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191 Dimethyl fumarate Alleviates Valproic Acid-Induced Autism in Wistar Rats via Activating NRF-2 and Inhibiting NF-κB Pathways
Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar
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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2
Procedia PDF Downloads 41190 Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers
Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean
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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics
Procedia PDF Downloads 299189 Interdisciplinary Method Development - A Way to Realize the Full Potential of Textile Resources
Authors: Nynne Nørup, Julie Helles Eriksen, Rikke M. Moalem, Else Skjold
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Despite a growing focus on the high environmental impact of textiles, textile waste is only recently considered as part of the waste field. Consequently, there is a general lack of knowledge and data within this field. Particularly the lack of a common perception of textiles generates several problems e.g., to recognize the full material potential the fraction contains, which is cruel if the textile must enter the circular economy. This study aims to qualify a method to make the resources in textile waste visible in a way that makes it possible to move them as high up in the waste hierarchy as possible. Textiles are complex and cover many different types of products, fibers and combinations of fibers and production methods. In garments alone, there is a great variety, even when narrowing it to only undergarments. However, textile waste is often reduced to one fraction, assessed solely by quantity, and compared to quantities of other waste fractions. Disregarding the complexity and reducing textiles to a single fraction that covers everything made of textiles increase the risk of neglecting the value of the materials, both with regards to their properties and economical. Instead of trying to fit textile waste into the current primarily linear waste system where volume is a key part of the business models, this study focused on integrating textile waste as a resource in the design and production phase. The study combined interdisciplinary methods for determining replacement rates used in Life Cycle Assessments and Mass Flow Analysis methods with the designer’s toolbox to hereby activate the properties of textile waste in a way that can unleash its potential optimally. It was hypothesized that by activating Denmark's tradition for design and high level of craftsmanship, it is possible to find solutions that can be used today and create circular resource models that reduce the use of virgin fibers. Through waste samples, case studies, and testing of various design approaches, this study explored how to functionalize the method so that the product after the end-use is kept as a material and only then processed at fiber level to obtain the best environmental utilization. The study showed that the designers' ability to decode the properties of the materials and understanding of craftsmanship were decisive for how well the materials could be utilized today. The later in the life cycle the textiles appeared as waste, the more demanding the description of the materials to be sufficient, especially if to achieve the best possible use of the resources and thus a higher replacement rate. In addition, it also required adaptation in relation to the current production because the materials often varied more. The study found good indications that part of the solution is to use geodata i.e., where in the life cycle the materials were discarded. An important conclusion is that a fully developed method can help support better utilization of textile resources. However, it stills requires a better understanding of materials by the designers, as well as structural changes in business and society.Keywords: circular economy, development of sustainable processes, environmental impacts, environmental management of textiles, environmental sustainability through textile recycling, interdisciplinary method development, resource optimization, recycled textile materials and the evaluation of recycling, sustainability and recycling opportunities in the textile and apparel sector
Procedia PDF Downloads 95188 Gas Chromatographic: Mass Spectroscopic Analysis of Citrus reticulata Fruit Peel, Zingiber officinale Rhizome, and Sesamum indicum Seed Ethanolic Extracts Possessing Antioxidant Activity and Lipid Profile Effects
Authors: Samar Saadeldin Abdelmotalab Omer, Ikram Mohamed Eltayeb Elsiddig, Saad Mohammed Hussein Ayoub
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A variety of herbal medicinal plants are known to confer beneficial effects in regards to modification of cardiovascular ri’=sk factors. The anti-hypercholesterolaemic and antioxidant activities of the crude ethanolic extracts of Citrus reticulate fruit peel, Zingiber officinale rhizome and Sesamum indicum seed extracts have been demonstrated. These plants are assumed to possess biologically active principles, which impart their pharmacologic activities. GC-MS analysis of the ethanolic extracts was carried out to identify the active principles and their percentages of occurrence in the analytes. Analysis of the extracts was carried out using (GS-MS QP) type Schimadzu 2010 equipped with a capillary column RTX-50 (restec), (length 30mm, diameter 0.25mm, and thickness 0.25mm). Helium was used as a carrier gas, the temperature was programmed at 200°C for 5 minutes at a rate of 15ml/minute, and the extracts were injected using split injection mode. The identification of different components was achieved from their Mass Spectra and Retention time, compared with those in the NIST library. The results revealed the presence of 80 compounds in Sudanese locally grown C. reticulata fruit peel extract, most of which were monoterpenoid compounds including Limonene (3.03%), Alpha & Gamma - terpinenes (2.61%), Linalool (1.38%), Citral (1.72%) which are known to have profound antioxidant effects. The Sesquiterpenoids Humulene (0.26%) and Caryophyllene (1.97%) were also identified, the latter known to have profound anti-anxiety and anti-depressant activity in addition to the beneficiary effects in lipid regulation. The analysis of the locally grown S. indicum oily and water soluble portions of seed extract revealed the presence of a total of 64 compounds with considerably high percentage of the mono-unsaturated fatty acid ester methyl oleate (66.99%) in addition to methyl stearate (9.35%) and palmitate (15.71%) of oil portion, whereas, plant sterols including Gamma-sitosterol (13.5%), fucosterol (2.11%) and stigmasterol (1.95%) in addition to gamma-tocopherol (1.16%) were detected in extract water-soluble portion. The latter indicate various principles known to have valuable pharmacological benefits including antioxidant activities and beneficiary effects on intestinal cholesterol absorption and regulation of serum cholesterol levels. Z. officinale rhizome extract analysis revealed the presence of 93 compounds, the most abundant were alpha-zingeberine (16.5%), gingerol (9.25%), alpha-sesquiphellandrene (8.3%), zingerone (6.78%), beta-bisabolene (4.19%), alpha-farnesene (3.56%), ar-curcumene (3.29%), gamma-elemene (1.25%) and a variety of other compounds. The presence of these active principles reflected on the activity of the extract. Activity could be assigned to a single or a combination of two or more extract components. GC-MS analysis concluded the occurrence of compounds known to possess antioxidant activity and lipid profile effects.Keywords: gas chromatography, indicum, officinale, reticulata
Procedia PDF Downloads 373187 A Rural Journey of Integrating Interprofessional Education to Foster Trust
Authors: Julia Wimmers Klick
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Interprofessional Education (IPE) is widely recognized as a valuable approach in healthcare education, despite the challenges it presents. This study explores IP surface anatomy lab sessions, with a focus on fostering trust and collaboration among healthcare students. The research is conducted within the context of rural healthcare settings in British Columbia (BC), where a medical school and a physical therapy (PT) program operate under the Faculty of Medicine at the University of British Columbia (UBC). While IPE sessions addressing soft skills have been implemented, the integration of hard skills, such as Anatomy, remains limited. To address this gap, a pilot feasibility study was conducted with a positive outcome, a follow-up study involved these IPE sessions aimed at exploring the influence of bonding and trust between medical and PT students. Data were collected through focus groups comprising participating students and faculty members, and a structured SWOC (Strengths, Weaknesses, Opportunities, and Challenges) analysis was conducted. The IPE sessions, 3 in total, consisted of a 2.5-hour lab on surface anatomy, where PT students took on the teaching role, and medical students were newly exposed to surface anatomy. The focus of the study was on the relationship-building process and trust development between the two student groups, rather than assessing the acquisition of surface anatomy skills. Results indicated that the surface anatomy lab served as a suitable tool for the application and learning of soft skills. Faculty members observed positive outcomes, including productive interaction between students, reversed hierarchy with PT students teaching medical students, practicing active listening skills, and using a mutual language of anatomy. Notably, there was no grade assessment or external pressure to perform. The students also reported an overall positive experience; however, the specific impact on the development of soft skill competencies could not be definitively determined. Participants expressed a sense of feeling respected, welcomed, and included, all of which contributed to feeling safe. Within the small group environment, students experienced becoming a part of a community of healthcare providers that bonded over a shared interest in health professions education. They enjoyed sharing diverse experiences related to learning across their varied contexts, without fear of judgment and reprisal that were often intimidating in single professional contexts. During a joint Christmas party for both cohorts, faculty members observed students mingling, laughing, and forming bonds. This emphasized the importance of early bonding and trust development among healthcare colleagues, particularly in rural settings. In conclusion, the findings emphasize the potential of IPE sessions to enhance trust and collaboration among healthcare students, with implications for their future professional lives in rural settings. Early bonding and trust development are crucial in rural settings, where healthcare professionals often rely on each other. Future research should continue to explore the impact of content-concentrated IPE on the development of soft skill competencies.Keywords: interprofessional education, rural healthcare settings, trust, surface anatomy
Procedia PDF Downloads 69186 Developing Effective Strategies to Reduce Hiv, Aids and Sexually Transmitted Infections, Nakuru, Kenya
Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi
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Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach
Procedia PDF Downloads 88185 A Study on Aquatic Bycatch Mortality Estimation Due to Prawn Seed Collection and Alteration of Collection Method through Sustainable Practices in Selected Areas of Sundarban Biosphere Reserve (SBR), India
Authors: Samrat Paul, Satyajit Pahari, Krishnendu Basak, Amitava Roy
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Fishing is one of the pivotal livelihood activities, especially in developing countries. Today it is considered an important occupation for human society from the era of human settlement began. In simple terms, non-target catches of any species during fishing can be considered as ‘bycatch,’ and fishing bycatch is neither a new fishery management issue nor a new problem. Sundarban is one of the world’s largest mangrove land expanding up to 10,200 sq. km in India and Bangladesh. This largest mangrove biome resource is used by the local inhabitants commercially to run their livelihood, especially by forest fringe villagers (FFVs). In Sundarban, over-fishing, especially post larvae collection of wild Penaeus monodon, is one of the major concerns, as during the collection of P. monodon, different aquatic species are destroyed as a result of bycatch mortality which changes in productivity and may negatively impact entire biodiversity, of the ecosystem. Wild prawn seed collection gear like a small mesh sized net poses a serious threat to aquatic stocks, where the collection isn’t only limited to prawn seed larvae. As prawn seed collection processes are inexpensive, require less monetary investment, and are lucrative; people are easily engaged here as their source of income. Wildlife Trust of India’s (WTI) intervention in selected forest fringe villages of Sundarban Tiger Reserve (STR) was to estimate and reduce the mortality of aquatic bycatches by involving local communities in newly developed release method and their time engagement in prawn seed collection (PSC) by involving them in Alternate Income Generation (AIG). The study was conducted for their taxonomic identification during the period of March to October 2019. Collected samples were preserved in 70% ethyl alcohol for identification, and all the preserved bycatch samples were identified morphologically by the expertise of the Zoological Survey of India (ZSI), Kolkata. Around 74 different aquatic species, where 11 different species are molluscs, 41 fish species, out of which 31 species were identified, and 22 species of crustacean collected, out of which 18 species were identified. Around 13 different species belong to a different order, and families were unable to identify them morphologically as they were collected in the juvenile stage. The study reveals that for collecting one single prawn seed, eight individual life of associated faunas are being lost. Zero bycatch mortality is not practical; rather, collectors should focus on bycatch reduction by avoiding capturing, allowing escaping, and mortality reduction, and must make changes in their fishing method by increasing net mesh size, which will avoid non-target captures. But as the prawns are small in size (generally 1-1.5 inches in length), thus increase net size making economically less or no profit for collectors if they do so. In this case, returning bycatches is considered one of the best ways to a reduction in bycatch mortality which is a more sustainable practice.Keywords: bycatch mortality, biodiversity, mangrove biome resource, sustainable practice, Alternate Income Generation (AIG)
Procedia PDF Downloads 151184 A Randomized, Controlled Trial to Test Habit Formation Theory for Low Intensity Physical Exercise Promotion in Older Adults
Authors: Patrick Louie Robles, Jerry Suls, Ciaran Friel, Mark Butler, Samantha Gordon, Frank Vicari, Joan Duer-Hefele, Karina W. Davidson
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Physical activity guidelines focus on increasing moderate-intensity activity for older adults, but adherence to recommendations remains low. This is despite the fact that scientific evidence finds increasing physical activity is positively associated with health benefits. Behavior change techniques (BCTs) have demonstrated some effectiveness in reducing sedentary behavior and promoting physical activity. This pilot study uses a personalized trials (N-of-1) design, delivered virtually, to evaluate the efficacy of using five BCTs in increasing low-intensity physical activity (by 2,000 steps of walking per day) in adults aged 45-75 years old. The 5 BCTs described in habit formation theory are goal setting, action planning, rehearsal, rehearsal in a consistent context, and self-monitoring. The study recruited health system employees in the target age range who had no mobility restrictions and expressed interest in increasing their daily activity by a minimum of 2,000 steps per day at least five days per week. Participants were sent a Fitbit Charge 4 fitness tracker with an established study account and password. Participants were recommended to wear the Fitbit device 24/7 but were required to wear it for a minimum of ten hours per day. Baseline physical activity was measured by Fitbit for two weeks. Participants then engaged remotely with a clinical research coordinator to establish a “walking plan” that included a time and day interval (e.g., between 7am -8am on Monday-Friday), a location for the walk (e.g., park), and how much time the plan would need to achieve a minimum of 2,000 steps over their baseline average step count (20 minutes). All elements of the walking plan were required to remain consistent throughout the study. In the 10-week intervention phase of the study, participants received all five BCTs in a single, time-sensitive text message. The text message was delivered 30 minutes prior to the established walk time and signaled participants to begin walking when the context (i.e., day of the week, time of day) they pre-selected is encountered. Participants were asked to log both the start and conclusion of their activity session by pressing a button on the Fitbit tracker. Within 30 minutes of the planned conclusion of the activity session, participants received a text message with a link to a secure survey. Here, they noted whether they engaged in the BCTs when prompted and completed an automaticity survey to identify how “automatic” their walking behavior had become. At the end of their trial, participants received a personalized summary of their step data over time, helping them learn more about their responses to the five BCTs. Whether the use of these 5 ‘habit formation’ BCTs in combination elicits a change in physical activity behavior among older adults will be reported. This study will inform the feasibility of a virtually-delivered N-of-1 study design to effectively promote physical activity as a component of healthy aging.Keywords: aging, exercise, habit, walking
Procedia PDF Downloads 138183 Knowledge and Attitude Towards Strabismus Among Adult Residents in Woreta Town, Northwest Ethiopia: A Community-Based Study
Authors: Henok Biruk Alemayehu, Kalkidan Berhane Tsegaye, Fozia Seid Ali, Nebiyat Feleke Adimassu, Getasew Alemu Mersha
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Background: Strabismus is a visual disorder where the eyes are misaligned and point in different directions. Untreated strabismus can lead to amblyopia, loss of binocular vision, and social stigma due to its appearance. Since it is assumed that knowledge is pertinent for early screening and prevention of strabismus, the main objective of this study was to assess knowledge and attitudes toward strabismus in Woreta town, Northwest Ethiopia. Providing data in this area is important for planning health policies. Methods: A community-based cross-sectional study was done in Woreta town from April–May 2020. The sample size was determined using a single population proportion formula by taking a 50% proportion of good knowledge, 95% confidence level, 5% margin of errors, and 10% non- response rate. Accordingly, the final computed sample size was 424. All four kebeles were included in the study. There were 42,595 people in total, with 39,684 adults and 9229 house holds. A sample fraction ’’k’’ was obtained by dividing the number of the household by the calculated sample size of 424. Systematic random sampling with proportional allocation was used to select the participating households with a sampling fraction (K) of 21 i.e. each household was approached in every 21 households included in the study. One individual was selected ran- domly from each household with more than one adult, using the lottery method to obtain a final sample size. The data was collected through a face-to-face interview with a pretested and semi-structured questionnaire which was translated from English to Amharic and back to English to maintain its consistency. Data were entered using epi-data version 3.1, then processed and analyzed via SPSS version- 20. Descriptive and analytical statistics were employed to summarize the data. A p-value of less than 0.05 was used to declare statistical significance. Result: A total of 401 individuals aged over 18 years participated, with a response rate of 94.5%. Of those who responded, 56.6% were males. Of all the participants, 36.9% were illiterate. The proportion of people with poor knowledge of strabismus was 45.1%. It was shown that 53.9% of the respondents had a favorable attitude. Older age, higher educational level, having a history of eye examination, and a having a family history of strabismus were significantly associated with good knowledge of strabismus. A higher educational level, older age, and hearing about strabismus were significantly associated with a favorable attitude toward strabismus. Conclusion and recommendation: The proportion of good knowledge and favorable attitude towards strabismus were lower than previously reported in Gondar City, Northwest Ethiopia. There is a need to provide health education and promotion campaigns on strabismus to the community: what strabismus is, its’ possible treatments and the need to bring children to the eye care center for early diagnosis and treatment. it advocate for prospective research endeavors to employ qualitative study design.Additionally, it suggest the exploration of studies that investigate causal-effect relationship.Keywords: strabismus, knowledge, attitude, Woreta
Procedia PDF Downloads 62182 Formulation of Lipid-Based Tableted Spray-Congealed Microparticles for Zero Order Release of Vildagliptin
Authors: Hend Ben Tkhayat , Khaled Al Zahabi, Husam Younes
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Introduction: Vildagliptin (VG), a dipeptidyl peptidase-4 inhibitor (DPP-4), was proven to be an active agent for the treatment of type 2 diabetes. VG works by enhancing and prolonging the activity of incretins which improves insulin secretion and decreases glucagon release, therefore lowering blood glucose level. It is usually used with various classes, such as insulin sensitizers or metformin. VG is currently only marketed as an immediate-release tablet that is administered twice daily. In this project, we aim to formulate an extended-release with a zero-order profile tableted lipid microparticles of VG that could be administered once daily ensuring the patient’s convenience. Method: The spray-congealing technique was used to prepare VG microparticles. Compritol® was heated at 10 oC above its melting point and VG was dispersed in the molten carrier using a homogenizer (IKA T25- USA) set at 13000 rpm. VG dispersed in the molten Compritol® was added dropwise to the molten Gelucire® 50/13 and PEG® (400, 6000, and 35000) in different ratios under manual stirring. The molten mixture was homogenized and Carbomer® amount was added. The melt was pumped through the two-fluid nozzle of the Buchi® Spray-Congealer (Buchi B-290, Switzerland) using a Pump drive (Master flex, USA) connected to a silicone tubing wrapped with silicone heating tape heated at the same temperature of the pumped mix. The physicochemical properties of the produced VG-loaded microparticles were characterized using Mastersizer, Scanning Electron Microscope (SEM), Differential Scanning Calorimeter (DSC) and X‐Ray Diffractometer (XRD). VG microparticles were then pressed into tablets using a single punch tablet machine (YDP-12, Minhua pharmaceutical Co. China) and in vitro dissolution study was investigated using Agilent Dissolution Tester (Agilent, USA). The dissolution test was carried out at 37±0.5 °C for 24 hours in three different dissolution media and time phases. The quantitative analysis of VG in samples was realized using a validated High-Pressure Liquid Chromatography (HPLC-UV) method. Results: The microparticles were spherical in shape with narrow distribution and smooth surface. DSC and XRD analyses confirmed the crystallinity of VG that was lost after being incorporated into the amorphous polymers. The total yields of the different formulas were between 70% and 80%. The VG content in the microparticles was found to be between 99% and 106%. The in vitro dissolution study showed that VG was released from the tableted particles in a controlled fashion. The adjustment of the hydrophilic/hydrophobic ratio of excipients, their concentration and the molecular weight of the used carriers resulted in tablets with zero-order kinetics. The Gelucire 50/13®, a hydrophilic polymer was characterized by a time-dependent profile with an important burst effect that was decreased by adding Compritol® as a lipophilic carrier to retard the release of VG which is highly soluble in water. PEG® (400,6000 and 35 000) were used for their gelling effect that led to a constant rate delivery and achieving a zero-order profile. Conclusion: Tableted spray-congealed lipid microparticles for extended-release of VG were successfully prepared and a zero-order profile was achieved.Keywords: vildagliptin, spray congealing, microparticles, controlled release
Procedia PDF Downloads 121181 Effect of Renin Angiotensin Pathway Inhibition on the Efficacy of Anti-programmed Cell Death (PD-1/L-1) Inhibitors in Advanced Non-small Cell Lung Cancer Patients- Comparison of Single Hospital Retrospective Assessment to the Published Literature
Authors: Esther Friedlander, Philip Friedlander
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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC
Procedia PDF Downloads 69180 The Recorded Interaction Task: A Validation Study of a New Observational Tool to Assess Mother-Infant Bonding
Authors: Hannah Edwards, Femke T. A. Buisman-Pijlman, Adrian Esterman, Craig Phillips, Sandra Orgeig, Andrea Gordon
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Mother-infant bonding is a term which refers to the early emotional connectedness between a mother and her infant. Strong mother-infant bonding promotes higher quality mother and infant interactions including prolonged breastfeeding, secure attachment and increased sensitive parenting and maternal responsiveness. Strengthening of all such interactions leads to improved social behavior, and emotional and cognitive development throughout childhood, adolescence and adulthood. The positive outcomes observed following strong mother-infant bonding emphasize the need to screen new mothers for disrupted mother-infant bonding, and in turn the need for a robust, valid tool to assess mother-infant bonding. A recent scoping review conducted by the research team identified four tools to assess mother-infant bonding, all of which employed self-rating scales. Thus, whilst these tools demonstrated both adequate validity and reliability, they rely on self-reported information from the mother. As such this may reflect a mother’s perception of bonding with their infant, rather than their actual behavior. Therefore, a new tool to assess mother-infant bonding has been developed. The Recorded Interaction Task (RIT) addresses shortcomings of previous tools by employing observational methods to assess bonding. The RIT focusses on the common interaction between mother and infant of changing a nappy, at the target age of 2-6 months, which is visually recorded and then later assessed. Thirteen maternal and seven infant behaviors are scored on the RIT Observation Scoring Sheet, and a final combined score of mother-infant bonding is determined. The aim of the current study was to assess the content validity and inter-rater reliability of the RIT. A panel of six experts with specialized expertise in bonding and infant behavior were consulted. Experts were provided with the RIT Observation Scoring Sheet, a visual recording of a nappy change interaction, and a feedback form. Experts scored the mother and infant interaction on the RIT Observation Scoring Sheet and completed the feedback form which collected their opinions on the validity of each item on the RIT Observation Scoring Sheet and the RIT as a whole. Twelve of the 20 items on the RIT Observation Scoring Sheet were scored ‘Valid’ by all (n=6) or most (n=5) experts. Two items received a ‘Not valid’ score from one expert. The remainder of the items received a mixture of ‘Valid’ and ‘Potentially Valid’ scores. Few changes were made to the RIT Observation Scoring Sheet following expert feedback, including rewording of items for clarity and the exclusion of an item focusing on behavior deemed not relevant for the target infant age. The overall ICC for single rater absolute agreement was 0.48 (95% CI 0.28 – 0.71). Experts (n=6) ratings were less consistent for infant behavior (ICC 0.27 (-0.01 – 0.82)) compared to mother behavior (ICC 0.55 (0.28 – 0.80)). Whilst previous tools employ self-report methods to assess mother-infant bonding, the RIT utilizes observational methods. The current study highlights adequate content validity and moderate inter-rater reliability of the RIT, supporting its use in future research. A convergent validity study comparing the RIT against an existing tool is currently being undertaken to confirm these results.Keywords: content validity, inter-rater reliability, mother-infant bonding, observational tool, recorded interaction task
Procedia PDF Downloads 181179 An Eco-Systemic Typology of Fashion Resale Business Models in Denmark
Authors: Mette Dalgaard Nielsen
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The paper serves the purpose of providing an eco-systemic typology of fashion resale business models in Denmark while pointing to possibilities to learn from its wisdom during a time when a fundamental break with the dominant linear fashion paradigm has become inevitable. As we transgress planetary boundaries and can no longer continue the unsustainable path of over-exploiting the Earth’s resources, the global fashion industry faces a tremendous need for change. One of the preferred answers to the fashion industry’s sustainability crises lies in the circular economy, which aims to maximize the utilization of resources by keeping garments in use for longer. Thus, in the context of fashion, resale business models that allow pre-owned garments to change hands with the purpose of being reused in continuous cycles are considered to be among the most efficient forms of circularity. Methodologies: The paper is based on empirical data from an ongoing project and a series of qualitative pilot studies that have been conducted on the Danish resale market over a 2-year time period from Fall 2021 to Fall 2023. The methodological framework is comprised of (n) ethnography and fieldwork in selected resale environments, as well as semi-structured interviews and a workshop with eight business partners from the Danish fashion and textiles industry. By focusing on the real-world circulation of pre-owned garments, which is enabled by the identified resale business models, the research lets go of simplistic hypotheses to the benefit of dynamic, vibrant and non-linear processes. As such, the paper contributes to the emerging research field of circular economy and fashion, which finds itself in a critical need to move from non-verified concepts and theories to empirical evidence. Findings: Based on the empirical data and anchored in the business partners, the paper analyses and presents five distinct resale business models with different product, service and design characteristics. These are 1) branded resale, 2) trade-in resale, 3) peer-2-peer resale, 4) resale boutiques and consignment shops and 5) resale shelf/square meter stores and flea markets. Together, the five business models represent a plurality of resale-promoting business model design elements that have been found to contribute to the circulation of pre-owned garments in various ways for different garments, users and businesses in Denmark. Hence, the provided typology points to the necessity of prioritizing several rather than single resale business model designs, services and initiatives for the resale market to help reconfigure the linear fashion model and create a circular-ish future. Conclusions: The article represents a twofold research ambition by 1) presenting an original, up-to-date eco-systemic typology of resale business models in Denmark and 2) using the typology and its eco-systemic traits as a tool to understand different business model design elements and possibilities to help fashion grow out of its linear growth model. By basing the typology on eco-systemic mechanisms and actual exemplars of resale business models, it becomes possible to envision the contours of a genuine alternative to business as usual that ultimately helps bend the linear fashion model towards circularity.Keywords: circular business models, circular economy, fashion, resale, strategic design, sustainability
Procedia PDF Downloads 59178 Comparing Radiographic Detection of Simulated Syndesmosis Instability Using Standard 2D Fluoroscopy Versus 3D Cone-Beam Computed Tomography
Authors: Diane Ghanem, Arjun Gupta, Rohan Vijayan, Ali Uneri, Babar Shafiq
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Introduction: Ankle sprains and fractures often result in syndesmosis injuries. Unstable syndesmotic injuries result from relative motion between the distal ends of the tibia and fibula, anatomic juncture which should otherwise be rigid, and warrant operative management. Clinical and radiological evaluations of intraoperative syndesmosis stability remain a challenging task as traditional 2D fluoroscopy is limited to a uniplanar translational displacement. The purpose of this pilot cadaveric study is to compare the 2D fluoroscopy and 3D cone beam computed tomography (CBCT) stress-induced syndesmosis displacements. Methods: Three fresh-frozen lower legs underwent 2D fluoroscopy and 3D CIOS CBCT to measure syndesmosis position before dissection. Syndesmotic injury was simulated by resecting the (1) anterior inferior tibiofibular ligament (AITFL), the (2) posterior inferior tibiofibular ligament (PITFL) and the inferior transverse ligament (ITL) simultaneously, followed by the (3) interosseous membrane (IOM). Manual external rotation and Cotton stress test were performed after each of the three resections and 2D and 3D images were acquired. Relevant 2D and 3D parameters included the tibiofibular overlap (TFO), tibiofibular clear space (TCS), relative rotation of the fibula, and anterior-posterior (AP) and medial-lateral (ML) translations of the fibula relative to the tibia. Parameters were measured by two independent observers. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) to determine measurement precision. Results: Significant mismatches were found in the trends between the 2D and 3D measurements when assessing for TFO, TCS and AP translation across the different resection states. Using 3D CBCT, TFO was inversely proportional to the number of resected ligaments while TCS was directly proportional to the latter across all cadavers and ‘resection + stress’ states. Using 2D fluoroscopy, this trend was not respected under the Cotton stress test. 3D AP translation did not show a reliable trend whereas 2D AP translation of the fibula was positive under the Cotton stress test and negative under the external rotation. 3D relative rotation of the fibula, assessed using the Tang et al. ratio method and Beisemann et al. angular method, suggested slight overall internal rotation with complete resection of the ligaments, with a change < 2mm - threshold which corresponds to the commonly used buffer to account for physiologic laxity as per clinical judgment of the surgeon. Excellent agreement (>0.90) was found between the two independent observers for each of the parameters in both 2D and 3D (overall ICC 0.9968, 95% CI 0.995 - 0.999). Conclusions: The 3D CIOS CBCT appears to reliably depict the trend in TFO and TCS. This might be due to the additional detection of relevant rotational malpositions of the fibula in comparison to the standard 2D fluoroscopy which is limited to a single plane translation. A better understanding of 3D imaging may help surgeons identify the precise measurements planes needed to achieve better syndesmosis repair.Keywords: 2D fluoroscopy, 3D computed tomography, image processing, syndesmosis injury
Procedia PDF Downloads 70177 Sustainable Marine Tourism: Opinion and Segmentation of Italian Generation Z
Authors: M. Bredice, M. B. Forleo, L. Quici
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Coastal tourism is currently facing huge challenges on how to balance environmental problems and tourist activities. Recent literature shows a growing interest in the issue of sustainable tourism from a so-called civilized tourists’ perspective by investigating opinions, perceptions, and behaviors. This study investigates the opinions of youth on what makes them responsible tourists and the ability of coastal marine areas to support tourism in future scenarios. A sample of 778 Italians attending the last year of high school was interviewed. Descriptive statistics, tests, and cluster analyses are applied to highlight the distribution of opinions among youth, detect significant differences based on demographic characteristics, and make segmentation of the different profiles based on students’ opinions and behaviors. Preliminary results show that students are largely convinced (62%) that by 2050 the quality of coastal environments could limit seaside tourism, while 10% of them believe that the problem can be solved simply by changing the tourist destination. Besides the cost of the holiday, the most relevant aspect respondents consider when choosing a marine destination is the presence of tourist attractions followed by the quality of the marine-coastal environment, the specificity of the local gastronomy and cultural traditions, and finally, the activities offered to guests such as sports and events. The reduction of waste and lower air emissions are considered the most important environmental areas in which marine-coastal tourism activities can contribute to preserving the quality of seas and coasts. Areas in which, as a tourist, they believe possible to give a personal contribution were (responses “very much” and “somewhat”); do not throw litter in the sea and on the beach (84%), do not buy single-use plastic products (66%), do not use soap or shampoo when showering in beaches (53%), do not have bonfires (47%), do not damage dunes (46%), and do not remove natural materials (e.g., sand, shells) from the beach (46%). About 6% of the sample stated that they were not interested in contributing to the aforementioned activities, while another 7% replied that they could not contribute at all. Finally, 80% of the sample has never participated in voluntary environmental initiatives or citizen science projects; moreover, about 64% of the students have never participated in events organized by environmental associations in marine or coastal areas. Regarding the test analysis -based on Kruskal-Wallis and Mann and Whitney tests - gender, region, and studying area of students reveals significance in terms of variables expressing knowledge and interest in sustainability topics and sustainable tourism behaviors. The classification of the education field is significant for a great number of variables, among which those related to several sustainable behaviors that respondents declare to be able to contribute as tourists. The ongoing cluster analysis will reveal different profiles in the sample and relevant variables. Based on preliminary results, implications are envisaged in the fields of education, policy, and business strategies for sustainable scenarios. Under these perspectives, the study has the potential to contribute to the conference debate about marine and coastal sustainable development and management.Keywords: cluster analysis, education, knowledge, young people
Procedia PDF Downloads 77176 A Flexible Piezoelectric - Polymer Composite for Non-Invasive Detection of Multiple Vital Signs of Human
Authors: Sarah Pasala, Elizabeth Zacharias
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Vital sign monitoring is crucial for both everyday health and medical diagnosis. A significant factor in assessing a human's health is their vital signs, which include heart rate, breathing rate, blood pressure, and electrocardiogram (ECG) readings. Vital sign monitoring has been the focus of many system and method innovations recently. Piezoelectrics are materials that convert mechanical energy into electrical energy and can be used for vital sign monitoring. Piezoelectric energy harvesters that are stretchable and flexible can detect very low frequencies like airflow, heartbeat, etc. Current advancements in piezoelectric materials and flexible sensors have made it possible to create wearable and implantable medical devices that can continuously monitor physiological signals in humans. But because of their non-biocompatible nature, they also produce a large amount of e-waste and require another surgery to remove the implant. This paper presents a biocompatible and flexible piezoelectric composite material for wearable and implantable devices that offers a high-performance platform for seamless and continuous monitoring of human physiological signals and tactile stimuli. It also addresses the issue of e-waste and secondary surgery. A Lead-free piezoelectric, SrBi4Ti4O15, is found to be suitable for this application because the properties can be tailored by suitable substitutions and also by varying the synthesis temperature protocols. In the present work, SrBi4Ti4O15 modified by rare-earth has been synthesized and studied. Coupling factors are calculated from resonant (fr) and anti-resonant frequencies (fa). It is observed that Samarium substitution in SBT has increased the Curie temperature, dielectric and piezoelectric properties. From impedance spectroscopy studies, relaxation, and non-Debye type behaviour are observed. The composite of bioresorbable poly(l-lactide) and Lead-free rare earth modified Bismuth Layered Ferroelectrics leads to a flexible piezoelectric device for non-invasive measurement of vital signs, such as heart rate, breathing rate, blood pressure, and electrocardiogram (ECG) readings and also artery pulse signals in near-surface arteries. These composites are suitable to detect slight movement of the muscles and joints. This Lead-free rare earth modified Bismuth Layered Ferroelectrics – polymer composite is synthesized using a ball mill and the solid-state double sintering method. XRD studies indicated the two phases in the composite. SEM studies revealed the grain size to be uniform and in the range of 100 nm. The electromechanical coupling factor is improved. The elastic constants are calculated and the mechanical flexibility is found to be improved as compared to the single-phase rare earth modified Bismuth Latered piezoelectric. The results indicate that this composite is suitable for the non-invasive detection of multiple vital signs of humans.Keywords: composites, flexible, non-invasive, piezoelectric
Procedia PDF Downloads 37175 Towards a Better Understanding of Planning for Urban Intensification: Case Study of Auckland, New Zealand
Authors: Wen Liu, Errol Haarhoff, Lee Beattie
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In 2010, New Zealand’s central government re-organise the local governments arrangements in Auckland, New Zealand by amalgamating its previous regional council and seven supporting local government units into a single unitary council, the Auckland Council. The Auckland Council is charged with providing local government services to approximately 1.5 million people (a third of New Zealand’s total population). This includes addressing Auckland’s strategic urban growth management and setting its urban planning policy directions for the next 40 years. This is expressed in the first ever spatial plan in the region – the Auckland Plan (2012). The Auckland plan supports implementing a compact city model by concentrating the larger part of future urban growth and development in, and around, existing and proposed transit centres, with the intention of Auckland to become globally competitive city and achieving ‘the most liveable city in the world’. Turning that vision into reality is operatized through the statutory land use plan, the Auckland Unitary Plan. The Unitary plan replaced the previous regional and local statutory plans when it became operative in 2016, becoming the ‘rule book’ on how to manage and develop the natural and built environment, using land use zones and zone standards. Common to the broad range of literature on urban growth management, one significant issue stands out about intensification. The ‘gap’ between strategic planning and what has been achieved is evident in the argument for the ‘compact’ urban form. Although the compact city model may have a wide range of merits, the extent to which these are actualized largely rely on how intensification actually is delivered. The transformation of the rhetoric of the residential intensification model into reality is of profound influence, yet has enjoyed limited empirical analysis. In Auckland, the establishment of the Auckland Plan set up the strategies to deliver intensification into diversified arenas. Nonetheless, planning policy itself does not necessarily achieve the envisaged objectives, delivering the planning system and high capacity to enhance and sustain plan implementation is another demanding agenda. Though the Auckland Plan provides a wide ranging strategic context, its actual delivery is beholden on the Unitary Plan. However, questions have been asked if the Unitary Plan has the necessary statutory tools to deliver the Auckland Plan’s policy outcomes. In Auckland, there is likely to be continuing tension between the strategies for intensification and their envisaged objectives, and made it doubtful whether the main principles of the intensification strategies could be realized. This raises questions over whether the Auckland Plan’s policy goals can be achieved in practice, including delivering ‘quality compact city’ and residential intensification. Taking Auckland as an example of traditionally sprawl cities, this article intends to investigate the efficacy plan making and implementation directed towards higher density development. This article explores the process of plan development, plan making and implementation frameworks of the first ever spatial plan in Auckland, so as to explicate the objectives and processes involved, and consider whether this will facilitate decision making processes to realize the anticipated intensive urban development.Keywords: urban intensification, sustainable development, plan making, governance and implementation
Procedia PDF Downloads 557174 Development of a Conceptual Framework for Supply Chain Management Strategies Maximizing Resilience in Volatile Business Environments: A Case of Ventilator Challenge UK
Authors: Elena Selezneva
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Over the last two decades, an unprecedented growth in uncertainty and volatility in all aspects of the business environment has caused major global supply chain disruptions and malfunctions. The effects of one failed company in a supply chain can ripple up and down the chain, causing a number of entities or an entire supply chain to collapse. The complicating factor is that an increasingly unstable and unpredictable business environment fuels the growing complexity of global supply chain networks. That makes supply chain operations extremely unpredictable and hard to manage with the established methods and strategies. It has caused the premature demise of many companies around the globe as they could not withstand or adapt to the storm of change. Solutions to this problem are not easy to come by. There is a lack of new empirically tested theories and practically viable supply chain resilience strategies. The mainstream organizational approach to managing supply chain resilience is rooted in well-established theories developed in the 1960-1980s. However, their effectiveness is questionable in currently extremely volatile business environments. The systems thinking approach offers an alternative view of supply chain resilience. Still, it is very much in the development stage. The aim of this explorative research is to investigate supply chain management strategies that are successful in taming complexity in volatile business environments and creating resilience in supply chains. The design of this research methodology was guided by an interpretivist paradigm. A literature review informed the selection of the systems thinking approach to supply chain resilience. Therefore, an explorative single case study of Ventilator Challenge UK was selected as a case study for its extremely resilient performance of its supply chain during a period of national crisis. Ventilator Challenge UK is intensive care ventilators supply project for the NHS. It ran for 3.5 months and finished in 2020. The participants moved on with their lives, and most of them are not employed by the same organizations anymore. Therefore, the study data includes documents, historical interviews, live interviews with participants, and social media postings. The data analysis was accomplished in two stages. First, data were thematically analyzed. In the second stage, pattern matching and pattern identification were used to identify themes that formed the findings of the research. The findings from the Ventilator Challenge UK case study supply management practices demonstrated all the features of an adaptive dynamic system. They cover all the elements of supply chain and employ an entire arsenal of adaptive dynamic system strategies enabling supply chain resilience. Also, it is not a simple sum of parts and strategies. Bonding elements and connections between the components of a supply chain and its environment enabled the amplification of resilience in the form of systemic emergence. Enablers are categorized into three subsystems: supply chain central strategy, supply chain operations, and supply chain communications. Together, these subsystems and their interconnections form the resilient supply chain system framework conceptualized by the author.Keywords: enablers of supply chain resilience, supply chain resilience strategies, systemic approach in supply chain management, resilient supply chain system framework, ventilator challenge UK
Procedia PDF Downloads 81173 Correlation of Hyperlipidemia with Platelet Parameters in Blood Donors
Authors: S. Nishat Fatima Rizvi, Tulika Chandra, Abbas Ali Mahdi, Devisha Agarwal
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Introduction: Blood components are an unexplored area prone to numerous discoveries which influence patient’s care. Experiments at different levels will further change the present concept of blood banking. Hyperlipidemia is a condition of elevated plasma level of low-density lipoprotein (LDL) as well as decreased plasma level of high-density lipoprotein (HDL). Studies show that platelets play a vital role in the progression of atherosclerosis and thrombosis, a major cause of death worldwide. They are activated by many triggers like elevated LDL in the blood resulting in aggregation and formation of plaques. Hyperlipidemic platelets are frequently transfused to patients with various disorders. Screening the random donor platelets for hyperlipidemia and correlating the condition with other donor criteria such as lipid rich diet, oral contraceptive pills intake, weight, alcohol intake, smoking, sedentary lifestyle, family history of heart diseases will lead to further deciding the exclusion criteria for donor selection. This will help in making the patients safe as well as the donor deferral criteria more stringent to improve the quality of blood supply. Technical evaluation and assessment will enable blood bankers to supply safe blood and improve the guidelines for blood safety. Thus, we try to study the correlation between hyperlipidemic platelets with platelets parameters, weight, and specific history of the donors. Methodology: This case control study included 100 blood samples of Blood donors, out of 100 only 30 samples were found to be hyperlipidemic and were included as cases, while rest were taken as controls. Lipid Profile were measured by fully automated analyzer (TRIGL:triglycerides),(LDL-C:LDL –Cholesterol plus 2nd generation),CHOL 2: Cholesterol Gen 2), HDL C 3: HDL-Cholesterol plus 3rdgeneration)-(Cobas C311-Roche Diagnostic).And Platelets parameters were analyzed by the Sysmex KX21 automated hematology analyzer. Results: A significant correlation was found amongst hyperlipidemic level in single time donor. In which 80% donors have history of heart disease, 66.66% donors have sedentary life style, 83.3% donors were smokers, 50% donors were alcoholic, and 63.33% donors had taken lipid rich diet. Active physical activity was found amongst 40% donors. We divided donors sample in two groups based on their body weight. In group 1, hyperlipidemic samples: Platelet Parameters were 75% in normal 25% abnormal in >70Kg weight while in 50-70Kg weight 90% were normal 10% were abnormal. In-group 2, Non Hyperlipidemic samples: platelet Parameters were 95% normal and 5% abnormal in >70Kg weight, while in 50-70Kg Weight, 66.66% normal and 33.33% abnormal. Conclusion: The findings indicate that Hyperlipidemic status of donors may affect the platelet parameters and can be distinguished on history by their weight, Smoking, Alcoholic intake, Sedentary lifestyle, Active physical activity, Lipid rich diet, Oral contraceptive pills intake, and Family history of heart disease. However further studies on a large sample size will affirm this finding.Keywords: blood donors, hyperlipidemia, platelet, weight
Procedia PDF Downloads 314172 Saline Aspiration Negative Intravascular Test: Mitigating Risk with Injectable Fillers
Authors: Marcelo Lopes Dias Kolling, Felipe Ferreira Laranjeira, Guilherme Augusto Hettwer, Pedro Salomão Piccinini, Marwan Masri, Carlos Oscar Uebel
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Introduction: Injectable fillers are among the most common nonsurgical cosmetic procedures, with significant growth yearly. Knowledge of rheological and mechanical characteristics of fillers, facial anatomy, and injection technique is essential for safety. Concepts such as the use of cannula versus needle, aspiration before injection, and facial danger zones have been well discussed. In case of an accidental intravascular puncture, the pressure inside the vessel may not be sufficient to push blood into the syringe due to the characteristics of the filler product; this is especially true for calcium hydroxyapatite (CaHA) or hyaluronic acid (HA) fillers with high G’. Since viscoelastic properties of normal saline are much lower than those of fillers, aspiration with saline prior to filler injection may decrease the risk of a false negative aspiration and subsequent catastrophic effects. We discuss a technique to add an additional safety step to the procedure with saline aspiration prior to injection, a ‘’reverse Seldinger’’ technique for intravascular access, which we term SANIT: Saline Aspiration Negative Intravascular Test. Objectives: To demonstrate the author’s (PSP) technique which adds an additional safety step to the process of filler injection, with both CaHA and HA, in order to decrease the risk of intravascular injection. Materials and Methods: Normal skin cleansing and topical anesthesia with prilocaine/lidocaine cream are performed; the facial subunits to be treated are marked. A 3mL Luer lock syringe is filled with 2mL of 0.9% normal saline and a 27G needle, which is turned one half rotation. When a cannula is to be used, the Luer lock syringe is attached to a 27G 4cm single hole disposable cannula. After skin puncture, the 3mL syringe is advanced with the plunger pulled back (negative pressure). Progress is made to the desired depth, all the while aspirating. Once the desired location of filler injection is reached, the syringe is exchanged for the syringe containing a filler, securely grabbing the hub of the needle and taking care to not dislodge the needle tip. Prior to this, we remove 0.1mL of filler to allow for space inside the syringe for aspiration. We again aspirate and inject retrograde. SANIT is especially useful for CaHA, since the G’ is much higher than HA, and thus reflux of blood into the syringe is less likely to occur. Results: The technique has been used safely for the past two years with no adverse events; the increase in cost is negligible (only the cost of 2mL of normal saline). Over 100 patients (over 300 syringes) have been treated with this technique. The risk of accidental intravascular puncture has been calculated to be between 1:6410 to 1:40882 syringes among expert injectors; however, the consequences of intravascular injection can be catastrophic even with board-certified physicians. Conclusions: While the risk of intravascular filler injection is low, the consequences can be disastrous. We believe that adding the SANIT technique can help further mitigate risk with no significant untoward effects and could be considered by all performing injectable fillers. Further follow-up is ongoing.Keywords: injectable fillers, safety, saline aspiration, injectable filler complications, hyaluronic acid, calcium hydroxyapatite
Procedia PDF Downloads 150171 Oncoplastic Augmentation Mastopexy: Aesthetic Revisional Surgery in Breast Conserving Therapy
Authors: Bar Y. Ainuz, Harry M. Salinas, Aleeza Ali, Eli B. Levitt, Austin J. Pourmoussa, Antoun Bouz, Miguel A. Medina
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Introduction: Breast conservation therapy remains the mainstay surgical treatment for early breast cancer. Oncoplastic techniques, in conjunction with lumpectomy and adjuvant radiotherapy, have been demonstrated to achieve good aesthetic results without adversely affecting cancer outcomes in the treatment of patients with macromastia or significant ptosis. In our patient population, many women present for breast conservation with pre-existing cosmetic implants or with breast volumes too small for soft tissue, only oncoplastic techniques. Our study evaluated a consecutive series of patients presenting for breast conservation undergoing concomitant oncoplastic-augmentation-mastopexy (OAM) with a contralateral augmentation-mastopexy for symmetry. Methods: OAM surgical technique involves simultaneous lumpectomy with exchange or placement of implants, oncoplastic mastopexy, and concomitant contralateral augmentation mastopexy for symmetry. Patients undergoing lumpectomy for breast conservation as outpatients were identified via retrospective chart review at a high volume private academic affiliated community-based cancer center. Patients with ptosis and either pre-existing breast implants or insufficient breast volume undergoing oncoplastic implant placement (or exchange) and mastopexy were included in the study. Operative details, aesthetic outcomes, and complications were assessed. Results: Over a continuous three-year period, with a two-surgeon cohort, 30 consecutive patients (56 breasts, 4 unilateral procedures) were identified. Patients had an average age of 52.5 years and an average BMI of 27.5, with 40% smokers or former smokers. The average operative time was 2.5 hours, the average implant size removed was 352 cc, and the average implant size placed was 300 cc. All new implants were smooth silicone, with the majority (92%) placed in a retropectoral fashion. 40% of patients received chemotherapy, and 80% of patients received whole breast adjuvant photon radiotherapy with a total radiation dose of either 42.56 or 52.56 Gy. The average and median length of follow-up were both 8.2 months. Of the 24 patients that received radiotherapy, 21% had asymmetry due to capsular contracture. A total of 7 patients (29.2%) underwent revisions for either positive margins (12.5%), capsular contracture (8.3%), implant loss (4.2%), or cosmetic concerns (4.2%). One patient developed a pulmonary embolism in the acute postoperative period and was treated with anticoagulant therapy. Conclusion: Oncoplastic augmentation mastopexy is a safe technique with good aesthetic outcomes and acceptable complication rates for ptotic patients with breast cancer and a paucity of breast volume or pre-existing implants who wish to pursue breast-conserving therapy. The revision rates compare favorably with single-stage cosmetic augmentation procedures as well as other oncoplastic techniques described in the literature. The short-term capsular contracture rates seem lower than the rates in patients undergoing radiation after mastectomy and implant-based reconstruction. Long term capsular contractures and revision rates are too early to know in this cohort.Keywords: breast conserving therapy, oncoplastic augmentation mastopexy, capsular contracture, breast reconstruction
Procedia PDF Downloads 137170 Investigating the Association between Escherichia Coli Infection and Breast Cancer Incidence: A Retrospective Analysis and Literature Review
Authors: Nadia Obaed, Lexi Frankel, Amalia Ardeljan, Denis Nigel, Anniki Witter, Omar Rashid
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Breast cancer is the most common cancer among women, with a lifetime risk of one in eight of all women in the United States. Although breast cancer is prevalent throughout the world, the uneven distribution in incidence and mortality rates is shaped by the variation in population structure, environment, genetics and known lifestyle risk factors. Furthermore, the bacterial profile in healthy and cancerous breast tissue differs with a higher relative abundance of bacteria capable of causing DNA damage in breast cancer patients. Previous bacterial infections may change the composition of the microbiome and partially account for the environmental factors promoting breast cancer. One study found that higher amounts of Staphylococcus, Bacillus, and Enterobacteriaceae, of which Escherichia coli (E. coli) is a part, were present in breast tumor tissue. Based on E. coli’s ability to damage DNA, it is hypothesized that there is an increased risk of breast cancer associated with previous E. coli infection. Therefore, the purpose of this study was to evaluate the correlation between E. coli infection and the incidence of breast cancer. Holy Cross Health, Fort Lauderdale, provided access to the Health Insurance Portability and Accountability (HIPAA) compliant national database for the purpose of academic research. International Classification of Disease 9th and 10th Codes (ICD-9, ICD-10) was then used to conduct a retrospective analysis using data from January 2010 to December 2019. All breast cancer diagnoses and all patients infected versus not infected with E. coli that underwent typical E. coli treatment were investigated. The obtained data were matched for age, Charlson Comorbidity Score (CCI score), and antibiotic treatment. Standard statistical methods were applied to determine statistical significance and an odds ratio was used to estimate the relative risk. A total of 81286 patients were identified and analyzed from the initial query and then reduced to 31894 antibiotic-specific treated patients in both the infected and control group, respectively. The incidence of breast cancer was 2.51% and present in 2043 patients in the E. coli group compared to 5.996% and present in 4874 patients in the control group. The incidence of breast cancer was 3.84% and present in 1223 patients in the treated E. coli group compared to 6.38% and present in 2034 patients in the treated control group. The decreased incidence of breast cancer in the E. coli and treated E. coli groups was statistically significant with a p-value of 2.2x10-16 and 2.264x10-16, respectively. The odds ratio in the E. coli and treated E. coli groups was 0.784 and 0.787 with a 95% confidence interval, respectively (0.756-0.813; 0.743-0.833). The current study shows a statistically significant decrease in breast cancer incidence in association with previous Escherichia coli infection. Researching the relationship between single bacterial species is important as only up to 10% of breast cancer risk is attributable to genetics, while the contribution of environmental factors including previous infections potentially accounts for a majority of the preventable risk. Further evaluation is recommended to assess the potential and mechanism of E. coli in decreasing the risk of breast cancer.Keywords: breast cancer, escherichia coli, incidence, infection, microbiome, risk
Procedia PDF Downloads 253169 The Effect of Students’ Social and Scholastic Background and Environmental Impact on Shaping Their Pattern of Digital Learning in Academia: A Pre- and Post-COVID Comparative View
Authors: Nitza Davidovitch, Yael Yossel-Eisenbach
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The purpose of the study was to inquire whether there was a change in the shaping of undergraduate students’ digitally-oriented study pattern in the pre-Covid (2016-2017) versus post-Covid period (2022-2023), as affected by three factors: social background characteristics, high school, and academic background characteristics. These two-time points were cauterized by dramatic changes in teaching and learning at institutions of higher education. The data were collected via cross-sectional surveys at two-time points, in the 2016-2017 academic school year (N=443) and in the 2022-2023 school year (N=326). The questionnaire was distributed on social media and it includes questions on demographic background characteristics, previous studies in high school and present academic studies, and questions on learning and reading habits. Method of analysis: A. Statistical descriptive analysis, B. Mean comparison tests were conducted to analyze the variations in the mean score for the digitally-oriented learning pattern variable at two-time points (pre- and post-Covid) in relation to each of the independent variables. C. Analysis of variance was performed to test the main effects and the interactions. D. Applying linear regression, the research aimed to examine the combined effect of the independent variables on shaping students' digitally-oriented learning habits. The analysis includes four models. In all four models, the dependent variable is students’ perception of digitally oriented learning. The first model included social background variables; the second model included scholastic background as well. In the third model, the academic background variables were added, and the fourth model includes all the independent variables together with the variable of period (pre- and post-COVID). E. Factor analysis confirms using the principal component method with varimax rotation; the variables were constructed by a weighted mean of all the relevant statements merged to form a single variable denoting a shared content world. The research findings indicate a significant rise in students’ perceptions of digitally-oriented learning in the post-COVID period. From a gender perspective, the impact of COVID on shaping a digital learning pattern was much more significant for female students. The socioeconomic status perspective is eliminated when controlling for the period, and the student’s job is affected - more than all other variables. It may be assumed that the student’s work pattern mediates effects related to the convenience offered by digital learning regarding distance and time. The significant effect of scholastic background on shaping students’ digital learning patterns remained stable, even when controlling for all explanatory variables. The advantage that universities had over colleges in shaping a digital learning pattern in the pre-COVID period dissipated. Therefore, it can be said that after COVID, there was a change in how colleges shape students’ digital learning patterns in such a way that no institutional differences are evident with regard to shaping the digital learning pattern. The study shows that period has a significant independent effect on shaping students’ digital learning patterns when controlling for the explanatory variables.Keywords: learning pattern, COVID, socioeconomic status, digital learning
Procedia PDF Downloads 62168 Anti-tuberculosis, Resistance Modulatory, Anti-pulmonary Fibrosis and Anti-silicosis Effects of Crinum Asiaticum Bulbs and Its Active Metabolite, Betulin
Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi
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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant
Procedia PDF Downloads 83167 Balancing Biodiversity and Agriculture: A Broad-Scale Analysis of the Land Sparing/Land Sharing Trade-Off for South African Birds
Authors: Chevonne Reynolds, Res Altwegg, Andrew Balmford, Claire N. Spottiswoode
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Modern agriculture has revolutionised the planet’s capacity to support humans, yet has simultaneously had a greater negative impact on biodiversity than any other human activity. Balancing the demand for food with the conservation of biodiversity is one of the most pressing issues of our time. Biodiversity-friendly farming (‘land sharing’), or alternatively, separation of conservation and production activities (‘land sparing’), are proposed as two strategies for mediating the trade-off between agriculture and biodiversity. However, there is much debate regarding the efficacy of each strategy, as this trade-off has typically been addressed by short term studies at fine spatial scales. These studies ignore processes that are relevant to biodiversity at larger scales, such as meta-population dynamics and landscape connectivity. Therefore, to better understand species response to agricultural land-use and provide evidence to underpin the planning of better production landscapes, we need to determine the merits of each strategy at larger scales. In South Africa, a remarkable citizen science project - the South African Bird Atlas Project 2 (SABAP2) – collates an extensive dataset describing the occurrence of birds at a 5-min by 5-min grid cell resolution. We use these data, along with fine-resolution data on agricultural land-use, to determine which strategy optimises the agriculture-biodiversity trade-off in a southern African context, and at a spatial scale never considered before. To empirically test this trade-off, we model bird species population density, derived for each 5-min grid cell by Royle-Nicols single-species occupancy modelling, against both the amount and configuration of different types of agricultural production in the same 5-min grid cell. In using both production amount and configuration, we can show not only how species population densities react to changes in yield, but also describe the production landscape patterns most conducive to conservation. Furthermore, the extent of both the SABAP2 and land-cover datasets allows us to test this trade-off across multiple regions to determine if bird populations respond in a consistent way and whether results can be extrapolated to other landscapes. We tested the land sparing/sharing trade-off for 281 bird species across three different biomes in South Africa. Overall, a higher proportion of species are classified as losers, and would benefit from land sparing. However, this proportion of loser-sparers is not consistent and varies across biomes and the different types of agricultural production. This is most likely because of differences in the intensity of agricultural land-use and the interactions between the differing types of natural vegetation and agriculture. Interestingly, we observe a higher number of species that benefit from agriculture than anticipated, suggesting that agriculture is a legitimate resource for certain bird species. Our results support those seen at smaller scales and across vastly different agricultural systems, that land sparing benefits the most species. However, our analysis suggests that land sparing needs to be implemented at spatial scales much larger than previously considered. Species persistence in agricultural landscapes will require the conservation of large tracts of land, and is an important consideration in developing countries, which are undergoing rapid agricultural development.Keywords: agriculture, birds, land sharing, land sparing
Procedia PDF Downloads 209166 Implementation of Synthesis and Quality Control Procedures of ¹⁸F-Fluoromisonidazole Radiopharmaceutical
Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva
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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements
Procedia PDF Downloads 193165 Morphological and Molecular Abnormalities of the Skeletal Muscle Tissue from Pediatric Patient Affected by a Rare Genetic Chaperonopathy Associated with Motor Neuropathy
Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia
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The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis
Procedia PDF Downloads 71164 Fully Autonomous Vertical Farm to Increase Crop Production
Authors: Simone Cinquemani, Lorenzo Mantovani, Aleksander Dabek
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New technologies in agriculture are opening new challenges and new opportunities. Among these, certainly, robotics, vision, and artificial intelligence are the ones that will make a significant leap, compared to traditional agricultural techniques, possible. In particular, the indoor farming sector will be the one that will benefit the most from these solutions. Vertical farming is a new field of research where mechanical engineering can bring knowledge and know-how to transform a highly labor-based business into a fully autonomous system. The aim of the research is to develop a multi-purpose, modular, and perfectly integrated platform for crop production in indoor vertical farming. Activities will be based both on hardware development such as automatic tools to perform different activities on soil and plants, as well as research to introduce an extensive use of monitoring techniques based on machine learning algorithms. This paper presents the preliminary results of a research project of a vertical farm living lab designed to (i) develop and test vertical farming cultivation practices, (ii) introduce a very high degree of mechanization and automation that makes all processes replicable, fully measurable, standardized and automated, (iii) develop a coordinated control and management environment for autonomous multiplatform or tele-operated robots in environments with the aim of carrying out complex tasks in the presence of environmental and cultivation constraints, (iv) integrate AI-based algorithms as decision support system to improve quality production. The coordinated management of multiplatform systems still presents innumerable challenges that require a strongly multidisciplinary approach right from the design, development, and implementation phases. The methodology is based on (i) the development of models capable of describing the dynamics of the various platforms and their interactions, (ii) the integrated design of mechatronic systems able to respond to the needs of the context and to exploit the strength characteristics highlighted by the models, (iii) implementation and experimental tests performed to test the real effectiveness of the systems created, evaluate any weaknesses so as to proceed with a targeted development. To these aims, a fully automated laboratory for growing plants in vertical farming has been developed and tested. The living lab makes extensive use of sensors to determine the overall state of the structure, crops, and systems used. The possibility of having specific measurements for each element involved in the cultivation process makes it possible to evaluate the effects of each variable of interest and allows for the creation of a robust model of the system as a whole. The automation of the laboratory is completed with the use of robots to carry out all the necessary operations, from sowing to handling to harvesting. These systems work synergistically thanks to the knowledge of detailed models developed based on the information collected, which allows for deepening the knowledge of these types of crops and guarantees the possibility of tracing every action performed on each single plant. To this end, artificial intelligence algorithms have been developed to allow synergistic operation of all systems.Keywords: automation, vertical farming, robot, artificial intelligence, vision, control
Procedia PDF Downloads 39163 Characteristics of Plasma Synthetic Jet Actuator in Repetitive Working Mode
Authors: Haohua Zong, Marios Kotsonis
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Plasma synthetic jet actuator (PSJA) is a new concept of zero net mass flow actuator which utilizes pulsed arc/spark discharge to rapidly pressurize gas in a small cavity under constant-volume conditions. The unique combination of high exit jet velocity (>400 m/s) and high actuation frequency (>5 kHz) provides a promising solution for high-speed high-Reynolds-number flow control. This paper focuses on the performance of PSJA in repetitive working mode which is more relevant to future flow control applications. A two-electrodes PSJA (cavity volume: 424 mm3, orifice diameter: 2 mm) together with a capacitive discharge circuit (discharge energy: 50 mJ-110 mJ) is designed to enable repetitive operation. Time-Resolved Particle Imaging Velocimetry (TR-PIV) system working at 10 kHz is exploited to investigate the influence of discharge frequency on performance of PSJA. In total, seven cases are tested, covering a wide range of discharge frequencies (20 Hz-560 Hz). The pertinent flow features (shock wave, vortex ring and jet) remain the same for single shot mode and repetitive working mode. Shock wave is issued prior to jet eruption. Two distinct vortex rings are formed in one cycle. The first one is produced by the starting jet whereas the second one is related with the shock wave reflection in cavity. A sudden pressure rise is induced at the throat inlet by the reflection of primary shock wave, promoting the shedding of second vortex ring. In one cycle, jet exit velocity first increases sharply, then decreases almost linearly. Afterwards, an alternate occurrence of multiple jet stages and refresh stages is observed. By monitoring the dynamic evolution of exit velocity in one cycle, some integral performance parameters of PSJA can be deduced. As frequency increases, the jet intensity in steady phase decreases monotonically. In the investigated frequency range, jet duration time drops from 250 µs to 210 µs and peak jet velocity decreases from 53 m/s to approximately 39 m/s. The jet impulse and the expelled gas mass (0.69 µN∙s and 0.027 mg at 20 Hz) decline by 48% and 40%, respectively. However, the electro-mechanical efficiency of PSJA defined by the ratio of jet mechanical energy to capacitor energy doesn’t show significant difference (o(0.01%)). Fourier transformation of the temporal exit velocity signal indicates two dominant frequencies. One corresponds to the discharge frequency, while the other accounts for the alternation frequency of jet stage and refresh stage in one cycle. The alternation period (300 µs approximately) is independent of discharge frequency, and possibly determined intrinsically by the actuator geometry. A simple analytical model is established to interpret the alternation of jet stage and refresh stage. Results show that the dynamic response of exit velocity to a small-scale disturbance (jump in cavity pressure) can be treated as a second-order under-damping system. Oscillation frequency of the exit velocity, namely alternation frequency, is positively proportional to exit area, but inversely proportional to cavity volume and throat length. Theoretical value of alternation period (305 µs) agrees well with the experimental value.Keywords: plasma, synthetic jet, actuator, frequency effect
Procedia PDF Downloads 254162 On the Possibility of Real Time Characterisation of Ambient Toxicity Using Multi-Wavelength Photoacoustic Instrument
Authors: Tibor Ajtai, Máté Pintér, Noémi Utry, Gergely Kiss-Albert, Andrea Palágyi, László Manczinger, Csaba Vágvölgyi, Gábor Szabó, Zoltán Bozóki
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According to the best knowledge of the authors, here we experimentally demonstrate first, a quantified correlation between the real-time measured optical feature of the ambient and the off-line measured toxicity data. Finally, using these correlations we are presenting a novel methodology for real time characterisation of ambient toxicity based on the multi wavelength aerosol phase photoacoustic measurement. Ambient carbonaceous particulate matter is one of the most intensively studied atmospheric constituent in climate science nowadays. Beyond their climatic impact, atmospheric soot also plays an important role as an air pollutant that harms human health. Moreover, according to the latest scientific assessments ambient soot is the second most important anthropogenic emission source, while in health aspect its being one of the most harmful atmospheric constituents as well. Despite of its importance, generally accepted standard methodology for the quantitative determination of ambient toxicology is not available yet. Dominantly, ambient toxicology measurement is based on the posterior analysis of filter accumulated aerosol with limited time resolution. Most of the toxicological studies are based on operational definitions using different measurement protocols therefore the comprehensive analysis of the existing data set is really limited in many cases. The situation is further complicated by the fact that even during its relatively short residence time the physicochemical features of the aerosol can be masked significantly by the actual ambient factors. Therefore, decreasing the time resolution of the existing methodology and developing real-time methodology for air quality monitoring are really actual issues in the air pollution research. During the last decades many experimental studies have verified that there is a relation between the chemical composition and the absorption feature quantified by Absorption Angström Exponent (AAE) of the carbonaceous particulate matter. Although the scientific community are in the common platform that the PhotoAcoustic Spectroscopy (PAS) is the only methodology that can measure the light absorption by aerosol with accurate and reliable way so far, the multi-wavelength PAS which are able to selectively characterise the wavelength dependency of absorption has become only available in the last decade. In this study, the first results of the intensive measurement campaign focusing the physicochemical and toxicological characterisation of ambient particulate matter are presented. Here we demonstrate the complete microphysical characterisation of winter time urban ambient including optical absorption and scattering as well as size distribution using our recently developed state of the art multi-wavelength photoacoustic instrument (4λ-PAS), integrating nephelometer (Aurora 3000) as well as single mobility particle sizer and optical particle counter (SMPS+C). Beyond this on-line characterisation of the ambient, we also demonstrate the results of the eco-, cyto- and genotoxicity measurements of ambient aerosol based on the posterior analysis of filter accumulated aerosol with 6h time resolution. We demonstrate a diurnal variation of toxicities and AAE data deduced directly from the multi-wavelength absorption measurement results.Keywords: photoacoustic spectroscopy, absorption Angström exponent, toxicity, Ames-test
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