Search results for: heat index (HI)
Commenced in January 2007
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Paper Count: 6271

Search results for: heat index (HI)

31 Relevance of Dosing Time for Everolimus Toxicity in Respect to the Circadian P-Glycoprotein Expression in Mdr1a::Luc Mice

Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

Abstract:

P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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30 Amphiphilic Compounds as Potential Non-Toxic Antifouling Agents: A Study of Biofilm Formation Assessed by Micro-titer Assays with Marine Bacteria and Eco-toxicological Effect on Marine Algae

Authors: D. Malouch, M. Berchel, C. Dreanno, S. Stachowski-Haberkorn, P-A. Jaffres

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Biofilm is a predominant lifestyle chosen by bacteria. Whether it is developed on an immerged surface or a mobile biofilm known as flocs, the bacteria within this form of life show properties different from its planktonic ones. Within the biofilm, the self-formed matrix of Extracellular Polymeric Substances (EPS) offers hydration, resources capture, enhanced resistance to antimicrobial agents, and allows cell-communication. Biofouling is a complex natural phenomenon that involves biological, physical and chemical properties related to the environment, the submerged surface and the living organisms involved. Bio-colonization of artificial structures can cause various economic and environmental impacts. The increase in costs associated with the over-consumption of fuel from biocolonized vessels has been widely studied. Measurement drifts from submerged sensors, as well as obstructions in heat exchangers, and deterioration of offshore structures are major difficulties that industries are dealing with. Therefore, surfaces that inhibit biocolonization are required in different areas (water treatment, marine paints, etc.) and many efforts have been devoted to produce efficient and eco-compatible antifouling agents. The different steps of surface fouling are widely described in literature. Studying the biofilm and its stages provides a better understanding of how to elaborate more efficient antifouling strategies. Several approaches are currently applied, such as the use of biocide anti-fouling paint6 (mainly with copper derivatives) and super-hydrophobic coatings. While these two processes are proving to be the most effective, they are not entirely satisfactory, especially in a context of a changing legislation. Nowadays, the challenge is to prevent biofouling with non-biocide compounds, offering a cost effective solution, but with no toxic effects on marine organisms. Since the micro-fouling phase plays an important role in the regulation of the following steps of biofilm formation7, it is desired to reduce or delate biofouling of a given surface by inhibiting the micro fouling at its early stages. In our recent works, we reported that some amphiphilic compounds exhibited bacteriostatic or bactericidal properties at a concentration that did not affect eukaryotic cells. These remarkable properties invited us to assess this type of bio-inspired phospholipids9 to prevent the colonization of surfaces by marine bacteria. Of note, other studies reported that amphiphilic compounds interacted with bacteria leading to a reduction of their development. An amphiphilic compound is a molecule consisting of a hydrophobic domain and a polar head (ionic or non-ionic). These compounds appear to have interesting antifouling properties: some ionic compounds have shown antimicrobial activity, and zwitterions can reduce nonspecific adsorption of proteins. Herein, we investigate the potential of amphiphilic compounds as inhibitors of bacterial growth and marine biofilm formation. The aim of this study is to compare the efficacy of four synthetic phospholipids that features a cationic charge (BSV36, KLN47) or a zwitterionic polar-head group (SL386, MB2871) to prevent microfouling with marine bacteria. We also study the toxicity of these compounds in order to identify the most promising compound that must feature high anti-adhesive properties and a low cytotoxicity on two links representative of coastal marine food webs: phytoplankton and oyster larvae.

Keywords: amphiphilic phospholipids, bacterial biofilm, marine microfouling, non-toxic antifouling

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29 HydroParks: Directives for Physical Environment Interventions Battling Childhood Overweight in Berlin, Germany

Authors: Alvaro Valera Sosa

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Background: In recent years, childhood overweight and obesity have become an increasing and challenging phenomenon in Berlin and Germany in general. The highest shares of childhood overweight in Berlin are district localities within the inner city ring with lowest socio-economic levels and the highest number of migration background populations. Most factors explaining overweight and obesity are linked to individual dispositions and nutrition balances. Among various strategies, to target drinking behaviors of children and adolescents has been proven to be effective. On the one hand, encouraging the intake of water – which does not contain energy and thus may support a healthy weight status – on the other hand, reducing the consumption of sugar-containing beverages – which are linked to weight gain and obesity. Anyhow, these preventive approaches have mostly developed into individual or educational interventions widely neglecting environmental modifications. Therefore, little is known on how urban physical environment patterns and features can act as influence factors for childhood overweight. Aiming the development of a physical environment intervention tackling children overweight, this study evaluated urban situations surrounding public playgrounds in Berlin where the issue is evident. It verified the presence and state of physical environmental conditions that can be conducive for children to engage physical activity and water intake. Methods: The study included public playgrounds for children from 0-12 y/o within district localities with the highest prevalence of childhood overweight, highest population density, and highest mixed uses. A systematic observation was realized to describe physical environment patterns and features that may affect children health behavior leading to overweight. Neighborhood walkability for all age groups was assessed using the Walkability for Health framework (TU-Berlin). Playground physical environment conditions were evaluated using Active Living Research assessment sheets. Finally, the food environment in the playground’s pedestrian catchment areas was reviewed focusing on: proximity to suppliers offering sugar-containing beverages, and physical access for 5 y/o children and up to drinking water following the Drinking Fountains and Public Health guidelines of the Pacific Institute. Findings: Out of 114 locations, only 7 had a child population over 3.000. Three with the lowest socio-economic index and highest percentage of migration background were selected. All three urban situations presented similar walkability: large trafficked avenues without buffer bordering at least one side of the playground, and important block to block disconnections for active travel. All three playgrounds rated equipment conditions from good to very good. None had water fountains at the reach of a 5 y/o. and all presented convenience stores and/or fast food outlets selling sugar-containing beverages nearby the perimeter. Conclusion: The three playground situations selected are representative of Berlin locations where most factors that influence children overweight are found. The results delivered urban and architectural design directives for an environmental intervention, used to study children health-related behavior. A post-intervention evaluation could prove associations between designed spaces and children overweight rate reduction creating a precedent in public health interventions and providing novel strategies for the health sector.

Keywords: children overweight, evaluation research, public playgrounds, urban design, urban health

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28 Pharmacophore-Based Modeling of a Series of Human Glutaminyl Cyclase Inhibitors to Identify Lead Molecules by Virtual Screening, Molecular Docking and Molecular Dynamics Simulation Study

Authors: Ankur Chaudhuri, Sibani Sen Chakraborty

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In human, glutaminyl cyclase activity is highly abundant in neuronal and secretory tissues and is preferentially restricted to hypothalamus and pituitary. The N-terminal modification of β-amyloids (Aβs) peptides by the generation of a pyro-glutamyl (pGlu) modified Aβs (pE-Aβs) is an important process in the initiation of the formation of neurotoxic plaques in Alzheimer’s disease (AD). This process is catalyzed by glutaminyl cyclase (QC). The expression of QC is characteristically up-regulated in the early stage of AD, and the hallmark of the inhibition of QC is the prevention of the formation of pE-Aβs and plaques. A computer-aided drug design (CADD) process was employed to give an idea for the designing of potentially active compounds to understand the inhibitory potency against human glutaminyl cyclase (QC). This work elaborates the ligand-based and structure-based pharmacophore exploration of glutaminyl cyclase (QC) by using the known inhibitors. Three dimensional (3D) quantitative structure-activity relationship (QSAR) methods were applied to 154 compounds with known IC50 values. All the inhibitors were divided into two sets, training-set, and test-sets. Generally, training-set was used to build the quantitative pharmacophore model based on the principle of structural diversity, whereas the test-set was employed to evaluate the predictive ability of the pharmacophore hypotheses. A chemical feature-based pharmacophore model was generated from the known 92 training-set compounds by HypoGen module implemented in Discovery Studio 2017 R2 software package. The best hypothesis was selected (Hypo1) based upon the highest correlation coefficient (0.8906), lowest total cost (463.72), and the lowest root mean square deviation (2.24Å) values. The highest correlation coefficient value indicates greater predictive activity of the hypothesis, whereas the lower root mean square deviation signifies a small deviation of experimental activity from the predicted one. The best pharmacophore model (Hypo1) of the candidate inhibitors predicted comprised four features: two hydrogen bond acceptor, one hydrogen bond donor, and one hydrophobic feature. The Hypo1 was validated by several parameters such as test set activity prediction, cost analysis, Fischer's randomization test, leave-one-out method, and heat map of ligand profiler. The predicted features were then used for virtual screening of potential compounds from NCI, ASINEX, Maybridge and Chembridge databases. More than seven million compounds were used for this purpose. The hit compounds were filtered by drug-likeness and pharmacokinetics properties. The selective hits were docked to the high-resolution three-dimensional structure of the target protein glutaminyl cyclase (PDB ID: 2AFU/2AFW) to filter these hits further. To validate the molecular docking results, the most active compound from the dataset was selected as a reference molecule. From the density functional theory (DFT) study, ten molecules were selected based on their highest HOMO (highest occupied molecular orbitals) energy and the lowest bandgap values. Molecular dynamics simulations with explicit solvation systems of the final ten hit compounds revealed that a large number of non-covalent interactions were formed with the binding site of the human glutaminyl cyclase. It was suggested that the hit compounds reported in this study could help in future designing of potent inhibitors as leads against human glutaminyl cyclase.

Keywords: glutaminyl cyclase, hit lead, pharmacophore model, simulation

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27 Biosynthesis of Silver Nanoparticles Using Zataria multiflora Extract, and Study of Their Antibacterial Effects on Negative Bacillus Bacteria Causing Urinary Tract Infection

Authors: F. Madani, M. Doudi, L. Rahimzadeh Torabi

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The irregular consumption of current antibiotics contributes to an escalation in antibiotic resistance among urinary pathogens on a global scale. The objective of this research was to investigate the process of biologically synthesized silver nanoparticles through the utilization of Zataria multiflora extract. Additionally, the study aimed to evaluate the efficacy of these synthesized nanoparticles in inhibiting the growth of multi-drug resistant negative bacillus bacteria, which commonly contribute to urinary tract infections. The botanical specimen utilized in the current research investigation was Z. multiflora, and its extract was produced employing the Soxhlet extraction technique. The study examined the green synthesis conditions of silver nanoparticles by considering three key parameters: the quantity of extract used, the concentration of silver nitrate salt, and the temperature. The particle dimensions were ascertained using the Zetasizer technique. In order to identify synthesized Silver nanoparticles TEM, XRD, and FTIR methods were used. For evaluating the antibacterial effects of nanoparticles synthesized through a biological method, different concentrations of silver nanoparticles were studied on 140 cases of Multiple drug resistance (MDR) bacteria strains Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus vulgaris,Citrobacter freundii, Acinetobacter bumanii and Pseudomonas aeruginosa, (each genus of bacteria, 20 samples), which all were MDR and cause urinary tract infections, for identification of bacteria were used of PCR test and laboratory methods (Agar well diffusion and Microdilution methods) to assess their sensitivity to Nanoparticles. The data were subjected to analysis using the statistical software SPSS, specifically employing nonparametric Kruskal-Wallis and Mann-Whitney tests. This study yielded noteworthy findings regarding the impacts of varying concentrations of silver nitrate, different quantities of Z. multiflora extract, and levels of temperature on nanoparticles. Specifically, it was observed that an increase in the concentration of silver nitrate, extract amount, and temperature resulted in a reduction in the size of the nanoparticles synthesized. However, the impact of the aforementioned factors on the index of particle diffusion was found to be statistically non-significant. According to the transmission electron microscopy (TEM) findings, the particles exhibited predominantly spherical morphology, with a diameter spanning from 25 to 50 nanometers. Nanoparticles in the examined sample. Nanocrystals of silver. FTIR method illustrated that the spectrums of Z. multiflora and synthesized nanoparticles had clear peaks in the ranges of 1500-2000, and 3500 - 4000. The obtained results of antibacterial effects of different concentrations of silver nanoparticles on according to agar well diffusion and microdilution method, biologically synthesized nanoparticles showed 1000 mg /ml highest and lowest mean inhibition zone diameter in E. coli, A. bumanii 23 and 15mm, respectively. MIC was observed for all of bacteria 125 mg/ml and for A. bumanii 250 mg/ml. Comparing the growth inhibitory effect of chemically synthesized the results obtained from the experiment indicated that both nanoparticles and biologically synthesized nanoparticles exhibit a notable growth inhibition effect. Specifically, the chemical method of synthesizing nanoparticles demonstrated the highest level of growth inhibition at a concentration of 62.5 mg/mL The present study demonstrated an inhibitory effect on bacterial growth, facilitating the causative factors of urine infection and multidrug resistance (MDR).

Keywords: multiple drug resistance, negative bacillus bacteria, urine infection, Zataria multiflora

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26 Force Sensing Resistor Testing of Hand Forces and Grasps during Daily Functional Activities in the Covid-19 Pandemic

Authors: Monique M. Keller, Roline Barnes, Corlia Brandt

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Introduction Scientific evidence on the hand forces and the types of grasps measurement during daily tasks are lacking, leaving a gap in the field of hand rehabilitation and robotics. Measuring the grasp forces and types produced by the individual fingers during daily functional tasks is valuable to inform and grade rehabilitation practices for second to fifth metacarpal fractures with robust scientific evidence. Feix et al, 2016 identified the most extensive and complete grasp study that resulted in the GRASP taxonomy. Covid-19 virus changed data collection across the globe and safety precautions in research are essential to ensure the health of participants and researchers. Methodology A cross-sectional study investigated six healthy adults aged 20 to 59 years, pilot participants’ hand forces during 105 tasks. The tasks were categorized into five sections namely, personal care, transport and moving around, home environment and inside, gardening and outside, and office. The predominant grasp of each task was identified guided by the GRASP Taxonomy. Grasp forces were measured with 13mm force-sensing resistors glued onto a glove attached to each of the dominant and non-dominant hand’s individual fingers. Testing equipment included Flexiforce 13millimetres FSR .5" circle, calibrated prior to testing, 10k 1/4w resistors, Arduino pro mini 5.0v – compatible, Esp-01-kit, Arduino uno r3 – compatible board, USB ab cable - 1m, Ftdi ft232 mini USB to serial, Sil 40 inline connectors, ribbon cable combo male header pins, female to female, male to female, two gloves, glue to attach the FSR to glove, Arduino software programme downloaded on a laptop. Grip strength measurements with Jamar dynamometer prior to testing and after every 25 daily tasks were taken to will avoid fatigue and ensure reliability in testing. Covid-19 precautions included wearing face masks at all times, screening questionnaires, temperatures taken, wearing surgical gloves before putting on the testing gloves 1.5 metres long wires attaching the FSR to the Arduino to maintain social distance. Findings Predominant grasps observed during 105 tasks included, adducted thumb (17), lateral tripod (10), prismatic three fingers (12), small diameter (9), prismatic two fingers (9), medium wrap (7), fixed hook (5), sphere four fingers (4), palmar (4), parallel extension (4), index finger extension (3), distal (3), power sphere (2), tripod (2), quadpod (2), prismatic four fingers (2), lateral (2), large-diameter (2), ventral (2), precision sphere (1), palmar pinch (1), light tool (1), inferior pincher (1), and writing tripod (1). Range of forces applied per category, personal care (1-25N), transport and moving around (1-9 N), home environment and inside (1-41N), gardening and outside (1-26.5N), and office (1-20N). Conclusion Scientifically measurements of finger forces with careful consideration to types of grasps used in daily tasks should guide rehabilitation practices and robotic design to ensure a return to the full participation of the individual into the community.

Keywords: activities of daily living (ADL), Covid-19, force-sensing resistors, grasps, hand forces

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25 Multiaxial Stress Based High Cycle Fatigue Model for Adhesive Joint Interfaces

Authors: Martin Alexander Eder, Sergei Semenov

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Many glass-epoxy composite structures, such as large utility wind turbine rotor blades (WTBs), comprise of adhesive joints with typically thick bond lines used to connect the different components during assembly. Performance optimization of rotor blades to increase power output by simultaneously maintaining high stiffness-to-low-mass ratios entails intricate geometries in conjunction with complex anisotropic material behavior. Consequently, adhesive joints in WTBs are subject to multiaxial stress states with significant stress gradients depending on the local joint geometry. Moreover, the dynamic aero-elastic interaction of the WTB with the airflow generates non-proportional, variable amplitude stress histories in the material. Empiricism shows that a prominent failure type in WTBs is high cycle fatigue failure of adhesive bond line interfaces, which in fact over time developed into a design driver as WTB sizes increase rapidly. Structural optimization employed at an early design stage, therefore, sets high demands on computationally efficient interface fatigue models capable of predicting the critical locations prone for interface failure. The numerical stress-based interface fatigue model presented in this work uses the Drucker-Prager criterion to compute three different damage indices corresponding to the two interface shear tractions and the outward normal traction. The two-parameter Drucker-Prager model was chosen because of its ability to consider shear strength enhancement under compression and shear strength reduction under tension. The governing interface damage index is taken as the maximum of the triple. The damage indices are computed through the well-known linear Palmgren-Miner rule after separate rain flow-counting of the equivalent shear stress history and the equivalent pure normal stress history. The equivalent stress signals are obtained by self-similar scaling of the Drucker-Prager surface whose shape is defined by the uniaxial tensile strength and the shear strength such that it intersects with the stress point at every time step. This approach implicitly assumes that the damage caused by the prevailing multiaxial stress state is the same as the damage caused by an amplified equivalent uniaxial stress state in the three interface directions. The model was implemented as Python plug-in for the commercially available finite element code Abaqus for its use with solid elements. The model was used to predict the interface damage of an adhesively bonded, tapered glass-epoxy composite cantilever I-beam tested by LM Wind Power under constant amplitude compression-compression tip load in the high cycle fatigue regime. Results show that the model was able to predict the location of debonding in the adhesive interface between the webfoot and the cap. Moreover, with a set of two different constant life diagrams namely in shear and tension, it was possible to predict both the fatigue lifetime and the failure mode of the sub-component with reasonable accuracy. It can be concluded that the fidelity, robustness and computational efficiency of the proposed model make it especially suitable for rapid fatigue damage screening of large 3D finite element models subject to complex dynamic load histories.

Keywords: adhesive, fatigue, interface, multiaxial stress

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24 Immunostimulatory Response of Supplement Feed in Fish against Aeromonas hydrophila

Authors: Shikha Rani, Neeta Sehgal, Vipin Kumar Verma, Om Prakash

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Introduction: Fish is an important protein source for humans and has great economic value. Fish cultures are affected due to various anthropogenic activities that lead to bacterial and viral infections. Aeromonas hydrophila is a fish pathogenic bacterium that causes several aquaculture outbreaks throughout the world and leads to huge mortalities. In this study, plants of no commercial value were used to investigate their immunostimulatory, antioxidant, anti-inflammatory, anti-bacterial, and disease resistance potential in fish against Aeromonas hydrophila, through fish feed fortification. Methods: The plant was dried at room temperature in the shade, dissolved in methanol, and analysed for biological compounds through GC-MS/MS. DPPH, FRAP, Phenolic, and flavonoids were estimated following standardized protocols. In silico molecular docking was also performed to validate its broad-spectrum activities based on binding affinity with specific proteins. Fish were divided into four groups (n=6; total 30 in a group): Group 1, non-challenged fish (fed on a non-supplemented diet); Group 2, fish challenged with bacteria (fed on a non-supplemented diet); Group 3 and 4, fish challenged with bacteria (A. hydrophila) and fed on plant supplemented feed at 2.5% and 5%. Blood was collected from the fish on 0, 7th, 14th, 21st, and 28th days. Serum was separated for glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase assay (ALP), lysozyme activity assay, superoxide dismutase assay (SOD), lipid peroxidation assay (LPO) and molecular parameters (including cytokine levels) were estimated through ELISA. The phagocytic activity of macrophages from the spleen and head kidney, along with quantitative analysis of immune-related genes, were analysed in different tissue samples. The digestive enzymes (Pepsin, Trypsin, and Chymotrypsin) were also measured to evaluate the effect of plant-supplemented feed on freshwater fish. Results and Discussion: GC-MS/MS analysis of a methanolic extract of plant validated the presence of key compounds having antioxidant, anti-inflammatory, anti-bacterial, anti-inflammatory, and immunomodulatory activities along with disease resistance properties. From biochemical investigations like ABTS, DPPH, and FRAP, the amount of total flavonoids, phenols, and promising binding affinities towards different proteins in molecular docking analysis helped us to realize the potential of this plant that can be used for investigation in the supplemented feed of fish. Measurement liver function tests, ALPs, oxidation-antioxidant enzyme concentrations, and immunoglobulin concentrations in the experimental groups (3 and 4) showed significant improvement as compared to the positive control group. The histopathological evaluation of the liver, spleen, and head kidney supports the biochemical findings. The isolated macrophages from the group fed on supplemented feed showed a higher percentage of phagocytosis and a phagocytic index, indicating an enhanced cell-mediated immune response. Significant improvements in digestive enzymes were also observed in fish fed on supplemented feed, even after weekly challenges with bacteria. Hence, the plant-fortified feed can be recommended as a regular feed to enhance fish immunity and disease resistance against the Aeromonas hydrophila infection after confirmation from the field trial.

Keywords: immunostimulation, antipathogen, plant fortified feed, macrophages, GC-MS/MS, in silico molecular docking

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23 A Novel Paradigm in the Management of Pancreatic Trauma

Authors: E. Tan, O. McKay, T. Clarnette T., D. Croagh

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Background: Historically with pancreatic trauma, complete disruption of the main pancreatic duct (MPD), classified as Grade IV-V by the American Association for the Surgery of Trauma (AAST), necessitated a damage-control laparotomy. This was to avoid mortality, shorten diet upgrade timeframe, and hence shorter length of stay. However, acute pancreatic resection entailed complications of pancreatic fistulas and leaks. With the advance of imaging-guided interventions, non-operative management such as percutaneous and transpapillary drainage of traumatic peripancreatic collections have been trialled favourably. The aim of this case series is to evaluate the efficacy of endoscopic ultrasound-guided (EUS) transmural drainage in managing traumatic peripancreatic collections as a less invasive alternative to traditional approaches. This study also highlights the importance of anatomical knowledge regarding peripancreatic collection’s common location in the lesser sac, the pancreas relationship to adjacent organs, and the formation of the main pancreatic duct in regards to the feasibility of therapeutic internal drainage. Methodology: A retrospective case series was conducted at a single tertiary endoscopy unit, analysing patient data over a 5-year period. Inclusion criteria outlined patients age 5 to 80-years-old, traumatic pancreatic injury of at least Grade IV and haemodynamic stability. Exclusion criteria involved previous episodes of pancreatitis or abdominal trauma. Patient demographics and clinicopathological characteristics were retrospectively collected. Results: The study identified 7 patients with traumatic pancreatic injuries that were managed from 2018-2022; age ranging from 5 to 34 years old, with majority being female (n=5). Majority of the mechanisms of trauma were a handlebar injury (n=4). Diagnosis was confirmed with an elevated lipase and computerized tomotography (CT) confirmation of proximal pancreatic transection with MPD disruption. All patients sustained an isolated single organ grade IV pancreatic injury, except case 4 and 5 with other intra-abdominal visceral Grade 1 injuries. 6 patients underwent early ERCP-guided transpapillary drainage with 1 being unsuccessful for pancreatic duct stent insertion (case 1) and 1 complication of stent migration (case 2). Surveillance imaging post ERCP showed the stents were unable to bridge the disrupted duct and development of symptomatic collections with an average size of 9.9cm. Hence, all patients proceeded to EUS-guided transmural drainage, with 2/7 patients requiring repeat drainages (case 6 and 7). Majority (n=6) had a cystogastrostomy, whilst 1 (case 6) had a cystoenterostomy due to feasibility of the peripancreatic collection being adjacent to duodenum rather than stomach. However, case 6 subsequently required repeat EUS-guided drainage with cystogastrostomy for ongoing collections. Hence all patients avoided initial laparotomy with an average index length of stay of 11.7 days. Successful transmural drainage was demonstrated, with no long-term complications of pancreatic insufficiency; except for 1 patient requiring a distal pancreatectomy at 2 year follow-up due to chronic pain. Conclusion: The early results of this series support EUS-guided transmural drainage as a viable management option for traumatic peripancreatic collections, showcasing successful outcomes, minimal complications, and long-term efficacy in avoiding surgical interventions. More studies are required before the adoption of this procedure as a less invasive and complication-prone management approach for traumatic peripancreatic collections.

Keywords: endoscopic ultrasound, cystogastrostomy, pancreatic trauma, traumatic peripancreatic collection, transmural drainage

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22 Multiple Primary Pulmonary Meningiomas: A Case Report

Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

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21 The Role of a Specialized Diet for Management of Fibromyalgia Symptoms: A Systematic Review

Authors: Siddhant Yadav, Rylea Ranum, Hannah Alberts, Abdul Kalaiger, Brent Bauer, Ryan Hurt, Ann Vincent, Loren Toussaint, Sanjeev Nanda

Abstract:

Background and significance: Fibromyalgia (FM) is a chronic pain disorder also characterized by chronic fatigue, morning stiffness, sleep, and cognitive symptoms, psychological disturbances (anxiety, depression), and is comorbid with multiple medical and psychiatric conditions. It has an incidence of 2-4% in the general population and is reported more commonly in women. Oxidative stress and inflammation are thought to contribute to pain in patients with FM, and the adoption of an antioxidant/anti-inflammatory diet has been suggested as a modality to alleviate symptoms. The aim of this systematic review was to evaluate the efficacy of specialized diets (ketogenic, gluten free, Mediterranean, and low carbohydrate) in improving FM symptoms. Methodology: A comprehensive search of the following databases from inception to July 15th, 2021, was conducted: Ovid MEDLINE and Epub ahead of print, in-process and other non-indexed citations and daily, Ovid Embase, Ovid EBM reviews, Cochrane central register of controlled trials, EBSCO host CINAHL with full text, Elsevier Scopus, website and citation index, web of science emerging sources citation and clinicaltrials.gov. We included randomized controlled trials, non-randomized experimental studies, cross-sectional studies, cohort studies, case series, and case reports in adults with fibromyalgia. The risk of bias was assessed with the Agency for Health Care Research and Quality designed, specific recommended criteria (AHRQ). Results: Thirteen studies were eligible for inclusion. This included a total of 761 participants. Twelve out of the 13 studies reported improvement in widespread body pain, joint stiffness, sleeping pattern, mood, and gastrointestinal symptoms, and one study reported no changes in symptomatology in patients with FM on specialized diets. None of the studies showed the worsening of symptoms associated with a specific diet. Most of the patient population was female, with the mean age at which fibromyalgia was diagnosed being 48.12 years. Improvement in symptoms was reported by the patient's adhering to a gluten-free diet, raw vegan diet, tryptophan- and magnesium-enriched Mediterranean diet, aspartame- and msg- elimination diet, and specifically a Khorasan wheat diet. Risk of bias assessment noted that 6 studies had a low risk of bias (5 clinical trials and 1 case series), four studies had a moderate risk of bias, and 3 had a high risk of bias. In many of the studies, the allocation of treatment (diets) was not adequately concealed, and the researchers did not rule out any potential impact from a concurrent intervention or an unintended exposure that might have biased the results. On the other hand, there was a low risk of attrition bias in all the trials; all were conducted with an intention-to-treat, and the inclusion/exclusion criteria, exposures/interventions, and primary outcomes were valid, reliable, and implemented consistently across all study participants. Concluding statement: Patients with fibromyalgia who followed specialized diets experienced a variable degree of improvement in their widespread body pain. Improvement was also seen in stiffness, fatigue, moods, sleeping patterns, and gastrointestinal symptoms. Additionally, the majority of the patients also reported improvement in overall quality of life.

Keywords: fibromyalgia, specialized diet, vegan, gluten free, Mediterranean, systematic review

Procedia PDF Downloads 51
20 Health and Climate Changes: "Ippocrate" a New Alert System to Monitor and Identify High Risk

Authors: A. Calabrese, V. F. Uricchio, D. di Noia, S. Favale, C. Caiati, G. P. Maggi, G. Donvito, D. Diacono, S. Tangaro, A. Italiano, E. Riezzo, M. Zippitelli, M. Toriello, E. Celiberti, D. Festa, A. Colaianni

Abstract:

Climate change has a severe impact on human health. There is a vast literature demonstrating temperature increase is causally related to cardiovascular problem and represents a high risk for human health, but there are not study that improve a solution. In this work, it is studied how the clime influenced the human parameter through the analysis of climatic conditions in an area of the Apulia Region: Capurso Municipality. At the same time, medical personnel involved identified a set of variables useful to define an index describing health condition. These scientific studies are the base of an innovative alert system, IPPOCRATE, whose aim is to asses climate risk and share information to population at risk to support prevention and mitigation actions. IPPOCRATE is an e-health system, it is designed to provide technological support to analysis of health risk related to climate and provide tools for prevention and management of critical events. It is the first integrated system of prevention of human risk caused by climate change. IPPOCRATE calculates risk weighting meteorological data with the vulnerability of monitored subjects and uses mobile and cloud technologies to acquire and share information on different data channels. It is composed of four components: Multichannel Hub. Multichannel Hub is the ICT infrastructure used to feed IPPOCRATE cloud with a different type of data coming from remote monitoring devices, or imported from meteorological databases. Such data are ingested, transformed and elaborated in order to be dispatched towards mobile app and VoIP phone systems. IPPOCRATE Multichannel Hub uses open communication protocols to create a set of APIs useful to interface IPPOCRATE with 3rd party applications. Internally, it uses non-relational paradigm to create flexible and highly scalable database. WeHeart and Smart Application The wearable device WeHeart is equipped with sensors designed to measure following biometric variables: heart rate, systolic blood pressure and diastolic blood pressure, blood oxygen saturation, body temperature and blood glucose for diabetic subjects. WeHeart is designed to be easy of use and non-invasive. For data acquisition, users need only to wear it and connect it to Smart Application by Bluetooth protocol. Easy Box was designed to take advantage from new technologies related to e-health care. EasyBox allows user to fully exploit all IPPOCRATE features. Its name, Easy Box, reveals its purpose of container for various devices that may be included depending on user needs. Territorial Registry is the IPPOCRATE web module reserved to medical personnel for monitoring, research and analysis activities. Territorial Registry allows to access to all information gathered by IPPOCRATE using GIS system in order to execute spatial analysis combining geographical data (climatological information and monitored data) with information regarding the clinical history of users and their personal details. Territorial Registry was designed for different type of users: control rooms managed by wide area health facilities, single health care center or single doctor. Territorial registry manages such hierarchy diversifying the access to system functionalities. IPPOCRATE is the first e-Health system focused on climate risk prevention.

Keywords: climate change, health risk, new technological system

Procedia PDF Downloads 837
19 Biotech Processes to Recover Valuable Fraction from Buffalo Whey Usable in Probiotic Growth, Cosmeceutical, Nutraceutical and Food Industries

Authors: Alberto Alfano, Sergio D’ambrosio, Darshankumar Parecha, Donatella Cimini, Chiara Schiraldi.

Abstract:

The main objective of this study regards the setup of an efficient small-scale platform for the conversion of local renewable waste materials, such as whey, into added-value products, thereby reducing environmental impact and costs deriving from the disposal of processing waste products. The buffalo milk whey derived from the cheese-making process, called second cheese whey, is the main by-product of the dairy industry. Whey is the main and most polluting by-product obtained from cheese manufacturing consisting of lactose, lactic acid, proteins, and salts, making whey an added-value product. In Italy, and in particular, in the Campania region, soft cheese production needs a large volume of liquid waste, especially during late spring and summer. This project is part of a circular economy perspective focused on the conversion of potentially polluting and difficult to purify waste into a resource to be exploited, and it embodies the concept of the three “R”: reduce, recycle, and reuse. Special focus was paid to the production of health-promoting biomolecules and biopolymers, which may be exploited in different segments of the food and pharmaceutical industries. These biomolecules may be recovered through appropriate processes and reused in an attempt to obtain added value products. So, ultrafiltration and nanofiltration processes were performed to fractionate bioactive components starting from buffalo milk whey. In this direction, the present study focused on the implementation of a downstream process that converts waste generated from food and food processing industries into added value products with potential applications. Owing to innovative downstream and biotechnological processes, rather than a waste product may be considered a resource to obtain high added value products, such as food supplements (probiotics), cosmeceuticals, biopolymers, and recyclable purified water. Besides targeting gastrointestinal disorders, probiotics such as Lactobacilli have been reported to improve immunomodulation and protection of the host against infections caused by viral and bacterial pathogens. Interestingly, also inactivated microbial (probiotic) cells and their metabolic products, indicated as parabiotic and postbiotics, respectively, have a crucial role and act as mediators in the modulation of the host’s immune function. To boost the production of biomass (both viable and/or heat inactivated cells) and/or the synthesis of growth-related postbiotics, such as EPS, efficient and sustainable fermentation processes are necessary. Based on a “zero-waste” approach, wastes generated from local industries can be recovered and recycled to develop sustainable biotechnological processes to obtain probiotics as well as post and parabiotic, to be tested as bioactive compounds against gastrointestinal disorders. The results have shown it was possible to recover an ultrafiltration retentate with suitable characteristics to be used in skin dehydration, to perform films (i.e., packaging for food industries), or as a wound repair agent and a nanofiltration retentate to recover lactic acid and carbon sources (e.g., lactose, glucose..) used for microbial cultivation. On the side, the last goal is to obtain purified water that can be reused throughout the process. In fact, water reclamation and reuse provide a unique and viable opportunity to augment traditional water supplies, a key issue nowadays.

Keywords: biotech process, downstream process, probiotic growth, from waste to product, buffalo whey

Procedia PDF Downloads 43
18 Modern Cardiac Surgical Outcomes in Nonagenarians: A Multicentre Retrospective Observational Study

Authors: Laurence Weinberg, Dominic Walpole, Dong-Kyu Lee, Michael D’Silva, Jian W. Chan, Lachlan F. Miles, Bradley Carp, Adam Wells, Tuck S. Ngun, Siven Seevanayagam, George Matalanis, Ziauddin Ansari, Rinaldo Bellomo, Michael Yii

Abstract:

Background: There have been multiple recent advancements in the selection, optimization and management of cardiac surgical patients. However, there is limited data regarding the outcomes of nonagenarians undergoing cardiac surgery, despite this vulnerable cohort increasingly receiving these interventions. This study describes the patient characteristics, management and outcomes of a group of nonagenarians undergoing cardiac surgery in the context of contemporary peri-operative care. Methods: A retrospective observational study was conducted of patients 90 to 99 years of age (i.e., nonagenarians) who had undergone cardiac surgery requiring a classic median sternotomy (i.e., open-heart surgery). All operative indications were included. Patients who underwent minimally invasive surgery, transcatheter aortic valve implantation and thoracic aorta surgery were excluded. Data were collected from four hospitals in Victoria, Australia, over an 8-year period (January 2012 – December 2019). The primary objective was to assess six-month mortality in nonagenarians undergoing open-heart surgery and to evaluate the incidence and severity of postoperative complications using the Clavien-Dindo classification system. The secondary objective was to provide a detailed description of the characteristics and peri-operative management of this group. Results: A total of 12,358 adult patients underwent cardiac surgery at the study centers during the observation period, of whom 18 nonagenarians (0.15%) fulfilled the inclusion criteria. The median (IQR) [min-max] age was 91 years (90.0:91.8) [90-94] and 14 patients (78%) were men. Cardiovascular comorbidities, polypharmacy and frailty, were common. The median (IQR) predicted in-hospital mortality by EuroSCORE II was 6.1% (4.1-14.5). All patients were optimized preoperatively by a multidisciplinary team of surgeons, cardiologists, geriatricians and anesthetists. All index surgeries were performed on cardiopulmonary bypass. Isolated coronary artery bypass grafting (CABG) and CABG with aortic valve replacement were the most common surgeries being performed in four and five patients, respectively. Half the study group underwent surgery involving two or more major procedures (e.g. CABG and valve replacement). Surgery was undertaken emergently in 44% of patients. All patients except one experienced at least one postoperative complication. The most common complications were acute kidney injury (72%), new atrial fibrillation (44%) and delirium (39%). The highest Clavien-Dindo complication grade was IIIb occurring once each in three patients. Clavien-Dindo grade IIIa complications occurred in only one patient. The median (IQR) postoperative length of stay was 11.6 days (9.8:17.6). One patient was discharged home and all others to an inpatient rehabilitation facility. Three patients had an unplanned readmission within 30 days of discharge. All patients had follow-up to at least six months after surgery and mortality over this period was zero. The median (IQR) duration of follow-up was 11.3 months (6.0:26.4) and there were no cases of mortality observed within the available follow-up records. Conclusion: In this group of nonagenarians undergoing cardiac surgery, postoperative six-month mortality was zero. Complications were common but generally of low severity. These findings support carefully selected nonagenarian patients being offered cardiac surgery in the context of contemporary, multidisciplinary perioperative care. Further, studies are needed to assess longer-term mortality and functional and quality of life outcomes in this vulnerable surgical cohort.

Keywords: cardiac surgery, mortality, nonagenarians, postoperative complications

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17 A Multi-Scale Approach to Space Use: Habitat Disturbance Alters Behavior, Movement and Energy Budgets in Sloths (Bradypus variegatus)

Authors: Heather E. Ewart, Keith Jensen, Rebecca N. Cliffe

Abstract:

Fragmentation and changes in the structural composition of tropical forests – as a result of intensifying anthropogenic disturbance – are increasing pressures on local biodiversity. Species with low dispersal abilities have some of the highest extinction risks in response to environmental change, as even small-scale environmental variation can substantially impact their space use and energetic balance. Understanding the implications of forest disturbance is therefore essential, ultimately allowing for more effective and targeted conservation initiatives. Here, the impact of different levels of forest disturbance on the space use, energetics, movement and behavior of 18 brown-throated sloths (Bradypus variegatus) were assessed in the South Caribbean of Costa Rica. A multi-scale framework was used to measure forest disturbance, including large-scale (landscape-level classifications) and fine-scale (within and surrounding individual home ranges) forest composition. Three landscape-level classifications were identified: primary forests (undisturbed), secondary forests (some disturbance, regenerating) and urban forests (high levels of disturbance and fragmentation). Finer-scale forest composition was determined using measurements of habitat structure and quality within and surrounding individual home ranges for each sloth (home range estimates were calculated using autocorrelated kernel density estimation [AKDE]). Measurements of forest quality included tree connectivity, density, diameter and height, species richness, and percentage of canopy cover. To determine space use, energetics, movement and behavior, six sloths in urban forests, seven sloths in secondary forests and five sloths in primary forests were tracked using a combination of Very High Frequency (VHF) radio transmitters and Global Positioning System (GPS) technology over an average period of 120 days. All sloths were also fitted with micro data-loggers (containing tri-axial accelerometers and pressure loggers) for an average of 30 days to allow for behavior-specific movement analyses (data analysis ongoing for data-loggers and primary forest sloths). Data-loggers included determination of activity budgets, circadian rhythms of activity and energy expenditure (using the vector of the dynamic body acceleration [VeDBA] as a proxy). Analyses to date indicate that home range size significantly increased with the level of forest disturbance. Female sloths inhabiting secondary forests averaged 0.67-hectare home ranges, while female sloths inhabiting urban forests averaged 1.93-hectare home ranges (estimates are represented by median values to account for the individual variation in home range size in sloths). Likewise, home range estimates for male sloths were 2.35 hectares in secondary forests and 4.83 in urban forests. Sloths in urban forests also used nearly double (median = 22.5) the number of trees as sloths in the secondary forest (median = 12). These preliminary data indicate that forest disturbance likely heightens the energetic requirements of sloths, a species already critically limited by low dispersal ability and rates of energy acquisition. Energetic and behavioral analyses from the data-loggers will be considered in the context of fine-scale forest composition measurements (i.e., habitat quality and structure) and are expected to reflect the observed home range and movement constraints. The implications of these results are far-reaching, presenting an opportunity to define a critical index of habitat connectivity for low dispersal species such as sloths.

Keywords: biodiversity conservation, forest disturbance, movement ecology, sloths

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16 Comparison of Titanium and Aluminum Functions as Spoilers for Dose Uniformity Achievement in Abutting Oblique Electron Fields: A Monte Carlo Simulation Study

Authors: Faranak Felfeliyan, Parvaneh Shokrani, Maryam Atarod

Abstract:

Introduction Using electron beam is widespread in radiotherapy. The main criteria in radiation therapy is to irradiate the tumor volume with maximum prescribed dose and minimum dose to vital organs around it. Using abutting fields is common in radiotherapy. The main problem in using abutting fields is dose inhomogeneity in the junction region. Electron beam divergence and lateral scattering may lead to hot and cold spots in the junction region. One solution for this problem is using of a spoiler to broaden the penumbra and uniform dose in the junction region. The goal of this research was to compare titanium and aluminum effects as a spoiler for dose uniformity achievement in the junction region of oblique electron fields with Monte Carlo simulation. Dose uniformity in the junction region depends on density, scattering power, thickness of the spoiler and the angle between two fields. Materials and Methods In this study, Monte Carlo model of Siemens Primus linear accelerator was simulated for a 5 MeV nominal energy electron beam using manufacture provided specifications. BEAMnrc and EGSnrc user code were used to simulate the treatment head in electron mode (simulation of beam model). The resulting phase space file was used as a source for dose calculations for 10×10 cm2 field size at SSD=100 cm in a 30×30×45 cm3 water phantom using DOSXYZnrc user code (dose calculations). An automatic MP3-M water phantom tank, MEPHYSTO mc2 software platform and a Semi-Flex Chamber-31010 with sensitive vol­ume of 0.125 cm3 (PTW, Freiburg, Germany) were used for dose distribution measurements. Moreover, the electron field size was 10×10 cm2 and SSD=100 cm. Validation of devel­oped beam model was done by comparing the measured and calculated depth and lateral dose distributions (verification of electron beam model). Simulation of spoilers (using SLAB compo­nent module) placed at the end of the electron applicator, was done using previously vali­dated phase space file for a 5 MeV nominal energy and 10×10 cm2 field size (simulation of spoiler). An in-house routine was developed in order to calculate the combined isodose curves re­sulting from the two simulated abutting fields (calculation of dose distribution in abutting electron fields). Results Verification of the developed 5.9 MeV elec­tron beam model was done by comparing the calculated and measured dose distributions. The maximum percentage difference between calculated and measured PDD was 1%, except for the build-up region in which the difference was 2%. The difference between calculated and measured profile was 2% at the edges of the field and less than 1% in other regions. The effect of PMMA, aluminum, titanium and chromium in dose uniformity achievement in abutting normal electron fields with equivalent thicknesses to 5mm PMMA was evaluated. Comparing R90 and uniformity index of different materials, aluminum was chosen as the optimum spoiler. Titanium has the maximum surface dose. Thus, aluminum and titanium had been chosen to use for dose uniformity achievement in oblique electron fields. Using the optimum beam spoiler, junction dose decreased from 160% to 110% for 15 degrees, from 180% to 120% for 30 degrees, from 160% to 120% for 45 degrees and from 180% to 100% for 60 degrees oblique abutting fields. Using Titanium spoiler, junction dose decreased from 160% to 120% for 15 degrees, 180% to 120% for 30 degrees, 160% to 120% for 45 degrees and 180% to 110% for 60 degrees. In addition, penumbra width for 15 degrees, without spoiler in the surface was 10 mm and was increased to 15.5 mm with titanium spoiler. For 30 degrees, from 9 mm to 15 mm, for 45 degrees from 4 mm to 6 mm and for 60 degrees, from 5 mm to 8 mm. Conclusion Using spoilers, penumbra width at the surface increased, size and depth of hot spots was decreased and dose homogeneity improved at the junc­tion of abutting electron fields. Dose at the junction region of abutting oblique fields was improved significantly by using spoiler. Maximum dose at the junction region for 15⁰, 30⁰, 45⁰ and 60⁰ was decreased about 40%, 60%, 40% and 70% respectively for Titanium and about 50%, 60%, 40% and 80% for Aluminum. Considering significantly decrease in maximum dose using titanium spoiler, unfortunately, dose distribution in the junction region was not decreased less than 110%.

Keywords: abutting fields, electron beam, radiation therapy, spoilers

Procedia PDF Downloads 143
15 Resilience Compendium: Strategies to Reduce Communities' Risk to Disasters

Authors: Caroline Spencer, Suzanne Cross, Dudley McArdle, Frank Archer

Abstract:

Objectives: The evolution of the Victorian Compendium of Community-Based Resilience Building Case Studies and its capacity to help communities implement activities that encourage adaptation to disaster risk reduction and promote community resilience in rural and urban locations provide this paper's objectives. Background: Between 2012 and 2019, community groups presented at the Monash University Disaster Resilience Initiative (MUDRI) 'Advancing Community Resilience Annual Forums', provided opportunities for communities to impart local resilience activities, how to solve challenges and share unforeseen learning and be considered for inclusion in the Compendium. A key tenet of the Compendium encourages compiling and sharing of grass-roots resilience building activities to help communities before, during, and after unexpected emergencies. The online Compendium provides free access for anyone wanting to help communities build expertise, reduce program duplication, and save valuable community resources. Identifying case study features across the emergency phases and analyzing critical success factors helps communities understand what worked and what did not work to achieve success and avoid known barriers. International exemplars inform the Compendium, which represents an Australian first and enhances Victorian community resilience initiatives. Emergency Management Victoria provided seed funding for the Compendium. MUDRI matched this support and continues to fund the project. A joint Steering Committee with broad-based user input and Human ethics approval guides its continued growth. Methods: A thematic analysis of the Compendium identified case study features, including critical success factors. Results: The Compendium comprises 38 case studies, representing all eight Victorian regions. Case studies addressed emergency phases, before (29), during (7), and after (17) events. Case studies addressed all hazards (23), bushfires (11), heat (2), fire safety (1), and house fires (1). Twenty case studies used a framework. Thirty received funding, of which nine received less than $20,000 and five received more than $100,000. Twenty-nine addressed a whole of community perspective. Case studies revealed unique and valuable learning in diverse settings. Critical success factors included strong governance; board support, leadership, and trust; partnerships; commitment, adaptability, and stamina; community-led initiatives. Other success factors included a paid facilitator and local government support; external funding, and celebrating success. Anecdotally, we are aware that community groups reference Compendium and that its value adds to community resilience planning. Discussion: The Compendium offers an innovative contribution to resilience research and practice. It augments the seven resilience characteristics to strengthen and encourage communities as outlined in the Statewide Community Resilience Framework for Emergency Management; brings together people from across sectors to deliver distinct, yet connected actions to strengthen resilience as a part of the Rockefeller funded Resilient Melbourne Strategy, and supports communities and economies to be resilient when a shock occurs as identified in the recently published Australian National Disaster Risk Reduction Framework. Each case study offers learning about connecting with community and how to increase their resilience to disaster risks and to keep their community safe from unexpected emergencies. Conclusion: The Compendium enables diverse communities to adopt or adapt proven resilience activities, thereby preserving valuable community resources and offers the opportunity to extend to a national or international Compendium.

Keywords: case study, community, compendium, disaster risk reduction, resilience

Procedia PDF Downloads 94
14 Industrial Waste to Energy Technology: Engineering Biowaste as High Potential Anode Electrode for Application in Lithium-Ion Batteries

Authors: Pejman Salimi, Sebastiano Tieuli, Somayeh Taghavi, Michela Signoretto, Remo Proietti Zaccaria

Abstract:

Increasing the growth of industrial waste due to the large quantities of production leads to numerous environmental and economic challenges, such as climate change, soil and water contamination, human disease, etc. Energy recovery of waste can be applied to produce heat or electricity. This strategy allows for the reduction of energy produced using coal or other fuels and directly reduces greenhouse gas emissions. Among different factories, leather manufacturing plays a very important role in the whole world from the socio-economic point of view. The leather industry plays a very important role in our society from a socio-economic point of view. Even though the leather industry uses a by-product from the meat industry as raw material, it is considered as an activity demanding integrated prevention and control of pollution. Along the entire process from raw skins/hides to finished leather, a huge amount of solid and water waste is generated. Solid wastes include fleshings, raw trimmings, shavings, buffing dust, etc. One of the most abundant solid wastes generated throughout leather tanning is shaving waste. Leather shaving is a mechanical process that aims at reducing the tanned skin to a specific thickness before tanning and finishing. This product consists mainly of collagen and tanning agent. At present, most of the world's leather processing is chrome-tanned based. Consequently, large amounts of chromium-containing shaving wastes need to be treated. The major concern about the management of this kind of solid waste is ascribed to chrome content, which makes the conventional disposal methods, such as landfilling and incineration, not practicable. Therefore, many efforts have been developed in recent decades to promote eco-friendly/alternative leather production and more effective waste management. Herein, shaving waste resulting from metal-free tanning technology is proposed as low-cost precursors for the preparation of carbon material as anodes for lithium-ion batteries (LIBs). In line with the philosophy of a reduced environmental impact, for preparing fully sustainable and environmentally friendly LIBs anodes, deionized water and carboxymethyl cellulose (CMC) have been used as alternatives to toxic/teratogen N-methyl-2- pyrrolidone (NMP) and to biologically hazardous Polyvinylidene fluoride (PVdF), respectively. Furthermore, going towards the reduced cost, we employed water solvent and fluoride-free bio-derived CMC binder (as an alternative to NMP and PVdF, respectively) together with LiFePO₄ (LFP) when a full cell was considered. These actions make closer to the 2030 goal of having green LIBs at 100 $ kW h⁻¹. Besides, the preparation of the water-based electrodes does not need a controlled environment and due to the higher vapour pressure of water in comparison with NMP, the water-based electrode drying is much faster. This aspect determines an important consequence, namely a reduced energy consumption for the electrode preparation. The electrode derived from leather waste demonstrated a discharge capacity of 735 mAh g⁻¹ after 1000 charge and discharge cycles at 0.5 A g⁻¹. This promising performance is ascribed to the synergistic effect of defects, interlayer spacing, heteroatoms-doped (N, O, and S), high specific surface area, and hierarchical micro/mesopore structure of the biochar. Interestingly, these features of activated biochars derived from the leather industry open the way for possible applications in other EESDs as well.

Keywords: biowaste, lithium-ion batteries, physical activation, waste management, leather industry

Procedia PDF Downloads 143
13 Microfabrication and Non-Invasive Imaging of Porous Osteogenic Structures Using Laser-Assisted Technologies

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

Abstract:

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

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

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12 Adequate Nutritional Support and Monitoring in Post-Traumatic High Output Duodenal Fistula

Authors: Richa Jaiswal, Vidisha Sharma, Amulya Rattan, Sushma Sagar, Subodh Kumar, Amit Gupta, Biplab Mishra, Maneesh Singhal

Abstract:

Background: Adequate nutritional support and daily patient monitoring have an independent therapeutic role in the successful management of high output fistulae and early recovery after abdominal trauma. Case presentation: An 18-year-old girl was brought to AIIMS emergency with alleged history of fall of a heavy weight (electric motor) over abdomen. She was evaluated as per Advanced Trauma Life Support(ATLS) protocols and diagnosed to have significant abdominal trauma. After stabilization, she was referred to Trauma center. Abdomen was guarded and focused assessment with sonography for trauma(FAST) was found positive. Complete duodenojejunal(DJ) junction transection was found at laparotomy, and end-to-end repair was done. However, patient was re-explored in view of biliary peritonitis on post-operative day3, and anastomotic leak was found with sloughing of duodenal end. Resection of non-viable segments was done followed by side-to-side anastomosis. Unfortunately, the anastomosis leaked again, this time due to a post-anastomotic kink, diagnosed on dye study. Due to hostile abdomen, the patient was planned for supportive care, with plan of build-up and delayed definitive surgery. Percutaneous transheptic biliary drainage (PTBD) and STSG were required in the course as well. Nutrition: In intensive care unit (ICU), major goals of nutritional therapy were to improve wound healing, optimize nutrition, minimize enteral feed associated complications, reduce biliary fistula output, and prepare the patient for definitive surgeries. Feeding jejunostomy (FJ) was started from day 4 at the rate of 30ml/h along with total parenteral nutrition (TPN) and intra-venous (IV) micronutrients support. Due to high bile output, bile refeed started from day 13.After 23 days of ICU stay, patient was transferred to general ward with body mass index (BMI)<11kg/m2 and serum albumin –1.5gm%. Patient was received in the ward in catabolic phase with high risk of refeeding syndrome. Patient was kept on FJ bolus feed at the rate of 30–50 ml/h. After 3–4 days, while maintaining patient diet book log it was observed that patient use to refuse feed at night and started becoming less responsive with every passing day. After few minutes of conversation with the patient for a couple of days, she complained about enteral feed discharge in urine, mild pain and sign of dumping syndrome. Dye study was done, which ruled out any enterovesical fistula and conservative management were planned. At this time, decision was taken for continuous slow rate feeding through commercial feeding pump at the rate of 2–3ml/min. Drastic improvement was observed from the second day in gastro-intestinal symptoms and general condition of the patient. Nutritional composition of feed, TPN and diet ranged between 800 and 2100 kcal and 50–95 g protein. After STSG, TPN was stopped. Periodic diet counselling was given to improve oral intake. At the time of discharge, serum albumin level was 2.1g%, weight – 38.6, BMI – 15.19 kg/m2. Patient got discharge on an oral diet. Conclusion: Successful management of post-traumatic proximal high output fistulae is a challenging task, due to impaired nutrient absorption and enteral feed associated complications. Strategic- and goal-based nutrition support can salvage such critically ill patients, as demonstrated in the present case.

Keywords: nutritional monitoring, nutritional support, duodenal fistula, abdominal trauma

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11 A Case Study on Utility of 18FDG-PET/CT Scan in Identifying Active Extra Lymph Nodes and Staging of Breast Cancer

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

Abstract:

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

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

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10 Correlation of Unsuited and Suited 5ᵗʰ Female Hybrid III Anthropometric Test Device Model under Multi-Axial Simulated Orion Abort and Landing Conditions

Authors: Christian J. Kennett, Mark A. Baldwin

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As several companies are working towards returning American astronauts back to space on US-made spacecraft, NASA developed a human flight certification-by-test and analysis approach due to the cost-prohibitive nature of extensive testing. This process relies heavily on the quality of analytical models to accurately predict crew injury potential specific to each spacecraft and under dynamic environments not tested. As the prime contractor on the Orion spacecraft, Lockheed Martin was tasked with quantifying the correlation of analytical anthropometric test devices (ATDs), also known as crash test dummies, against test measurements under representative impact conditions. Multiple dynamic impact sled tests were conducted to characterize Hybrid III 5th ATD lumbar, head, and neck responses with and without a modified shuttle-era advanced crew escape suit (ACES) under simulated Orion landing and abort conditions. Each ATD was restrained via a 5-point harness in a mockup Orion seat fixed to a dynamic impact sled at the Wright Patterson Air Force Base (WPAFB) Biodynamics Laboratory in the horizontal impact accelerator (HIA). ATDs were subject to multiple impact magnitudes, half-sine pulse rise times, and XZ - ‘eyeballs out/down’ or Z-axis ‘eyeballs down’ orientations for landing or an X-axis ‘eyeballs in’ orientation for abort. Several helmet constraint devices were evaluated during suited testing. Unique finite element models (FEMs) were developed of the unsuited and suited sled test configurations using an analytical 5th ATD model developed by LSTC (Livermore, CA) and deformable representations of the seat, suit, helmet constraint countermeasures, and body restraints. Explicit FE analyses were conducted using the non-linear solver LS-DYNA. Head linear and rotational acceleration, head rotational velocity, upper neck force and moment, and lumbar force time histories were compared between test and analysis using the enhanced error assessment of response time histories (EEARTH) composite score index. The EEARTH rating paired with the correlation and analysis (CORA) corridor rating provided a composite ISO score that was used to asses model correlation accuracy. NASA occupant protection subject matter experts established an ISO score of 0.5 or greater as the minimum expectation for correlating analytical and experimental ATD responses. Unsuited 5th ATD head X, Z, and resultant linear accelerations, head Y rotational accelerations and velocities, neck X and Z forces, and lumbar Z forces all showed consistent ISO scores above 0.5 in the XZ impact orientation, regardless of peak g-level or rise time. Upper neck Y moments were near or above the 0.5 score for most of the XZ cases. Similar trends were found in the XZ and Z-axis suited tests despite the addition of several different countermeasures for restraining the helmet. For the X-axis ‘eyeballs in’ loading direction, only resultant head linear acceleration and lumbar Z-axis force produced ISO scores above 0.5 whether unsuited or suited. The analytical LSTC 5th ATD model showed good correlation across multiple head, neck, and lumbar responses in both the unsuited and suited configurations when loaded in the XZ ‘eyeballs out/down’ direction. Upper neck moments were consistently the most difficult to predict, regardless of impact direction or test configuration.

Keywords: impact biomechanics, manned spaceflight, model correlation, multi-axial loading

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9 A Low-Cost Disposable PDMS Microfluidic Cartridge with Reagent Storage Silicone Blisters for Isothermal DNA Amplification

Authors: L. Ereku, R. E. Mackay, A. Naveenathayalan, K. Ajayi, W. Balachandran

Abstract:

Over the past decade the increase of sexually transmitted infections (STIs) especially in the developing world due to high cost and lack of sufficient medical testing have given rise to the need for a rapid, low cost point of care medical diagnostic that is disposable and most significantly reproduces equivocal results achieved within centralised laboratories. This paper present the development of a disposable PDMS microfluidic cartridge incorporating blisters filled with reagents required for isothermal DNA amplification in clinical diagnostics and point-of-care testing. In view of circumventing the necessity for external complex microfluidic pumps, designing on-chip pressurised fluid reservoirs is embraced using finger actuation and blister storage. The fabrication of the blisters takes into consideration three proponents that include: material characteristics, fluid volume and structural design. Silicone rubber is the chosen material due to its good chemical stability, considerable tear resistance and moderate tension/compression strength. The case of fluid capacity and structural form go hand in hand as the reagent need for the experimental analysis determines the volume size of the blisters, whereas the structural form has to be designed to provide low compression stress when deformed for fluid expulsion. Furthermore, the top and bottom section of the blisters are embedded with miniature polar opposite magnets at a defined parallel distance. These magnets are needed to lock or restrain the blisters when fully compressed so as to prevent unneeded backflow as a result of elasticity. The integrated chip is bonded onto a large microscope glass slide (50mm x 75mm). Each part is manufactured using a 3D printed mould designed using Solidworks software. Die-casting is employed, using 3D printed moulds, to form the deformable blisters by forcing a proprietary liquid silicone rubber through the positive mould cavity. The set silicone rubber is removed from the cast and prefilled with liquid reagent and then sealed with a thin (0.3mm) burstable layer of recast silicone rubber. The main microfluidic cartridge is fabricated using classical soft lithographic techniques. The cartridge incorporates microchannel circuitry, mixing chamber, inlet port, outlet port, reaction chamber and waste chamber. Polydimethylsiloxane (PDMS, QSil 216) is mixed and degassed using a centrifuge (ratio 10:1) is then poured after the prefilled blisters are correctly positioned on the negative mould. Heat treatment of about 50C to 60C in the oven for about 3hours is needed to achieve curing. The latter chip production stage involves bonding the cured PDMS to the glass slide. A plasma coroner treater device BD20-AC (Electro-Technic Products Inc., US) is used to activate the PDMS and glass slide before they are both joined and adequately compressed together, then left in the oven over the night to ensure bonding. There are two blisters in total needed for experimentation; the first will be used as a wash buffer to remove any remaining cell debris and unbound DNA while the second will contain 100uL amplification reagents. This paper will present results of chemical cell lysis, extraction using a biopolymer paper membrane and isothermal amplification on a low-cost platform using the finger actuated blisters for reagent storage. The platform has been shown to detect 1x105 copies of Chlamydia trachomatis using Recombinase Polymerase Amplification (RPA).

Keywords: finger actuation, point of care, reagent storage, silicone blisters

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8 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

Abstract:

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

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7 Predicting Acceptance and Adoption of Renewable Energy Community solutions: The Prosumer Psychology

Authors: Francois Brambati, Daniele Ruscio, Federica Biassoni, Rebecca Hueting, Alessandra Tedeschi

Abstract:

This research, in the frame of social acceptance of renewable energies and community-based production and consumption models, aims at (1) supporting a data-driven approachable to dealing with climate change and (2) identifying & quantifying the psycho-sociological dimensions and factors that could support the transition from a technology-driven approach to a consumer-driven approach throughout the emerging “prosumer business models.” In addition to the existing Social Acceptance dimensions, this research tries to identify a purely individual psychological fourth dimension to understand processes and factors underling individual acceptance and adoption of renewable energy business models, realizing a Prosumer Acceptance Index. Questionnaire data collection has been performed throughout an online survey platform, combining standardized and ad-hoc questions adapted for the research purposes. To identify the main factors (individual/social) influencing the relation with renewable energy technology (RET) adoption, a Factorial Analysis has been conducted to identify the latent variables that are related to each other, revealing 5 latent psychological factors: Factor 1. Concern about environmental issues: global environmental issues awareness, strong beliefs and pro-environmental attitudes rising concern on environmental issues. Factor 2. Interest in energy sharing: attentiveness to solutions for local community’s collective consumption, to reduce individual environmental impact, sustainably improve the local community, and sell extra energy to the general electricity grid. Factor 3. Concern on climate change: environmental issues consequences on climate change awareness, especially on a global scale level, developing pro-environmental attitudes on global climate change course and sensitivity about behaviours aimed at mitigating such human impact. Factor 4. Social influence: social support seeking from peers. With RET, advice from significant others is looked for internalizing common perceived social norms of the national/geographical region. Factor 5. Impact on bill cost: inclination to adopt a RET when economic incentives from the behaviour perception affect the decision-making process could result in less expensive or unvaried bills. Linear regression has been conducted to identify and quantify the factors that could better predict behavioural intention to become a prosumer. An overall scale measuring “acceptance of a renewable energy solution” was used as the dependent variable, allowing us to quantify the five factors that contribute to measuring: awareness of environmental issues and climate change; environmental attitudes; social influence; and environmental risk perception. Three variables can significantly measure and predict the scores of the “Acceptance in becoming a prosumer” ad hoc scale. Variable 1. Attitude: the agreement to specific environmental issues and global climate change issues of concerns and evaluations towards a behavioural intention. Variable 2. Economic incentive: the perceived behavioural control and its related environmental risk perception, in terms of perceived short-term benefits and long-term costs, both part of the decision-making process as expected outcomes of the behaviour itself. Variable 3. Age: despite fewer economic possibilities, younger adults seem to be more sensitive to environmental dimensions and issues as opposed to older adults. This research can facilitate policymakers and relevant stakeholders to better understand which relevant psycho-sociological factors are intervening in these processes and what and how specifically target when proposing change towards sustainable energy production and consumption.

Keywords: behavioural intention, environmental risk perception, prosumer, renewable energy technology, social acceptance

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6 A Regional Comparison of Hunter and Harvest Trends of Sika Deer (Cervus n. nippon) and Wild Boar (Sus s. leucomystax) in Japan from 1990 to 2013

Authors: Arthur Müller

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The study treats human dimensions of hunting by conducting statistical data analysis and providing decision-making support by examples of good prefectural governance and successful wildlife management, crucial to reduce pest species and sustain a stable hunter population in the future. Therefore it analyzes recent revision of wildlife legislation, reveals differences in administrative management structures, as well as socio-demographic characteristics of hunters in correlation with harvest trends of sika deer and wild boar in 47 prefectures in Japan between 1990 and 2013. In a wider context, Japan’s decentralized license hunting system might take the potential future role of a regional pioneer in East Asia. Consequently, the study contributes to similar issues in premature hunting systems of South Korea and Taiwan. Firstly, a quantitative comparison of seven mainland regions was conducted in Hokkaido, Tohoku, Kanto, Chubu, Kinki, Chugoku, and Kyushu. Example prefectures were chosen by a cluster analysis. Shifts, differences, mean values and exponential growth rates between trap and gun hunters, age classes and common occupation types of hunters were statistically exterminated. While western Japan is characterized by high numbers of aged trap-hunters, occupied in agricultural- and forestry, the north-eastern prefectures show higher relative numbers of younger gun-hunters occupied in the field of production and process workers. With the exception of Okinawa island, most hunters in all prefectures are 60 years and older. Hence, unemployed and retired hunters are the fastest growing occupation group. Despite to drastic decrease in hunter population in absolute numbers, Hunting Recruitment Index indicated that all age classes tend to continue their hunting activity over a longer period, above ten years from 2004 to 2013 than during the former decade. Associated with a rapid population increase and distribution of sika deer and wild boar since 1978, a number of harvest from hunting and culling also have been rapidly increasing. Both wild boar hunting and culling is particularly high in western Japan, while sika hunting and culling proofs most successful in Hokkaido, central and western Japan. Since the Wildlife Protection and Proper Hunting Act in 1999 distinct prefectural hunting management authorities with different power, sets apply management approaches under the principles of subsidiarity and guidelines of the Ministry of Environment. Additionally, the Act on Special Measures for Prevention of Damage Related to Agriculture, Forestry, and Fisheries Caused by Wildlife from 2008 supports local hunters in damage prevention measures through subsidies by the Ministry of Agriculture and Forestry, which caused a rise of trap hunting, especially in western Japan. Secondly, prefectural staff in charge of wildlife management in seven regions was contacted. In summary, Hokkaido serves as a role model for dynamic, integrative, adaptive “feedback” management of Ezo sika deer, as well as a diverse network between management organizations, while Hyogo takes active measures to trap-hunt wild boars effectively. Both prefectures take the leadership in institutional performance and capacity. Northern prefectures in Tohoku, Chubu and Kanto region, firstly confronted with the emergence of wild boars and rising sika deer numbers, demand new institution and capacity building, as well as organizational learning.

Keywords: hunting and culling harvest trends, hunter socio-demographics, regional comparison, wildlife management approach

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5 Targeting Tumour Survival and Angiogenic Migration after Radiosensitization with an Estrone Analogue in an in vitro Bone Metastasis Model

Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

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Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

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4 Femicide: The Political and Social Blind Spot in the Legal and Welfare State of Germany

Authors: Kristina F. Wolff

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Background: In the Federal Republic of Germany, violence against women is deeply embedded in society. Germany is, as of March 2020, the most populous member state of the European Union with 83.2 million inhabitants and, although more than half of its inhabitants are women, gender equality was not certified in the Basic Law until 1957. Women have only been allowed to enter paid employment without their husband's consent since 1977 and have marital rape prosecuted only since 1997. While the lack of equality between men and women is named in the preamble of the Istanbul Convention as the cause of gender-specific, structural, traditional violence against women, Germany continues to sink on the latest Gender Equality Index. According to Police Crime Statistics (PCS), women are significantly more often victims of lethal violence, emanating from men than vice versa. The PCS, which, since 2015, also collects gender-specific data on violent crimes, is kept by the Federal Criminal Police Office, but without taking into account the relevant criteria for targeted prevention, such as the history of violence of the perpetrator/killer, weapon, motivation, etc.. Institutions such as EIGE or the World Health Organization have been asking Germany for years in vain for comparable data on violence against women in order to gain an overview or to develop cross-border synergies. The PCS are the only official data collection on violence against women. All players involved are depend on this data set, which is published only in November of the following year and is thus already completely outdated at the time of publication. In order to combat German femicides causally, purposefully and efficiently, evidence-based data was urgently needed. Methodology: Beginning in January 2019, a database was set up that now tracks more than 600 German femicides, broken down by more than 100 crime-related individual criteria, which in turn go far beyond the official PCS. These data are evaluated on the one hand by daily media research, and on the other hand by case-specific inquiries at the respective public prosecutor's offices and courts nationwide. This quantitative long-term study covers domestic violence as well as a variety of different types of gender-specific, lethal violence, including, for example, femicides committed by German citizens abroad. Additionallyalcohol/ narcotic and/or drug abuse, infanticides and the gender aspect in the judiciary are also considered. Results: Since November 2020, evidence-based data from a scientific survey have been available for the first time in Germany, supplementing the rudimentary picture of reality provided by PCS with a number of relevant parameters. The most important goal of the study is to identify "red flags" that enable general preventive awareness, that serve increasingly precise hazard assessment in acute hazard situations, and from which concrete instructions for action can be identified. Already at a very early stage of the study it could be proven that in more than half of all femicides with a sexual perpetrator/victim constellation there was an age difference of five years or more. Summary: Without reliable data and an understanding of the nature and extent, cause and effect, it is impossible to sustainably curb violence against girls and women, which increasingly often culminates in femicide. In Germany, valid data from a scientific survey has been available for the first time since November 2020, supplementing the rudimentary reality picture of the official and, to date, sole crime statistics with several relevant parameters. The basic research provides insights into geo-concentration, monthly peaks and the modus operandi of male violent excesses. A significant increase of child homicides in the course of femicides and/or child homicides as an instrument of violence against the mother could be proven as well as a danger of affected persons due to an age difference of five years and more. In view of the steadily increasing wave of violence against women, these study results are an eminent contribution to the preventive containment of German femicides.

Keywords: femicide, violence against women, gender specific data, rule Of law, Istanbul convention, gender equality, gender based violence

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3 Acute Severe Hyponatremia in Patient with Psychogenic Polydipsia, Learning Disability and Epilepsy

Authors: Anisa Suraya Ab Razak, Izza Hayat

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Introduction: The diagnosis and management of severe hyponatremia in neuropsychiatric patients present a significant challenge to physicians. Several factors contribute, including diagnostic shadowing and attributing abnormal behavior to intellectual disability or psychiatric conditions. Hyponatraemia is the commonest electrolyte abnormality in the inpatient population, ranging from mild/asymptomatic, moderate to severe levels with life-threatening symptoms such as seizures, coma and death. There are several documented fatal case reports in the literature of severe hyponatremia secondary to psychogenic polydipsia, often diagnosed only in autopsy. This paper presents a case study of acute severe hyponatremia in a neuropsychiatric patient with early diagnosis and admission to intensive care. Case study: A 21-year old Caucasian male with known epilepsy and learning disability was admitted from residential living with generalized tonic-clonic self-terminating seizures after refusing medications for several weeks. Evidence of superficial head injury was detected on physical examination. His laboratory data demonstrated mild hyponatremia (125 mmol/L). Computed tomography imaging of his brain demonstrated no acute bleed or space-occupying lesion. He exhibited abnormal behavior - restlessness, drinking water from bathroom taps, inability to engage, paranoia, and hypersexuality. No collateral history was available to establish his baseline behavior. He was loaded with intravenous sodium valproate and leveritircaetam. Three hours later, he developed vomiting and a generalized tonic-clonic seizure lasting forty seconds. He remained drowsy for several hours and regained minimal recovery of consciousness. A repeat set of blood tests demonstrated profound hyponatremia (117 mmol/L). Outcomes: He was referred to intensive care for peripheral intravenous infusion of 2.7% sodium chloride solution with two-hourly laboratory monitoring of sodium concentration. Laboratory monitoring identified dangerously rapid correction of serum sodium concentration, and hypertonic saline was switched to a 5% dextrose solution to reduce the risk of acute large-volume fluid shifts from the cerebral intracellular compartment to the extracellular compartment. He underwent urethral catheterization and produced 8 liters of urine over 24 hours. Serum sodium concentration remained stable after 24 hours of correction fluids. His GCS recovered to baseline after 48 hours with improvement in behavior -he engaged with healthcare professionals, understood the importance of taking medications, admitted to illicit drug use and drinking massive amounts of water. He was transferred from high-dependency care to ward level and was initiated on multiple trials of anti-epileptics before achieving seizure-free days two weeks after resolution of acute hyponatremia. Conclusion: Psychogenic polydipsia is often found in young patients with intellectual disability or psychiatric disorders. Patients drink large volumes of water daily ranging from ten to forty liters, resulting in acute severe hyponatremia with mortality rates as high as 20%. Poor outcomes are due to challenges faced by physicians in making an early diagnosis and treating acute hyponatremia safely. A low index of suspicion of water intoxication is required in this population, including patients with known epilepsy. Monitoring urine output proved to be clinically effective in aiding diagnosis. Early referral and admission to intensive care should be considered for safe correction of sodium concentration while minimizing risk of fatal complications e.g. central pontine myelinolysis.

Keywords: epilepsy, psychogenic polydipsia, seizure, severe hyponatremia

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2 Numerical Simulation of Von Karman Swirling Bioconvection Nanofluid Flow from a Deformable Rotating Disk

Authors: Ali Kadir, S. R. Mishra, M. Shamshuddin, O. Anwar Beg

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Motivation- Rotating disk bio-reactors are fundamental to numerous medical/biochemical engineering processes including oxygen transfer, chromatography, purification and swirl-assisted pumping. The modern upsurge in biologically-enhanced engineering devices has embraced new phenomena including bioconvection of micro-organisms (photo-tactic, oxy-tactic, gyrotactic etc). The proven thermal performance superiority of nanofluids i.e. base fluids doped with engineered nanoparticles has also stimulated immense implementation in biomedical designs. Motivated by these emerging applications, we present a numerical thermofluid dynamic simulation of the transport phenomena in bioconvection nanofluid rotating disk bioreactor flow. Methodology- We study analytically and computationally the time-dependent three-dimensional viscous gyrotactic bioconvection in swirling nanofluid flow from a rotating disk configuration. The disk is also deformable i.e. able to extend (stretch) in the radial direction. Stefan blowing is included. The Buongiorno dilute nanofluid model is adopted wherein Brownian motion and thermophoresis are the dominant nanoscale effects. The primitive conservation equations for mass, radial, tangential and axial momentum, heat (energy), nanoparticle concentration and micro-organism density function are formulated in a cylindrical polar coordinate system with appropriate wall and free stream boundary conditions. A mass convective condition is also incorporated at the disk surface. Forced convection is considered i.e. buoyancy forces are neglected. This highly nonlinear, strongly coupled system of unsteady partial differential equations is normalized with the classical Von Karman and other transformations to render the boundary value problem (BVP) into an ordinary differential system which is solved with the efficient Adomian decomposition method (ADM). Validation with earlier Runge-Kutta shooting computations in the literature is also conducted. Extensive computations are presented (with the aid of MATLAB symbolic software) for radial and circumferential velocity components, temperature, nanoparticle concentration, micro-organism density number and gradients of these functions at the disk surface (radial local skin friction, local circumferential skin friction, Local Nusselt number, Local Sherwood number, motile microorganism mass transfer rate). Main Findings- Increasing radial stretching parameter decreases radial velocity and radial skin friction, reduces azimuthal velocity and skin friction, decreases local Nusselt number and motile micro-organism mass wall flux whereas it increases nano-particle local Sherwood number. Disk deceleration accelerates the radial flow, damps the azimuthal flow, decreases temperatures and thermal boundary layer thickness, depletes the nano-particle concentration magnitudes (and associated nano-particle species boundary layer thickness) and furthermore decreases the micro-organism density number and gyrotactic micro-organism species boundary layer thickness. Increasing Stefan blowing accelerates the radial flow and azimuthal (circumferential flow), elevates temperatures of the nanofluid, boosts nano-particle concentration (volume fraction) and gyrotactic micro-organism density number magnitudes whereas suction generates the reverse effects. Increasing suction effect reduces radial skin friction and azimuthal skin friction, local Nusselt number, and motile micro-organism wall mass flux whereas it enhances the nano-particle species local Sherwood number. Conclusions - Important transport characteristics are identified of relevance to real bioreactor nanotechnological systems not discussed in previous works. ADM is shown to achieve very rapid convergence and highly accurate solutions and shows excellent promise in simulating swirling multi-physical nano-bioconvection fluid dynamics problems. Furthermore, it provides an excellent complement to more general commercial computational fluid dynamics simulations.

Keywords: bio-nanofluids, rotating disk bioreactors, Von Karman swirling flow, numerical solutions

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