Search results for: evidence weight

Authors: Catherine P. Bradshaw, Elise T. Pas, Katrina J. Debnam, Jessika H. Bottiani, Michael Rosenberg

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Worldwide, ethnically and culturally diverse students are at increased risk for school failure, discipline problems, and dropout. Despite decades of concern about this issue of disparities in education and other fields (e.g., 'school to prison pipeline'), there has been limited empirical examination of models that can actually reduce these gaps in schools. Moreover, few studies have examined the effectiveness of in-service teacher interventions and supports specifically designed to reduce discipline disparities and improve student engagement. This session provides an overview of the evidence-based Double Check model which serves as a framework for teachers to use culturally-responsive strategies to engage ethnically and culturally diverse students in the classroom and reduce discipline problems. Specifically, Double Check is a school-based prevention program which includes three core components: (a) enhancements to the school-wide Positive Behavioral Interventions and Supports (PBIS) tier-1 level of support; (b) five one-hour professional development training sessions, each of which addresses five domains of cultural competence (i.e., connection to the curriculum, authentic relationships, reflective thinking, effective communication, and sensitivity to students’ culture); and (c) coaching of classroom teachers using an adapted version of the Classroom Check-Up, which intends to increase teachers’ use of effective classroom management and culturally-responsive strategies using research-based motivational interviewing and data-informed problem-solving approaches. This paper presents findings from a randomized controlled trial (RCT) testing the impact of Double Check, on office discipline referrals (disaggregated by race) and independently observed and self-reported culturally-responsive practices and classroom behavior management. The RCT included 12 elementary and middle schools; 159 classroom teachers were randomized either to receive coaching or serve as comparisons. Specifically, multilevel analyses indicated that teacher self-reported culturally responsive behavior management improved over the course of the school year for teachers who received the coaching and professional development. However, the average annual office discipline referrals issued to black students were reduced among teachers who were randomly assigned to receive coaching relative to comparison teachers. Similarly, observations conducted by trained external raters indicated significantly more teacher proactive behavior management and anticipation of student problems, higher student compliance, less student non-compliance, and less socially disruptive behaviors in classrooms led by coached teachers than classrooms led teachers randomly assigned to the non-coached condition. These findings indicated promising effects of the Double Check model on a range of teacher and student outcomes, including disproportionality in office discipline referrals among Black students. These results also suggest that the Double Check model is one of only a few systematic approaches to promoting culturally-responsive behavior management which has been rigorously tested and shown to be associated with improvements in either student or staff outcomes indicated significant reductions in discipline problems and improvements in behavior management. Implications of these findings are considered within the broader context of globalization and demographic shifts, and their impacts on schools. These issues are particularly timely, given growing concerns about immigration policies in the U.S. and abroad.

Keywords: ethnically and culturally diverse students, student engagement, school-based prevention, academic achievement

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Authors: Wissam Saliba, Mandy Nicholson

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Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: Claire Williams

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Randomised controlled Trials (RCTs) of efficacy are still perceived as the gold standard for the generation of evidence, and whilst advances in data collection methods are well developed, this progress has not been matched for the reporting of adverse events (AEs). Assessment and reporting of AEs in clinical trials are fraught with human error and inefficiency and are extremely time and resource intensive. Recent research conducted into the quality of reporting of AEs during clinical trials concluded it is substandard and reporting is inconsistent. Investigators commonly send reports to sponsors who are incorrectly categorised and lacking in critical information, which can complicate the detection of valid safety signals. In our presentation, we will describe an electronic data capture system, which has been designed to support clinical trial processes by reducing the resource burden on investigators, improving overall trial efficiencies, and making trials safer for patients. This proprietary technology was developed using expertise proven in the delivery of the world’s first prospective, phase 3b real-world trial, ‘The Salford Lung Study, ’ which enabled robust safety monitoring and reporting processes to be accomplished by the remote monitoring of patients’ EHRs. This technology enables safety alerts that are pre-defined by the protocol to be detected from the data extracted directly from the patients EHR. Based on study-specific criteria, which are created from the standard definition of a serious adverse event (SAE) and the safety profile of the medicinal product, the system alerts the investigator or study team to the safety alert. Each safety alert will require a clinical review by the investigator or delegate; examples of the types of alerts include hospital admission, death, hepatotoxicity, neutropenia, and acute renal failure. This is achieved in near real-time; safety alerts can be reviewed along with any additional information available to determine whether they meet the protocol-defined criteria for reporting or withdrawal. This active surveillance technology helps reduce the resource burden of the more traditional methods of AE detection for the investigators and study teams and can help eliminate reporting bias. Integration of multiple healthcare data sources enables much more complete and accurate safety data to be collected as part of a trial and can also provide an opportunity to evaluate a drug’s safety profile long-term, in post-trial follow-up. By utilising this robust and proven method for safety monitoring and reporting, a much higher risk of patient cohorts can be enrolled into trials, thus promoting inclusivity and diversity. Broadening eligibility criteria and adopting more inclusive recruitment practices in the later stages of drug development will increase the ability to understand the medicinal products risk-benefit profile across the patient population that is likely to use the product in clinical practice. Furthermore, this ground-breaking approach to AE detection not only provides sponsors with better-quality safety data for their products, but it reduces the resource burden on the investigator and study teams. With the data taken directly from the source, trial costs are reduced, with minimal data validation required and near real-time reporting enables safety concerns and signals to be detected more quickly than in a traditional RCT.

Keywords: more comprehensive and accurate safety data, near real-time safety alerts, reduced resource burden, safer trials

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Authors: Mohamed Abdelmongy

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Autologous Blood for Conjunctival Autograft Fixation in Primary Pterygium Surgery: A Systematic Review and Meta-analysis Hossam Zein1,2, Ammar Ismail1,3, Mohamed Abdelmongy1,4, Sherif Elsherif1,5,6, Ahmad Hassanen1,4, Basma Muhammad2, Fathy Assaf1,3, Ahmed Elsehili1,7, Ahmed Negida1,7, Shin Yamane9, Mohamed M. Abdel-Daim8,9 and Kazuaki Kadonosono9 https://www.ncbi.nlm.nih.gov/pubmed/30277146 BACKGROUND: Pterygium is a benign ocular lesion characterized by triangular fibrovascular growth of conjunctival tissue over the cornea. Patients complain of the bad cosmetic appearance, ocular surface irritation and decreased visual acuity if the pterygium is large enough to cause astigmatism or encroach on the pupil. The definitive treatment of pterygium is surgical removal. However, outcomes are compromised by recurrence . The aim of the current study is to systematically review the current literature to explore the efficacy and safety of fibrin glue, suture and autologous blood coagulum for conjunctivalautograft fixation in primary pterygium surgery. OBJECTIVES: To assess the effectiveness of fibrin glue compared to sutures and autologous blood coagulum in conjunctival autografting for the surgical treatment of pterygium. METHODS: During preparing this manuscript, we followed the steps adequately illustrated in the Cochrane Handbook for Systematic Reviews of Interventions version 5.3, and reported it according to the preferred reporting of systematic review and meta-analysis (PRISMA) statement guidelines. We searched PubMed, Ovid (both through Medline), ISI Web of Science, and Cochrane Central Register of Controlled Trials (Central) through January 2017, using the following keywords “Pterygium AND (blood OR glue OR suture)” SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that met the following criteria: 1) comparing autologous blood vs fibrin glue for conjunctivalautograft fixation in primary pterygium surgery 2) comparing autologous blood vs sutures for conjunctivalautograft fixation in primary pterygium surgery DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. The extracted data included A) study design, sample size, and main findings, B) Baseline characteristics of patients included in this review including their age, sex, pterygium site and grade, and graft size. C) Study outcomes comprising 1) primary outcomes: recurrence rate 2) secondary outcomes: graft stability outcomes (graft retraction, graft displacement), operation time (min) and postoperative symptoms (pain, discomfort, foreign body sensation, tearing) MAIN RESULTS: We included 7 RCTs and The review included662eyes (Blood: 293; Glue: 198; Suture: 171). we assess the 1) primary outcomes: recurrence rate 2) secondary outcomes: graft stability outcomes (graft retraction, graft displacement), operation time (min) and postoperative symptoms (pain, discomfort, foreign body sensation, tearing) CONCLUSIONS: Autologous blood for conjunctivalautograft fixation in pterygium surgery is associated with lower graft stability than fibrin glue or sutures. It was not inferior to fibrin glue or sutures regarding recurrence rate. The overall quality of evidence is low. Further well designed RCTs are needed to fully explore the efficacy of this new technique.

Keywords: pterygium, autograft, ophthalmology, cornea

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Authors: Rachel Danielson, Brendan Bohannan, S.M. Tsai, Kyle Meyer, Jorge L.M. Rodrigues

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The Amazon Rainforest is a global diversity hotspot and crucial carbon sink, but approximately 20% of its total extent has been deforested- primarily for the establishment of cattle pasture. Understanding the impact of this large-scale disturbance on soil microbial community composition and activity is crucial in understanding potentially consequential shifts in nutrient or greenhouse gas cycling, as well as adding to the body of knowledge concerning how these complex communities respond to human disturbance. In this study, surface soils (0-10cm) were collected from three forests and three 45-year-old pastures in Rondonia, Brazil (the Amazon state with the greatest rate of forest destruction) in order to determine the impact of forest conversion on microbial communities involved in nitrogen fixation. Soil chemical and physical parameters were paired with measurements of microbial activity and genetic profiles to determine how community composition and process rates relate to environmental conditions. Measuring both the natural abundance of 15N in total soil N, as well as incorporation of enriched 15N2 under incubation has revealed that conversion of primary forest to cattle pasture results in a significant increase in the rate of nitrogen fixation by free-living diazotrophs. Quantification of nifH gene copy numbers (an essential subunit encoding the nitrogenase enzyme) correspondingly reveals a significant increase of genes in pasture compared to forest soils. Additionally, genetic sequencing of both nifH genes and transcripts shows a significant increase in the diversity of the present and metabolically active diazotrophs within the soil community. Levels of both organic and inorganic nitrogen tend to be lower in pastures compared to forests, with ammonium rather than nitrate as the dominant inorganic form. However, no significant or consistent differences in total, extractable, permanganate-oxidizable, or loss-on-ignition carbon are present between the two land-use types. Forest conversion is associated with a 0.5- 1.0 unit pH increase, but concentrations of many biologically relevant nutrients such as phosphorus do not increase consistently. Increases in free-living diazotrophic community abundance and activity appear to be related to shifts in carbon to nitrogen pool ratios. Furthermore, there may be an important impact of transient, low molecular weight plant-root-derived organic carbon on free-living diazotroph communities not captured in this study. Preliminary analysis of nitrogenase gene variant composition using NovoSeq metagenomic sequencing indicates that conversion of forest to pasture may significantly enrich vanadium-based nitrogenases. This indication is complemented by a significant decrease in available soil molybdenum. Very little is known about the ecology of diazotrophs utilizing vanadium-based nitrogenases, so further analysis may reveal important environmental conditions favoring their abundance and diversity in soil systems. Taken together, the results of this study indicate a significant change in nitrogen cycling and diazotroph community composition with the conversion of the Amazon Rainforest. This may have important implications for the sustainability of cattle pastures once established since nitrogen is a crucial nutrient for forage grass productivity.

Keywords: free-living diazotrophs, land use change, metagenomic sequencing, nitrogen fixation

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Authors: Merrick Lopez, Aashish Abraham, Melissa Egge, Marissa Hood, Jui Shah

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A 3 year old male with unknown medical history presented initially with encephalopathy, intubated for respiratory failure, and admitted to the pediatric intensive care unit (PICU) with refractory shock. During resuscitation in the emergency department, he was found to be in severe metabolic acidosis with a pH of 7.03 and escalated on vasopressor drips for hypotension. His initial sodium was 174. He was noted to have burn injuries to his scalp, forehead, right axilla, bilateral arm creases and lower legs. He had rhabdomyolysis (initial creatinine kinase 5,430 U/L with peak levels of 62,340 normal <335 U/L), cardiac injury (initial troponin 88 ng/L with peak at 145 ng/L, normal <15ng/L), hypernatremia (peak 174, normal 140), hypocalcemia, liver injury, acute kidney injury, and neuronal loss on magnetic resonance imaging (MRI). Soft restraints and a shock collar were found in the home. He was critically ill for 8 days, but was gradually weaned off drips, extubated, and started on feeds. Discussion Electrical injury, specifically lightning injury is an uncommon but devastating cause of injury in pediatric patients. This patient with suspected abusive use of a dog shock collar presented similar to a lightning strike. Common entrance points include the hands and head, similar to our patient with linear wounds on his forehead. When current enters, it passes through tissues with the least resistance. Nerves, blood vessels, and muscles, have high fluid and electrolyte content and are commonly affected. Exit points are extremities: our child who had circumferential burns around his arm creases and ankles. Linear burns preferentially follow areas of high sweat concentration, and are thought to be due to vaporization of water on the skin’s surface. The most common cause of death from a lightning strike is due to cardiopulmonary arrest. The massive depolarization of the myocardium can result in arrhythmias and myocardial necrosis. The patient presented in cardiogenic shock with evident cardiac damage. Electricity going through vessels can lead to vaporization of intravascular water. This can explain his severe hypernatremia. He also sustained other internal organ injuries (adrenal glands, pancreas, liver, and kidney). Electrical discharge also leads to direct skeletal muscle injury in addition to prolonged muscular spasm. Rhabdomyolysis, the acute damage of muscle, leads to release of potentially toxic components into the circulation which could lead to acute renal failure. The patient had severe rhabdomyolysis and renal injury. Early hypocalcemia has been consistently demonstrated in patients with rhabdomyolysis. This was present in the patient and led to increased vasopressor needs. Central nervous system injuries are also common which can include encephalopathy, hypoxic injury, and cerebral infarction. The patient had evidence of brain injury as seen on MRI. Conclusion Electrical injuries due to lightning strikes and abusive use of a dog shock collar are rare, but can both present in similar ways with respiratory failure, shock, hypernatremia, rhabdomyolysis, brain injury, and multiorgan damage. Although rare, it is essential for early identification and prompt management for acute and chronic complications in these children.

Keywords: cardiogenic shock, dog shock collar, lightning strike, rhabdomyolysis

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Authors: Viktorya Sargsyan, Arax Hovhannesyan, Karine Abelyan

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Introduction: During the last decade, scientific studies have proven the importance of Early Childhood Development (ECD) interventions. These interventions are shown to create strong foundations for children’s intellectual, emotional and physical well-being, as well as the impact they have on learning and economic outcomes for children as they mature into adulthood. Many children in rural Armenia fail to reach their full development potential due to lack of early brain stimulation (playing, singing, reading, etc.) from their parents, and lack of community tools and services to follow-up children’s neurocognitive development. This is exacerbated by high rates of stunting and anemia among children under 3(CU3). This research study tested the effectiveness of an integrated ECD and Maternal, Newborn and Childhood Health (MNCH) model, called “Go Baby, Go!” (GBG), against the traditional (MNCH) strategy which focuses solely on preventive health and nutrition interventions. The hypothesis of this quasi-experimental study was: Children exposed to GBG will have better neurocognitive and nutrition outcomes compared to those receiving only the MNCH intervention. The secondary objective was to assess the effect of GBG on parental child care and nutrition practices. Methodology: The 14 month long study, targeted all 1,300 children aged 0 to 23 months, living in 43 study communities the in Gavar and Vardenis regions (Gegharkunik province, Armenia). Twenty-three intervention communities, 680 children, received GBG, and 20 control communities, 630 children, received MCHN interventions only. Baseline and evaluation data on child development, nutrition status and parental child care and nutrition practices were collected (caregiver interview, direct child assessment). In the intervention sites, in addition to MNCH (maternity schools, supportive supervision for Health Care Providers (HCP), the trained GBG facilitators conducted six interactive group sessions for mothers (key messages, information, group discussions, role playing, video-watching, toys/books preparation, according to GBG curriculum), and two sessions (condensed GBG) for adult family members (husbands, grandmothers). The trained HCPs received quality supervision for ECD counseling and screening. Findings: The GBG model proved to be effective in improving ECD outcomes. Children in the intervention sites had 83% higher odd of total ECD composite score (cognitive, language, motor) compared to children in the control sites (aOR 1.83; 95 percent CI: 1.08-3.09; p=0.025). Caregivers also demonstrated better child care and nutrition practices (minimum dietary diversity in intervention site is 55 percent higher compared to control (aOR=1.55, 95 percent CI 1.10-2.19, p =0.013); support for learning and disciplining practices (aOR=2.22, 95 percent CI 1.19-4.16, p=0.012)). However, there was no evidence of stunting reduction in either study arm. he effect of the integrated model was more prominent in Vardenis, a community which is characterised by high food insecurity and limited knowledge of positive parenting skills. Conclusion: The GBG model is effective and could be applied in target areas with the greatest economic disadvantages and parenting challenges to improve ECD, care practices and developmental outcomes. Longitudinal studies are needed to view the long-term effects of GBG on learning and school readiness.

Keywords: early childhood development, integrated interventions, parental practices, quasi-experimental study

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Authors: David A. Olasehinde, Peter I. Olasehinde, Segun M. A. Adelana, Dapo O. Olasehinde

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An investigation was carried out on underground water system dynamics within Ilorin metropolis to monitor the subsurface flow and its corresponding pollution. Africa population growth rate is the highest among the regions of the world, especially in urban areas. A corresponding increase in waste generation and a change in waste composition from predominantly organic to non-organic waste has also been observed. Percolation of leachate from non-engineered landfills, the chief means of waste disposal in many of its cities, constitutes a threat to the underground water bodies. Ilorin city, a transboundary town in southwestern Nigeria, is a ready microcosm of Africa’s unique challenge. In spite of the fact that groundwater is naturally protected from common contaminants such as bacteria as the subsurface provides natural attenuation process, groundwater samples have been noted to however possesses relatively higher dissolved chemical contaminants such as bicarbonate, sodium, and chloride which poses a great threat to environmental receptors and human consumption. The Geographic Information System (GIS) was used as a tool to illustrate, subsurface dynamics and the corresponding pollutant indicators. Forty-four sampling points were selected around known groundwater pollutant, major old dumpsites without landfill liners. The results of the groundwater flow directions and the corresponding contaminant transport were presented using expert geospatial software. The experimental results were subjected to four descriptive statistical analyses, namely: principal component analysis, Pearson correlation analysis, scree plot analysis, and Ward cluster analysis. Regression model was also developed aimed at finding functional relationships that can adequately relate or describe the behaviour of water qualities and the hypothetical factors landfill characteristics that may influence them namely; distance of source of water body from dumpsites, static water level of groundwater, subsurface permeability (inferred from hydraulic gradient), and soil infiltration. The regression equations developed were validated using the graphical approach. Underground water seems to flow from the northern portion of Ilorin metropolis down southwards transporting contaminants. Pollution pattern in the study area generally assumed a bimodal pattern with the major concentration of the chemical pollutants in the underground watershed and the recharge. The correlation between contaminant concentrations and the spread of pollution indicates that areas of lower subsurface permeability display a higher concentration of dissolved chemical content. The principal component analysis showed that conductivity, suspended solids, calcium hardness, total dissolved solids, total coliforms, and coliforms were the chief contaminant indicators in the underground water system in the study area. Pearson correlation revealed a high correlation of electrical conductivity for many parameters analyzed. In the same vein, the regression models suggest that the heavier the molecular weight of a chemical contaminant of a pollutant from a point source, the greater the pollution of the underground water system at a short distance. The study concludes that the associative properties of landfill have a significant effect on groundwater quality in the study area.

Keywords: dumpsite, leachate, groundwater pollution, linear regression, principal component

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Authors: Kuladip Jana

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Jia H. Wong, Jingli Zhang, Habsah Mohamad, Iswatun H. Abdullah Ripain, Muhammad Bilal, Amelia J. Lloyd, Abdul A. Mohamed Yusoff, Jafri M. Abdullah

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Epilepsy is one of the most common neurological diseases affecting more than 50 million of people worldwide. Epilepsy is a state of recurrent, spontaneous seizures with multiple syndromes and symptoms of different causes of brain dysfunction, prognosis, and treatments; characterized by transient, occasional and stereotyped interruptions of behavior whereby the excitatory-inhibitory activities within the central nervous system (CNS) are thrown out of balance due to various kinds of interferences. The goal of antiepileptic treatment is to enable patients to be free from seizures or to achieve control of seizures through surgical treatment and/or pharmacotherapy. Pharmacotherapy through AED plays an important role especially in countries with epilepsy treatment gap due to costs and availability of health facilities, skills and resources, yet there are about one-third of the people with epilepsy have drug-resistant seizures. Hence, this poses considerable challenges to the healthcare system and the effort in providing cost-effective treatment as well as the search for alternatives to treatment and management of epilepsy. Enhancement of γ-aminobutyric acid (GABA)-mediated inhibitory neurotransmission is one of the key mechanisms of actions of antiepileptic drugs. GABA type > a receptors (GABAAR) are ligand-gated ion channels that mediate rapid inhibitory neurotransmission upon the binding of GABA with a heteropentameric structure forming a central pore that is permeable to the influx of chloride ions in its activated state. The major isoform of GABAA receptors consists of two α1, two β2, and one γ2 subunit. It is the most abundantly expressed combinations in the brain and the most commonly researched through Xenopus laevis oocytes. With the advancing studies on ethnomedicine and traditional treatments using medicinal plants, increasing evidence reveal that spice and herb plants with medicinal properties play an important role in the treatment of ailments within communities across different cultures. Capsaicin is the primary natural capsaicinoid in hot peppers of plant genus Capsicum, consist of an aromatic ring, an amide linkage and a hydrophobic side chain. The study showed that capsaicins conferred neuroprotection in status epilepticus mouse models through anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic actions in a dose-dependent manner. In this study, five capsaicin derivatives were tested for their ability to increase the GABA-induced chloride current on α1β2γ2S of GABAAR expressed on Xenopus laevis oocytes using the method of two-microelectrode voltage clamp. Two of the capsaicin derivatives, IS5 (N-(4-hydroxy-3-methoxybenzyl)-3-methylbutyramide) and IS10 (N-(4-hydroxy-3-methoxybenzyl)-decanamide) at a concentration of 30µM were able to significantly increase the GABA-induced chloride current with p=0.002 and p=0.026 respectively. This study were able to show the enhancement effect of two capsaicin derivatives with moderate length of hydrocarbon chain on this receptor subtype, revealing the promising inhibitory activity of capsaicin derivatives through enhancement of GABA-induced chloride current and further investigations should be carried out to verify its antiepileptic effects in animal models.

Keywords: α1β2γ2 GABAA receptors, α1β2γ2S, antiepileptic, capsaicin derivatives, two-microelectrode voltage clamp, Xenopus laevis oocytes

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Authors: Boris Nemzer, Nebiyu Abshiru, Z. B. Pietrzkowski

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Coffee cherry is one of the most ubiquitous agricultural commodities which possess nutritional and human health beneficial properties. Between the two most widely used coffee cherries Coffea arabica (Arabica) and Coffea canephora (Robusta), Coffea arabica remains superior due to its sensory properties and, therefore, remains in great demand in the global coffee market. In this study, the phytochemical contents and pharmacokinetics of Coffeeberry® Energy (CBE), a commercially available Arabica whole coffee fruit caffeine extract, are investigated. For phytochemical screening, 20 mg of CBE was dissolved in an aqueous methanol solution for analysis by mass spectrometry (MS). Quantification of caffeine and chlorogenic acids (CGAs) contents of CBE was performed using HPLC. For the bioavailability study, serum samples were collected from human subjects before and after 1, 2 and 3 h post-ingestion of 150mg CBE extract. Protein precipitation and extraction were carried out using methanol. Identification of compounds was performed using an untargeted metabolomic approach on Q-Exactive Orbitrap MS coupled to reversed-phase chromatography. Data processing was performed using Thermo Scientific Compound Discover 3.3 software. Phytochemical screening identified a total of 170 compounds, including organic acids, phenolic acids, CGAs, diterpenoids and hydroxytryptamine. Caffeine & CGAs make up more than, respectively, 70% & 9% of the total CBE composition. For serum samples, a total of 82 metabolites representing 32 caffeine- and 50 phenolic-derived metabolites were identified. Volcano plot analysis revealed 32 differential metabolites (24 caffeine- and 8 phenolic-derived) that showed an increase in serum level post-CBE dosing. Caffeine, uric acid, and trimethyluric acid isomers exhibited 4- to 10-fold increase in serum abundance post-dosing. 7-Methyluric acid, 1,7-dimethyluric acid, paraxanthine and theophylline exhibited a minimum of 1.5-fold increase in serum level. Among the phenolic-derived metabolites, iso-feruloyl quinic acid isomers (3-, 4- and 5-iFQA) showed the highest increase in serum level. These compounds were essentially absent in serum collected before dosage. More interestingly, the iFQA isomers were not originally present in the CBE extract, as our phytochemical screen did not identify these compounds. This suggests the potential formation of the isomers during the digestion and absorption processes. Pharmacokinetics parameters (Cmax, Tmax and AUC0-3h) of caffeine- and phenolic-derived metabolites were also investigated. Caffeine was rapidly absorbed, reaching a maximum concentration (Cmax) of 10.95 µg/ml in just 1 hour. Thereafter, caffeine level steadily dropped from the peak level, although it did not return to baseline within the 3-hour dosing period. The disappearance of caffeine from circulation was mirrored by the rise in the concentration of its methylxanthine metabolites. Similarly, serum concentration of iFQA isomers steadily increased, reaching maximum (Cmax: 3-iFQA, 1.54 ng/ml; 4-iFQA, 2.47 ng/ml; 5-iFQA, 2.91 ng/ml) at tmax of 1.5 hours. The isomers remained well above the baseline during the 3-hour dosing period, allowing them to remain in circulation long enough for absorption into the body. Overall, the current study provides evidence of the potential health benefits of a uniquely formulated whole coffee fruit product. Consumption of this product resulted in a distinct serum profile of bioactive compounds, as demonstrated by the more than 32 metabolites that exhibited a significant change in systemic exposure.

Keywords: phytochemicals, mass spectrometry, pharmacokinetics, differential metabolites, chlorogenic acids

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Authors: Aidan Ryan, Nahima Miah, Sahaj Kaur, Imogen Sutherland, Mohamed Saleh

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Pulmonary symptoms are a common presentation to the emergency department. Due to a lack of understanding of the underlying pathophysiology, chronic liver disease is not often considered a cause of dyspnea. We present three patients who were admitted with significant respiratory distress secondary to hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. The first is a 27-year-old male with a 6-month history of progressive dyspnea. The patient developed a severe type 1 respiratory failure with a PaO₂ of 6.3kPa and was escalated to critical care, where he was managed with non-invasive ventilation to maintain oxygen saturation. He had an agitated saline contrast echocardiogram, which showed the presence of a possible shunt. A CT angiogram revealed significant liver cirrhosis, portal hypertension, and large para esophageal varices. Ultrasound of the abdomen showed coarse liver echo patter and enlarged spleen. Along with these imaging findings, his biochemistry demonstrated impaired synthetic liver function with an elevated international normalized ratio (INR) of 1.4 and hypoalbuminaemia of 28g/L. The patient was then transferred to a tertiary center for further management. Further investigations confirmed a shunt of 56%, and liver biopsy confirmed cirrhosis suggestive of alpha-1-antitripsyin deficiency. The findings were consistent with a diagnosis of hepatopulmonary syndrome, and the patient is awaiting a liver transplant. The second patient is a 56-year-old male with a 12-month history of worsening dyspnoea, jaundice, confusion. His medical history included liver cirrhosis, portal hypertension, and grade 1 oesophageal varices secondary to significant alcohol excess. On admission, he developed a type 1 respiratory failure with PaO₂ of 6.8kPa requiring 10L of oxygen. CT pulmonary angiogram was negative for pulmonary embolism but showed evidence of chronic pulmonary hypertension, liver cirrhosis, and portal hypertension. An echocardiogram revealed a grossly dilated right heart with reduced function, pulmonary and tricuspid regurgitation, and pulmonary artery pressures estimated at 78mmHg. His biochemical markers showed impaired synthetic liver function with an INR of 3.2, albumin of 29g/L, along with raised bilirubin of 148mg/dL. During his long admission, he was managed with diuretics with little improvement. After three weeks, he was diagnosed with portopulmonary hypertension and was commenced on terlipressin. This resulted in successfully weaning off oxygen, and he was discharged home. The third patient is a 61-year-old male who presented to the local ambulatory care unit for therapeutic paracentesis on a background of decompensated liver cirrhosis. On presenting, he complained of a 2-day history of worsening dyspnoea and a productive cough. Chest x-ray showed a large pleural effusion, increasing in size over the previous eight months, and his abdomen was visibly distended with ascitic fluid. Unfortunately, the patient deteriorated, developing a larger effusion along with an increase in oxygen demand, and passed away. Without underlying cardiorespiratory disease, in the presence of a persistent pleural effusion with underlying decompensated cirrhosis, he was diagnosed with hepatic hydrothorax. While each presented with dyspnoea, the cause and underlying pathophysiology differ significantly from case to case. By describing these complications, we hope to improve awareness and aid prompt and accurate diagnosis, vital for improving outcomes.

Keywords: dyspnea, hepatic hydrothorax, hepatopulmonary syndrome, portopulmonary syndrome

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Authors: Jessica Ho

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AI has helped government, businesses and industries transform the way they do things. AI is used in automating tasks to improve decision-making and efficiency. AI is embedded in sensors and used in automation to help save time and eliminate human errors in repetitive tasks. Today, we saw the growth in AI using the collection of vast amounts of data to forecast with greater accuracy, inform decision-making, adapt to changing market conditions and offer more personalised service based on consumer habits and preferences. Government around the world share the opportunity to leverage these disruptive technologies to improve productivity while reducing costs. In addition, these intelligent solutions can also help streamline government processes to deliver more seamless and intuitive user experiences for employees and citizens. This is a critical challenge for NSW Government as we are unable to determine the risk that is brought by the unprecedented pace of adoption of AI solutions in government. Government agencies must ensure that their use of AI complies with relevant laws and regulatory requirements, including those related to data privacy and security. Furthermore, there will always be ethical concerns surrounding the use of AI, such as the potential for bias, intellectual property rights and its impact on job security. Within NSW’s public sector, agencies are already testing AI for crowd control, infrastructure management, fraud compliance, public safety, transport, and police surveillance. Citizens are also attracted to the ease of use and accessibility of AI solutions without requiring specialised technical skills. This increased accessibility also comes with balancing a higher risk and exposure to the health and safety of citizens. On the other side, public agencies struggle with keeping up with this pace while minimising risks, but the low entry cost and open-source nature of generative AI led to a rapid increase in the development of AI powered apps organically – “There is an AI for That” in Government. Other challenges include the fact that there appeared to be no legislative provisions that expressly authorise the NSW Government to use an AI to make decision. On the global stage, there were too many actors in the regulatory space, and a sovereign response is needed to minimise multiplicity and regulatory burden. Therefore, traditional corporate risk and governance framework and regulation and legislation frameworks will need to be evaluated for AI unique challenges due to their rapidly evolving nature, ethical considerations, and heightened regulatory scrutiny impacting the safety of consumers and increased risks for Government. Creating an effective, efficient NSW Government’s governance regime, adapted to the range of different approaches to the applications of AI, is not a mere matter of overcoming technical challenges. Technologies have a wide range of social effects on our surroundings and behaviours. There is compelling evidence to show that Australia's sustained social and economic advancement depends on AI's ability to spur economic growth, boost productivity, and address a wide range of societal and political issues. AI may also inflict significant damage. If such harm is not addressed, the public's confidence in this kind of innovation will be weakened. This paper suggests several AI regulatory approaches for consideration that is forward-looking and agile while simultaneously fostering innovation and human rights. The anticipated outcome is to ensure that NSW Government matches the rising levels of innovation in AI technologies with the appropriate and balanced innovation in AI governance.

Keywords: artificial inteligence, machine learning, rules, governance, government

Procedia PDF Downloads 41

Authors: Jana Chakrabarti, Madhushrita Das, Ankhi Haldar, Roshni Chatterjee, Tanmoy Dey, Pubali Dhar

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High incidences of Protein Energy Malnutrition as a consequence of low protein intake are quite prevalent among the children in developing countries. Thus prevention of under-nutrition has emerged as a critical challenge to India’s developmental Planners in recent times. Increase in population over the last decade has led to greater pressure on the existing animal protein sources. But these resources are currently declining due to persistent drought, diseases, natural disasters, high-cost of feed, and low productivity of local breeds and this decline in productivity is most evident in some developing countries. So the need of the hour is to search for efficient utilization of unconventional low-cost animal protein resources. Molluscs, as a group is regarded as under-exploited source of health-benefit molecules. Bivalve is the second largest class of phylum Mollusca. Annual harvests of bivalves for human consumption represent about 5% by weight of the total world harvest of aquatic resources. The freshwater mussel Lamellidens marginalis is widely distributed in ponds and large bodies of perennial waters in the Indian sub-continent and well accepted as food all over India. Moreover, ethno-medicinal uses of the flesh of Lamellidens among the rural people to treat hypertension have been documented. Present investigation thus attempts to evaluate the potential of Lamellidens marginalis as functional food. Mussels were collected from freshwater ponds and brought to the laboratory two days before experimentation for acclimatization in laboratory conditions. Shells were removed and fleshes were preserved at- 20oC until analysis. Tissue homogenate was prepared for proximate studies. Fatty acids and amino acids composition were analyzed. Vitamins, Minerals and Heavy metal contents were also studied. Mussel Protein hydrolysate was prepared using Alcalase 2.4 L and degree of hydrolysis was evaluated to analyze its Functional properties. Ferric Reducing Antioxidant Power (FRAP) and DPPH Antioxidant assays were performed. Anti-hypertensive property was evaluated by measuring Angiotensin Converting Enzyme (ACE) inhibition assay. Proximate analysis indicates that mussel meat contains moderate amount of protein (8.30±0.67%), carbohydrate (8.01±0.38%) and reducing sugar (4.75±0.07%), but less amount of fat (1.02±0.20%). Moisture content is quite high but ash content is very low. Phospholipid content is significantly high (19.43 %). Lipid constitutes, substantial amount of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which have proven prophylactic values. Trace elements are found present in substantial amount. Comparative study of proximate nutrients between Labeo rohita, Lamellidens and cow’s milk indicates that mussel meat can be used as complementary food source. Functionality analyses of protein hydrolysate show increase in Fat absorption, Emulsification, Foaming capacity and Protein solubility. Progressive anti-oxidant and anti-hypertensive properties have also been documented. Lamellidens marginalis can thus be regarded as a functional food source as this may combine effectively with other food components for providing essential elements to the body. Moreover, mussel protein hydrolysate provides opportunities for utilizing it in various food formulations and pharmaceuticals. The observations presented herein should be viewed as a prelude to what future holds.

Keywords: functional food, functional properties, Lamellidens marginalis, protein hydrolysate

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Authors: Michael Sigruener, Dirk Muscat, Nicole Struebbe

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Fiber reinforcement is a state of the art to enhance mechanical properties in plastics. For concrete and civil engineering, steel reinforcements are commonly used. Steel reinforcements show disadvantages in their chemical resistance and weight, whereas polymer fibers' major problems are in fiber-matrix adhesion and mechanical properties. In spite of these facts, longevity and easy handling, as well as chemical resistance motivate researches to develop a polymeric material for fiber reinforced concrete. Adhesion and interfacial mechanism in fiber-polymer-composites are already studied thoroughly. For polymer fibers used as concrete reinforcement, the bonding behavior still requires a deeper investigation. Therefore, several differing polymers (e.g., polypropylene (PP), polyamide 6 (PA6) and polyetheretherketone (PEEK)) were spun into fibers via single screw extrusion and monoaxial stretching. Fibers then were embedded in a concrete matrix, and Single-Fiber-Pull-Out-Tests (SFPT) were conducted to investigate bonding characteristics and microstructural interface of the composite. Differences in maximum pull-out-force, displacement and slope of the linear part of force vs displacement-function, which depicts the adhesion strength and the ductility of the interfacial bond were studied. In SFPT fiber, debonding is an inhomogeneous process, where the combination of interfacial bonding and friction mechanisms add up to a resulting value. Therefore, correlations between polymeric properties and pull-out-mechanisms have to be emphasized. To investigate these correlations, all fibers were introduced to a series of analysis such as differential scanning calorimetry (DSC), contact angle measurement, surface roughness and hardness analysis, tensile testing and scanning electron microscope (SEM). Of each polymer, smooth and abraded fibers were tested, first to simulate the abrasion and damage caused by a concrete mixing process and secondly to estimate the influence of mechanical anchoring of rough surfaces. In general, abraded fibers showed a significant increase in maximum pull-out-force due to better mechanical anchoring. Friction processes therefore play a major role to increase the maximum pull-out-force. The polymer hardness affects the tribological behavior and polymers with high hardness lead to lower surface roughness verified by SEM and surface roughness measurements. This concludes into a decreased maximum pull-out-force for hard polymers. High surface energy polymers show better interfacial bonding strength in general, which coincides with the conducted SFPT investigation. Polymers such as PEEK or PA6 show higher bonding strength in smooth and roughened fibers, revealed through high pull-out-force and concrete particles bonded on the fiber surface pictured via SEM analysis. The surface energy divides into dispersive and polar part, at which the slope is correlating with the polar part. Only polar polymers increase their SFPT-function slope due to better wetting abilities when showing a higher bonding area through rough surfaces. Hence, the maximum force and the bonding strength of an embedded fiber is a function of polarity, hardness, and consequently surface roughness. Other properties such as crystallinity or tensile strength do not affect bonding behavior. Through the conducted analysis, it is now feasible to understand and resolve different effects in pull-out-behavior step-by-step based on the polymer properties itself. This investigation developed a roadmap on how to engineer high adhering polymeric materials for fiber reinforcement of concrete.

Keywords: fiber-matrix interface, polymeric fibers, fiber reinforced concrete, single fiber pull-out test

Procedia PDF Downloads 86

Authors: Christina Kirsch, Adam Hatzigiannis

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Rail operators and maintainers worldwide are increasingly replacing walking patrols in the rail corridor with mechanized track patrols -essentially data capture on trains- and on-screen reviews of track infrastructure in centralized review facilities. The benefit is that infrastructure workers are less exposed to the dangers of the rail corridor. The impact is a significant change in work design from walking track sections and direct observation in the real world to sedentary jobs in the review facility reviewing captured data on screens. Defects in rail infrastructure can have catastrophic consequences. Reviewer performance regarding accuracy and efficiency of reviews within the available time frame is essential to ensure safety and operational performance. Rail operators must optimize workload and resource loading to transition to on-screen reviews successfully. Therefore, they need to know what workload assessment methodologies will provide reliable and valid data to optimize resourcing for on-screen reviews. This paper compares objective workload measures, including track difficulty ratings and review distance covered per hour, and subjective workload assessments (NASA TLX) and analyses the link between workload and reviewer performance, including sensitivity, precision, and overall accuracy. An experimental study was completed with eight on-screen reviewers, including infrastructure workers and engineers, reviewing track sections with different levels of track difficulty over nine days. Each day the reviewers completed four 90-minute sessions of on-screen inspection of the track infrastructure. Data regarding the speed of review (km/ hour), detected defects, false negatives, and false positives were collected. Additionally, all reviewers completed a subjective workload assessment (NASA TLX) after each 90-minute session and a short employee engagement survey at the end of the study period that captured impacts on job satisfaction and motivation. The results showed that objective measures for tracking difficulty align with subjective mental demand, temporal demand, effort, and frustration in the NASA TLX. Interestingly, review speed correlated with subjective assessments of physical and temporal demand, but to mental demand. Subjective performance ratings correlated with all accuracy measures and review speed. The results showed that subjective NASA TLX workload assessments accurately reflect objective workload. The analysis of the impact of workload on performance showed that subjective mental demand correlated with high precision -accurately detected defects, not false positives. Conversely, high temporal demand was negatively correlated with sensitivity and the percentage of detected existing defects. Review speed was significantly correlated with false negatives. With an increase in review speed, accuracy declined. On the other hand, review speed correlated with subjective performance assessments. Reviewers thought their performance was higher when they reviewed the track sections faster, despite the decline in accuracy. The study results were used to optimize resourcing and ensure that reviewers had enough time to review the allocated track sections to improve defect detection rates in accordance with the efficiency-thoroughness trade-off. Overall, the study showed the importance of a multi-method approach to workload assessment and optimization, combining subjective workload assessments with objective workload and performance measures to ensure that recommendations for work system optimization are evidence-based and reliable.

Keywords: automation, efficiency-thoroughness trade-off, human factors, job design, NASA TLX, performance optimization, subjective workload assessment, workload analysis

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Authors: Keshari Shrestha, Philip Vatterott

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Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

Procedia PDF Downloads 142

Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

Procedia PDF Downloads 47

Authors: Magdy I. A. Alshourbagi

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Background: The National Institute for Deafness and Communication Disorders defines idiopathic sudden sensorineural hearing loss as the idiopathic loss of hearing of at least 30 dB across 3 contiguous frequencies occurring within 3 days.The most common clinical presentation involves an individual experiencing a sudden unilateral hearing loss, tinnitus, a sensation of aural fullness and vertigo. The etiologies and pathologies of ISSNHL remain unclear. Several pathophysiological mechanisms have been described including: vascular occlusion, viral infections, labyrinthine membrane breaks, immune associated disease, abnormal cochlear stress response, trauma, abnormal tissue growth, toxins, ototoxic drugs and cochlear membrane damage. The rationale for the use of hyperbaric oxygen to treat ISSHL is supported by an understanding of the high metabolism and paucity of vascularity to the cochlea. The cochlea and the structures within it require a high oxygen supply. The direct vascular supply, particularly to the organ of Corti, is minimal. Tissue oxygenation to the structures within the cochlea occurs via oxygen diffusion from cochlear capillary networks into the perilymph and the cortilymph. . The perilymph is the primary oxygen source for these intracochlear structures. Unfortunately, perilymph oxygen tension is decreased significantly in patients with ISSHL. To achieve a consistent rise of perilymph oxygen content, the arterial-perilymphatic oxygen concentration difference must be extremely high. This can be restored with hyperbaric oxygen therapy. Subject and Methods: A 37 year old man was presented at the clinic with a five days history of muffled hearing and tinnitus of the right ear. Symptoms were sudden onset, with no associated pain, dizziness or otorrhea and no past history of hearing problems or medical illness. Family history was negative. Physical examination was normal. Otologic examination revealed normal tympanic membranes bilaterally, with no evidence of cerumen or middle ear effusion. Tuning fork examination showed positive Rinne test bilaterally but with lateralization of Weber test to the left side, indicating right ear sensorineural hearing loss. Audiometric analysis confirmed sensorineural hearing loss across all frequencies of about 70- dB in the right ear. Routine lab work were all within normal limits. Clinical diagnosis of idiopathic sudden sensorineural hearing loss of the right ear was made and the patient began a medical treatment (corticosteroid, vasodilator and HBO therapy). The recommended treatment profile consists of 100% O2 at 2.5 atmospheres absolute for 60 minutes daily (six days per week) for 40 treatments .The optimal number of HBOT treatments will vary, depending on the severity and duration of symptomatology and the response to treatment. Results: As HBOT is not yet a standard for idiopathic sudden sensorineural hearing loss, it was introduced to this patient as an adjuvant therapy. The HBOT program was scheduled for 40 sessions, we used a 12-seat multi place chamber for the HBOT, which was started at day seven after the hearing loss onset. After the tenth session of HBOT, improvement of both hearing (by audiogram) and tinnitus was obtained in the affected ear (right). Conclusions: In conclusion, HBOT may be used for idiopathic sudden sensorineural hearing loss as an adjuvant therapy. It may promote oxygenation to the inner ear apparatus and revive hearing ability. Patients who fail to respond to oral and intratympanic steroids may benefit from this treatment. Further investigation is warranted, including animal studies to understand the molecular and histopathological aspects of HBOT and randomized control clinical studies.

Keywords: idiopathic sudden sensorineural hearing loss (issnhl), hyperbaric oxygen therapy (hbot), the decibel (db), oxygen (o2)

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Authors: Juliet Sorensen, Anna Maitland

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Introduction: Characterized by lack of water and sanitation, food insecurity, and low access to hospitals and clinics, informal urban settlements in Lagos, Nigeria have very poor health outcomes. With little education and a general inability to demand basic rights, these communities are often disempowered and isolated from understanding, claiming, or owning their health needs. Utilizing community-based participatory research characterized by interdisciplinary, cross-cultural partnerships, evidence-based assessments, and both primary and secondary source research, a holistic health education and advocacy program was developed in Lagos to address health barriers for targeted communities. This includes a first of its kind guide formulated to teach community-based health educators how to transmit health information to low-literacy Nigerian audiences while supporting behavior change models and social support mechanisms. This paper discusses the interdisciplinary contributions to developing a health education program while also looking at the need for greater beneficiary ownership and implementation of health justice and access. Methods: In March 2016, an interdisciplinary group of medical, legal, and business graduate students and faculty from Northwestern University conduced a Health Needs Assessment (HNA) in Lagos with a partner and a local non-governmental organization. The HNA revealed that members of informal urban communities in Lagos were lacking basic health literacy, but desired to remedy this lacuna. Further, the HNA revealed that even where the government mandates specific services, many vulnerable populations are unable to access these services. The HNA concluded that a program focused on education, advocacy, and organizing around anatomy, maternal and sexual health, infectious disease and malaria, HIV/AIDS, emergency care, and water and sanitation would respond to stated needs while also building capacity in communities to address health barriers. Results: Based on the HNA, including both primary and secondary source research on integrated health education approaches and behavior change models and responsive, adaptive material development, a holistic program was developed for the Lagos partners and first implemented in November 2016. This program trained community-nominated health educators in adult, low-literacy, knowledge exchange approaches, utilizing information identified by communities as a priority. After a second training in March 2017, these educators will teach community-based groups and will support and facilitate behavior change models and peer-support methods around basic issues like hand washing and disease transmission. They will be supported by community paralegals who will help ensure that newly trained community groups can act on education around access, such as receiving free vaccinations, maternal health care, and HIV/AIDS medicines. Materials will continue to be updated as needs and issues arise, with a focus on identifying best practices around health improvements that can be shared across these partner communities. Conclusion: These materials are the first of their kind, and address a void of health information and understanding pervasive in informal-urban Lagos communities. Initial feedback indicates high levels of commitment and interest, as well as investment by communities in these materials, largely because they are responsive, targeted, and build community capacity. This methodology is an important step in dignity-based health justice solutions, albeit in the process of refinement.

Keywords: community health educators, interdisciplinary and cross cultural partnerships, health justice and access, Nigeria

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Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS

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Authors: Ipsita Pujari, Abitha Thomas, Vidhu S. Babu, K. Satyamoorthy

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Orchids are esteemed as celebrities in cut flower industry globally, due to their long-lasting fragrance and freshness. Apart from splendor, the unique metabolites endowed with pharmaceutical potency have made them one of the most hunted in plant kingdom. This had led to their trafficking, resulting in habitat loss, subsequently making them occupiers of IUCN red list as RET species. Many of the orchids especially wild varieties still remain undiscovered. In view to protect and conserve the wild germplasm, researchers have been inventing novel micropropagation protocols; thereby conserving Orchids. India is overflowing with exclusive wild cultivars of Orchids, whose pharmaceutical properties remain untapped and are not marketed owing to relatively small flowers. However, their germplasm is quite pertinent to be preserved for making unusual hybrids. Dendrobium genus is the second largest among Orchids exists in India and has highest demand attributable to enduring cut flowers and significant therapeutic uses in traditional medicinal system. Though the genus is quite endemic in Western Ghat regions of the country, many species are still anonymous with their unknown curative properties. A standard breeding cycle in Orchids usually takes five to seven years (Dendrobium hybrids taking a long juvenile phase of two to five years reaching maturity and flowering stage) and this extensive life cycle has always hindered the development of Dendrobium breeding. Dendrobium is reported with essential therapeutic plant bio-chemicals and ‘Moscatilin’ is one, found exclusive to this famous Dendrobium genus. Moscatilin is reported to have anti-mutagenic and anti-cancer properties, whose positive action has very recently been demonstrated against a range of cancers. Our preliminary study here established a simple and economic small-scale propagation protocol of Dendrobium ovatum describing in vitro production of Moscatilin. Subsequently for enhancing the content of Moscatilin, an efficient experimental related to the organization of transgenic (hairy) D. ovatum root cultures through infection of Agrobacterium rhizogenes 2364 strain on MS basal medium is being reported in the present study. Hairy roots generated on almost half of the explants used (spherules, in vitro plantlets and calli) maintained through suspension cultures, after 8 weeks of co-cultivation with Agrobacterium rhizogenes. GFP assay performed with isolated hairy roots has confirmed the integrative transformation which was further positively confirmed by PCR using rolB gene specific primers. Reverse phase-high performance liquid chromatography and mass spectrometry techniques were used for quantification and accurate identification of Moscatilin respectively from transgenic systems. A noticeable ~3 fold increase in contents were observed in transformed D. ovatum root cultures as compared to the simple in vitro culture, callus culture and callus regeneration plantlets. Role of elicitors e.g., Methyl jasmonate, Salicylic acid, Yeast extract and Chitosan were tested for elevating the Moscatilin content to obtain a comprehensive optimized protocol facilitating the in vitro production of valuable Moscatilin with larger yield. This study would provide evidence towards the in vitro assembly of Moscatilin within a short time-period through not a so-expensive technology for the first time. It also serves as an appropriate basis for bioreactor scale-up resulting in commercial bioproduction of Moscatilin.

Keywords: bioproduction, Dendrobium ovatum, hairy root culture, moscatilin

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Authors: Irina Alexandra Paun, Mona Mihailescu, Marian Zamfirescu, Catalin Romeo Luculescu, Adriana Maria Acasandrei, Cosmin Catalin Mustaciosu, Roxana Cristina Popescu, Maria Dinescu

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A major concern in bone tissue engineering is to develop complex 3D architectures that mimic the natural cells environment, facilitate the cells growth in a defined manner and allow the flow transport of nutrients and metabolic waste. In particular, porous structures of controlled pore size and positioning are indispensable for growing human-like bone structures. Another concern is to monitor both the structures and the seeded cells with high spatial resolution and without interfering with the cells natural environment. The present approach relies on laser-based technologies employed for fabricating porous biomimetic structures that support the growth of osteoblast-like cells and for their non-invasive 3D imaging. Specifically, the porous structures were built by two photon polymerization –direct writing (2PP_DW) of the commercially available photoresists IL-L780, using the Photonic Professional 3D lithography system. The structures consist of vertical tubes with micrometer-sized heights and diameters, in a honeycomb-like spatial arrangement. These were fabricated by irradiating the IP-L780 photoresist with focused laser pulses with wavelength centered at 780 nm, 120 fs pulse duration and 80 MHz repetition rate. The samples were precisely scanned in 3D by piezo stages. The coarse positioning was done by XY motorized stages. The scanning path was programmed through a writing language (GWL) script developed by Nanoscribe. Following laser irradiation, the unexposed regions of the photoresist were washed out by immersing the samples in the Propylene Glycol Monomethyl Ether Acetate (PGMEA). The porous structures were seeded with osteoblast like MG-63 cells and their osteogenic potential was tested in vitro. The cell-seeded structures were analyzed in 3D using the digital holographic microscopy technique (DHM). DHM is a marker free and high spatial resolution imaging tool, where the hologram acquisition is performed non-invasively i.e. without interfering with the cells natural environment. Following hologram recording, a digital algorithm provided a 3D image of the sample, as well as information about its refractive index, which is correlated with the intracellular content. The axial resolution of the images went down to the nanoscale, while the temporal scales ranged from milliseconds up to hours. The hologram did not involve sample scanning and the whole image was available in one frame recorded going over 200μm field of view. The digital holograms processing provided 3D quantitative information on the porous structures and allowed a quantitative analysis of the cellular response in respect to the porous architectures. The cellular shape and dimensions were found to be influenced by the underlying micro relief. Furthermore, the intracellular content gave evidence on the beneficial role of the porous structures in promoting osteoblast differentiation. In all, the proposed laser-based protocol emerges as a promising tool for the fabrication and non-invasive imaging of porous constructs for bone tissue engineering. Acknowledgments: This work was supported by a grant of the Romanian Authority for Scientific Research and Innovation, CNCS-UEFISCDI, project PN-II-RU-TE-2014-4-2534 (contract 97 from 01/10/2015) and by UEFISCDI PN-II-PT-PCCA no. 6/2012. A part of this work was performed in the CETAL laser facility, supported by the National Program PN 16 47 - LAPLAS IV.

Keywords: biomimetic, holography, laser, osteoblast, two photon polymerization

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Authors: Sandhya Manjunath

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The World Association for Sport Management (WASM) was established in 2012, and its mission is "to facilitate sport management research, teaching, and learning excellence and professional practice worldwide". As the field of sport management evolves, it have seen increasing globalization of not only the sport product but many educators have also internationalized courses and curriculums. Curricula should reflect globally recognized issues and disseminate specific intercultural knowledge, skills, and practices, but regional disparities still exist. For example, while India has some of the most ardent sports fans and events in the world, sport management education programs and the development of a proper curriculum in India are still in their nascent stages, especially in comparison to the United States and Europe. Using the extant literature on professionalization and institutional theory, this study aims to investigate the source of knowledge and professionalism of sports managers in India with limited sport management education programs and to subsequently develop a conceptual framework that addresses any gaps or disparities across regions. This study will contribute to WASM's (2022) mission statement of research practice worldwide, specifically to fill the existing disparities between regions. Additionally, this study may emphasize the value of higher education among professionals entering the workforce in the sport industry. Most importantly, this will be a pioneer study highlighting the social issue of limited sport management higher education programs in India and improving professional research practices. Sport management became a field of study in the 1980s, and scholars have studied its professionalization since this time. Dowling, Edwards, & Washington (2013) suggest that professionalization can be categorized into three broad categories of organizational, systemic, and occupational professionalization. However, scant research has integrated the concept of professionalization with institutional theory. A comprehensive review of the literature reveals that sports industry research is progressing in every country worldwide at its own pace. However, there is very little research evidence about the Indian sports industry and the country's limited higher education sport management programs. A growing need exists for sports scholars to pursue research in developing countries like India to develop theoretical frameworks and academic instruments to evaluate the current standards of qualified professionals in sport management, sport marketing, venue and facilities management, sport governance, and development-related activities. This study may postulate a model highlighting the value of higher education in sports management. Education stakeholders include governments, sports organizations and their representatives, educational institutions, and accrediting bodies. As these stakeholders work collaboratively in developed countries like the United States and Europe and developing countries like India, they simultaneously influence the professionalization (i.e., organizational, systemic, and occupational) of sport management education globally. The results of this quantitative study will investigate the current standards of education in India and the source of knowledge among industry professionals. Sports industry professionals will be randomly selected to complete the COSM survey on PsychData and rate their perceived knowledge and professionalism on a Likert scale. Additionally, they will answer questions involving their competencies, experience, or challenges in contributing to Indian sports management research. Multivariate regression will be used to measure the degree to which the various independent variables impact the current knowledge, contribution to research, and professionalism of India's sports industry professionals. This quantitative study will contribute to the limited academic literature available to Indian sports practitioners. Additionally, it shall synthesize knowledge from previous work on professionalism and institutional knowledge, providing a springboard for new research that will fill the existing knowledge gaps. While a further empirical investigation is warranted, our conceptualization contributes to and highlights India's burgeoning sport management industry.

Keywords: sport management, professionalism, source of knowledge, higher education, India

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Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

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Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

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Authors: Nur A. Özdemir, Sude Erkin, Hatice K. Güney, Cemre S. Atılgan, Enes Huylu, Hüseyin Y. Altıntaş, Aysemin Top, Özak Durmuş

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Carbon emissions produced during a product’s life cycle, from extraction of raw materials up to waste disposal and market consumption activities are the major contributors to global warming. In the light of the science-based targets (SBT) leading the way to a zero-carbon economy for sustainable growth of the companies, carbon footprint reporting of the purchased goods has become critical for identifying hotspots and best practices for emission reduction opportunities. In line with Ford Otosan's corporate sustainability strategy, research was conducted to evaluate the carbon footprint of purchased products in accordance with Scope 3 of the Greenhouse Gas Protocol (GHG). The purpose of this paper is to develop a systematic and transparent methodology to calculate carbon footprint of the products produced by automotive OEMs (Original Equipment Manufacturers) within the context of automobile supply chain management. To begin with, primary material data were collected through IMDS (International Material Database System) corresponds to company’s three distinct types of vehicles including Light Commercial Vehicle (Courier), Medium Commercial Vehicle (Transit and Transit Custom), Heavy Commercial Vehicle (F-MAX). Obtained material data was classified as metals, plastics, liquids, electronics, and others to get insights about the overall material distribution of produced vehicles and matched to the SimaPro Ecoinvent 3 database which is one of the most extent versions for modelling material data related to the product life cycle. Product life cycle analysis was calculated within the framework of ISO 14040 – 14044 standards by addressing the requirements and procedures. A comprehensive literature review and cooperation with suppliers were undertaken to identify the production methods of parts used in vehicles and to find out the amount of scrap generated during part production. Cumulative weight and material information with related production process belonging the components were listed by multiplying with current sales figures. The results of the study show a key modelling on carbon footprint of products and processes based on a scientific approach to drive sustainable growth by setting straightforward, science-based emission reduction targets. Hence, this study targets to identify the hotspots and correspondingly provide broad ideas about our understanding of how to integrate carbon footprint estimates into our company's supply chain management by defining convenient actions in line with climate science. According to emission values arising from the production phase including raw material extraction and material processing for Ford OTOSAN vehicles subjected in this study, GHG emissions from the production of metals used for HCV, MCV and LCV account for more than half of the carbon footprint of the vehicle's production. Correspondingly, aluminum and steel have the largest share among all material types and achieving carbon neutrality in the steel and aluminum industry is of great significance to the world, which will also present an immense impact on the automobile industry. Strategic product sustainability plan which includes the use of secondary materials, conversion to green energy and low-energy process design is required to reduce emissions of steel, aluminum, and plastics due to the projected increase in total volume by 2030.

Keywords: automotive, carbon footprint, IMDS, scope 3, SimaPro, sustainability

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Authors: Rajwanlop Kumpoopong, Sukit Yindeesuk, Pornchai Silarom

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On May 5, 2014, an earthquake of magnitude 6.3 Richter hit the Northern part of Thailand. The epicenter was in Phan District, Chiang Rai Province. This earthquake or the so-called 2014-Chiang Rai Earthquake is the strongest ground shaking that Thailand has ever been experienced in her modern history. The 2014-Chiang Rai Earthquake confirms the geological evidence, which has previously been ignored by most engineers, that earthquakes of considerable magnitudes 6 to 7 Richter can occurr within the country. This promptly stimulates authorized agencies to pay more attention at the safety of their assets and promotes the comprehensive review of seismic resistance design of their building structures. The focus of this paper is to summarize the damages of highway bridges as a result of the 2014-Chiang Rai ground shaking, the remedy actions, and the research needs. The 2014-Chiang Rai Earthquake caused considerable damages to nearby structures such as houses, schools, and temples. The ground shaking, however, caused damage to only one highway bridge, Mae Laos Bridge, located several kilometers away from the epicenter. The damage of Mae Laos Bridge was in the form of concrete spalling caused by pounding of cap beam on the deck structure. The damage occurred only at the end or abutment span. The damage caused by pounding is not a surprise, but the pounding by only one bridge requires further investigation and discussion. Mae Laos Bridge is a river crossing bridge with relatively large approach structure. In as much, the approach structure is confined by strong retaining walls. This results in a rigid-like approach structure which vibrates at the acceleration approximately equal to the ground acceleration during the earthquake and exerts a huge force to the abutment causing the pounding of cap beam on the deck structure. Other bridges nearby have relatively small approach structures, and therefore have no capability to generate pounding. The effect of mass of the approach structure on pounding of cap beam on the deck structure is also evident by the damage of one pedestrian bridge in front of Thanthong Wittaya School located 50 meters from Mae Laos Bridge. The width of the approach stair of this bridge is wider than the typical one to accommodate the stream of students during pre- and post-school times. This results in a relatively large mass of the approach stair which in turn exerts a huge force to the pier causing pounding of cap beam on the deck structure during ground shaking. No sign of pounding was observed for a typical pedestrian bridge located at another end of Mae Laos Bridge. Although pounding of cap beam on the deck structure of the above mentioned bridges does not cause serious damage to bridge structure, this incident promotes the comprehensive review of seismic resistance design of highway bridges in Thailand. Given a proper mass and confinement of the approach structure, the pounding of cap beam on the deck structure can be easily excited even at the low to moderate ground shaking. In as much, if the ground shaking becomes stronger, the pounding is certainly more powerful. This may cause the deck structure to be unseated and fall off in the case of unrestrained bridge. For the bridge with restrainer between cap beam and the deck structure, the restrainer may prevent the deck structure from falling off. However, preventing free movement of the pier by the restrainer may damage the pier itself. Most highway bridges in Thailand have dowel bars embedded connecting cap beam and the deck structure. The purpose of the existence of dowel bars is, however, not intended for any seismic resistance. Their ability to prevent the deck structure from unseating and their effect on the potential damage of the pier should be evaluated. In response to this expected situation, Thailand Department of Highways (DOH) has set up a team to revise the standard practices for the seismic resistance design of highway bridges in Thailand. In addition, DOH has also funded the research project 'Seismic Resistance Evaluation of Pre- and Post-Design Modifications of DOH’s Bridges' with the scope of full-scale tests of single span bridges under reversed cyclic static loadings for both longitudinal and transverse directions and computer simulations to evaluate the seismic performance of the existing bridges and the design modification bridges. The research is expected to start in October, 2015.

Keywords: earthquake, highway bridge, Thailand, damage, pounding, seismic resistance

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Authors: Priyanka Botny Srinath, Alessandro Suglia, Mel McKendrick

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Background: Organizational cultural studies integrate sociology and anthropology, portraying man as a creator of symbols, languages, beliefs, and ideologies -essentially, a creator and manager of meaning. In our research, we leverage analytical measures to discern whether an organization embodies a singular culture or a myriad of subcultures. Fast-forward to 2023, our research thesis focuses on digitally measuring culture, coining it as the "Work Culture Quotient." This entails conceptually mapping common experiential patterns to provide executives insights into the digital organization journey, aiding in understanding their current position and identifying future steps. Objectives: Finding the new age skills that help in defining the culture; understand the implications of post-COVID effects; derive a digital framework for measuring skillsets. Method: We conducted two comprehensive Delphi studies to distill essential insights. Delphi 1: Through a thematic analysis of interviews with 20 high-level leaders representing companies across diverse regions -India, Japan, the US, Canada, Morocco, and Uganda- we identified 20 key skills critical for cultivating a robust organizational culture. The skills are -influence, self-confidence, optimism, empathy, leadership, collaboration and cooperation, developing others, commitment, innovativeness, leveraging diversity, change management, team capabilities, self-control, digital communication, emotional awareness, team bonding, communication, problem solving, adaptability, and trustworthiness. Delphi 2: Subject matter experts were asked to complete a questionnaire derived from the thematic analysis in stage 1 to formalise themes and draw consensus amongst experts on the most important workplace skills. Results: The thematic analysis resulted in 20 workplace employee skills being identified. These skills were all included in the Delphi round 2 questionnaire. From the outputs, we analysed the data using R Studio for arriving at agreement and consensus, we also used sum of squares method to compare various agreements to extract various themes with a threshold of 80% agreements. This yielded three themes at over 80% agreement (leadership, collaboration and cooperation, communication) and three further themes at over 60% agreement (commitment, empathy, trustworthiness). From this, we selected five questionnaires to be included in the primary data collection phase, and these will be paired with the digital footprints to provide a workplace culture quotient. Implications: The findings from these studies bear profound implications for decision-makers, revolutionizing their comprehension of organizational culture. Tackling the challenge of mapping the digital organization journey involves innovative methodologies that probe not only external landscapes but also internal cultural dynamics. This holistic approach furnishes decision-makers with a nuanced understanding of their organizational culture and visualizes pivotal skills for employee growth. This clarity enables informed choices resonating with the organization's unique cultural fabric. Anticipated outcomes transcend mere individual cultural measurements, aligning with organizational goals to unveil a comprehensive view of culture, exposing artifacts and depth. Armed with this profound understanding, decision-makers gain tangible evidence for informed decision-making, strategically leveraging cultural strengths to cultivate an environment conducive to growth, innovation, and enduring success, ultimately leading to measurable outcomes.

Keywords: leadership, cooperation, collaboration, teamwork, work culture

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

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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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