Search results for: rapid drug releasing
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4520

Search results for: rapid drug releasing

890 Microalgae Hydrothermal Liquefaction Process Optimization and Comprehension to Produce High Quality Biofuel

Authors: Lucie Matricon, Anne Roubaud, Geert Haarlemmer, Christophe Geantet

Abstract:

Introduction: This case discusses the management of two floor of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. Case Report: A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Discussion: Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk, and second primary cancer development.

Keywords: microalgae, biofuels, hydrothermal liquefaction, biomass

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889 Synthesis of Fluorescent PET-Type “Turn-Off” Triazolyl Coumarin Based Chemosensors for the Sensitive and Selective Sensing of Fe⁺³ Ions in Aqueous Solutions

Authors: Aidan Battison, Neliswa Mama

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Environmental pollution by ionic species has been identified as one of the biggest challenges to the sustainable development of communities. The widespread use of organic and inorganic chemical products and the release of toxic chemical species from industrial waste have resulted in a need for advanced monitoring technologies for environment protection, remediation and restoration. Some of the disadvantages of conventional sensing methods include expensive instrumentation, well-controlled experimental conditions, time-consuming procedures and sometimes complicated sample preparation. On the contrary, the development of fluorescent chemosensors for biological and environmental detection of metal ions has attracted a great deal of attention due to their simplicity, high selectivity, eidetic recognition, rapid response and real-life monitoring. Coumarin derivatives S1 and S2 (Scheme 1) containing 1,2,3-triazole moieties at position -3- have been designed and synthesized from azide and alkyne derivatives by CuAAC “click” reactions for the detection of metal ions. These compounds displayed a strong preference for Fe3+ ions with complexation resulting in fluorescent quenching through photo-induced electron transfer (PET) by the “sphere of action” static quenching model. The tested metal ions included Cd2+, Pb2+, Ag+, Na+, Ca2+, Cr3+, Fe3+, Al3+, Cd2+, Ba2+, Cu2+, Co2+, Hg2+, Zn2+ and Ni2+. The detection limits of S1 and S2 were determined to be 4.1 and 5.1 uM, respectively. Compound S1 displayed the greatest selectivity towards Fe3+ in the presence of competing for metal cations. S1 could also be used for the detection of Fe3+ in a mixture of CH3CN/H¬2¬O. Binding stoichiometry between S1 and Fe3+ was determined by using both Jobs-plot and Benesi-Hildebrand analysis. The binding was shown to occur in a 1:1 ratio between the sensor and a metal cation. Reversibility studies between S1 and Fe3+ were conducted by using EDTA. The binding site of Fe3+ to S1 was determined by using 13 C NMR and Molecular Modelling studies. Complexation was suggested to occur between the lone-pair of electrons from the coumarin-carbonyl and the triazole-carbon double bond.

Keywords: chemosensor, "click" chemistry, coumarin, fluorescence, static quenching, triazole

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888 Mesoporous Titania Thin Films for Gentamicin Delivery and Bone Morphogenetic Protein-2 Immobilization

Authors: Ane Escobar, Paula Angelomé, Mihaela Delcea, Marek Grzelczak, Sergio Enrique Moya

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The antibacterial capacity of bone-anchoring implants can be improved by the use of antibiotics that can be delivered to the media after the surgery. Mesoporous films have shown great potential in drug delivery for orthopedic applications, since pore size and thickness can be tuned to produce different surface area and free volume inside the material. This work shows the synthesis of mesoporous titania films (MTF) by sol-gel chemistry and evaporation-induced self-assembly (EISA) on top of glass substrates. Pores with a diameter of 12nm were observed by Transmission Electron Microscopy (TEM). A film thickness of 100 nm was measured by Scanning Electron Microscopy (SEM). Gentamicin was used to study the antibiotic delivery from the film by means of High-performance liquid chromatography (HPLC). The Staphilococcus aureus strand was used to evaluate the effectiveness of the penicillin loaded films toward inhibiting bacterial colonization. MC3T3-E1 pre-osteoblast cell proliferation experiments proved that MTFs have a good biocompatibility and are a suitable surface for MC3T3-E1 cell proliferation. Moreover, images taken by Confocal Fluorescence Microscopy using labeled vinculin, showed good adhesion of the MC3T3-E1 cells to the MTFs, as well as complex actin filaments arrangement. In order to improve cell proliferation Bone Morphogenetic Protein-2 (BMP-2) was adsorbed on top of the mesoporous film. The deposition of the protein was proved by measurements in the contact angle, showing an increment in the hydrophobicity while the protein concentration is higher. By measuring the dehydrogenase activity in MC3T3-E1 cells cultured in dually functionalized mesoporous titatina films with gentamicin and BMP-2 is possible to find an improvement in cell proliferation. For this purpose, the absorption of a yellow-color formazan dye, product of a water-soluble salt (WST-8) reduction by the dehydrogenases, is measured. In summary, this study proves that by means of the surface modification of MTFs with proteins and loading of gentamicin is possible to achieve an antibacterial effect and a cell growth improvement.

Keywords: antibacterial, biocompatibility, bone morphogenetic protein-2, cell proliferation, gentamicin, implants, mesoporous titania films, osteoblasts

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887 Oncological and Antiresorptive Treatment of Breast Cancer: Dental Assessment and Risk of MRONJ Development

Authors: Magdalena Korytowska, Gunnar Lengstrand, Cecilia Larsson Wexell

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Background: Breast cancer (BC) is the most common cancer among women worldwide, and cases are continuing to increase in Sweden. Bone is the most common metastatic site in breast cancer patients, where > 65-75% of women with advanced breast cancer develop bone metastases during their disease. To prevent the skeletal-related events of metastases (e.g., pathological fractures, bone loss, cancer-induced bone pain, and hypercalcemia bone), two different classes of antiresorptive medications (AR), bisphosphonate and denosumab are typically administered every 3 to 4 weeks. Since 2015, adjuvant bisphosphonate treatment has been used every six months for three to five years in postmenopausal women for the prevention of skeletal metastases and improved survival. Methods: A case-control study was conducted to test the hypotheses that patients treated with high-dose AR are at higher risk of developing MRONJ than breast cancer patients with adjuvant bisphosphonate treatment at a lower dose. Medical and odontological data was collected between 2015-2020. Assessment of oral health and dental care before and during oncological treatment took place at the specialist clinic for Orofacial medicine linked to the specific hospital. Results: In total, 220 patients were included, 101 patients in the high-dose group and 119 patients in the adjuvant BP-treatment group. MRONJ was diagnosed in 13 patients (14%) in the high-dose group. The mandible was affected in most of the cases (84.6%), with a mean duration of high-dose treatment of 19.7 months. In 46.2% of cases, no dental cause of MRONJ could be identified. Overall, estrogen receptor-positive (ER+) BC was the most representative type in 172 patients (78.2%). However, this was 83.9% in the high-dose cases group. The most used drug was denosumab. Twenty-five patients (26.9%) switched their medication from ZOL to denosumab during their oncological treatment. Patients with ER+ breast cancer were reported in 88 patients (87.8%) in the adjuvant group that was treated with ZOL. Conclusions: MRONJ was diagnosed only in the high-dose AR group. Dental assessment and care of patients in the adjuvant group should be considered, with a recommendation to potentially prolong ZOL treatment from 3 to 5 years, with concomitant use of hormonal therapy in patients diagnosed with ER+ breast cancer to prevent bone loss induced by oncological treatment. A new referral for dental assessment is very important in the case of bone metastases when treatment with high dose AR will be required since it is associated with a higher risk of MRONJ.

Keywords: antiresorptive therapy, breast cancer, dental care, MRONJ

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886 Ultrasensitive Detection and Discrimination of Cancer-Related Single Nucleotide Polymorphisms Using Poly-Enzyme Polymer Bead Amplification

Authors: Lorico D. S. Lapitan Jr., Yihan Xu, Yuan Guo, Dejian Zhou

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The ability of ultrasensitive detection of specific genes and discrimination of single nucleotide polymorphisms is important for clinical diagnosis and biomedical research. Herein, we report the development of a new ultrasensitive approach for label-free DNA detection using magnetic nanoparticle (MNP) assisted rapid target capture/separation in combination with signal amplification using poly-enzyme tagged polymer nanobead. The sensor uses an MNP linked capture DNA and a biotin modified signal DNA to sandwich bind the target followed by ligation to provide high single-nucleotide polymorphism discrimination. Only the presence of a perfect match target DNA yields a covalent linkage between the capture and signal DNAs for subsequent conjugation of a neutravidin-modified horseradish peroxidase (HRP) enzyme through the strong biotin-nuetravidin interaction. This converts each captured DNA target into an HRP which can convert millions of copies of a non-fluorescent substrate (amplex red) to a highly fluorescent product (resorufin), for great signal amplification. The use of polymer nanobead each tagged with thousands of copies of HRPs as the signal amplifier greatly improves the signal amplification power, leading to greatly improved sensitivity. We show our biosensing approach can specifically detect an unlabeled DNA target down to 10 aM with a wide dynamic range of 5 orders of magnitude (from 0.001 fM to 100.0 fM). Furthermore, our approach has a high discrimination between a perfectly matched gene and its cancer-related single-base mismatch targets (SNPs): It can positively detect the perfect match DNA target even in the presence of 100 fold excess of co-existing SNPs. This sensing approach also works robustly in clinical relevant media (e.g. 10% human serum) and gives almost the same SNP discrimination ratio as that in clean buffers. Therefore, this ultrasensitive SNP biosensor appears to be well-suited for potential diagnostic applications of genetic diseases.

Keywords: DNA detection, polymer beads, signal amplification, single nucleotide polymorphisms

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885 Longitudinal Profile of Antibody Response to SARS-CoV-2 in Patients with Covid-19 in a Setting from Sub–Saharan Africa: A Prospective Longitudinal Study

Authors: Teklay Gebrecherkos

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Background: Serological testing for SARS-CoV-2 plays an important role in epidemiological studies, in aiding the diagnosis of COVID-19 and assess vaccine responses. Little is known about the dynamics of SARS-CoV-2 serology in African settings. Here, we aimed to characterize the longitudinal antibody response profile to SARS-CoV-2 in Ethiopia. Methods: In this prospective study, a total of 102 PCR-confirmed COVID-19 patients were enrolled. We obtained 802 plasma samples collected serially. SARS-CoV-2 antibodies were determined using four lateral flow immune assays (LFIAs) and an electrochemiluminescent immunoassay. We determined longitudinal antibody response to SARS-CoV-2 as well as seroconversion dynamics. Results: Serological positivity rate ranged between 12%-91%, depending on timing after symptom onset. There was no difference in the positivity rate between severe and non-severe COVID-19 cases. The specificity ranged between 90%-97%. Agreement between different assays ranged between 84%-92%. The estimated positive predictive value (PPV) for IgM or IgG in a scenario with seroprevalence at 5% varies from 33% to 58%. Nonetheless, when the population seroprevalence increases to 25% and 50%, there is a corresponding increase in the estimated PPVs. The estimated negative-predictive value (NPV) in a low seroprevalence scenario (5%) is high (>99%). However, the estimated NPV in a high seroprevalence scenario (50%) for IgM or IgG is reduced significantly from 80% to 85%. Overall, 28/102 (27.5%) seroconverted by one or more assays tested within a median time of 11 (IQR: 9–15) days post symptom onset. The median seroconversion time among symptomatic cases tended to be shorter when compared to asymptomatic patients [9 (IQR: 6–11) vs. 15 (IQR: 13–21) days; p = 0.002]. Overall, seroconversion reached 100% 5.5 weeks after the onset of symptoms. Notably, of the remaining 74 COVID-19 patients included in the cohort, 64 (62.8%) were positive for antibodies at the time of enrollment, and 10 (9.8%) patients failed to mount a detectable antibody response by any of the assays tested during follow-up. Conclusions: Longitudinal assessment of antibody response in African COVID-19 patients revealed heterogeneous responses. This underscores the need for a comprehensive evaluation of serum assays before implementation. Factors associated with failure to seroconvert need further research.

Keywords: COVID-19, antibody, rapid diagnostic tests, ethiopia

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884 Scenarios for the Energy Transition in Residential Buildings for the European Regions

Authors: Domenico Carmelo Mongelli, Laura Carnieletto, Michele De Carli, Filippo Busato

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Starting from the current context in which the Russian invasion in Ukraine has highlighted Europe's dependence on natural gas imports for heating buildings, this study proposes solutions to resolve this dependency and evaluates related scenarios in the near future. In the first part of this work the methodologies and results of the economic impact are indicated by simulating a massive replacement of boilers powered by fossil fuels with electrically powered hightemperature air-water heat pumps for heating residential buildings in different European climates, without changing the current energy mix. For each individual European region, the costs for the purchase and installation of heat pumps for all residential buildings have been determined. Again for each individual European region, the economic savings during the operation phase that would be obtained in this future scenario of energy transition from fossil fuels to the electrification of domestic heating were calculated. For the European regions for which the economic savings were identified as positive, the payback times of the economic investments were analysed. In the second part of the work, hypothesizing different scenarios for a possible greater use of renewable energy sources and therefore with different possible future scenarios of the energy mix, the methodologies and results of the simulations on the economic analysis and on the environmental analysis are reported which have allowed us to evaluate the future effects of the energy transition from boilers to heat pumps for each European region. In the third part, assuming a rapid short-term diffusion of cooling for European residential buildings, the penetration shares in the cooling market and future projections of energy needs for cooling for each European region have been identified. A database was created where the results of this research relating to 38 European Nations divided into 179 regions were reported. Other previous works on the topics covered were limited to analyzing individual European nations, without ever going into detail about the individual regions within each nation, while the original contribution of the present work lies in the fact that the results achieved allow a specific numerical analysis and punctual for every single European region.

Keywords: buildings, energy, Europe, future

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883 Optimising Post-Process Heat Treatments of Selective Laser Melting-Produced Ti-6Al-4V Parts to Achieve Superior Mechanical Properties

Authors: Gerrit Ter Haar, Thorsten Becker, Deborah Blaine

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The Additive Manufacturing (AM) process of Selective Laser Melting (SLM) has seen an exponential growth in sales and development in the past fifteen years. Whereas the capability of SLM was initially limited to rapid prototyping, progress in research and development (R&D) has allowed SLM to be capable of fully functional parts. This technology is still at a primitive stage and technical knowledge of the vast number of variables influencing final part quality is limited. Ongoing research and development of the sensitive printing process and post processes is of utmost importance in order to qualify SLM parts to meet international standards. Quality concerns in Ti-6Al-4V manufactured through SLM has been identified, which include: high residual stresses, part porosity, low ductility and anisotropic mechanical properties. Whereas significant quality improvements have been made through optimising printing parameters, research indicates as-produced part ductility to be a major limiting factor when compared to its wrought counterpart. This study aims at achieving an in-depth understanding of the underlining links between SLM produced Ti-6Al-4V microstructure and its mechanical properties. Knowledge of microstructural transformation kinetics of Ti-6Al-4V allows for the optimisation of post-process heat treatments thereby achieving the required process route to manufacture high quality SLM produced Ti-6Al-4V parts. Experimental methods used to evaluate the kinematics of microstructural transformation of SLM Ti-6Al-4V are: optical microscopy and electron backscatter diffraction. Results show that a low-temperature heat treatment is capable of transforming the as-produced, martensitic microstructure into a duel-phase microstructure exhibiting both a high strength and improved ductility. Furthermore, isotropy of mechanical properties can be achieved through certain annealing routes. Mechanical properties identical to that of wrought Ti-6Al-4V can, therefore, be achieved through an optimised process route.

Keywords: EBSD analysis, heat treatments, microstructural characterisation, selective laser melting, tensile behaviour, Ti-6Al-4V

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882 A Study of Topical and Similarity of Sebum Layer Using Interactive Technology in Image Narratives

Authors: Chao Wang

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Under rapid innovation of information technology, the media plays a very important role in the dissemination of information, and it has a totally different analogy generations face. However, the involvement of narrative images provides more possibilities of narrative text. "Images" through the process of aperture, a camera shutter and developable photosensitive processes are manufactured, recorded and stamped on paper, displayed on a computer screen-concretely saved. They exist in different forms of files, data, or evidence as the ultimate looks of events. By the interface of media and network platforms and special visual field of the viewer, class body space exists and extends out as thin as sebum layer, extremely soft and delicate with real full tension. The physical space of sebum layer of confuses the fact that physical objects exist, needs to be established under a perceived consensus. As at the scene, the existing concepts and boundaries of physical perceptions are blurred. Sebum layer physical simulation shapes the “Topical-Similarity" immersing, leading the contemporary social practice communities, groups, network users with a kind of illusion without the presence, i.e. a non-real illusion. From the investigation and discussion of literatures, digital movies editing manufacture and produce the variability characteristics of time (for example, slices, rupture, set, and reset) are analyzed. Interactive eBook has an unique interaction in "Waiting-Greeting" and "Expectation-Response" that makes the operation of image narrative structure more interpretations functionally. The works of digital editing and interactive technology are combined and further analyze concept and results. After digitization of Interventional Imaging and interactive technology, real events exist linked and the media handing cannot be cut relationship through movies, interactive art, practical case discussion and analysis. Audience needs more rational thinking about images carried by the authenticity of the text.

Keywords: sebum layer, topical and similarity, interactive technology, image narrative

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881 The Relationship between Vitamin D and Vitamin B12 Concentrations in Cataract Patients (Senile vs Diabetic)

Authors: Ali Showail Ali Alasmari

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Introduction: Cataract is the loss of transparency of the lens inside the eye. It is the most common cause of visual loss and blindness worldwide. This study provides a systemic review of the recent findings on the association of vitamin D, and vitamin B12, and their possible role in preventing cataracts in senile (S) and diabetic mellitus (DM) patient groups. Objective: This study was intended to establish and investigate if there is any role between vitamin D and vitamin B12? Secondly, the connection between serum level of vitamin D and vitamin B12 in cataract incidence senile (s) vs. diabetic mellitus (DM) cataract patient groups. Furthermore, to evaluate and analyze cataract occurrence regarding vitamin D and vitamin B12 levels with other risk factors. Finally, to evaluate lens opacities pre and post treatment with vitamin D and vitaminB12 linked to age and visual acuity loss in both senile(S) and diabetic mellitus (DM) cataract patients’ groups. Methods: This study conducted at the ophthalmology clinic at Muhyail General Hospital. Select a prospective case-control to study the effect of vitamin D and Vit B12 on senile(S) cataracts that caused by age and diabetic mellitus (DM)cataract patients; then we compare these two groups. This study prospectively enrolled a total of 50 samples, 25 with senile cataract and 25 with diabetic cataract, from ophthalmology clinic at Muhyail General Hospital. Measuring 25-hydroxy vitamin D and vitamin B12 level concentrations in the assigned samples. Analyses were performed using SAS (statistical analysis software) program. Results: The most important finding in this study was that the senile(s) cataract patients’ group greatly benefited by the combination therapy of vitamin D, and Vitamin B12 reached (28.5±1.50 and 521.1±21.10) respectively; on the contrary, the diabetic cataract patient group hardly shows any significant improvement (21.5 ± 1.00 and 197.2 ± 7.20) respectively. This is because of the Metformin, the first line drug for treating diabetes, has been reported to potentially decrease vitamin B-12 status. This epigenetic modification was correlated with the diabetic mellitus (DM) cataract patients’ group not responding. Vitamin B12 deficiency also leads to an impairment of the conversion of methylmalonyl-CoA to succinyl-CoA, which has been associated with insulin resistance. There was no significant difference between the age, body mass index (BMI), the mean of Vit-D pre-treatments, and the mean values of Hemoglobin A1C of both senile (S) and diabetic mellitus (DM) cataract patient groups. On other hand, there was a highly significant difference between the mean values of glucose levels in both senile (S) and diabetic mellitus (DM) cataract patient groups. Conclusion: Here we conclude that diabetic mellitus (DM) cataract patient group hardly benefited from this combination therapy vitamin D and vitamin B12; on the other hand senile patient group (s) benefited a lot from the therapy.

Keywords: cataract patients, senile, diabetes mellitus, vitamin B12, vitamin D, Muhyail General Hospital, Saudi Arabia

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880 Calcein Release from Liposomes Mediated by Phospholipase A₂ Activity: Effect of Cholesterol and Amphipathic Di and Tri Blocks Copolymers

Authors: Marco Soto-Arriaza, Eduardo Cena-Ahumada, Jaime Melendez-Rojel

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Background: Liposomes have been widely used as a model of lipid bilayer to study the physicochemical properties of biological membrane, encapsulation, transport and release of different molecules. Furthermore, extensive research has focused on improving the efficiency in the transport of drugs, developing tools that improve the release of the encapsulated drug from liposomes. In this context, the enzymatic activity of PLA₂, despite having been shown to be an effective tool to promote the release of drugs from liposomes, is still an open field of research. Aim: The aim of the present study is to explore the effect of cholesterol (Cho) and amphipathic di- and tri-block copolymers, on calcein release mediated by enzymatic activity of PLA2 in Dipalmitoylphosphatidylcholine (DPPC) liposomes under physiological conditions. Methods: Different dispersions of DPPC, cholesterol, di-block POE₄₅-PCL₅₂ or tri-block PCL₁₂-POE₄₅-PCL₁₂ were prepared by the extrusion method after five freezing/thawing cycles; in Phosphate buffer 10mM pH 7.4 in presence of calcein. DPPC liposomes/Calcein were centrifuged at 15000rpm 10 min to separate free calcein. Enzymatic activity assays of PLA₂ were performed at 37°C using the TBS buffer pH 7.4. The size distribution, polydispersity, Z-potential and Calcein encapsulation of DPPC liposomes was monitored. Results: PLA₂ activity showed a slower kinetic of calcein release up to 20 mol% of cholesterol, evidencing a minimum at 10 mol% and then a maximum at 18 mol%. Regardless of the percentage of cholesterol, up to 18 mol% a one-hundred percentage release of calcein was observed. At higher cholesterol concentrations, PLA₂ showed to be inefficient or not to be involved in calcein release. In assays where copolymers were added in a concentration lower than their cmc, a similar behavior to those showed in the presence of Cho was observed, that is a slower kinetic in calcein release. In both experimental approaches, a one-hundred percentage of calcein release was observed. PLA₂ was shown to be sensitive to the 4-(4-Octadecylphenyl)-4-oxobutenoic acid inhibitor and calcium, reducing the release of calcein to 0%. Cell viability of HeLa cells decreased 7% in the presence of DPPC liposomes after 3 hours of incubation and 17% and 23% at 5 and 15 hours, respectively. Conclusion: Calcein release from DPPC liposomes, mediated by PLA₂ activity, depends on the percentage of cholesterol and the presence of copolymers. Both, cholesterol up to 20 mol% and copolymers below it cmc could be applied to the regulation of the kinetics of antitumoral drugs release without inducing cell toxicity per se.

Keywords: amphipathic copolymers, calcein release, cholesterol, DPPC liposome, phospholipase A₂

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879 Experimental Investigation of the Out-of-Plane Dynamic Behavior of Adhesively Bonded Composite Joints at High Strain Rates

Authors: Sonia Sassi, Mostapha Tarfaoui, Hamza Ben Yahia

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In this investigation, an experimental technique in which the dynamic response, damage kinetic and heat dissipation are measured simultaneously during high strain rates on adhesively bonded joints materials. The material used in this study is widely used in the design of structures for military applications. It was composed of a 45° Bi-axial fiber-glass mat of 0.286 mm thickness in a Polyester resin matrix. In adhesive bonding, a NORPOL Polyvinylester of 1 mm thickness was used to assemble the composite substrate. The experimental setup consists of a compression Split Hopkinson Pressure Bar (SHPB), a high-speed infrared camera and a high-speed Fastcam rapid camera. For the dynamic compression tests, 13 mm x 13 mm x 9 mm samples for out-of-plane tests were considered from 372 to 1030 s-1. Specimen surface is controlled and monitored in situ and in real time using the high-speed camera which acquires the damage progressive in specimens and with the infrared camera which provides thermal images in time sequence. Preliminary compressive stress-strain vs. strain rates data obtained show that the dynamic material strength increases with increasing strain rates. Damage investigations have revealed that the failure mainly occurred in the adhesive/adherent interface because of the brittle nature of the polymeric adhesive. Results have shown the dependency of the dynamic parameters on strain rates. Significant temperature rise was observed in dynamic compression tests. Experimental results show that the temperature change depending on the strain rate and the damage mode and their maximum exceed 100 °C. The dependence of these results on strain rate indicates that there exists a strong correlation between damage rate sensitivity and heat dissipation, which might be useful when developing damage models under dynamic loading tacking into account the effect of the energy balance of adhesively bonded joints.

Keywords: adhesive bonded joints, Hopkinson bars, out-of-plane tests, dynamic compression properties, damage mechanisms, heat dissipation

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878 An Experimental Study on the Thermal Properties of Concrete Aggregates in Relation to Their Mineral Composition

Authors: Kyung Suk Cho, Heung Youl Kim

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The analysis of the petrologic characteristics and thermal properties of crushed aggregates for concrete such as granite, gneiss, dolomite, shale and andesite found that rock-forming minerals decided the thermal properties of the aggregates. The thermal expansion coefficients of aggregates containing lots of quartz increased rapidly at 573 degrees due to quartz transition. The mass of aggregate containing carbonate minerals decreased rapidly at 750 degrees due to decarboxylation, while its specific heat capacity increased relatively. The mass of aggregates containing hydrated silicate minerals decreased more significantly, and their specific heat capacities were greater when compared with aggregates containing feldspar or quartz. It is deduced that the hydroxyl group (OH) in hydrated silicate dissolved as its bond became loose at high temperatures. Aggregates containing mafic minerals turned red at high temperatures due to oxidation response. Moreover, the comparison of cooling methods showed that rapid cooling using water resulted in more reduction in aggregate mass than slow cooling at room temperatures. In order to observe the fire resistance performance of concrete composed of the identical but coarse aggregate, mass loss and compressive strength reduction factor at 200, 400, 600 and 800 degrees were measured. It was found from the analysis of granite and gneiss that the difference in thermal expansion coefficients between cement paste and aggregates caused by quartz transit at 573 degrees resulted in thermal stress inside the concrete and thus triggered concrete cracking. The ferromagnesian hydrated silicate in andesite and shale caused greater reduction in both initial stiffness and mass compared with other aggregates. However, the thermal expansion coefficient of andesite and shale was similar to that of cement paste. Since they were low in thermal conductivity and high in specific heat capacity, concrete cracking was relatively less severe. Being slow in heat transfer, they were judged to be materials of high heat capacity.

Keywords: crush-aggregates, fire resistance, thermal expansion, heat transfer

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877 Transit Facility Planning in Fringe Areas of Kolkata Metropolitan Region

Authors: Soumen Mitra, Aparna Saha

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The perceived link between the city and the countryside is evolving rapidly and is getting shifted away from the assumptions of mainstream paradigms to new conceptual networks where rural-urban links are being redefined. In this conceptual field, the fringe interface is still considered as a transitional zone between city and countryside, and is defined as a diffused area rather than a discrete territory. In developing countries fringe areas are said to have both rural and urban characteristics but are devoid of basic municipal facilities. Again, when the urban core areas envelopes the fringe areas along with it the character of fringe changes but services are not well facilitated which in turn results to uneven growth, rapid and haphazard development. One of the major services present in fringe areas is inter-linkages in terms of transit corridors. Planning for the appropriate and sustainable future of fringe areas requires a sheer focus on these corridors pertaining to transit facility, for better accessibility and mobility. Inducing a transit facility plan enhances the various facilities and also increases their proximity for user groups. The study focuses on the western fringe region of Kolkata metropolis which is a major source of industrial hub and housing sector, thus converting the agricultural lands into non-agricultural use. The study emphasizes on providing transit facilities both physical (stops, sheds, terminals, etc.) and operational (ticketing system, route prioritization, integration of transit modes, etc.), to facilitate the region as well as accelerate the growth pattern systematically. Hence, the scope of this work is on the basis of prevailing conditions in fringe areas and attempts for an effective transit facility plan. The strategies and recommendations are in terms of road widening, service coverage, feeder route prioritization, bus stops facilitation, pedestrian facilities, etc, which in turn enhances the region’s growth pattern. Thus, this context of transit facility planning acts as a catalytic agent to avoid the future unplanned growth and accelerates it towards an integrated development.

Keywords: feeder route, fringe, municipal planning, transit facility

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876 Modelling of Recovery and Application of Low-Grade Thermal Resources in the Mining and Mineral Processing Industry

Authors: S. McLean, J. A. Scott

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The research topic is focusing on improving sustainable operation through recovery and reuse of waste heat in process water streams, an area in the mining industry that is often overlooked. There are significant advantages to the application of this topic, including economic and environmental benefits. The smelting process in the mining industry presents an opportunity to recover waste heat and apply it to alternative uses, thereby enhancing the overall process. This applied research has been conducted at the Sudbury Integrated Nickel Operations smelter site, in particular on the water cooling towers. The aim was to determine and optimize methods for appropriate recovery and subsequent upgrading of thermally low-grade heat lost from the water cooling towers in a manner that makes it useful for repurposing in applications, such as within an acid plant. This would be valuable to mining companies as it would be an opportunity to reduce the cost of the process, as well as decrease environmental impact and primary fuel usage. The waste heat from the cooling towers needs to be upgraded before it can be beneficially applied, as lower temperatures result in a decrease of the number of potential applications. Temperature and flow rate data were collected from the water cooling towers at an acid plant over two years. The research includes process control strategies and the development of a model capable of determining if the proposed heat recovery technique is economically viable, as well as assessing any environmental impact with the reduction in net energy consumption by the process. Therefore, comprehensive cost and impact analyses are carried out to determine the best area of application for the recovered waste heat. This method will allow engineers to easily identify the value of thermal resources available to them and determine if a full feasibility study should be carried out. The rapid scoping model developed will be applicable to any site that generates large amounts of waste heat. Results show that heat pumps are an economically viable solution for this application, allowing for reduced cost and CO₂ emissions.

Keywords: environment, heat recovery, mining engineering, sustainability

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875 Multi-Scale Modelling of the Cerebral Lymphatic System and Its Failure

Authors: Alexandra K. Diem, Giles Richardson, Roxana O. Carare, Neil W. Bressloff

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Alzheimer's disease (AD) is the most common form of dementia and although it has been researched for over 100 years, there is still no cure or preventive medication. Its onset and progression is closely related to the accumulation of the neuronal metabolite Aβ. This raises the question of how metabolites and waste products are eliminated from the brain as the brain does not have a traditional lymphatic system. In recent years the rapid uptake of Aβ into cerebral artery walls and its clearance along those arteries towards the lymph nodes in the neck has been suggested and confirmed in mice studies, which has led to the hypothesis that interstitial fluid (ISF), in the basement membranes in the walls of cerebral arteries, provides the pathways for the lymphatic drainage of Aβ. This mechanism, however, requires a net reverse flow of ISF inside the blood vessel wall compared to the blood flow and the driving forces for such a mechanism remain unknown. While possible driving mechanisms have been studied using mathematical models in the past, a mechanism for net reverse flow has not been discovered yet. Here, we aim to address the question of the driving force of this reverse lymphatic drainage of Aβ (also called perivascular drainage) by using multi-scale numerical and analytical modelling. The numerical simulation software COMSOL Multiphysics 4.4 is used to develop a fluid-structure interaction model of a cerebral artery, which models blood flow and displacements in the artery wall due to blood pressure changes. An analytical model of a layer of basement membrane inside the wall governs the flow of ISF and, therefore, solute drainage based on the pressure changes and wall displacements obtained from the cerebral artery model. The findings suggest that an active role in facilitating a reverse flow is played by the components of the basement membrane and that stiffening of the artery wall during age is a major risk factor for the impairment of brain lymphatics. Additionally, our model supports the hypothesis of a close association between cerebrovascular diseases and the failure of perivascular drainage.

Keywords: Alzheimer's disease, artery wall mechanics, cerebral blood flow, cerebral lymphatics

Procedia PDF Downloads 518
874 Simulating the Surface Runoff for the Urbanized Watershed of Mula-Mutha River from Western Maharashtra, India

Authors: Anargha A. Dhorde, Deshpande Gauri, Amit G. Dhorde

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Mula-Mutha basin is one of the speedily urbanizing watersheds, wherein two major urban centers, Pune and Pimpri-Chinchwad, have developed at a shocking rate in the last two decades. Such changing land use/land cover (LULC) is prone to hydrological problems and flash floods are a frequent, eventuality in the lower reaches of the basin. The present research brings out the impact of varying LULC, impervious surfaces on urban surface hydrology and generates storm-runoff scenarios for the hydrological units. The two multi-temporal satellite images were processed and supervised classification is performed with > 75% accuracy. The built-up has increased from 14.4% to 34.37% in the 28 years span, which is concentrated in and around the Pune-PCMC region. Impervious surfaces that were obtained by population calibrated multiple regression models. Almost 50% area of the watershed is impervious, which attribute to increase surface runoff and flash floods. The SCS-CN method was employed to calculate surface runoff of the watershed. The comparison between calculated and measured values of runoff was performed in a statistically precise way which shows no significant difference. Increasing built-up areas, as well as impervious surface areas due to rapid urbanization and industrialization, may lead to generating high runoff volumes in the basin especially in the urbanized areas of the watershed and along the major transportation arteries. Simulations generated with 50 mm and 100 mm rainstorm depth conspicuously noted that most of the changes in terms of increased runoff are constricted to the highly urbanized areas. Considering whole watershed area, the runoff values 39 m³ generated with 1'' rainfall whereas only urbanized areas of the basin (Pune and Pimpari-Chinchwad) were generated 11154 m³ runoff. Such analysis is crucial in providing information regarding their intensity and location, which proves instrumental in their analysis in order to formulate proper mitigation measures and rehabilitation strategies.

Keywords: land use/land cover, LULC, impervious surfaces, surface hydrology, storm-runoff scenarios

Procedia PDF Downloads 207
873 Preparation of Indium Tin Oxide Nanoparticle-Modified 3-Aminopropyltrimethoxysilane-Functionalized Indium Tin Oxide Electrode for Electrochemical Sulfide Detection

Authors: Md. Abdul Aziz

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Sulfide ion is water soluble, highly corrosive, toxic and harmful to the human beings. As a result, knowing the exact concentration of sulfide in water is very important. However, the existing detection and quantification methods have several shortcomings, such as high cost, low sensitivity, and massive instrumentation. Consequently, the development of novel sulfide sensor is relevant. Nevertheless, electrochemical methods gained enormous popularity due to a vast improvement in the technique and instrumentation, portability, low cost, rapid analysis and simplicity of design. Successful field application of electrochemical devices still requires vast improvement, which depends on the physical, chemical and electrochemical aspects of the working electrode. The working electrode made of bulk gold (Au) and platinum (Pt) are quite common, being very robust and endowed with good electrocatalytic properties. High cost, and electrode poisoning, however, have so far hindered their practical application in many industries. To overcome these obstacles, we developed a sulfide sensor based on an indium tin oxide nanoparticle (ITONP)-modified ITO electrode. To prepare ITONP-modified ITO, various methods were tested. Drop-drying of ITONPs (aq.) on aminopropyltrimethoxysilane-functionalized ITO (APTMS/ITO) was found to be the best method on the basis of voltammetric analysis of the sulfide ion. ITONP-modified APTMS/ITO (ITONP/APTMS/ITO) yielded much better electrocatalytic properties toward sulfide electro-οxidation than did bare or APTMS/ITO electrodes. The ITONPs and ITONP-modified ITO were also characterized using transmission electron microscopy and field emission scanning electron microscopy, respectively. Optimization of the type of inert electrolyte and pH yielded an ITONP/APTMS/ITO detector whose amperometrically and chronocoulοmetrically determined limits of detection for sulfide in aqueous solution were 3.0 µM and 0.90 µM, respectively. ITONP/APTMS/ITO electrodes which displayed reproducible performances were highly stable and were not susceptible to interference by common contaminants. Thus, the developed electrode can be considered as a promising tool for sensing sulfide.

Keywords: amperometry, chronocoulometry, electrocatalytic properties, ITO-nanoparticle-modified ITO, sulfide sensor

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872 Molecular Approach for the Detection of Lactic Acid Bacteria in the Kenyan Spontaneously Fermented Milk, Mursik

Authors: John Masani Nduko, Joseph Wafula Matofari

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Many spontaneously fermented milk products are produced in Kenya, where they are integral to the human diet and play a central role in enhancing food security and income generation via small-scale enterprises. Fermentation enhances product properties such as taste, aroma, shelf-life, safety, texture, and nutritional value. Some of these products have demonstrated therapeutic and probiotic effects although recent reports have linked some to death, biotoxin infections, and esophageal cancer. These products are mostly processed from poor quality raw materials under unhygienic conditions resulting to inconsistent product quality and limited shelf-lives. Though very popular, research on their processing technologies is low, and none of the products has been produced under controlled conditions using starter cultures. To modernize the processing technologies for these products, our study aims at describing the microbiology and biochemistry of a representative Kenyan spontaneously fermented milk product, Mursik using modern biotechnology (DNA sequencing) and their chemical composition. Moreover, co-creation processes reflecting stakeholders’ experiences on traditional fermented milk production technologies and utilization, ideals and senses of value, which will allow the generation of products based on common ground for rapid progress will be discussed. Knowledge of the value of clean starting raw material will be emphasized, the need for the definition of fermentation parameters highlighted, and standard equipment employment to attain controlled fermentation discussed. This presentation will review the available information regarding traditional fermented milk (Mursik) and highlight our current research work on the application of molecular approaches (metagenomics) for the valorization of Mursik production process through starter culture/ probiotic strains isolation and identification, and quality and safety aspects of the product. The importance of the research and future research areas on the same subject will also be highlighted.

Keywords: lactic acid bacteria, high throughput biotechnology, spontaneous fermentation, Mursik

Procedia PDF Downloads 278
871 Television, Internet, and Internet Social Media Direct-To-Consumer Prescription Medication Advertisements: Intention and Behavior to Seek Additional Prescription Medication Information

Authors: Joshua Fogel, Rivka Herzog

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Although direct-to-consumer prescription medication advertisements (DTCA) are viewed or heard in many venues, there does not appear to be any research for internet social media DTCA. We study the association of traditional media DTCA and digital media DTCA including internet social media of YouTube, Facebook, and Twitter with three different outcomes. There was one intentions outcome and two different behavior outcomes. The intentions outcome was the agreement level for seeking additional information about a prescription medication after seeing a DTCA. One behavior outcome was the agreement level for obtaining additional information about a prescription medication after seeing a DTCA. The other behavior outcome was the frequency level for obtaining additional information about a prescription medication after seeing a DTCA. Surveys were completed by 635 college students. Predictors included demographic variables, theory of planned behavior variables, health variables, and advertisements seen or heard. Also, in the behavior analyses, additional predictors of intentions and sources for seeking additional prescription drug information were included. Multivariate linear regression analyses were conducted. We found that increased age was associated with increased behavior, women were associated with increased intentions, and Hispanic race/ethnicity was associated with decreased behavior. For the theory of planned behavior variables, increased attitudes were associated with increased intentions, increased social norms were associated with increased intentions and behavior, and increased intentions were associated with increased behavior. Very good perceived health was associated with increased intentions. Advertisements seen in spam mail were associated with decreased intentions. Advertisements seen on traditional or cable television were associated with decreased behavior. Advertisements seen on television watched on the internet were associated with increased behavior. The source of seeking additional information of reading internet print content was associated with increased behavior. No internet social media advertisements were associated with either intentions or behavior. In conclusion, pharmaceutical brand managers and marketers should consider these findings when tailoring their DTCA advertising campaigns and directing their DTCA advertising budget towards young adults such as college students. They need to reconsider the current approach for traditional television DTCA and also consider dedicating a larger advertising budget toward internet television DTCA. Although internet social media is a popular place to advertise, the financial expenditures do not appear worthwhile for DTCA when targeting young adults such as college students.

Keywords: brand managers, direct-to-consumer advertising, internet, social media

Procedia PDF Downloads 251
870 Transnational Initiatives, Local Perspectives: The Potential of Australia-Asia BRIDGE School Partnerships Project to Support Teacher Professional Development in India

Authors: Atiya Khan

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Recent research on the condition of school education in India has reaffirmed the importance of quality teacher professional development, especially in light of the rapid changes in teaching methods, learning theories, curriculum, and major shifts in information and technology that education systems are experiencing around the world. However, the quality of programs of teacher professional development in India is often uneven, in some cases non-existing. The educational authorities in India have long recognized this and have developed a range of programs to assist in-service teacher education. But, these programs have been mostly inadequate at improving the quality of teachers in India. Policy literature and reports indicate that the unevenness of these programs and more generally the lack of quality teacher professional development in India are due to factors such as a large number of teachers, budgetary constraints, top-down decision making, teacher overload, lack of infrastructure, and little or no follow-up. The disparity between the government stated goals for quality teacher professional development in India and its inability to meet the learning needs of teachers suggests that new interventions are needed. The realization that globalization has brought about an increase in the social, cultural, political and economic interconnectedness between countries has also given rise to transnational opportunities for education systems, such as India’s, aiming to build their capacity to support teacher professional development. Moreover, new developments in communication technologies seem to present a plausible means of achieving high-quality professional development for teachers through the creation of social learning spaces, such as transnational learning networks. This case study investigates the potential of one such transnational learning network to support the quality of teacher professional development in India, namely the Australia-Asia BRIDGE School Partnerships Project. It explores the participation of some fifteen teachers and their principals from BRIDGE participating schools in Delhi region of India; focusing on their professional development expectations from the BRIDGE program and account for their experiences in the program, in order to determine the program’s potential for the professional development of teachers in this study.

Keywords: case study, Australia-Asia BRIDGE Project, teacher professional development, transnational learning networks

Procedia PDF Downloads 251
869 Placebo Analgesia in Older Age: Evidence from Event-Related Potentials

Authors: Angelika Dierolf, K. Rischer, A. Gonzalez-Roldan, P. Montoya, F. Anton, M. Van der Meulen

Abstract:

Placebo analgesia is a powerful cognitive endogenous pain modulation mechanism with high relevance in pain treatment. Older people would benefit, especially from non-pharmacologic pain interventions, since this age group is disproportionately affected by acute and chronic pain, while pharmacological treatments are less suitable due to polypharmacy and age-related changes in drug metabolism. Although aging is known to affect neurobiological and physiological aspects of pain perception, as for example, changes in pain threshold and pain tolerance, its effects on cognitive pain modulation strategies, including placebo analgesia, have hardly been investigated so far. In the present study, we are assessing placebo analgesia in 35 older adults (60 years and older) and 35 younger adults (between 18 and 35 years). Acute pain was induced with short transdermal electrical pulses to the inner forearm, using a concentric stimulating electrode. Stimulation intensities were individually adjusted to the participant’s threshold. Next to the stimulation site, we applied sham transcutaneous electrical nerve stimulation (TENS). Participants were informed that sometimes the TENS device would be switched on (placebo condition), and sometimes it would be switched off (control condition). In reality, it was always switched off. Participants received alternating blocks of painful stimuli in the placebo and control condition and were asked to rate the intensity and unpleasantness of each stimulus on a visual analog scale (VAS). Pain-related evoked potentials were recorded with a 64-channel EEG. Preliminary results show a reduced placebo effect in older compared to younger adults in both behavioral and neurophysiological data. Older people experienced less subjective pain reduction under sham TENS treatment compared to younger adults, as evidenced by the VAS ratings. The N1 and P2 event-related potential components were generally reduced in the older group. While younger adults showed a reduced N1 and P2 under sham TENS treatment, this reduction was considerably smaller in older people. This reduced placebo effect in the older group suggests that cognitive pain modulation is altered in aging and may at least partly explain why older adults experience more pain. Our results highlight the need for a better understanding of the efficacy of non-pharmacological pain treatments in older adults and how these can be optimized to meet the specific requirements of this population.

Keywords: placebo analgesia, aging, acute pain, TENS, EEG

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868 Magnetophotonics 3D MEMS/NEMS System for Quantitative Mitochondrial DNA Defect Profiling

Authors: Dar-Bin Shieh, Gwo-Bin Lee, Chen-Ming Chang, Chen Sheng Yeh, Chih-Chia Huang, Tsung-Ju Li

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Mitochondrial defects have a significant impact in many human diseases and aging associated phenotypes. The pathogenic mitochondrial DNA (mtDNA) mutations are diverse and usually present as heteroplasmic. mtDNA 4977bps deletion is one of the common mtDNA defects, and the ratio of mutated versus normal copy is significantly associated with clinical symptoms thus their quantitative detection has become an important unmet needs for advanced disease diagnosis and therapeutic guidelines. This study revealed a Micro-electro-mechanical-system (MEMS) enabled automatic microfluidic chip that only required minimal sample. The system integrated multiple laboratory operation steps into a Lab-on-a-Chip for high-sensitive and prompt measurement. The entire process including magnetic nanoparticle based mtDNA extraction in chip, mutation selective photonic DNA cleavage, and nanoparticle accelerated photonic quantitative polymerase chain reaction (qPCR). All subsystems were packed inside a miniature three-dimensional micro structured system and operated in an automatic manner. Integration of magnetic beads with microfluidic transportation could promptly extract and enrich the specific mtDNA. The near infrared responsive magnetic nanoparticles enabled micro-PCR to be operated by pulse-width-modulation controlled laser pulsing to amplify the desired mtDNA while quantified by fluorescence intensity captured by a complementary metal oxide system array detector. The proportions of pathogenic mtDNA in total DNA were thus obtained. Micro capillary electrophoresis module was used to analyze the amplicone products. In conclusion, this study demonstrated a new magnetophotonic based qPCR MEMS system that successfully detects and quantify specific disease related DNA mutations thus provides a promising future for rapid diagnosis of mitochondria diseases.

Keywords: mitochondrial DNA, micro-electro-mechanical-system, magnetophotonics, PCR

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867 A Qualitative Study Exploring Factors Influencing the Uptake of and Engagement with Health and Wellbeing Smartphone Apps

Authors: D. Szinay, O. Perski, A. Jones, T. Chadborn, J. Brown, F. Naughton

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Background: The uptake of health and wellbeing smartphone apps is largely influenced by popularity indicators (e.g., rankings), rather than evidence-based content. Rapid disengagement is common. This study aims to explore how and why potential users 1) select and 2) engage with such apps, and 3) how increased engagement could be promoted. Methods: Semi-structured interviews and a think-aloud approach were used to allow participants to verbalise their thoughts whilst searching for a health or wellbeing app online, followed by a guided search in the UK National Health Service (NHS) 'Apps Library' and Public Health England’s (PHE) 'One You' website. Recruitment took place between June and August 2019. Adults interested in using an app for behaviour change were recruited through social media. Data were analysed using the framework approach. The analysis is both inductive and deductive, with the coding framework being informed by the Theoretical Domains Framework. The results are further mapped onto the COM-B (Capability, Opportunity, Motivation - Behaviour) model. The study protocol is registered on the Open Science Framework (https://osf.io/jrkd3/). Results: The following targets were identified as playing a key role in increasing the uptake of and engagement with health and wellbeing apps: 1) psychological capability (e.g., reduced cognitive load); 2) physical opportunity (e.g., low financial cost); 3) social opportunity (e.g., embedded social media); 4) automatic motivation (e.g., positive feedback). Participants believed that the promotion of evidence-based apps on NHS-related websites could be enhanced through active promotion on social media, adverts on the internet, and in general practitioner practices. Future Implications: These results can inform the development of interventions aiming to promote the uptake of and engagement with evidence-based health and wellbeing apps, a priority within the UK NHS Long Term Plan ('digital first'). The targets identified across the COM-B domains could help organisations that provide platforms for such apps to increase impact through better selection of apps.

Keywords: behaviour change, COM-B model, digital health, mhealth

Procedia PDF Downloads 147
866 Phenotype Prediction of DNA Sequence Data: A Machine and Statistical Learning Approach

Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 156
865 Phenotype Prediction of DNA Sequence Data: A Machine and Statistical Learning Approach

Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 142
864 Performance Evaluation of the CSAN Pronto Point-of-Care Whole Blood Analyzer for Regular Hematological Monitoring During Clozapine Treatment

Authors: Farzana Esmailkassam, Usakorn Kunanuvat, Zahraa Mohammed Ali

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Objective: The key barrier in Clozapine treatment of treatment-resistant schizophrenia (TRS) includes frequent bloods draws to monitor neutropenia, the main drug side effect. WBC and ANC monitoring must occur throughout treatment. Accurate WBC and ANC counts are necessary for clinical decisions to halt, modify or continue clozapine treatment. The CSAN Pronto point-of-care (POC) analyzer generates white blood cells (WBC) and absolute neutrophils (ANC) through image analysis of capillary blood. POC monitoring offers significant advantages over central laboratory testing. This study evaluated the performance of the CSAN Pronto against the Beckman DxH900 Hematology laboratory analyzer. Methods: Forty venous samples (EDTA whole blood) with varying concentrations of WBC and ANC as established on the DxH900 analyzer were tested in duplicates on three CSAN Pronto analyzers. Additionally, both venous and capillary samples were concomitantly collected from 20 volunteers and assessed on the CSAN Pronto and the DxH900 analyzer. The analytical performance including precision using liquid quality controls (QCs) as well as patient samples near the medical decision points, and linearity using a mix of high and low patient samples to create five concentrations was also evaluated. Results: In the precision study for QCs and whole blood, WBC and ANC showed CV inside the limits established according to manufacturer and laboratory acceptability standards. WBC and ANC were found to be linear across the measurement range with a correlation of 0.99. WBC and ANC from all analyzers correlated well in venous samples on the DxH900 across the tested sample ranges with a correlation of > 0.95. Mean bias in ANC obtained on the CSAN pronto versus the DxH900 was 0.07× 109 cells/L (95% L.O.A -0.25 to 0.49) for concentrations <4.0 × 109 cells/L, which includes decision-making cut-offs for continuing clozapine treatment. Mean bias in WBC obtained on the CSAN pronto versus the DxH900 was 0.34× 109 cells/L (95% L.O.A -0.13 to 0.72) for concentrations <5.0 × 109 cells/L. The mean bias was higher (-11% for ANC, 5% for WBC) at higher concentrations. The correlations between capillary and venous samples showed more variability with mean bias of 0.20 × 109 cells/L for the ANC. Conclusions: The CSAN pronto showed acceptable performance in WBC and ANC measurements from venous and capillary samples and was approved for clinical use. This testing will facilitate treatment decisions and improve clozapine uptake and compliance.

Keywords: absolute neutrophil counts, clozapine, point of care, white blood cells

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863 In vitro Evaluation of Capsaicin Patches for Transdermal Drug Delivery

Authors: Alija Uzunovic, Sasa Pilipovic, Aida Sapcanin, Zahida Ademovic, Berina Pilipović

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Capsaicin is a naturally occurring alkaloid extracted from capsicum fruit extracts of different of Capsicum species. It has been employed topically to treat many diseases such as rheumatoid arthritis, osteoarthritis, cancer pain and nerve pain in diabetes. The high degree of pre-systemic metabolism of intragastrical capsaicin and the short half-life of capsaicin by intravenous administration made topical application of capsaicin advantageous. In this study, we have evaluated differences in the dissolution characteristics of capsaicin patch 11 mg (purchased from market) at different dissolution rotation speed. The proposed patch area is 308 cm2 (22 cm x 14 cm; it contains 36 µg of capsaicin per square centimeter of adhesive). USP Apparatus 5 (Paddle Over Disc) is used for transdermal patch testing. The dissolution study was conducted using USP apparatus 5 (n=6), ERWEKA DT800 dissolution tester (paddle-type) with addition of a disc. The fabricated patch of 308 cm2 is to be cut into 9 cm2 was placed against a disc (delivery side up) retained with the stainless-steel screen and exposed to 500 mL of phosphate buffer solution pH 7.4. All dissolution studies were carried out at 32 ± 0.5 °C and different rotation speed (50± 5; 100± 5 and 150± 5 rpm). 5 ml aliquots of samples were withdrawn at various time intervals (1, 4, 8 and 12 hours) and replaced with 5 ml of dissolution medium. Withdrawn were appropriately diluted and analyzed by reversed-phase liquid chromatography (RP-LC). A Reversed Phase Liquid Chromatography (RP-LC) method has been developed, optimized and validated for the separation and quantitation of capsaicin in a transdermal patch. The method uses a ProntoSIL 120-3-C18 AQ 125 x 4,0 mm (3 μm) column maintained at 600C. The mobile phase consisted of acetonitrile: water (50:50 v/v), the flow rate of 0.9 mL/min, the injection volume 10 μL and the detection wavelength 222 nm. The used RP-LC method is simple, sensitive and accurate and can be applied for fast (total chromatographic run time was 4.0 minutes) and simultaneous analysis of capsaicin and dihydrocapsaicin in a transdermal patch. According to the results obtained in this study, we can conclude that the relative difference of dissolution rate of capsaicin after 12 hours was elevated by increase of dissolution rotation speed (100 rpm vs 50 rpm: 84.9± 11.3% and 150 rpm vs 100 rpm: 39.8± 8.3%). Although several apparatus and procedures (USP apparatus 5, 6, 7 and a paddle over extraction cell method) have been used to study in vitro release characteristics of transdermal patches, USP Apparatus 5 (Paddle Over Disc) could be considered as a discriminatory test. would be able to point out the differences in the dissolution rate of capsaicin at different rotation speed.

Keywords: capsaicin, in vitro, patch, RP-LC, transdermal

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862 The Revival of Cultural Heritage through Social Space Upliftment: Case Study of the Walled City of Ajmer, India

Authors: Vaishali Sharma

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The research is an attempt to hunt a scientific and objective method to transform Ajmer's traditional walled city into a living cultural heritage space, exploring urban management methods to elevate local economy and social space in relation to specific cultural-based initiatives. Ajmer is among the oldest and religiously diverse settlements in Rajasthan, that has seen superimposed developments through the eras. With numerous agencies operating towards the development of the town core of Ajmer, it becomes essential to structure development changes in tune with the transformations and the existing heritage. The study was radio-controlled by the subsequent analysis question: What is the way to overcome the genetic social and economic stress inside the communities and revive public life? In order to create necessary interventions at the neighbourhood level, fifteen neighbourhoods were identified. Each of those was analyzed relatively on three major dimensions: Heritage, Social and Local Economy. Each dimension was further broken down into multiple sub-aspects for an overall and exhaustive understanding. The average median values of the responses were used to develop a color-coded matrix to represent the scores in an exceedingly structured quantified manner, moreover, linking it to the spatial structure. Respondent perceptions on numerous dimensions were additionally recorded, so that the proposals are inclusive in nature. The goals are targeted at Ajmer's traditional walled towns, which will make it easier for the community to regulate the rapid transformations and commercialization occurring within the space. The study recommends the necessity for accrued support in methods and policies from the non-public sector, businesses as well as local stakeholders. An expansion, revitalization and maintenance of the major business and heritage corridors, for an increased local and visitor experience, can produce an impetus for promotion of the intangible heritage, to spur the local economic processes, conservation of heritage precincts and upward development.

Keywords: cultural heritage, economic revitalization, neighbourhoods in walled cities, social space, tangible and intangible heritage

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861 Pre-Operative Psychological Factors Significantly Add to the Predictability of Chronic Narcotic Use: A Two Year Prospective Study

Authors: Dana El-Mughayyar, Neil Manson, Erin Bigney, Eden Richardson, Dean Tripp, Edward Abraham

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Use of narcotics to treat pain has increased over the past two decades and is a contributing factor to the current public health crisis. Understanding the pre-operative risks of chronic narcotic use may be aided through investigation of psychological measures. The objective of the reported study is to determine predictors of narcotic use two years post-surgery in a thoracolumbar spine surgery population, including an array of psychological factors. A prospective observational study of 191 consecutively enrolled adult patients having undergone thoracolumbar spine surgery is presented. Baseline measures of interest included the Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia, Multidimensional Scale for Perceived Social Support (MSPSS), Chronic Pain Acceptance Questionnaire (CPAQ-8), Oswestry Disability Index (ODI), Numeric Rating Scales for back and leg pain (NRS-B/L), SF-12’s Mental Component Summary (MCS), narcotic use and demographic variables. The post-operative measure of interest is narcotic use at 2-year follow-up. Narcotic use is collapsed into binary categories of use and no use. Descriptive statistics are run. Chi Square analysis is used for categorical variables and an ANOVA for continuous variables. Significant variables are built into a hierarchical logistic regression to determine predictors of post-operative narcotic use. Significance is set at α < 0.05. Results: A total of 27.23% of the sample were using narcotics two years after surgery. The regression model included ODI, NRS-Leg, time with condition, chief complaint, pre-operative drug use, gender, MCS, PCS subscale helplessness, and CPAQ subscale pain willingness and was significant χ² (13, N=191)= 54.99; p = .000. The model accounted for 39.6% of the variance in narcotic use and correctly predicted in 79.7% of cases. Psychological variables accounted for 9.6% of the variance over and above the other predictors. Conclusions: Managing chronic narcotic usage is central to the patient’s overall health and quality of life. Psychological factors in the preoperative period are significant predictors of narcotic use 2 years post-operatively. The psychological variables are malleable, potentially allowing surgeons to direct their patients to preventative resources prior to surgery.

Keywords: narcotics, psychological factors, quality of life, spine surgery

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