and, the importance of long-term weight management. A clinical pathway for adult weight management is delivered by the multidisciplinary team with recognition of the impact of and adjustments needed for other comorbidities. The model allowed for intensification of intervention such as bariatric surgery according to recommendations, patient desires and suitability. A randomised controlled trial is ongoing, with the aim to evaluate standard care (diabetes-focused management) compared with an obesity-related approach with additional dietetic, physiotherapy, psychology and lifestyle advice. Key barriers and enablers to guideline implementation were identified that fall under the following themes: 1) health care delivery changes and the project framework development; 2) capacity and team-building; 3) stakeholder engagement; and, 4) the research project and partnerships. Engagement of not only local hospital but also state-wide health executives and surgical services committee were paramount to the success of the project. Staff training and collective development of the framework allowed for shared understanding. Staff capacity was increased with most taking on other activities (e.g., surgery coordination). Barriers were often related to differences of opinions in focus of the project; a desire to remain evidenced based (e.g., exercise prescription) without adjusting the model to allow for consideration of comorbidities. While barriers did exist and challenges overcome; the development of critical partnerships did enable the capacity for a potential model of obesity care for rural regional areas. Importantly, the findings contribute to the evidence base for models of diabetes and obesity care that coordinate limited resources.

Keywords: diabetes, interdisciplinary, model of care, obesity, rural regional

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8 Clinically-Based Improvement Project Focused on Reducing Risks Associated with Diabetes Insipidus, Syndrome of Inappropriate ADH, and Cerebral Salt Wasting in Paediatric Post-Neurosurgical and Traumatic Brain Injury Patients

Authors: Shreya Saxena, Felix Miller-Molloy, Phillipa Bowen, Greg Fellows, Elizabeth Bowen

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Background: Complex fluid balance abnormalities are well-established post-neurosurgery and traumatic brain injury (TBI). The triple-phase response requires fluid management strategies reactive to urine output and sodium homeostasis as patients shift between Diabetes Insipidus (DI) and Syndrome of Inappropriate ADH (SIADH). It was observed, at a tertiary paediatric center, a relatively high prevalence of the above complications within a cohort of paediatric post-neurosurgical and TBI patients. An audit of the clinical practice against set institutional guidelines was undertaken and analyzed to understand why this was occurring. Based on those results, new guidelines were developed with structured educational packages for the specialist teams involved. This was then reaudited, and the findings were compared. Methods: Two independent audits were conducted across two time periods, pre and post guideline change. Primary data was collected retrospectively, including both qualitative and quantitative data sets from the CQUIN neurosurgical database and electronic medical records. All paediatric patients post posterior fossa (PFT) or supratentorial surgery or with a TBI were included. A literature review of evidence-based practice, initial audit data, and stakeholder feedback was used to develop new clinical guidelines and nursing standard operation procedures. Compliance against these newly developed guidelines was re-assessed and a thematic, trend-based analysis of the two sets of results was conducted. Results: Audit-1 January2017-June2018, n=80; Audit-2 January2020-June2021, n=30 (reduced operative capacity due to COVID-19 pandemic). Overall, improvements in the monitoring of both fluid balance and electrolyte trends were demonstrated; 51% vs. 77% and 78% vs. 94%, respectively. The number of clear fluid management plans documented postoperatively also increased (odds ratio of 4), leading to earlier recognition and management of evolving fluid-balance abnormalities. The local paediatric endocrine team was involved in the care of all complex cases and notified sooner for those considered to be developing DI or SIADH (14% to 35%). However, significant Na fluctuations (>12mmol in 24 hours) remained similar – 5 vs six patients – found to be due to complex pituitary hypothalamic pathology – and the recommended adaptive fluid management strategy was still not always used. Qualitative data regarding useability and understanding of fluid-balance abnormalities and the revised guidelines were obtained from health professionals via surveys and discussion in the specialist teams providing care. The feedback highlighted the new guidelines provided a more consistent approach to the post-operative care of these patients and was a better platform for communication amongst the different specialist teams involved. The potential limitation to our study would be the small sample size on which to conduct formal analyses; however, this reflects the population that we were investigating, which we cannot control. Conclusion: The revised clinical guidelines, based on audited data, evidence-based literature review and stakeholder consultations, have demonstrated an improvement in understanding of the neuro-endocrine complications that are possible, as well as increased compliance to post-operative monitoring of fluid balance and electrolytes in this cohort of patients. Emphasis has been placed on preventative rather than treatment of DI and SIADH. Consequently, this has positively impacted patient safety for the center and highlighted the importance of educational awareness and multi-disciplinary team working.

Keywords: post-operative, fluid-balance management, neuro-endocrine complications, paediatric

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7 Geological, Geochronological, Geochemical, and Geophysical Characteristics of the Dalli Porphyry Cu-Au Deposit in Central Iran; Implications for Exploration

Authors: Hooshag Asadi Haroni, Maryam Veiskarami, Yongjun Lu

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The Dalli gold-rich porphyry deposit (17 Mt @ 0.5% Cu and 0.65 g/t Au) is located in the Urumieh-Dokhtar Magmatic Arc (UDMA), a small segment of the Tethyan metallogenic belt, hosting several porphyry Cu (Mo-Au) systems in Iran. This research characterizes the Dalli deposit to define exploration criteria in advanced exploration such as the drilling of possible blind porphyry centers. Geological map, trench/drill hole geochemical and ground magnetic data, and age dating and isotope trace element analyses, carried out at the John De Laeter Research Center of Curtin University, were used to characterize the Delli deposit. Mineralization at Dalli is hosted by NE-trending quartz-diorite porphyry stocks (~ 200m in diameter) intruded by a wall-rock andesite porphyry. Disseminated and stockwork Cu-Au mineralization is related to potassic alteration, comprising magnetite, late K-feldspar and biotite, and quartz-sericite-specularite overprint, surrounded by extensive barren argillic and propylitic alterations. In the peripheries of the porphyry centers, there are N-trending vuggy quartz veins, hosting epithermal Au-Ag-As-Sb mineralization. Geochemical analyses of drill core samples showed that the core of the porphyry stocks is low-grade, whereas the high-grade disseminated and stockwork mineralization (~ 1% Cu and ~ 1.2 g/t Au) occurred at the contact of the porphyry stocks and andesite porphyry. Geochemical studies of the drill hole and trench samples showed a strong correlation between Cu and Au and both show a second-order correlation with Fe and As. Magnetic survey revealed two significant magnetic anomalies, associated with intensive potassic alteration, in the reduced-to-the-pole magnetic map of the area. A relatively weaker magnetic anomaly, showing no surface porphyry expressions, is located on a lithocap, consisting of advanced argillic alteration, vuggy quartz veins, and surface expressions of epithermal geochemical signatures. The association of the lithocap and the weak magnetic anomaly could be indicative of a hidden mineralized porphyry center. Litho-geochemical analyses of the least altered Dalli intrusions and volcanic rocks indicated high Sr/Y (49-61) and Eu/Eu* (0.89-0.92), features typical of Cu porphyries. The U-Pb dating of zircons of the mineralized quartz diorite and andesite porphyry, carried out by laser ablation inductively coupled plasma mass spectrometry, yielded magmatic crystallization ages of 15.4-16.0 Ma (Middle Miocene). The zircon trace element concentrations of Dalli are characterized by high Eu/Eu* (0.3-0.8), (Ce/Nd)/Y (0.01-0.3), and 10000*(Eu/Eu*)/Y (2-15) ratios, similar to fertile porphyry suites such as the giant Sar-Cheshmeh and Qulong porphyry Cu deposits along the Tethyan belt. This suggests that the Middle Miocene Dalli intrusions are fertile and require extensive deep drillings to define their potential. Chondrite-normalized rare earth element (REE) patterns show no significant Eu anomalies, and are characterized by light-REE enrichments (La/Sm)n = 2.57–6.40). In normalized multi-element diagrams, analyzed rocks are characterized by enrichments in large ion lithophile elements (LILE) and depletions in high field strength elements (HFSE), and display typical features of subduction-related calc-alkaline magmas. The characteristics of the Dalli deposit provided several recognition criteria for detailed exploration of Cu-Au porphyry deposits and highlighted the importance of the UDMA as a potentially significant, economically important, but relatively underexplored porphyry province.

Keywords: porphyry, gold, geochronology, magnetic, exploration

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6 Settlement Prediction in Cape Flats Sands Using Shear Wave Velocity – Penetration Resistance Correlations

Authors: Nanine Fouche

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The Cape Flats is a low-lying sand-covered expanse of approximately 460 square kilometres, situated to the southeast of the central business district of Cape Town in the Western Cape of South Africa. The aeolian sands masking this area are often loose and compressible in the upper 1m to 1.5m of the surface, and there is a general exceedance of the maximum allowable settlement in these sands. The settlement of shallow foundations on Cape Flats sands is commonly predicted using the results of in-situ tests such as the SPT or DPSH due to the difficulty of retrieving undisturbed samples for laboratory testing. Varying degrees of accuracy and reliability are associated with these methods. More recently, shear wave velocity (Vs) profiles obtained from seismic testing, such as continuous surface wave tests (CSW), are being used for settlement prediction. Such predictions have the advantage of considering non-linear stress-strain behaviour of soil and the degradation of stiffness with increasing strain. CSW tests are rarely executed in the Cape Flats, whereas SPT’s are commonly performed. For this reason, and to facilitate better settlement predictions in Cape Flats sand, equations representing shear wave velocity (Vs) as a function of SPT blow count (N60) and vertical effective stress (v’) were generated by statistical regression of site investigation data. To reveal the most appropriate method of overburden correction, analyses were performed with a separate overburden term (Pa/σ’v) as well as using stress corrected shear wave velocity and SPT blow counts (correcting Vs. and N60 to Vs1and (N1)60respectively). Shear wave velocity profiles and SPT blow count data from three sites masked by Cape Flats sands were utilised to generate 80 Vs-SPT N data pairs for analysis. Investigated terrains included sites in the suburbs of Athlone, Muizenburg, and Atlantis, all underlain by windblown deposits comprising fine and medium sand with varying fines contents. Elastic settlement analysis was also undertaken for the Cape Flats sands, using a non-linear stepwise method based on small-strain stiffness estimates, which was obtained from the best Vs-N60 model and compared to settlement estimates using the general elastic solution with stiffness profiles determined using Stroud’s (1989) and Webb’s (1969) SPT N60-E transformation models. Stroud’s method considers strain level indirectly whereasWebb’smethod does not take account of the variation in elastic modulus with strain. The expression of Vs. in terms of N60 and Pa/σv’ derived from the Atlantis data set revealed the best fit with R2 = 0.83 and a standard error of 83.5m/s. Less accurate Vs-SPT N relations associated with the combined data set is presumably the result of inversion routines used in the analysis of the CSW results showcasing significant variation in relative density and stiffness with depth. The regression analyses revealed that the inclusion of a separate overburden term in the regression of Vs and N60, produces improved fits, as opposed to the stress corrected equations in which the R2 of the regression is notably lower. It is the correction of Vs and N60 to Vs1 and (N1)60 with empirical constants ‘n’ and ‘m’ prior to regression, that introduces bias with respect to overburden pressure. When comparing settlement prediction methods, both Stroud’s method (considering strain level indirectly) and the small strain stiffness method predict higher stiffnesses for medium dense and dense profiles than Webb’s method, which takes no account of strain level in the determination of soil stiffness. Webb’s method appears to be suitable for loose sands only. The Versak software appears to underestimate differences in settlement between square and strip footings of similar width. In conclusion, settlement analysis using small-strain stiffness data from the proposed Vs-N60 model for Cape Flats sands provides a way to take account of the non-linear stress-strain behaviour of the sands when calculating settlement.

Keywords: sands, settlement prediction, continuous surface wave test, small-strain stiffness, shear wave velocity, penetration resistance

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5 The Integration of Digital Humanities into the Sociology of Knowledge Approach to Discourse Analysis

Authors: Gertraud Koch, Teresa Stumpf, Alejandra Tijerina García

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Discourse analysis research approaches belong to the central research strategies applied throughout the humanities; they focus on the countless forms and ways digital texts and images shape present-day notions of the world. Despite the constantly growing number of relevant digital, multimodal discourse resources, digital humanities (DH) methods are thus far not systematically developed and accessible for discourse analysis approaches. Specifically, the significance of multimodality and meaning plurality modelling are yet to be sufficiently addressed. In order to address this research gap, the D-WISE project aims to develop a prototypical working environment as digital support for the sociology of knowledge approach to discourse analysis and new IT-analysis approaches for the use of context-oriented embedding representations. Playing an essential role throughout our research endeavor is the constant optimization of hermeneutical methodology in the use of (semi)automated processes and their corresponding epistemological reflection. Among the discourse analyses, the sociology of knowledge approach to discourse analysis is characterised by the reconstructive and accompanying research into the formation of knowledge systems in social negotiation processes. The approach analyses how dominant understandings of a phenomenon develop, i.e., the way they are expressed and consolidated by various actors in specific arenas of discourse until a specific understanding of the phenomenon and its socially accepted structure are established. This article presents insights and initial findings from D-WISE, a joint research project running since 2021 between the Institute of Anthropological Studies in Culture and History and the Language Technology Group of the Department of Informatics at the University of Hamburg. As an interdisciplinary team, we develop central innovations with regard to the availability of relevant DH applications by building up a uniform working environment, which supports the procedure of the sociology of knowledge approach to discourse analysis within open corpora and heterogeneous, multimodal data sources for researchers in the humanities. We are hereby expanding the existing range of DH methods by developing contextualized embeddings for improved modelling of the plurality of meaning and the integrated processing of multimodal data. The alignment of this methodological and technical innovation is based on the epistemological working methods according to grounded theory as a hermeneutic methodology. In order to systematically relate, compare, and reflect the approaches of structural-IT and hermeneutic-interpretative analysis, the discourse analysis is carried out both manually and digitally. Using the example of current discourses on digitization in the healthcare sector and the associated issues regarding data protection, we have manually built an initial data corpus of which the relevant actors and discourse positions are analysed in conventional qualitative discourse analysis. At the same time, we are building an extensive digital corpus on the same topic based on the use and further development of entity-centered research tools such as topic crawlers and automated newsreaders. In addition to the text material, this consists of multimodal sources such as images, video sequences, and apps. In a blended reading process, the data material is filtered, annotated, and finally coded with the help of NLP tools such as dependency parsing, named entity recognition, co-reference resolution, entity linking, sentiment analysis, and other project-specific tools that are being adapted and developed. The coding process is carried out (semi-)automated by programs that propose coding paradigms based on the calculated entities and their relationships. Simultaneously, these can be specifically trained by manual coding in a closed reading process and specified according to the content issues. Overall, this approach enables purely qualitative, fully automated, and semi-automated analyses to be compared and reflected upon.

Keywords: entanglement of structural IT and hermeneutic-interpretative analysis, multimodality, plurality of meaning, sociology of knowledge approach to discourse analysis

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4 Knowledge of the Doctors Regarding International Patient Safety Goal

Authors: Fatima Saeed, Abdullah Mudassar

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Introduction: Patient safety remains a global priority in the ever-evolving healthcare landscape. At the forefront of this endeavor are the International Patient Safety Goals (IPSGs), a standardized framework designed to mitigate risks and elevate the quality of care. Doctors, positioned as primary caregivers, wield a pivotal role in upholding and adhering to IPSGs, underscoring the critical significance of their knowledge and understanding of these goals. This research embarks on a comprehensive exploration into the depth of Doctors ' comprehension of IPSGs, aiming to unearth potential gaps and provide insights for targeted educational interventions. Established by influential healthcare bodies, including the World Health Organization (WHO), IPSGs represent a universally applicable set of objectives spanning crucial domains such as medication safety, infection control, surgical site safety, and patient identification. Adherence to these goals has exhibited substantial reductions in adverse events, fostering an overall enhancement in the quality of care. This study operates on the fundamental premise that an informed Doctors workforce is indispensable for effectively implementing IPSGs. A nuanced understanding of these goals empowers Doctors to identify potential risks, advocate for necessary changes, and actively contribute to a safety-centric culture within healthcare institutions. Despite the acknowledged importance of IPSGs, there is a growing concern that nurses may need more knowledge to integrate these goals into their practice seamlessly. Methodology: A Comprehensive research methodology covering study design, setting, duration, sample size determination, sampling technique, and data analysis. It introduces the philosophical framework guiding the research and details material, methods, and the analysis framework. The descriptive quantitative cross-sectional study in teaching care hospitals utilized convenient sampling over six months. Data collection involved written informed consent and questionnaires, analyzed with SPSS version 23, presenting results graphically and descriptively. The chapter ensures a clear understanding of the study's design, execution, and analytical processes. Result: The survey results reveal a substantial distribution across hospitals, with 34.52% in MTIKTH and 65.48% in HMC MTI. There is a notable prevalence of patient safety incidents, emphasizing the significance of adherence to IPSGs. Positive trends are observed, including 77.0% affirming the "time-out" procedure, 81.6% acknowledging effective healthcare provider communication, and high recognition (82.7%) of the purpose of IPSGs to improve patient safety. While the survey reflects a good understanding of IPSGs, areas for improvement are identified, suggesting opportunities for targeted interventions. Discussion: The study underscores the need for tailored care approaches and highlights the bio-socio-cultural context of 'contagion,' suggesting areas for further research amid antimicrobial resistance. Shifting the focus to patient safety practices, the survey chapter provides a detailed overview of results, emphasizing workplace distribution, patient safety incidents, and positive reflections on IPSGs. The findings indicate a positive trend in patient safety practices with areas for improvement, emphasizing the ongoing need for reinforcing safety protocols and cultivating a safety-centric culture in healthcare. Conclusion: In summary, the survey indicates a positive trend in patient safety practices with a good understanding of IPSGs among participants. However, identifying areas for potential improvement suggests opportunities for targeted interventions to enhance patient safety further. Ongoing efforts to reinforce adherence to safety protocols, address identified gaps, and foster a safety culture will contribute to continuous improvements in patient care and outcomes.

Keywords: infection control, international patient safety, patient safety practices, proper medication

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3 Open Science Philosophy, Research and Innovation

Authors: C.Ardil

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Open Science translates the understanding and application of various theories and practices in open science philosophy, systems, paradigms and epistemology. Open Science originates with the premise that universal scientific knowledge is a product of a collective scholarly and social collaboration involving all stakeholders and knowledge belongs to the global society. Scientific outputs generated by public research are a public good that should be available to all at no cost and without barriers or restrictions. Open Science has the potential to increase the quality, impact and benefits of science and to accelerate advancement of knowledge by making it more reliable, more efficient and accurate, better understandable by society and responsive to societal challenges, and has the potential to enable growth and innovation through reuse of scientific results by all stakeholders at all levels of society, and ultimately contribute to growth and competitiveness of global society. Open Science is a global movement to improve accessibility to and reusability of research practices and outputs. In its broadest definition, it encompasses open access to publications, open research data and methods, open source, open educational resources, open evaluation, and citizen science. The implementation of open science provides an excellent opportunity to renegotiate the social roles and responsibilities of publicly funded research and to rethink the science system as a whole. Open Science is the practice of science in such a way that others can collaborate and contribute, where research data, lab notes and other research processes are freely available, under terms that enable reuse, redistribution and reproduction of the research and its underlying data and methods. Open Science represents a novel systematic approach to the scientific process, shifting from the standard practices of publishing research results in scientific publications towards sharing and using all available knowledge at an earlier stage in the research process, based on cooperative work and diffusing scholarly knowledge with no barriers and restrictions. Open Science refers to efforts to make the primary outputs of publicly funded research results (publications and the research data) publicly accessible in digital format with no limitations. Open Science is about extending the principles of openness to the whole research cycle, fostering, sharing and collaboration as early as possible, thus entailing a systemic change to the way science and research is done. Open Science is the ongoing transition in how open research is carried out, disseminated, deployed, and transformed to make scholarly research more open, global, collaborative, creative and closer to society. Open Science involves various movements aiming to remove the barriers for sharing any kind of output, resources, methods or tools, at any stage of the research process. Open Science embraces open access to publications, research data, source software, collaboration, peer review, notebooks, educational resources, monographs, citizen science, or research crowdfunding. The recognition and adoption of open science practices, including open science policies that increase open access to scientific literature and encourage data and code sharing, is increasing in the open science philosophy. Revolutionary open science policies are motivated by ethical, moral or utilitarian arguments, such as the right to access digital research literature for open source research or science data accumulation, research indicators, transparency in the field of academic practice, and reproducibility. Open science philosophy is adopted primarily to demonstrate the benefits of open science practices. Researchers use open science applications for their own advantage in order to get more offers, increase citations, attract media attention, potential collaborators, career opportunities, donations and funding opportunities. In open science philosophy, open data findings are evidence that open science practices provide significant benefits to researchers in scientific research creation, collaboration, communication, and evaluation according to more traditional closed science practices. Open science considers concerns such as the rigor of peer review, common research facts such as financing and career development, and the sacrifice of author rights. Therefore, researchers are recommended to implement open science research within the framework of existing academic evaluation and incentives. As a result, open science research issues are addressed in the areas of publishing, financing, collaboration, resource management and sharing, career development, discussion of open science questions and conclusions.

Keywords: Open Science, Open Science Philosophy, Open Science Research, Open Science Data

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2 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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1 An Intelligent Search and Retrieval System for Mining Clinical Data Repositories Based on Computational Imaging Markers and Genomic Expression Signatures for Investigative Research and Decision Support

Authors: David J. Foran, Nhan Do, Samuel Ajjarapu, Wenjin Chen, Tahsin Kurc, Joel H. Saltz

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The large-scale data and computational requirements of investigators throughout the clinical and research communities demand an informatics infrastructure that supports both existing and new investigative and translational projects in a robust, secure environment. In some subspecialties of medicine and research, the capacity to generate data has outpaced the methods and technology used to aggregate, organize, access, and reliably retrieve this information. Leading health care centers now recognize the utility of establishing an enterprise-wide, clinical data warehouse. The primary benefits that can be realized through such efforts include cost savings, efficient tracking of outcomes, advanced clinical decision support, improved prognostic accuracy, and more reliable clinical trials matching. The overarching objective of the work presented here is the development and implementation of a flexible Intelligent Retrieval and Interrogation System (IRIS) that exploits the combined use of computational imaging, genomics, and data-mining capabilities to facilitate clinical assessments and translational research in oncology. The proposed System includes a multi-modal, Clinical & Research Data Warehouse (CRDW) that is tightly integrated with a suite of computational and machine-learning tools to provide insight into the underlying tumor characteristics that are not be apparent by human inspection alone. A key distinguishing feature of the System is a configurable Extract, Transform and Load (ETL) interface that enables it to adapt to different clinical and research data environments. This project is motivated by the growing emphasis on establishing Learning Health Systems in which cyclical hypothesis generation and evidence evaluation become integral to improving the quality of patient care. To facilitate iterative prototyping and optimization of the algorithms and workflows for the System, the team has already implemented a fully functional Warehouse that can reliably aggregate information originating from multiple data sources including EHR’s, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology PAC systems, Digital Pathology archives, Unstructured Clinical Documents, and Next Generation Sequencing services. The System enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information about patient tumors individually or as part of large cohorts to identify patterns that may influence treatment decisions and outcomes. The CRDW core system has facilitated peer-reviewed publications and funded projects, including an NIH-sponsored collaboration to enhance the cancer registries in Georgia, Kentucky, New Jersey, and New York, with machine-learning based classifications and quantitative pathomics, feature sets. The CRDW has also resulted in a collaboration with the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) at the U.S. Department of Veterans Affairs to develop algorithms and workflows to automate the analysis of lung adenocarcinoma. Those studies showed that combining computational nuclear signatures with traditional WHO criteria through the use of deep convolutional neural networks (CNNs) led to improved discrimination among tumor growth patterns. The team has also leveraged the Warehouse to support studies to investigate the potential of utilizing a combination of genomic and computational imaging signatures to characterize prostate cancer. The results of those studies show that integrating image biomarkers with genomic pathway scores is more strongly correlated with disease recurrence than using standard clinical markers.

Keywords: clinical data warehouse, decision support, data-mining, intelligent databases, machine-learning.

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